On examination he appears thinner than previously and looks depressed. He is afebrile. His oral mucosa is coated with numerous thick white plaques (Figure 51.2). He has generalized lymphadenopathy, the nodes being 1–2 cm in size. You refer him to a hospital infectious diseases clinic. His blood screens reveal his haemoglobin has dropped to 112 g/L but his complete blood count is otherwise normal, his CD4⁺ lymphocyte count has dropped to 210 cells/µL and the HIV viral load is >200 000 copies/µL.

Figure 51.2

Q.7

What does Figure 51.2 show? What has happened? What are the principles of management?

The patient is counselled and commences antiretroviral therapy with tenofovir/emtricitabine 300 mg/200 mg as a fixed-dose combination tablet and boosted atazanavir 300 mg/ritonavir 100 mg all taken once daily. His oral candidiasis is treated with fluconazole 100 mg daily. If his CD4⁺ count drops further (below 200 cells/µL) he will require Pneumocystis prophylaxis with co-trimoxazole 160 mg/800 mg daily. He is reviewed monthly.

Q.8

The patient asks if this treatment will cure his HIV infection and whether he has AIDS. Give an appropriate reply.

Answers

A.1

• The patient’s understanding of the meaning of a positive HIV antibody test. The implications of the positive test must be explained to the patient in a sensitive manner.

• History of risk factors for the acquisition of HIV infection: intravenous drug use, sexual history (including other sexual partners while in a relationship and condom use), travel and sexual intercourse overseas, blood transfusion prior to 1990, and tattoos and body piercing.

• Whether the partner knows the HIV diagnosis and whether he has been tested.

• History of other sexually transmitted diseases and other blood-borne virus infections.

• A full review of symptoms to elicit symptoms attributable to HIV infection, immune deficiency or opportunistic infections.

A.2 HIV seroconversion illness which is also known as acute retroviral syndrome. This is a mononucleosis-like illness with fevers, malaise, sore throat, lymphadenopathy and rash. It occurs 10 days to 6 weeks after HIV infection and coincides with the appearance of HIV antibodies in the blood. It is estimated that 50–90% of people with acute HIV infection experience acute retroviral syndrome but, because it is non-specific, it is often not recognized at the time.

A.3

• Evidence of ill health: weight loss, fever, anaemia, marks of recent intravenous drug use.

• Assessment of global neurological function: e.g. mental state examination.

• Skin eruptions: seborrhoeic dermatitis, boils/furuncles, Kaposi’s sarcoma, onychomycosis.

• Oral lesions: oral candidiasis, oral hairy leucoplakia, ulceration, periodontal disease.

• Generalized lymphadenopathy.

• Abnormalities in specific systems: respiratory, focal neurological defects.

• Perianal disease: warts/malignancy, herpes simplex ulcers.

• In women: vaginal examination for cervical warts/malignancy.

A.4

1. Investigations to assess HIV infection and readiness for treatment:

• Repeat HIV serology (including Western blot) to confirm positive.

• CD4⁺ cell count, CD4⁺ percentage, CD4⁺:CD8⁺ ratio and HIV viral load.

• HIV resistance testing.

• HLA*B5701 genotype: this reliably predicts hypersensitivity to abacavir – a nucleoside analogue.

• Electrolytes, renal and liver function and complete blood examination.

2. Sexual health screen:

• Serology for hepatitis A, B and C viruses.

• Gonorrhoea: throat and rectal swabs for culture and PCR.

• Chlamydia: urine for PCR.

• Syphilis serology.

3. Investigations to identify opportunistic infections:

• Serology for cryptococcal antigen, CMV, EBV, toxoplasmosis.

• If history/risk of tuberculosis exposure: chest X-ray, CT chest and sputum for TB culture.

• CT or MRI brain if neurologic deficits found on examination.

