HIV/AIDS: Naturopathic Medical Principles and Practice

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Chapter 173 HIV/AIDS

Naturopathic Medical Principles and Practice

Kevin L. Conroy, ND, Steven C. Milkis, ND

Diagnostic Summary

• A diagnosis of human immunodeficiency virus–positive (HIV+) infection is most commonly made after a positive test for HIV antibodies by enzyme-linked immunosorbent assay (ELISA); it is confirmed via Western blot analysis.

• An acute onset (acute antiretroviral syndrome) resembles common influenza. Most persons experience this syndrome 2 to 6 weeks after initial infection; it often goes undiagnosed as HIV owing to its similarity to the flu. Signs and symptoms can include fever, lymphadenopathy, skin rash, pharyngitis, myalgia, arthralgia, headache, diarrhea, and oral ulcerations. Laboratory findings might include leukopenia, thrombocytopenia, and elevated transaminases.

• An insidious onset may manifest as an acquired immunodeficiency syndrome (AIDS)–associated opportunistic infection (OI) or as unexplained progressive fatigue, weight loss, fever, diarrhea, or generalized lymphadenopathy.

• AIDS is diagnosed after positive serology and either a CD4+ T-cell count at or below 200/mm³ or the presence of a designated AIDS-indicator condition (from the Centers for Disease Control and Prevention [CDC] guidelines of 2008). Primary infection is also characterized by a high level of virus production, high concentrations of viral particles and RNA in plasma, and a rapid and steep decline in CD4+ T-helper cells. Peak viral titers can reach 10⁷ virons per milliliter during this phase. Viral production can range up to 10 billion copies per day. After the initial viremia, high levels of viral p24 antigen appear.

• The lower the CD4+ count and the higher the viral load, the higher the risk of contracting OIs, neoplasms, or neurologic abnormalities and the higher the mortality rate.

• Groups at high risk for contracting HIV include injection drug users, homosexual and bisexual men, hemophiliacs and others receiving transfused blood or other blood products (highest risk to recipients before May 1985, when regular screening of the blood supply began), regular sex partners of people in the aforementioned groups, heterosexual people with greater than one sex partner in the past 12 months, and those who have had unprotected sex during the previous 6 months.

Introduction

HIV has been described as a retrovirus containing two single strands of RNA. It enters the body via the transfer of body fluids and subsequently binds to and infects CD4-expressing cells of the human immune system (T-helper lymphocytes, blood monocytes, tissue macrophages, Langerhans cells in the skin, and microglial and multinucleated cells in the central nervous system). AIDS is a secondary syndrome resulting from long-term HIV infection. AIDS is defined by one or more of the following: levels of CD4+ cells, the presence of certain specific indicator conditions, or secondary malignancies known to be associated with HIV. Many theories exist as to what causes AIDS, ranging from HIV to multifactorial (environmental and infectious) assaults on the immune system. In this science’s infancy, there is no definitive answer, but current medical thinking is that AIDS is caused by HIV.

Focus and Goals of Chapter

This chapter is written for the naturopathic physician, although conventionally trained physicians and other holistic practitioners may find the perspective, treatment principles, and some of the treatment suggestions helpful. The field of HIV/AIDS medicine is rapidly changing. HIV/AIDS was first reported to the CDC only in 1981, and it has since exploded into an international pandemic. Highly active antiretroviral drug therapy (HAART), introduced in 1996, is the use of multiple drugs in combination with the goal of decreasing viral load and increasing CD4+ T-cell counts. Although this innovation resulted in a dramatic slowing in the death rate from AIDS, with it came complicated drug side effects, drug interactions, and unique symptoms that require frequent follow-up between the patient and physician and affect the quality of life of individuals on those regimens.

Studies indicate that more than 70% of HIV+ persons are using some form of complementary/alternative medicine (CAM) in their treatment, resulting in improvements in their quality of life and better outcomes.¹ The goal of this chapter is to help the physician better understand the condition and to appropriately guide this affected population with unique and complicated health issues.

Biology of HIV

Two types of HIV have been identified. HIV-1 is found throughout the world. The majority of infections in the United States are caused by HIV-1. HIV-2 was first identified in West Africa in 1986 and has been found to have a genetic sequence approximately 50% similar to HIV-1. HIV-2 is considered less virulent than HIV-1 and shows lower rates of sexual and perinatal transmission and a lower viral load with a slower rate of CD4 cell decline. This results in a slower rate of disease progression in infected people.² Research shows that the virus is mutating, and multiple subtypes or clades are spreading throughout the world.¹ The existence of multiple clades raises the theoretical possibility that a single individual could become infected with multiple subtypes of the virus. Research has not conclusively demonstrated the existence of a “superinfection,” but the possibility of this phenomenon would significantly enhance virulence as well as increase resistance to present treatments.

Existing research has failed to isolate an intact HIV entity; although fragments believed to belong to the HIV virus have been isolated and identified. Despite this shortcoming, the virus is believed to consist of a bilayer lipid envelope covered with envelope glycoproteins (gp120 receptor and gp41 transmembrane), a viral core containing two single strands of RNA and the reverse transcriptase enzyme, and structural core proteins (p24 capsid protein and p18 matrix protein). It is believed that HIV binds to CD4-expressing cells of the immune system and, through a series of steps, replicates itself and incorporates its genome into the host cell’s genome.

The various classes of antiretroviral medications have been developed to interrupt viral replication during various steps in this process. The key to understanding the mechanisms of action of the various medications is to understand those steps. Fusion is the process by which the HIV particle contacts and binds to the target cell. This occurs through the interaction of the viral gp120 and gp41 transmembrane proteins with CD4 and chemokine receptors on the cell’s membrane. Fusion inhibitors are designed to inhibit this process by altering the cellular receptor sites. Transcription occurs when the viral reverse transcriptase enzyme translates the viral RNA into a double strand of DNA. Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) are designed to disrupt this process.

Integration occurs when the double strand of proviral DNA migrates to the cell’s nucleus and is inserted into the host’s chromosome via the integrase enzyme. The provirus is then permanently integrated into the host DNA. It can remain essentially dormant (equilibrium of viral production and destruction) or become activated and initiate the production of large chains of new viral RNA subunits independent of the host cell’s replication process. Integrase inhibitors prevent the integrase enzyme from inserting the viral DNA into the host DNA. After a period of normal cell function, the infected cell becomes activated, initiating transcription of the proviral DNA into mRNA, which is then translated in the cytoplasm to produce long chains of viral polypeptides. Cleavage occurs when the protease enzyme cuts up these viral polypeptides. The pieces are then joined together to form new retroviruses. Protease inhibitors block the action of the protease enzyme and thereby prevent the reassembly of new viral polypeptides. Packaging is a poorly understood step in this process, where the new RNA viruses are wound up tightly and encapsulated into new viral particles. Budding occurs when the HIV nucleocapsid containing the new viral RNA moves to the host cell’s membrane and binds to the inside of the membrane. It is then enveloped by the membrane as it leaves the cell.

Transmission

HIV has been found in body fluids and tissues that contain lymphocytes. This includes blood and blood products, semen, vaginal fluids, breast milk, cerebrospinal fluid, synovial fluid, pleural fluid, amniotic fluid, and infected tissues. It has also been found in small amounts in saliva, tears, feces, and urine. According to the CDC, the only documented cases of transmission are via blood, semen, vaginal secretions, breast milk, and transplanted organs from an infected person. Variables affecting transmission rates include the infectivity of the source partner (higher viral load), the presence of sexually transmitted diseases (STDs) (especially with ulcerations), and the type of contact (increased risk with anal intercourse and vaginal intercourse during menses because blood is present).

The most significant routes of transmission are via sexual contact (vaginal, anal, and less frequently oral intercourse); intravenous drug use (sharing contaminated needles and syringes); transfusion of blood or blood products (highest risk prior to May 1985 when screening of the blood supply in the United States for HIV began); and from an HIV-infected mother to her baby (before or during birth or through breastfeeding). Transmission can also potentially occur via percutaneous needlestick, mucous membrane exposure, or exposure of infected fluid into an open wound. Studies show the risk of seroconversion following a needlestick from an HIV+ source to be 0.25% per exposure. They also show that there have been no known seroconverters following splash exposure. The CDC has identified one documented case of transmission from acupuncture.

There is no evidence that HIV can be transmitted via air, water, insects, or dried body fluids. Universal infection control precautions as developed by the CDC should always be employed by health care workers to minimize the risk of HIV transmission in the health care setting. Always assume that all blood and body fluids are potentially hazardous and that all patients are potentially infected.³

The Immune System’s Response

Both the humoral and cellular immune systems have a role in the body’s response to HIV infection. The humoral response involves the initial production of transient IgM antibodies to viral core and envelope proteins. Permanent IgG antibodies are subsequently established (this may take several weeks) to core p24 and envelope gp160, gp120, and gp41, corresponding to the resolution of clinical symptoms. The development of these IgG antibodies results in a rapid decrease in circulating virons and p24 antigen titers. Seroconversion occurs when the body starts making antibodies to HIV antigens and those antibodies become detectable by conventionally used laboratory tests (enzyme-linked immunoassays and Western blot analysis).

There is a window of time between initial infection (when patients remain antibody-negative or seronegative as measured by ELISA tests) and when seroconversion (antibody-positive or seropositive by ELISA) occurs. The length of this window varies depending on the individual and can range from 10 to 14 days to 6 months. The cellular immune response is characterized by the elevation of various cytokines (including interferons and tumor necrosis factor), CD4+ lymphopenia, and CD8+ lymphocytosis. Cytotoxic T cells reduce the plasma viremia, whereas natural killer (NK) cells may be involved with killing infected T cells.

Clinical Progression to AIDS

Assuming no antiretroviral treatment, a typical scenario of HIV infection might unfold as follows: Within 2 to 3 weeks of initial infection with the virus, an acute retroviral syndrome occurs. Recovery and seroconversion usually follow in 2 to 3 weeks. After recovery from the initial acute syndrome, HIV plasma concentrations decline to a viral “set point” and equilibrium is established between the production and destruction of CD4+ cells. The level of viral replication after acute infection and seroconversion coupled with the CD4+ count is predictive of long-term prognosis. A lower level of replication with a higher CD4+ count indicates a longer asymptomatic course. Conversely, a higher level of replication with lower CD4+ counts generally indicates a shorter asymptomatic course. Over time, a gradual decline in T-cell numbers begins with a concurrent gradual increase in the amount of virus in the body. This period can last 5 to 15 years. Eventually there are not enough T cells for the body’s immune system to function properly. This is when the risk of OIs increases, with the ultimate result being death.⁴

Box 173-1 lists the CDC’s 2008 revised surveillance case definition of AIDS for adults and adolescents (13 years of age or older). It creates stages of HIV infection based on CD4+ cell counts/percentages and/or clinical symptoms. The primary criterion used is positive serology (i.e., positive for antibodies to HIV via ELISA and Western blot testing and/or positive HIV antigen detection via polymerase chain reaction [PCR] or other specific HIV antigen test). Given a positive serology, a diagnosis of stage 3 HIV or AIDS is given when CD4+ counts fall below 200/mm³ (<14%), any of the noted AIDS-defining conditions occurs, or both.⁵

BOX 173-1 Centers for Disease Control and Prevention (CDC) 2008 Surveillance Case Definition for HIV Infection among Adults and Adolescents above 13 Years of Age ^*

Stage 1: CD4+ T-lymphocyte count of >500/microliter (µl) or >29%; no clinical evidence required and no AIDS-defining condition present

Stage 2: CD4+ T-lymphocyte count of 200 to 299/µL or 14% to 28%; no clinical evidence required and no AIDS-defining condition present

Stage 3 (AIDS): CD4+ T-lymphocyte count <200 /µL or <14% or documentation of an AIDS-defining condition

Stage unknown: no information of CD4+ T-lymphocyte count or percentage; no information on presence of AIDS-defining conditions

The specific AIDS indicator conditions include the following:

Candidiasis of esophagus, bronchi, trachea, or lungs

Cervical cancer, invasive

Coccidioidomycosis, disseminated or extrapulmonary

Cryptococcosis, extrapulmonary

Cryptosporidiosis, chronic intestinal (>1 month’s duration)

Cytomegalovirus disease (other than liver, spleen, or lymph nodes), onset at age >1 month

Cytomegalovirus retinitis (with loss of vision)

Encephalopathy, HIV-related

Herpes simplex with chronic ulcers (>1 month’s duration) or bronchitis, pneumonitis, or esophagitis (onset at age >1 month)

Histoplasmosis, disseminated or extrapulmonary

Isosporiasis, chronic intestinal (>1 month’s duration)

Kaposi sarcoma

Lymphoid interstitial pneumonia or pulmonary lymphoid hyperplasia complex

Lymphoma—Burkitt’s, immunoblastic, primary (brain/central nervous system)

Mycobacterium avium complex or Mycobacterium kansasii, disseminated or extrapulmonary

Mycobacterium tuberculosis of any site, pulmonary, disseminated, or extrapulmonary

Pneumocystis jirovecii pneumonia

Pneumonia, recurrent

Progressive multifocal leukoencephalopathy

Salmonella septicemia, recurrent

Toxoplasmosis of brain, onset at age >1 month

Wasting syndrome due to HIV—involuntary weight loss >10% of baseline plus chronic diarrhea (>2 loose stools/day for >30 days) or chronic weakness and documented enigmatic fever >30 days

From Schneider E, Whitmore S, Glynn KM, et al. Revised surveillance case definitions for HIV infection among adults, adolescents, and children aged <18 months and for HIV infection and AIDS among children aged 18 months to <13 years United States, 2008. Morbidity Mortality Weekly Report, 2008, Dec 5; 57(RR10);1-8.

^* In all stages laboratory confirmation is required.

Clinically, patients tend to be susceptible to certain complications (both infectious and noninfectious) on the basis of their CD4+ cell counts.⁶ Although there is always individual variation, these data are helpful in predicting probable clinical presentations. Generally a higher viral load represents a greater risk for complications and should always be factored into any such consideration.

• When the CD4+ cell count is greater than 500/mm³, a patient could manifest acute retroviral syndrome, candidal vaginitis, persistent generalized lymphadenopathy (PGL), Guillain-Barré syndrome, myopathy, or aseptic meningitis.

• When the CD4+ count is between 200 and 500/mm³, possible complications include pneumococcal or other bacterial pneumonia, pulmonary tuberculosis, herpes zoster, oropharyngeal candidiasis/thrush, cryptosporidiosis (self-limited), Kaposi sarcoma, oral hairy leukoplakia, cervical and anal dysplasia/cancer, B-cell lymphoma, anemia, mononeuritis multiplex, idiopathic thrombocytopenic purpura, Hodgkin’s lymphoma, or lymphocytic interstitial pneumonitis.

• When the CD4+ count is below 200/mm³, complications might include Pneumocystis jirovecii pneumonia, disseminated histoplasmosis and coccidioidomycosis, miliary/extrapulmonary tuberculosis, progressive multifocal leukoencephalopathy (PML), wasting, peripheral neuropathy, HIV-associated dementia, cardiomyopathy, vacuolar myelopathy, progressive polyradiculopathy, or non-Hodgkin’s lymphoma.

• When the CD4+ count is below 100/mm³, complications might include disseminated herpes simplex, toxoplasmosis, cryptococcosis, chronic cryptosporidiosis, microsporidiosis, or candidal esophagitis.

• When the CD4+ count is below 50/mm³, complications might include disseminated cytomegalovirus (CMV), disseminated Mycobacterium avium complex (MAC), or central nervous system lymphoma.

Diagnosis and Work up

Diagnostic Testing

Box 173-2 lists the most recent CDC guidelines for HIV testing.⁷ Standard serologic testing for the presence of HIV begins with an ELISA test using recombinant antigens to measure antibodies to HIV in the blood.⁸ If this test is positive, it is repeated on the same blood sample. If it is positive a second time, a Western blot test (using electrophoresis to detect antibodies to specific HIV proteins) is used for confirmation.⁹ Together, these tests have a sensitivity and specificity approaching 100%.

BOX 173-2 Revised Recommendations for HIV Testing of Adults, Adolescents, and Pregnant Women in Health Care Settings as of 2006

Screening for HIV Infection

• Routine testing for all patients 13 to 64 years old

• Pregnant women

• All patients initiating treatment for tuberculosis

• All patients seeking treatment or evaluation at clinics treating sexually transmitted diseases

• All persons with signs or symptoms consistent with HIV or with an opportunistic infection consistent with HIV/AIDS

Repeat Screening

• Annual screening (minimally) for persons in high-risk groups (includes injection-drug users and their sex partners, persons who exchange sex for money or drugs, sex partners of HIV-infected persons, and men who have sex with men or heterosexual persons who themselves or whose sex partners have had more than one sex partner since their most recent HIV test)

• Patients and their prospective partners before initiating a new sexual relationship

• Any person whose blood or body fluid is the source of an occupational exposure to a health care provider should be informed of the incident and tested at the time of the exposure

Data from Branson BM, Handsfield HH, Lampe MA, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. Morbidity Mortality Weekly Report, 2006, Sept 22;55(RR14):1-17.

A number of rapid HIV tests have been developed and are currently approved for use by the U.S. Food and Drug Administration (FDA). They all use similar technology to detect antibodies and vary in category assigned by the Clinical Laboratory Improvement Amendments (CLIA) from “waived” to “moderately complex.” Options include OraQuick Advance, Uni-Gold Recombigen, Reveal G-3, MultiSpot Rapid Test, Clearview Stat-Pak, Clearview Complete, and Vitros. Additionally, Home Access Health Corp. (www.HomeAccess.com) produces a kit where the specimen is self-obtained at home and mailed in for analysis. Results are available in 1 or 5 days depending on the price paid. These tests use either whole blood, serum, plasma, or oral fluids and have sensitivity and specificity rates of 99% to 100%.^10,¹¹ If an ELISA test is negative and risk factors suggest likely infection, the test should be repeated at 6-week, 3-month, and 6-month intervals. There is no reason to repeat if one of those tests comes back positive.

Although routine testing is now recommended, HIV testing remains voluntary. Testing recommendations should be discussed with each individual patient and informed consent (either written or verbal) obtained prior to testing. Patients have the right to opt out should they wish to do so. Risk screening should be incorportated into routine primary care and risk reduction counseling offered as applicable. All states require that newly diagnosed cases of HIV/AIDS be reported to local health departments and that providers have case reporting forms available.

Medical History

Initiation of care of an HIV+ patient should begin with a standard medical history including a detailed diet history, exercise patterns, and a complete review of systems. A number of additional historical details should be obtained as well (Box 173-3).

BOX 173-3 Historical Data Recommended for HIV-Positive Patients

• Dates of infection and subsequent diagnosis, as well as probable source of infection (IV drug use, sexual contact, transfusion). If date of infection is unknown, the naturopathic physician should determine if there was any history of acute retroviral syndrome. Additionally, past and current risk factors for HIV exposure should be determined. This information helps to estimate overall health and vital force and long-term prognosis.

• Vaccination history and adverse reactions to past vaccines.

• History of other sexually transmitted diseases. This information should include date and duration of infection as well as therapies (efficacy, adverse reactions, and duration of treatment). Particular infections to screen for include syphilis, gonorrhea, Chlamydia, herpes simplex (all types), hepatitis (A, B, and C or E), and HPV (skin, genital, or anal).