A.5 The classic cause of a painless genital ulcer is the chancre of primary syphilis. Figure 51.1 shows an erythematous painless ulcer on the edge of the glans (the foreskin is retracted in the photograph). Where the foreskin rests on the primary ulcer, a secondary ulcer has occurred, termed a ‘kiss-lesion’. This is a classic appearance of primary syphilis. This ulcer is highly infectious, containing millions of spirochaetes. Even without treatment, this ulcer will heal in 10–14 days, followed later by lesions of secondary syphilis. For many years syphilis has been extremely rare; however, since 2005 there have been increasing numbers of cases of primary syphilis among men who have sex with men. Other possible diagnoses include herpes simplex ulcers (usually painful) or cancer (the history is too short). Diagnosis of primary syphilis requires demonstrating the spirochaetes in the lesion with dark field microscopy or polymerase chain reaction for treponemal DNA. Treatment is one single dose of 1.8 g IM benzathine penicillin. The partner must also receive treatment, even if his serology is negative.

A.6 The patient should be counselled together with his partner. The partner needs to be tested for HIV infection. If the partner is negative, further tests need to be done 3 months after the last risk exposure to ensure he is not in the window period (HIV infected but seroconversion has not yet occurred).

The couple need to be informed of the methods by which HIV is transmitted. They should be informed about post-exposure prophylaxis with antiretroviral therapy in case of accidental exposure.

In many countries, diagnosis of HIV infection requires notification of public health authorities.

A new diagnosis of HIV infection is psychologically challenging for the patient. Issues that may need to be addressed include: his own mortality, fear of illness/disability/death, infidelity in a relationship, occupational issues, parenting in a heterosexual relationship, isolation/loneliness if his social situation is such that he cannot discuss the diagnosis freely for fear of ostracism. It is important the patient is offered access to appropriate support services.

A.7 Figure 51.2 illustrates white plaques of oral candida infection on the hard palate. The patient’s CD4⁺ count is 210 cells/µL indicating advanced immunodeficiency; he has developed accompanying constitutional symptoms, lymphadenopathy and an opportunistic infection (oral candidiasis). He has symptomatic HIV infection with uncontrolled HIV replication as demonstrated by his high viral load. He should be managed in conjunction with a clinic specializing in HIV medicine.

Principles of HIV Management

1. Control HIV replication, aiming for complete suppression so HIV is no longer detectable in plasma. This requires combination antiretroviral therapy for the rest of his life. Antiretroviral drug classes are nucleoside/nucleotide analogues (tenofovir/emtricitabine), non-nucleoside reverse transcriptase inhibitors (efavirenz), protease inhibitors (atazanavir, ritonavir) and the new classes of integrase inhibitors and CCR5 inhibitors. Combination treatment is necessary as HIV replicates rapidly and mutates to become resistant to therapy with a single agent.

2. Treat and administer prophylaxis against opportunistic infections: necessary when the CD4⁺ count is below 200 cells/µL. Co-trimoxazole is used to prevent Pneumocystis jirovecii pneumonia (previously known as P. carinii or PCP) and toxoplasmosis, azithromycin to prevent disseminated Mycobacterium avium complex infection, fluconazole to prevent candida infections, and ganciclovir to prevent CMV disease.

3. Monitor for the emergence of malignancies, such as cerebral lymphoma, squamous cell carcinoma of the anal canal or cervix, Kaposi’s sarcoma and other malignancies.

4. Manage associated co-morbidities: the HIV-infected person is at increased risk of developing metabolic diseases such dyslipidaemias, diabetes mellitus, coronary artery disease and osteoporosis. Long-term management of HIV patients includes prevention and treatment of these conditions.

5. Support in the terminal phases of HIV infection.

A.8 The treatment will not cure the patient’s HIV infection. Pro-viral HIV DNA persists for the lifetime of the person. Antiretroviral therapy prevents active HIV replication. This allows restoration of CD4⁺ cell counts and recovery of immune function. There is no known mechanism for removal of pro-viral DNA once integration into the host has occurred. If antiretroviral therapy stops, HIV reappears in the plasma (within days to weeks) and immune damage resumes.

The World Health Organization divides HIV infection into four stages for clinical and surveillance purposes (Table 51.1). This patient has CD4⁺ count of 210 cells/µL, weight loss and persistent oral candidiasis. He has stage 3 disease with advanced HIV-associated immunodeficiency. Acquired immune deficiency syndrome (AIDS) is said to be present when a patient has stage 4 immunodeficiency and an ‘AIDS defining condition’ has been diagnosed. This patient does not have AIDS, but he does have advanced immunodeficiency (stage 3) due to his HIV infection.

Table 51.1 2007 WHO clinical staging and immunological classification for adults with confirmed HIV infection