• Chronologic history of HIV-related problems including history of OIs or cofactor viruses/infections (mononucleosis, EBV, molluscum contagiosum, CMV, or yeast infections—vaginal, gastrointestinal, skin), skin rashes or other lesions, oral lesions or tongue coating, lymphadenopathy, fevers, night sweats, weight loss, diarrhea, anorexia, fatigue, malaise, shortness of breath, or cough.

• Specific for females, history of abnormal Pap smears and frequency of gynecologic examinations.

• HIV viral load and trend of CD4 count; good indicators of the patient’s susceptibility to OIs, indication for and effectiveness of HAART, as well as long-term prognosis.

• History of all past and present HAART as well as all other prophylactic antibiotic prescription medication with duration of treatment, response and side effects, intolerance, and allergies.

• Family history of chronic disease, with particular emphasis on cardiovascular disease (including lipid problems), diabetes, and cancer.

• History of psychoemotional trauma and issues (abuse history, anxiety, depression).

• Patients’ spiritual lives and support systems, life goals, and meaning of HIV in their lives.

• Clear identification of complete medical care team as well as reasons for seeking naturopathic medical care.

• The initial physical examination must be both comprehensive and appropriately focused as directed by the history. In addition, all patients should have particularly thorough examinations of the mouth and throat, skin, and genitalia. If a full pelvic examination and Pap smear cannot be done on a new female patient at the initial evaluation, these should be scheduled for shortly thereafter.

CMV, cytomegalovirus; EBV, Epstein-Barr virus; HAART, highly active antiretroviral drug therapy; HIV, human immunodeficiency virus; HPV, human papillomavirus; IV, intravenous; OI, opportunistic infection.

Laboratory Assessment and Monitoring

Basic initial screening tests for all HIV+ patients should include a complete blood count (CBC) and a fasting serum chemistry panel (to monitor liver, kidney, and pancreatic function; electrolytes; blood proteins; glucose; and lipids). The baseline serum albumin level can serve as an independent predictor of prognosis in HIV+ women.¹² Additional testing should include a urinalysis, screening for STDs (syphilis, Chlamydia, gonorrhea, herpes simplex), hepatitis (A, B, and C), toxoplasmosis, tuberculosis, and varicella (if unknown history of chickenpox or shingles). An optional test is glucose-6-phosphate dehydrogenase (based on risk factors).¹¹ Female patients should have regular Pap smears with initial testing for human papillomavirus (HPV), because there is a significant increase in cervical cancer rates in HIV+ women.¹³ A recent development is the use of the anal Pap smear in male patients engaging in anal sex. Anal squamous cell cancer is similar to cervical cancer in that it is caused by HPV infection and rates are increased in HIV+ men as compared with the general population. Currently, there is some controversy about the use of this test, with no clear consensus on whether to make it part of routine screening. Studies are ongoing.¹¹

HIV-specific testing includes measurement of viral load and T-cell counts as part of the initial evaluation and then at 3- to 6-month intervals. The viral load test detects the presence of viral RNA in the plasma or DNA in white blood cells (WBCs) and uses PCR branched-chain DNA (bDNA) or nucleic acid sequence–based amplification technology. A number of viral load tests exist with varying levels of sensitivity. The most sensitive test currently available detects virus to 20 copies per cubic millimeter of plasma.¹⁴ Below any specific test’s threshold, the viral load is deemed “undetectable.” This means that the virus may exist in concentrations in the blood below the ability of the given test to detect. Additionally, note that these assays are not reflective of viral presence or concentration in body compartments beyond the blood (e.g., tissues, cerebrospinal fluid, breast milk). This is an important point for patients to understand, as they can still infect others even if the virus is “undetectable” according to the test they were given.

Other key tests involve T-cell counts. CD4+ helper cells and CD8+ suppressor cells are quantified (absolute numbers and relative percentages), along with the CD4:CD8 ratio. This information is used to stage HIV, predict susceptibility to various OIs, and monitor response to antiretroviral therapy. Many factors can influence CD4+ cell counts, including total WBCs, acute infection, certain medications (e.g., corticosteroids, interferon), as well as other medical conditions. There are also seasonal and diurnal variations in these counts.

Resistance to antiretroviral medications is a growing problem in treatment-naive patients and remains a problem in patients currently undergoing this therapy. Therefore, resistance testing is now recommended at the time of diagnosis as part of baseline screening as well as before changing therapy owing to failure of a current regimen. Two types of tests are available: genotypic and phenotypic. There are advantages and disadvantages to each, but in general this testing can help to identify antiviral medications that the patient might be either resistant or susceptible to and thereby allow the physician to formulate the most effective medication regimen.¹¹

Therapeutic Considerations

Medical Management of HIV and AIDS

The medical understanding and treatment of HIV/AIDS continue to evolve. AIDS is a complex, multifactorial disease that has both immunodeficiency and autoimmune inflammatory aspects involving virtually every system of the body. HIV enters the body and infects CD4+-expressing cells of the immune system. It inserts itself into cellular DNA and can lie dormant indefinitely. Those cells can be activated for the reproduction and multiplication of HIV virions by antigens, oxidative stress, proinflammatory cytokines, and overstressed liver detoxification and immune systems.

Conventional medical management of HIV/AIDS revolves around the following treatment principles:

• Frequent monitoring, including laboratory and physical examination

• Vaccinations administered as appropriate (may include hepatitis A, hepatitis B, influenza, mumps-measles-rubella [MMR], pneumonia tetanus-diptheria, varicella, HPV, and travel-related vaccines)¹¹

• Highly active antiretroviral therapy (HAART) for inactivation or slowing HIV replication and increasing CD4+ cell counts

• Antibiotic prophylaxis for patients with abnormally low CD4 lymphocyte counts

• Antimicrobial treatment of OIs

• Symptomatic care of HIV- or HAART-induced adverse drug reactions

• Radiation, chemotherapy, or both for HIV-related neoplasms

• Psychosocial support via counseling, clinical social work, and medication

Up-to-date resources should always be consulted prior to making any management decisions. The AIDS information website, administered by the U.S. Department of Health and Human Services (www.aidsinfo.nih.gov/) provides an excellent resource for determining the most up-to-date conventional treatment guidelines as well as information on prevention, FDA-approved and investigational drugs, clinical trials, and vaccinations. Another fine resource is the Johns Hopkins AIDS website (www.hopkinsguides.com). Their HIV guide provides detailed information on the diagnosis and management of HIV and its associated OIs, medications, and resistance. Johns Hopkins University School of Medicine/Knowledge Source Solutions LLC also publishes a helpful text called the Medical Management of HIV Infection, 2009-10, 15th ed, by JG Bartlett, JE Gallant, and PA Pham. It can be ordered on the website. The best resource for patient education is www.thebody.com/index.shtml. This site contains valuable information on signs, symptoms, treatments, and future possibilities, all from a patient-centered perspective.

Naturopathic Management of HIV and AIDS

The naturopathic medical management of HIV and AIDS revolves around a number of treatment principles that should guide the physician in helping patients to optimize their health, slow disease progression, improve their quality of life, and improve immune function.

Specific goals include the following:

A resource specifically geared toward complementary practitioners is AIDS and Complementary and Alternative Medicine, Current Science and Practice by Standish, Calabrese, and Galantino, published by Churchill Livingstone in 2002.

Enhance Overall Integration with Primary Care Physicians and Build a Caregiving Team

In the area of HIV, naturopathic physicians should lead the effort to optimize integrated care. A holistic provider who identifies advantages of all available treatments and encourages positive relationships with all available providers creates a unique and trusting relationship with patients who have often experienced lifetimes of fear, discrimination, victimization, and abuse. Naturopathic medicine offers an important opportunity to empower HIV+ patients.

One of the first priorities is to ensure that each HIV+ patient has a complete care-providing team beginning with a conventional Western medicine HIV specialist. HIV specialists ensure the accessibility of HAART when appropriate and have the greatest familiarity with the multitude of signs, symptoms, adverse reactions, and other issues unique to the HIV+ population. A growing body of literature reports that HIV+ patients have better objective indices of health (low viral load and high CD4 counts), better compliance with medications, and better long-term survival when they work with HIV specialists.^15,¹⁶

The specialist’s obligations constitute a full-time job, precluding many other aspects of care that have demonstrated efficacy for the overall health of HIV+ patients. Additional providers can support HIV+ patients with general health and lifestyle promotion, specific nutrient and other nondrug recommendations, social services, psychoneuroimmunologic support, counseling, personal empowerment, and end-of-life care. In fact, although naturopathic physicians might be legally able to prescribe prophylactic antimicrobial therapy and HAART in a growing number of states, the greater need is to provide nondrug holistic care in the areas just mentioned.

Complement and Enhance the Positive Effects of Conventional Medical Treatment and Minimize the Negative Effects

One of the paradigms of natural/preventative/holistic medicine is to minimize the need for higher-force (drug, surgery, radiation) interventions. This goal remains valid in the care of patients with HIV, but there are no therapies known to be as effective as HAART in suppressing viral load or increasing CD4 T-lymphocyte cell numbers. CAM providers may be the best practitioners to teach HIV+ patients that there are no realistic “alternatives” to HAART. Risks of OIs and other serious complications increase exponentially when CD4 cell counts drop below 200/µL. The current standard of care is to initiate HAART when the CD4 count drops below 350/µL in asymptomatic patients, those with an AIDS-defining illness (regardless of CD4 count), pregnant women, patients with HIV-associated nephropathy, or hepatitis B coinfection (when treatment of the hepatitis is indicated). HAART initiation may be considered when CD4 cell counts are greater than 350/µL in discordant relationships (one partner is HIV+ and the other HIV–), rapid CD4 decline, advanced age, or high viral load (more than 100,000 copies per milliliter).¹⁷ The choice of specific antiretrovirals for either initial regimens or the modification of existing therapy is complex, and there are many factors to consider. Additionally, the guidelines change frequently. The best resource for the most current recommendations is the “Guidelines for the Use of Antiretroviral Agents in HIV-1-infected Adults and Adolescents,” available on the AIDS information website (www.aidsinfo.hih.gov/ContentFiles/AdultandAdolescentGL.pdf). The most recent guidelines were compiled on December 1, 2009.

Some HIV+ patients may never need HAART and others may be resistant to HAART, but the option of HAART should always be considered and should not be discouraged. With or without HAART, there is significant evidence that HIV+ patients receive many benefits from nondrug therapies.¹⁸ Naturopathic physicians must actively understand, integrate, and use the entire therapeutic order (most subtle, lower force through most high force, often invasive therapies) to ensure that each patient has the best options to maximize his or her quality of life as well as length of life. Finally, physicians working with HIV must stay current with the global effort to find solutions for this pandemic in order to provide the best possible treatment options to match patients’ short-term needs while also including strategic health goals and future possibilities.

Factors to be considered in the holistic care of HIV+ patients include complications (from immune suppression) of health challenges that existed prior to HIV infection. In addition, the social, psychological, and spiritual challenges that exist with the diagnosis of HIV create a need for health care that extends far beyond the best drug or nutrient necessary for optimal heath. Holistic physicians have a vital role in the care of each patient with HIV.

The majority of HIV+ patients in North America are using HAART. Many of those same patients are also using CAM therapies. Therefore, one of the first priorities of the naturopathic provider should be to ensure that the patient is safe from adverse drug-nutrient interactions. In order to ensure safety, it is necessary to understand the mechanisms of HAART as well as those of common nutrients being used by HIV+ patients.

Five main classes of HAART are currently being used in the care of HIV+ patients in various combinations designed to disrupt the virus’ life cycle at multiple junctures.¹⁷ These include:

• Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs, or “nukes”)

• Nonnucleoside reverse transcriptase inhibitors (NNRTIs, or “nonnukes”)

• Protease inhibitors (PIs)

• Entry inhibitors (including fusion inhibitors and CCR5 inhibitors)

• Integrase inhibitors

Additionally, a number of fixed-dose formulations exist that combine multiple drugs and classes. This has helped to simplify dosing and decrease pill burden for patients using HAART.

As a result of the rapidly evolving resistance of HIV to specific drugs, there has been great pressure to quickly develop and approve new medications. As a result, most HAART medications have been generally fast-tracked through the FDA approval process. Therefore, new drugs are typically prescribed as soon as they are approved and usually before the full extent of their adverse reactions are known. As the adverse drug reactions and interactions with HAART are myriad and potentially quite harmful, the clinician is advised to consult up-to-date resources to determine specific issues with each individual medication.

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors

NRTIs were the first class of antiretroviral drugs approved for use in the United States by the FDA. These drugs work during the transcription phase of the HIV life cycle by competitive inhibition of HIV reverse transcriptase (RT), leading to DNA chain termination. Nucleoside (or nucleotide) analogues act as substrates and bind to the active site of the RT enzyme. Then they are added to the new chain of DNA. Once they have been inserted, the normal links between pieces of the chain will not form and the viral chain will be terminated without being inserted into the cell’s DNA.

The following is a list of NRTIs. All are nucleoside analogues except tenofovir, which is the only nucleotide analogue that is FDA-approved:

• 3TC: lamivudine (Epivir)

• ABC: abacavir (Ziagen)

• AZT: azidothymidine, zidovudine (Retrovir; the first FDA-approved HIV medication in 1986)

• DDC: zalcitabine (Hivid; no longer manufactured)

• DDI: didanosine (Videx, Videx EC)

• D4T: stavudine (Zerit)

• FTC: emtricitabine (Emtriva)

• TDF: tenofovir, disoproxil (Viread, a nucleotide)

The NRTIs are fairly well tolerated after introduction (initial mild to severe nausea usually resolves), with minimal long-term adverse effects. Exceptions include AZT and the remaining “D” drugs (DDI and D4T). A common side effect of AZT is bone marrow suppression, leading to macrocytic anemia.¹⁹ The D drugs are less commonly used today except in the case of multidrug resistance. They have been associated with mild to severe peripheral neuropathy and, of greater concern, pancreatitis.²⁰ These side effects manifest secondary to neural inhibition of mitochondrial DNA polymerase and reduced mitochondrial DNA content.²¹ Therefore, patients on D drug therapy should be provided with ample mitochondrial support. Acetyl-L-carnitine, coenzyme Q₁₀ (CoQ₁₀), essential fatty acids (EFAs), α-lipoic acid, and B vitamins have been shown to decrease signs or progression of these side effects when taken in large doses.²²^–²⁶ Additionally, the thymidine analogues (d4T, ddI, AZT) have been associated with lipoatrophy, also as a result of mitochondrial toxicity. Because the NRTIs have been on the market longer than the other drugs, it is no surprise that they are backed with the greatest amount of research regarding nutrient interactions. Although there are no studies indicating that vitamins or other nutrients deplete AZT, there is evidence that AZT may deplete cellular levels of carnitine, copper, zinc, and vitamin B₁₂.^27,²⁸ With the exception of carnitine, these nutrients can be found in a good hypoallergenic multivitamin/multimineral supplement. In addition to deficiency caused by NRTI drugs, carnitine deficiency has been found in HIV+ patients not on HAART. Further, there are many other indications for carnitine in patients with HIV, making this nutrient a high priority for supplementation.

Some nutrients have been found to enhance the efficacy of NRTIs when taken in combination with these drugs, including vitamin E, zinc, and folate.²⁹^–³¹ These nutrients are easily supplemented through a nutritious diet full of whole grains, colorful vegetables and fruits, and a good multivitamin/multimineral supplement.

Overall, NRTIs are fairly well tolerated and some have the additional benefit of being active against hepatitis B virus (3TC, FTC, TDF).³²^–³⁴

Nonnucleoside Reverse Transcriptase Inhibitors

The second class of HAART comprises the NNRTIs. NNRTIs also affect the transcription process and work by allosterically binding to HIV-1 reverse transcriptase and inhibiting both RNA- and DNA-directed DNA polymerase functions of the RT enzyme.

The following is a list of the NNRTIs:

• EFV: efavirenz (Sustiva)

• ETV or TCM-125: etravirine (Intelence)

• DLV: delavirine (Rescriptor; rarely used)

• NVP: nevirapine (Viramune)

• RPV, TMC278: rilpivirine (Edurant)

NNRTI drugs are also fairly well tolerated after introduction, with low long-term toxicity. Other than an initial transient mild to severe skin rash, typical side effects (depending on the specific drug) include insomnia, abnormal dreams, elevated liver enzymes, and gynecomastia (all manageable with naturopathic support).³⁵^–³⁷ Resistance to this class of HAART can occur easily if the viral load is unsuppressed, so this type of medication may not be an optimal choice for someone who is inconsistent with taking medications.No nutrients are known to be depleted by NNRTIs or to enhance their efficacy.

Large randomized, double-blind placebo-controlled studies have shown that when used in combination with NRTIs, NNRTIs produce sustained reductions in plasma viral loads and improvements in immunologic responses.³⁸^–⁴¹ The advantage of this type of protocol is the fewest number of side effects, excellent long-term viral suppression, and ease of dosing (fewer pills).

Protease Inhibitors

The third class of HAART is the PIs. PIs intervene during the cleavage part of the viral life cycle by binding competitively to the substrate site of the viral protease (the enzyme responsible for the posttranslational processing), resulting in inhibition of the enzyme and the production of immature virus particles.

The following is a list of the PIs:

• ATV: atazanavir (Reyataz)

• DRV: darunavir (Prezista)

• FPV: fosamprenavir (Lexiva); amprenavir (Agenerase, formulation discontinued)

• IDV: indinavir (Crixivan)

• LPV-r: lopinavir+ritonavir (Kaletra; fixed-dose combination)

• NFV: nelfinavir (Viracept)

• SQV: saquinavir (Invirase; Fortovase formulation discontinued)

• TPV: tipranavir (Aptivus)

• RTV: ritonovir (Norvir; always used in combination with another PI to increase effectiveness)

Although PIs are effective at viral suppression, they are associated with the greatest number and most significant adverse drug reactions. These include chronic and persistent gastrointestinal (GI) abnormalities; lipodystrophy and lipoatrophy; elevations of cholesterol and triglycerides; insulin resistance leading to diabetes; and liver, kidney, and musculoskeletal complaints.

It is essential to realize that NNRTIs and PIs also work by inhibiting cytochrome P450 3A4 enzyme metabolism. Inhibition of this enzyme slows down the metabolic breakdown of the drug and effectively prolongs higher blood levels, which results in better viral suppression. Many foods, nutrients, and botanicals have been known to upregulate this enzyme function, and two have gained noteworthy attention. Some small studies (of fewer than 25 subjects) in healthy HIV-negative (HIV–) individuals as well as in vitro studies have demonstrated that garlic and St. John’s wort decrease NNRTI and PI drug levels. In the human trials, subjects initiated NNRTI or PI therapy to establish the drug levels necessary to suppress viral load. Garlic or St. John’s wort was then introduced at levels typically used for therapeutic effect. Blood levels were then measured and found to be lower than the levels believed to be necessary to maintain optimal viral suppression. Garlic or St. John’s wort was then discontinued and NNRTI or PI blood levels subsequently measured and found to be back in the therapeutic range.⁴²^–⁴⁵ Although these studies certainly do not conclusively demonstrate that garlic and St. John’s wort interfere with HAART viral suppression (small number of participants, single antiretroviral vs. typical multidrug HAART protocol, HIV– vs. HIV+, drug-naive vs. long-term HAART), these therapies should be avoided in patients with HIV on HAART. The lesson learned from these studies is to be intimately aware of the mechanisms of action when adding new nondrug therapies intended for patients on multidrug treatments. The potential for drug-nutrient interactions also should encourage and reinforce the use of the multitude of low-force interventions (e.g., diet, lifestyle, homeopathy, physical medicine, counseling) for conditions commonly treated by garlic or St. John’s wort in order to avoid potentially decreasing NNRTI or PI blood levels and risking increases in drug resistance.

Milk thistle may be considered for the treatment of significant GI and liver complications with PIs. To date, there have been limited studies investigating the drug interactions of this herb. In one with 10 HIV–, drug-naive patients taking milk thistle at 175 mg three times daily, investigators concluded that milk thistle did not significantly alter blood levels of indinavir despite a decrease of as much as 25% in trough levels.⁴⁶ Another study showed no effect on indinavir levels in healthy subjects.⁴⁷ Yet another tested cellular uptake of ritonavir in the presence of various herbal substances including milk thistle (silybinin) and found no change in the efflux of ritonavir or any effect on CYP 3A4.⁴⁸ An in vivo study with coadministration of nifedipine and silymarin in 16 healthy male volunteers concluded that silymarin is not a potent CYP 3A4 inhibitor in vivo.⁴⁹ Currently there is no evidence suggesting that milk thistle should be avoided by HIV+ patients on HAART, but more studies are necessary. No nutrients are known to be depleted by PIs or to enhance their efficacy. However, if gastrointestinal side effects are present it could lead to micro- and macronutrient deficiencies.

Establish a Foundation of Health and Wellness on the Basis of Naturopathic Principles

The naturopathic standard of incorporating healthy diet and lifestyle practices cannot be overemphasized for HIV+ individuals. These patients are likely to be taking a large number of medications, nutritional supplements, or both, resulting in additional biochemical stress on the body. Therefore, each patient should be clearly encouraged and continually reminded to maintain dietary habits designed to ensure optimal GI health and nutritional intake.

The most important recommendation is to encourage a high intake of filtered or safe water so as to decrease oxidative stress and reduce the toxic load of the HIV and medications.⁵⁰ These patients should also be encouraged to maintain an optimal intake of protein.^51,⁵² Protein requirements can be as high as 100 to 150 g per day, particularly when patients are experiencing malabsorption and/or diarrhea; it may be necessary to provide supplemental protein to prevent weight loss. Studies using large doses of whey protein and amino acids (L-glutamine, L-arginine) have proved effective in reversing or preventing HIV-induced wasting.⁵³^–⁵⁵ Essential fatty acids have also been found to be deficient in HIV+ patients. Studies have demonstrated that HIV+ patients consuming generous amounts of EFAs have an increased body cell mass and a decreased risk of progression to AIDS.⁵⁶^–⁵⁸ HIV+ patients and healthy subjects ingesting fruit juices or a fruit-vegetable concentrate on a long-term basis were found to have higher micronutrient and antioxidant levels.^59,⁶⁰ From this it can be concluded that HIV+ patients should be continually encouraged to include colorful vegetables and fruits in their diets to help maintain levels of essential micronutrients and fiber.^61,⁶²

HIV+ patients commonly require appetite stimulation, digestive enzyme support, or both to combat the adverse effects of HIV, HAART, and prophylactic antibiotics on the GI system.^63,⁶⁴ Further, with high oxidation already present in the digestive system, all patients should be strongly encouraged to avoid additional GI stressors such as high-sodium, high-fructose corn syrup in processed foods, alcohol, caffeine, fried foods, and cigarette smoke. Raw eggs, unpasteurized milk, undercooked meat or fish, and potentially contaminated foods must also be avoided to decrease the risk of gastrointestinal OIs and parasites.

Naturopathic physicians should exercise extreme caution in considering allergy elimination diets in HIV+ patients owing to the likelihood of nutrient deficiencies, maldigestion, and malabsorption caused by HIV itself and HAART medications. A safer alternative is to recommend replacement of common food allergens one food at a time in order to make sure that patients can maintain replacement diets without decreasing caloric and nutrient intake over time. Removing food vices and irritating foods may be one of the most challenging aspects of moving HIV+ patients toward optimal wellness, because there are so many other higher-priority challenges and a vital need to maintain body mass.

Lifestyle factors should be part of the naturopathic foundation with each HIV+ patient. Aerobic exercise has been demonstrated to provide benefit to individuals with immunodeficiency diseases, particularly through stress alleviation and mood enhancement. HIV+ individuals had increases in CD4, CD8, and NK cells immediately following aerobic exercise, and long-term exercise has demonstrated increases in immune parameters.^65,⁶⁶ HIV+ individuals practicing Tai Qi demonstrated a greater overall perception of health and significant improvements in several measures of physical function as compared with controls.⁶⁷ Other patients practicing yoga reported increased self-confidence and a quicker return to athletic activities after medical interventions.⁶⁸

All patients should be encouraged to create an optimal sleeping environment and to sleep 8 to 10 hours each night. Sleep is essential for the repair and rebuilding of tissues and has been demonstrated to increase circulating NK cells and lymphocytes.^69,⁷⁰

HIV+ patients involved with group activities have better prognoses as well as decreased stress and anxiety. Anecdotal evidence links long-term AIDS survival with one or more of the following: having a positive attitude toward the illness, participating in health-promoting behaviors, engaging in spiritual activities, and taking part in activities that support the HIV+ community. Structured, brief group intervention for bereavement due to the loss of loved ones has been shown to decrease plasma cortisol and improve several immune markers in patients with HIV.^71,⁷² Other forms of stress relief and management have proved effective for HIV+ patient health care. Cognitive behavioral stress management is a guided form of relaxation training. It has been shown to improve the quality of life in HIV+ women, decrease herpes simplex 2 antibody titers in HIV+ men, improve HIV laboratory values, and have lasting effects on quality of life and psychological well-being of patients.⁷³^–⁷⁸

Engaging in prayer, including distance healing, has demonstrated fewer new AIDS-defining illnesses, decreased illness severity, significantly fewer doctor visits, fewer hospitalizations, and significant improvements in mood.⁷⁹ For individuals not on HAART, participation in spiritual activities (prayer, meditation, affirmations, psychic healing, visualizations) resulted in a reduced risk of death over a one-year period.⁸⁰ Finally, laughter has been associated with improvement in WBC values and decreased stress.⁸¹

Establish a Core Nutrient Protocol

Replace Known Nutrient Deficiencies Caused by HIV

Vitamin and mineral replenishment has been demonstrated to be efficacious in HIV+ patients.⁸²^–⁸⁴ A double-blind placebo-controlled study involving 1078 pregnant Tanzanian women infected by HIV reported that taking vitamin A (preformed vitamin A and beta-carotene) and a low-cost multivitamin (vitamins B, C, and E) resulted in delayed progression to AIDS as well as a delay in the requirement to initiate antiretroviral therapy. Adding the low-cost multivitamins was statistically significant versus placebo or vitamin A alone.⁸⁵ Numerous vitamin and mineral deficiencies have been identified with HIV disease progression.⁸⁶ These deficiencies are likely due to loss, poor absorption, or rapid use and consumption.

Box 173-4 summarizes the nutrients that have been found to be deficient in patients with HIV. Typical daily doses required to replete deficiencies taken in divided doses throughout the day are noted in parentheses followed by the rationale or benefits.

BOX 173-4 Nutrient Deficiencies in HIV Patients

• Vitamin A (15,000-30,000 IU taken with food) slows progression to AIDS and decreases mortality, improves growth in infants, decreases stunting associated with chronic diarrhea, and prevents GI deterioration in mothers and infants.²¹⁴^–²¹⁷ May increase the risk of HIV transmission by breastfeeding but has no effect on mortality by 24 months.²¹⁸ Deficiencies can be due to decreased dietary intake, poor GI absorption, high urinary loss, impaired hepatic protein synthesis, and increased needs due to chronic infection.

• Beta-carotene (60-120 mg/150,000 IU taken with food) replenishment increased CD4+ count, CD4/CD8 ratios, total lymphocyte count, and decreased mortality.²¹⁹^–²²¹ Deficiency found in all HIV+ patients is likely due to poor digestion, decreased free radical elimination, and high lipid peroxidation.²²²

• Folate (400 mcg) normalized cell differentiation. Deficiency is most likely due to malabsorption; AZT-induced deficiency may increase risk of bone marrow toxicity.^223,²²⁴

• Vitamin B₁ (50 mg) replenishment is associated with increased survival in HIV+ patients and decreased progression to AIDS.²²⁵^–²²⁷

• Vitamin B₆ (50 mg) is essential in nucleic acid and protein metabolism and cellular and humoral immune responses.^228,²²⁹ Vitamin B₆ repletion both alone and in conjunction with CoQ₁₀ increased circulating IgG, CD4+ cells, and CD4/CD8 ratios.²³⁰

• Vitamin B₁₂ (1000 mcg hydroxy-, methyl- or cyanocobalamin best taken via intramuscular injections 3 times a week—alternate form is daily 1000 mcg sublingual) is important in several parameters of immune function, proper cell differentiation and nerve function, and in decreasing homocysteine levels. Vitamin B₁₂ repletion can improve lymphocyte counts, CD4/CD8 ratios, and NK cell activity.²³¹ Supplementation has also been found to reverse AIDS dementia complex when associated with low levels.²³² Deficiency has been associated with increased risk of progression to AIDS and with HIV disease in general.²³³^–²³⁵

• Vitamin D (5000 IU) deficiency commonly found in urban HIV-infected men with suppressed viral load and CD4 > 200; tobacco use was correlated with severe deficiency.²³⁶ Undetectable levels of vitamin D in HIV+ patients correlated with more advanced HIV infection, lower CD4 count, higher levels of TNF-alpha.²³⁷ Lower bone-mineral density was found HIV patients using tenofovir/emtriciabine combination.²³⁸

• Vitamin E (800 IU daily—mixed tocopherols taken with food) is indicated to decrease lipid peroxidation, protect against AZT-induced oxidative damage to cardiac mitochondria, normalize immune function, and slow progression to AIDS.²³⁹^–²⁴⁴ Deficiency is found in most HIV+ patients, with wasting, and in progression to AIDS.²⁴⁵

• Copper (2 mg) can inhibit HIV protease and viral replication.²⁴⁶ Deficiencies of copper are associated with AZT therapy and AIDS.^247,²⁴⁸

• Magnesium (300 mg) deficiency is found in AIDS patients.^249,²⁵⁰

• Selenium (400 mcg) to suppress the progression of HIV-1, viral burden, and provide indirect improvement of CD4 count.²⁵¹ Decreases HIV-associated mortality, decreases anxiety in HIV+ recreational drug users, and decreases hospitalizations and costs of caring for HIV+ patients.²⁵²^–²⁵⁵ Severity of deficiency in patients progressing to AIDS may be due to decreased calorie and protein intake, malabsorption, and various infections.²⁵⁶

• Zinc (15 mg—optimal intake levels have not been determined) has been found to decrease frequency of OIs.^257,²⁵⁸ Deficiency is noted in all HIV+ patients progressing to AIDS.²⁵⁹

• Acetyl-L-carnitine (2-6 g best taken away from other proteins to optimize absorption) is essential for proper energy supply as well as critical metabolic functions. Deficiency is common in HIV+ patients and increases the risk for alterations in fatty-acid oxidation.²⁶⁰^–²⁶² Repletion has also been linked with a reduction in serum triglycerides, decreased risk of wasting, increase in CD4 cells and reduced apoptosis, increased levels of serum insulin-like growth factor, reduction in mitochondrial neurotoxicity, and treatment of peripheral neuropathy.²⁶³^–²⁶⁸ It has also been demonstrated as an effective treatment for NRTI-induced lactic acidosis.²⁶⁹

• DHEA (15-50 mg taken with food) repletion helps to increase CD4 count, stimulate immune function, and improve quality of life.^270,²⁷¹

• Testosterone (intramuscular injection weekly) is indicated if serum levels are low in order to decrease loss of lean body and muscle mass.²⁷²

• Glutathione/GSH (increased through selenium and N-acetyl-cysteine or whey protein powder) has been found to decrease disease progression and mortality.²⁷³^–²⁷⁶ Deficiencies are found in both symptom-free HIV+ and AIDS patients.^277,²⁷⁸

Many of these nutrients can be replenished through the use of a highly nutritious diet and a good multivitamin. A few multivitamins have been specifically developed to replace the deficiencies of HIV+ patients and include high doses of carotenoids, B vitamins, antioxidants, and sometimes digestive enzymes. Taking one multivitamin designed specifically for HIV reduces pill burden and enhances compliance. Conversely, it is generally more cost effective to use a basic multivitamin and supplement individually with additional nutrients.

AIDS, acquired immunodeficiency syndrome; DHEA, dehydroepiandrosterone; GI, gastrointestinal; GSH, growth-stimulating hormone; HIV, human immunodeficiency virus; NK, natural killer; NRTI, nucleoside/tide reverse transcriptase inhibitors; OI, opportunistic infection.

Nutrient deficiencies (high doses of beta-carotene, vitamin D, acetyl-L-carnitine, dehydroepiandrosterone [DHEA], testosterone, reduced glutathione, and catalase) not commonly included in a multivitamin/multimineral supplement must be replaced through specific dietary regimens or through additional supplementation. Natural forms of beta-carotene should be used, as evidence suggests that synthetic forms can increase the risk of lung cancer in individuals who smoke.⁸⁷ Consider acetyl-L-carnitine as a high-priority nutrient, despite its high cost, on the basis of the number of benefits.

Provide Other Nutrients to Support Optimal Immune Function

Box 173-5 summarizes nutrients that have been found to replace or reduce other nutrient deficiencies or have beneficial action in patients with HIV, their daily doses divided throughout the day, and effects of supplementation.

BOX 173-5 Nutrients That Have Been Found to Replace or Reduce Other Nutrient Deficiencies or Have Beneficial Actions in HIV Patients

• Silybum marianum/milk thistle (300 mg standardized extract away from HAART) is indicated for all patients on HAART to improve liver function, decrease liver damage, and increase the antioxidant activity of blood cells.²⁷⁹

• NAC (2-8 g best taken away from other nutrients but may need to be taken with food to decrease GI distress) is indicated to prevent loss of sulfur containing amino acids, increase GSH, decrease TNF-α activity, and increase CD4 cell count.²⁸⁰^–²⁸²

• CoQ₁₀ (100-300 mg) optimized mitochondrial function and replaced deficiency.^283,²⁸⁴ Repletion with CoQ₁₀ increased circulating IgG, CD4+ cells, and CD4/CD8 ratios.^285,²⁸⁶

• Vitamin C (2-6 g) when combined with vitamin E significantly lowered oxidative stress and has demonstrated a trend toward lowered viral load.²⁸⁷

• Alpha-lipoic acid (600 mg) protected the liver, inhibited viral replication, increased intracellular GSH, increased CD4/CD8 ratios, and potentially decreases peripheral neuropathic pain by its antioxidant effect on nervous tissue.²⁸⁸^–²⁹³

• L-arginine (7.4 g taken away from food) improved lean body mass and increased NK cell activity. Must be used with caution because large amounts of arginine can aggravate herpesvirus outbreaks. Prophylactic L-lysine may prevent or reduce this effect.

• EFAs (5 g taken with food; best from fish oil) improved lean body mass, increased NK cell activity, and was beneficial as adjuvant therapy in patients with tuberculosis.

• L-Methionine (1000 mg taken away from other proteins) slowed decline of CD4 cells.²⁹⁴

CoQ₁₀, Coenzyme Q₁₀; EFAs, essential fatty acids; GSH, growth stimulating hormone; HAART, highly active antiviral therapy; NAC, N-acetylcysteine; NK, natural killer; TNF-α, tumor necrosis factor alpha; EFAs, essential fatty acids.

All these nutrients have benefits, but they significantly increase overall cost and pill burden. Therefore priority should be given to the most essential (EFAs and DHEA) and lower-cost (vitamin C) nutrients or to address specific symptoms as described in the next section.

Provide Therapies to Address Constitutional Symptoms, Medication Side Effects, and Symptoms of Immunosuppression

The following are some approaches for specific health conditions and OIs. The naturopathic physician should endeavor to identify and remove the cause, tonify systems, and, treat each patient individually.

Candida albicans/Oral Thrush

Overgrowth of this fungal organism may occur as a result of HIV itself (a low CD4+ count, reducing the body’s immune capacity) or secondary to prophylactic antibiotic treatment. Orally, it can cause pain and make eating difficult, which can lead to reduced caloric intake and subsequent problems. In the intestines, it can cause inflammation and compromise nutrient absorption. In the esophagus, it can cause pain and should be dealt with swiftly via antifungal pharmaceuticals.

For treatment, patients should avoid foods that promote yeast growth, such as simple carbohydrates, sugar, baked goods, and starchy vegetables. These options should be considered:

• Probiotics: Provide and support healthy flora via the consumption of fermented foods as well as using supplements with at least 8 billion colony-forming units (CFUs), best taken with food. Beneficial species include Lactobacillus acidophilus/bifidus; Lactobacillus GG, a well-researched strain from Germany; or Saccharomyces boulardii, which is best for antibiotic-induced colitis and can help displace pathogenic flora.⁸⁸^–⁹²

• Garlic (1 to 2 g best taken before meals): Garlic is a potent antifungal found to spare nonpathogenic flora; note that patients on HAART should not take supplemental garlic.⁹³

• Oregano oil (300 mg best taken away from food): This is also a potent antifungal.⁹⁴

• Nystatin and fluconazole: Both are pharmaceutic antifungals.

Cardiovascular Disease

This issue is becoming increasingly problematic and prevalent in the HIV+ population. The adverse effects on serum lipids and glucose that accompany the use of HAART medications (specifically PIs and D-type NRTIs) significantly promote cardiovascular disease, particularly in patients already at high risk (where there are predisposing factors such as a positive family history).

All patients on HAART should be encouraged to institute a preventive diet, adopt a healthy lifestyle, and implement exercise recommendations to promote cardiovascular health. Exercise in particular has been demonstrated to increase functional aerobic capacity, eliminate functional aerobic impairment, and improve measures of exercise performance (improved peak oxygen consumption, oxygen pulse, tidal volume, ventilation, and leg power).^95,⁹⁶ Garlic should be avoided owing to its adverse interaction with HAART medications. The following specific nutrients should be considered:

• Acetyl-L-carnitine (2-6 g best taken away from other proteins to optimize absorption) repletion has also been linked with a reduction in serum triglycerides.

• CoQ₁₀ (100-300 mg) may enhance cardiovascular function.⁹⁷

• Arginine (7.4 g taken away from food) decreases atherosclerosis.⁹⁸

• EFAs (5 g taken with food) may lower lipids.⁹⁹

Diarrhea

This is a common complaint and an issue that can greatly affect quality of life. An HIV+ person might develop diarrhea for numerous reasons; the specific etiology guides the choice of treatment. Causes might include HIV-associated enteropathy, HAART side effects (see specific medications—this is particularly an issue with PIs), antibiotic side effects, gastrointestinal infections, and food allergies or intolerances. An osmotic-type diarrhea can also result from the consumption of too many indigestible gelcaps (from medications and supplements) building up in the intestinal lumen.

The first treatment priority is to remove the cause if at all possible. There is an increased incidence of gluten intolerance in HIV+ individuals.¹⁰⁰ Lactose intolerance and irritable bowel syndrome are also possibilities. Food allergies/sensitivities should be cautiously ruled out. Stool cultures and testing for ova and parasites should be considered to screen for suspected infectious causes, and patients should be treated as indicated for each microbial etiology. All nutrient supplementation may be stopped on a temporary basis to screen for an osmotic cause and then reintroduced one at a time to determine potential causes.

Steps for prevention include avoiding unfiltered tap water, unpasteurized milk or dairy products, ice made from unfiltered tap water, raw fruits and vegetables unless they can be peeled personally or washed with appropriate antimicrobial agents, raw or rare meat and fish, meat or shellfish that is not hot when served, and food from street vendors. Dehydration can be prevented by replacing electrolytes; broths, soups, fruit and vegetable juices, or high-nutrient drinks should be included.

Prevent malnutrition; if diarrhea is present, malabsorption of nutrients is a likely consequence. Ensure adequate micro- and macronutrient intake with a multivitamin/multimineral supplement and maintain adequate protein intake (requirements may increase to 100 to 150 g/day). Initial dietary intervention may include simplifying the diet (BRAT diet: bananas, rice, applesauce, toast) or using 1 tbsp tomato juice combined with 1 tbsp sauerkraut juice (a protocol taught by Dr. John Bastyr to two generations of naturopathic students and used with considerable clinical success by the senior editor to facilitate electrolyte replacement and promote enterocyte healing). Carob powder is an astringent that can help symptomatically. Begin with 1 tsp in applesauce and increase up to 6 tsp/day as needed.

Consider these additional supplements:

• Provide and support healthy flora as described earlier in the care of candidal infection.⁸⁸^–⁹²

• L-glutamine (9 to 40 g best taken away from other proteins) is an amino acid that provides fuel for small intestinal enterocytes. Using a powder is most efficient and cost-effective. Start with 3 g three times daily. This can be increased up to 40 g daily if necessary. This high dose can lead to psychoses, so the patient should be monitored closely.¹⁰¹

• Diphenoxylate and atropine (Lomotil), loperamide (Imodium), and psyllium husk (Metamucil) are common pharmaceutical interventions.

Herpes Simplex Virus/Herpes Zoster/Shingles

All conditions with a herpes-type virus etiology are considered together, as the treatment approach is similar for each. The sequelae of herpesviruses tend to manifest on the skin in a dermatomal pattern of distribution. These symptoms can occur secondary to various types of stress, hormonal fluctuations, or a poor immune system response. First and foremost, try to identify and remove causes of stress (including dietary, emotional, and sunlight exposure) and support immune function. Secondarily, address the symptoms (most often pain is at the forefront).

Naturopathic physicians should consider the following:

• Dietary suggestions include eliminating foods high in L-arginine (promotes herpes replication), such as chocolate, nuts, and peanuts, and increasing foods high in L-lysine (antagonizes L-arginine), such as whole grains, dairy, fish, lima beans, and soy.

• L-lysine: 1000 mg three times daily away from food during an outbreak; 500 mg three times daily away from food prophylactically.¹⁰²

• Olive leaf extract: 2000 mg is an effective antiviral.¹⁰³

• Monolaurin: this antiviral, taken at 300 to 600 mg three times daily, is effective against encapsulated DNA viruses.¹⁰⁴

• Melissa officinalis: an antiviral botanical used topically.¹⁰⁵

• Glycyrrhiza glabra: an antiviral oral and topical botanical.¹⁰⁶

• Herbal tincture (as parts): Hydrastis (1), Taraxacum officinale (the root) (2), Lomatium (2), Passiflora (1), Astragalus (1), Gelsemium (15 drops/oz); 60 drops every 2 hours during prodrome, four times daily during an outbreak, twice daily for prevention.

• Acyclovir/valacyclovir: pharmaceutical antiviral therapy.

Kaposi Sarcoma

Kaposi sarcoma (KS) is an HIV-associated neoplasm of vascular origin that tends to occur when CD4+ counts fall below 500/mm³. KS is rarely found outside of the HIV+ population. The etiology of AIDS-associated KS is poorly understood, but several factors are thought to contribute, including the presence of human herpesvirus (HHV) type 8, a compromised immune response, and hormones (it occurs rarely in women, and androgen therapy causes increased proliferation of the tumors). It is most commonly found in iron-rich geographic areas. Interestingly, 90% of AIDS-related cases in the United States occur in homosexual men, making it rare in heterosexual men, women, and IV drug users.

KS begins as macules or elevated papules and can progress to large plaques or nodules. The color ranges from pink to purple or brownish-black. The lesions may be round or oval and do not blanch when pressure is applied to them. The lesions often appear first on the skin of the upper body or mucosal surfaces. In their aggressive form they can become widely disseminated and can manifest anywhere on the skin, mucous membranes, lymph nodes, or viscera (including the GI tract from the mouth to anus, lungs, liver, spleen, or pancreas).

KS tumors secrete increased amounts of angiogenic growth factors, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, basic fibroblast growth factor, platelet-derived growth factor, and oncostatin-M.¹⁰⁷^–¹¹²

The level of immunosuppression of an affected person determines the clinical course of KS in AIDS. Currently there are no known cures; the various local and systemic approaches are aimed at palliation.

Treatment may involve the use of chemotherapeutic agents such as doxorubicin as well as standard HAART. Surgical excision can successfully remove a lesion, but there is a high rate of recurrence at the affected site. Other researched options that have produced varying results include radiation therapy, cryotherapy with liquid nitrogen, and electrical stimulation with direct current.

The following treatments should also be considered:

• Topical and systemic retinoids.¹¹³

• Topical vitamin D (1, 25-dihydroxyvitamin D3).¹¹⁴

• Iron has been shown to stimulate the growth of KS cells in vitro, whereas iron chelators reduced their growth.^115,¹¹⁶ Given this information, it may be sensible to limit iron intake and ensure that serum iron and ferritin levels are at the low end of normal.

• The use of various cytokine inhibitors and antiangiogenesis compounds might have a benefit for reducing the proliferation of these vascular tumors.

• Because there are no known curative therapies and the palliative treatment of KS is difficult at best, naturopathic physicians have an opportunity to be creative and make a contribution in this area. Given the association between KS and HHV type 8, it may be beneficial to use antiherpetic therapies if a patient is known to be herpes simplex virus–positive.¹¹⁷ Topical application of a medicinal peat preparation has resulted in remission of topical KS lesions in several patients. Glutathione (NAC as a precursor) could be helpful in the treatment of KS lesions as well.¹¹⁸^–¹²⁰

Lipodystrophy

Lipodystrophy is a redistribution of adipose tissue from the extremities to the trunk. It often manifests with a Cushingoid “buffalo hump” over the upper thoracic region of the back or with truncal obesity. Self-image issues are often most significant for patients experiencing this condition. Lipodystrophy can occur as a result of alterations in lipid metabolism secondary to HAART or simply chronic HIV infection (greater than 15 years).¹²¹ Given the appearance of the buffalo hump, it is possible that adrenal abnormalities contribute to the problem. Increases in serum cortisol lead to increases in insulin release from the pancreas, which drives blood glucose into storage in adipose cells. This leads to increased truncal obesity,¹²²^–¹²⁵ a physiologic mechanism that bears consideration in the therapeutic approach as well as in future research. Lipodystrophy has also been found to increase with lack of exercise.¹²⁶ In addition to correcting dietary nutrient insufficiencies, supplementing nutrients as per the general protocol, increasing exercise, and ensuring that blood glucose is appropriately regulated, use of the following can be considered:

• L-glutamine (10 g in divided doses away from food).^127,¹²⁸

• Acetyl-L-carnitine (2-6 g away from food) to optimize mitochondrial function.¹²⁹^–¹³¹

• Uridine (36 g three times daily for 10 consecutive days per month) to normalize subcutaneous fat.¹³²

• Testosterone (10 g of testosterone gel daily) in HIV+ men with abdominal obesity and low testosterone; decreased whole-body, total, and abdominal fat mass; and increased lean body mass.¹³³

• Nandrolone decanoate (150 mg IM every 2 weeks) may increase lean body mass more effectively than testosterone.¹³⁴

• Tesamorelin, a growth hormone–releasing factor analogue (2 mg per subcutaneous injection), decreases visceral adipose tissue and triglycerides without aggravating glucose.¹³⁵

• Dimethyl sulfoxide (DMSO)/bromelain (5% bromelain compounded in DMSO gel applied two to three times daily). Topical applications have resulted in the reduction of Cushingoid adipose deposits.

• Conventional treatment may include surgical removal of the truncal adipose deposits. Although this may not be the most desirable approach owing to its invasiveness, patients who undergo this procedure tend to be happy afterward because of their more positive self-image.

• Buccal injections of polylactic acid (PLA/Nufill) have been found to be safe and can reduce the cosmetic signs and depressive symptoms of lipodystrophy and wasting.¹³⁶

Macrocytic Anemia

Macrocytic anemia can be a secondary effect from the malabsorption of nutrients or a side effect of HAART (AZT causes bone marrow toxicity; PIs may cause malabsorption).^137,¹³⁸ The following treatments can be considered:

• Vitamin B₁₂ (hydroxycobalamin/methylcobalamin/cyanocobalamin 1000 mcg/mL given IM three times a week) is an important nutrient for proper cell division and differentiation.¹³⁹ If an IM injection is unavailable, sublingual tablets at 1000 mcg/day can be used to bypass intestinal absorption issues.

• Folic acid (400 mcg/day, found in most good multivitamin/multimineral supplements) and vitamin B complex (3 mL IM each week) are also indicated for proper cell division and differentiation.^140,¹⁴¹

Neuropathy

This is usually manifested in the periphery, particularly in the feet. It can work its way proximally as it increases in severity. It is most often seen either as a result of long-term HIV infection or as a side effect of the D-type NRTIs and their toxic effect on the mitochondria in neurons.^142,¹⁴³ Diabetes mellitus type 2 can also be a factor, as can overdoses of vitamin B₆ (greater than 200 mg/day).¹⁴⁴

The following treatments can also be considered:

Psychological Conditions

Issues such as depression, anxiety, post-traumatic stress disorder, sexual dysfunction, and substance abuse are extremely common in the HIV+ population. These problems potentially have physiologic as well as psychological components but may not be adequately addressed by other providers.

Suicidal ideations and suicide attempts can also be an issue for this population. As quality of life deteriorates, the burden of ongoing medical treatment increases, and close friends die, the desire to live can wane. It is critical that practitioners always be vigilant for signs of suicidal thinking or loss of hope in patients. These signs should be taken seriously, and there should be no hesitation in bringing in experienced professional help to assist these patients.

In contemplating the treatment of any psychological issue in this patient population, extreme caution must be exercised owing to issues of polypharmacy and drug-nutrient interactions. Many of these patients are taking a substantial number of pharmaceutical medications. Interactions among many nutrients and these medications and even among the medications themselves are likely. Before instituting any treatment, all potential interactions must be researched, identified, and considered.

An example of this problem is the potential use of St. John’s wort, a commonly used herbal antidepressant. As previously discussed, St. John’s wort is an inducer of the cytochrome P-450 detoxification enzyme 3A4 in the liver and has been found to reduce serum levels of various HAART medications. Therefore, it can theoretically reduce the effectiveness of those medications and potentially lead to increased issues with resistance. The use of St. John’s wort should be avoided in any patient who is undergoing HAART.

Modalities such as counseling, lifestyle modification, and homeopathy can be quite useful in treating these psychological conditions. Meditation and mindfulness have been found to be effective for psychological health. For example, a mindfulness-based stress reduction meditation program showed stabilization of CD4+ T-lymphocyte counts independent of antiretroviral medication use.¹⁵² In another study, mantram repetition—a word or phrase with spiritual associations repeated silently throughout the day—was found to reduce anger as well as to increase spiritual faith and spiritual connectedness; it was inversely associated with non-HIV-related intrusive thoughts and positively associated with quality of life, total existential spiritual well-being, and meaning/peace.¹⁵³ Additional therapies to consider follow:

Wasting

In 1987, the CDC defined HIV-associated wasting syndrome as an involuntary weight loss of greater than 10% of baseline body weight accompanied by chronic fever, weakness, or diarrhea. A more complete definition is available in The AIDS Reader¹⁶³ (Box 173-6).

BOX 173-6 AIDS Wasting Syndrome Criteria

AIDS wasting syndrome must meet one of the following criteria:

Unintentional weight loss of >10% over 12 months

Unintentional weight loss of >7.5% over 6 months

BCM loss of <5% over 6 months

Men: BCM <35% of TBW and BMI <27 kg/m²

Women: BCM <23% of TBW and BMI <27 kg/m²

BMI <20 kg/m²

BCM, body cell mass; BMI, body mass index; TBW, total body weight

Body cell mass (BCM) can be measured via bioimpedance assay. Research shows that BCM is a better predictor of survival than CD4 counts. Key issues to be addressed with patients include perceived weight loss, changes in appetite, diarrhea, energy level, and difficulties in performing activities of daily living.

The etiology of wasting is most likely multifactorial in nature; some possible etiologies include the following ¹⁶⁴:

• Decreased food intake—anorexia (decreased desire to eat or loss of appetite with corresponding decrease in food intake) or nausea secondary to medications, systemic illness, or GI pathology; finances; dependence on others; poor food choices.

• Malabsorption/chronic diarrhea—results in decreased nutrient intake; influenced by many pathologies and dysfunctions (affecting any part of the GI tract: oral, esophageal, stomach, pancreatic, biliary, hepatic, and small and large intestine); problems might include infections, medication side effects, enzyme deficiencies, and malignancies; all might result in the inability to absorb macro- and micronutrients.

• Alterations of metabolism—studies show that resting energy expenditure (REE) is higher in HIV/AIDS patients than in HIV–controls; studies also show the REE does not downregulate if anorexia or malabsorption is present (therefore, the combination of decreased caloric intake with a metabolic rate that does not adjust to that state would result in a negative energy balance and weight loss).

• Cytokine abnormalities—not well understood; TNF, IL-1 may induce anorexia and affect lipid, protein, and carbohydrate utilization; an example is cachexia in cancer.

• Endocrine abnormalities—thyroid abnormalities, adrenal insufficiency (cortisol, DHEA), hypogonadism (testosterone), growth hormone deficiency.

• Alcohol abuse—studies show that progression to AIDS is much quicker in HIV+ patients who consume large amounts of ethyl alcohol (ETOH) versus normal expectations; ETOH can stimulate HIV production, suppress immune defenses (lower CD4 cell counts), and deplete tissue micronutrients (specifically, antioxidants).

As per general recommendations, the naturopathic physician should endeavor to remove the cause if it is identifiable and removal is feasible. Then he or she should identify and remove possible food allergies/intolerances (gluten and dairy in particular) and ensure adequate and appropriate nutritional intake via dietary counseling; patients should also be helped to access social service assistance if necessary. Patients are likely to need superdoses of nutrients. Protein intake should be increased to 100 to 150 g/day. Patients should be active and engage in daily exercise.

The following therapies can be considered:

Provide Specific Antiviral Therapy and Immunomodulation Using Other Nondrug Treatments

This section summarizes the botanical, homeopathic, and physical medicine studies that have been found to have potential for patients with HIV. They are not substitutes for HAART. This list is intended to assist health providers to find additional nondrug solutions that resonate with the unique needs of individual HIV+ patients. Further, the majority of the following studies are based on initial or empirical findings encouraging additional areas for research and exploration.

Botanical Medicines

Box 173-7 includes botanicals that have demonstrated efficacy in treating HIV.

BOX 173-7 Botanicals That Have Demonstrated Efficacy in Treating HIV

• Glycyrrhiza glabra/licorice (1500 mg) inhibited HIV fusion and viral transcription.²⁹⁵^–²⁹⁷ It should not be used in patients with a history of hypertension or with renal or cardiac problems.

• Curcuma longa/tumeric (1200 mg) inhibited HIV integrase and proteases and viral transcription and decreased nuclear factor kappa β.²⁹⁸^–³⁰⁰

• Olea sp./olive leaf extract (2-6 g) increased NK-cell function and was effective against HIV and herpesviruses.^301,³⁰²

• Phyllanthus amarus (1200 mg) demonstrated in vitro and ex vivo HIV-1 inhibition of reverse transcriptase, receptors, and proteases and is also effective against HBV.³⁰³

• Lentinus edodes/shitake mushrooms (1-5 mg IV twice weekly) inhibited reverse transcriptase, increased CD4 couts, and decreased p24 (surface marker).^304,³⁰⁵

• Andrographis paniculata (1500 mg) inhibited fusion, viral replication, and HIV-1 cell-to-cell transmission. It also stimulated objective measures of immune function, increased the effectiveness of AZT, protected against liver damage, and decreased diarrhea.³⁰⁶ Toxicity questions remain; further study is necessary.

• Silybum marianum/milk thistle (300 mg extract) improved liver function and antioxidant activity of blood cells.

• Hyssopus officinalis/hyssop (1-4 ml tincture) exhibited anti-HIV activity and inhibited integration of proviral genome into host genome.^307,³⁰⁸

• Prunella vulgaris/self-heal (10 mg/mL IV) inhibited HIV replication and binding and prevented cell-to-cell infection.^309,³¹⁰

• Rosmarinus officinalis/rosemary (use liberally in food) decreased HIV replication and protease activity.³¹¹

• Momordica charantia/bitter melon (6 oz fresh juice) normalized CD4+/CD8+ ratios and inactivated viral DNA.³¹²

• Spirulina platensis/blue-green algae (use liberally in food) reduced fusion and viral production.³¹³

• Scutellaria baicalensis/skullcap (6-15 g whole root) inhibited HIV-1 reverse transcriptase.³¹⁴

• Podophyllum resin (25% solution as a single topical application) resulted in resolution of hairy leukoplakia.³¹⁵

• Melaleuca leucadendron/tea tree oral solution was effective for fluconazole-refractory oropharyngeal candidiasis in patients with AIDS.³¹⁶

• Hypericum perforatum/St. John’s wort (900 mg) inhibited protein kinase C and viral uncoating, fusion, and assembly.³¹⁷ Do not use in patients on NNRTI or PI.

• Allium sativa/garlic (4 g fresh garlic) selectively killed HIV-1 infected cells in vitro.³¹⁸ It should not be used in patients on NNRTI or PI.

AIDS, acquired immunodeficiency syndrome; HBV, hepatitis B virus; HIV, human immunodeficiency virus; IV, intravenous; NK, natural killer; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Homeopathy

Homeopathy may offer a most interesting possibility in the care of HIV+ patients. The British Journal of Homeopathy published a report on the use of constitutional homeopathic remedies (30C-1M doses) given to 129 asymptomatic HIV+ patients in India. As a result, 12 patients became ELISA negative after 3 to 16 months.¹⁷⁷ In another study, 100 HIV+ patients between 17 and 50 years of age (71% men) were randomized to receive either a single homeopathic remedy or a placebo. The experimental group receiving remedies showed statistically significant increases in CD4+ T cells after 6 months.¹⁷⁸

Other studies in homeopathy have demonstrated success with symptom care in HIV.¹⁷⁹ For example, Bissuel and colleagues¹⁸⁰ reported the use of homeopathic sulfamethoxazole and trimethoprim (Bactrim), preventing the hypersensitivity reaction commonly associated with this drug. In a randomized, double-blind, placebo-controlled trial of 24 HIV+ adults with baseline CD4+ counts between 125 and 500/mL, as reported by Brewitt and colleagues,¹⁸¹ oral doses of homeopathic growth hormone resulted in statistically significant improvements in CD4 cells, CD8 cells, ESR, weight gain, and viral load; reduced occurrences of OI; and increased platelet counts.

The use of constitutional homeopathy should be considered an essential aspect of the care of all HIV+ patients considering the amazing potential, minimal side effects, and overall affordability.