Human immunodeficiency syndrome

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CHAPTER 64 Human immunodeficiency syndrome

Saurabh V. Phadnis, Margaret A. Johnson

Introduction

Over 50% of all individuals infected with human immunodeficiency virus (HIV) are women (Joint United Nations Programme on HIV/AIDS 2008). Whilst HIV itself has no major specific gynaecological manifestations, it does impinge heavily on gynaecological practice. Some problems, such as recurrent vaginal candidiasis, florid human papilloma virus (HPV) infection and an increased prevalence of cervical intraepithelial neoplasia (CIN), are the result of increasing immunosuppression. However, many of the current gynaecological issues encountered in the HIV-infected woman, such as contraception, pregnancy and infertility management, are a result of dramatic improvements in available therapy and consequent improvement in overall prognosis.

Background

HIV is a retrovirus, a double-stranded RNA virus that uses the enzyme reverse transcriptase to form DNA and integrate itself into the host cell which then becomes a ‘factory’ for producing more virus (Figure 64.1). T-cell helper lymphocytes bearing the CD4 receptor, pivotal in the cell-mediated immune response, are targeted by the virus and destroyed.

Figure 64.1 HIV lifecycle and action of antiretroviral agents.

The natural history of HIV is characterized by gradual clinical deterioration. A decreasing CD4 lymphocyte count and increasing levels of virus in the blood plasma are used in monitoring the course of the disease in conjunction with clinical events. Most evidence regarding the natural history of HIV infection is based on studies of men, and it is not clear whether this is directly applicable to women. Seroconversion, the development of antibodies to HIV detectable in the serum, usually occurs soon after infection and the new fourth-generation combined antigen–antibody assays enable an accurate diagnosis to be made within 14 days of infection. Up to 50% of patients may experience an acute infectious mononucleosis-like syndrome, the ‘primary HIV infection’, at the time of seroconversion with rash, fever, myalgia, arthralgia, headache, diarrhoea and sore throat.

Acquired immunodeficiency syndrome (AIDS) diagnoses represent a range of disorders including infection and neoplasia (Centers for Disease Control and Prevention 1992). The risk of severe immunodeficiency and AIDS increases with the duration of infection. The median time to development of AIDS in untreated HIV-positive patients is approximately 7–10 years. Prior to the development of AIDS, patients may either be asymptomatic or experience persistent generalized lymphadenopathy (enlarged lymph nodes in at least two extrainguinal sites, lasting for at least 3 months and not attributable to any other cause) or symptoms due to immune deterioration that has many manifestations.

Early in the epidemic, before the widespread use of antiretroviral therapy and prophylaxis against opportunistic infections, median survival after an AIDS-defining illness was 11 months. Early studies did suggest a worse prognosis for women with HIV, although this finding is likely to have been the result of inequalities in access to care rather than biological gender differences. The course of infection varies between individuals, and there are ‘long-term non-progressors’ who are infected for long periods of time but manifest no evidence of immunocompromise in terms of either peripheral CD4 count or clinically detectable disease.

Treatment

In the last decade, widespread use of combination antiretroviral therapy in Europe and the USA has substantially reduced the rate of progression to AIDS and improved survival. Deaths that included AIDS-related causes decreased from 3.79/100 person-years in 1996 to 0.32/100 person-years in 2004 (Palella et al 2006). Six classes of antiretroviral agents are now available — nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, integrase inhibitors, entry inhibitors (or fusion inhibitors) and maturation inhibitors — all of which interrupt the virus’ lifecycle (Figure 64.1). The aim of highly active antiretroviral therapy (HAART), a combination of three or more drugs usually including a protease inhibitor or an NNRTI, is to slow progression of the disease by reducing viral load and thus increasing CD4 count. The British HIV Association has published guidelines on when to start HAART (British HIV Association Treatment Guidelines Writing Group 2008). Efavirenz should be considered as the first-line therapy in all patients, unless the patient is trying to conceive and has primary NRTI or NNRTI resistance. After treatment is commenced, viral load should reach ‘undetectable’ levels, usually less than 50 copies/ml. The CD4 count should rise, with levels below 200 × 10⁶/l representing a significant risk of development of an opportunistic infection. Compliance with HAART regimes needs to be in excess of 95% (Paterson et al 2000) for treatment to be effective and to reduce the chance of emergence of resistant virus.

Transmission

HIV has been isolated in blood, seminal fluid, vaginal secretions, cerebrospinal fluid, saliva, lacrimal secretions and breast milk. The concentration in different body fluids varies. The virus may be transmitted by sexual intercourse, intravenous drug use, transfusion, occupational exposure and vertically from mother to child. The predominant route of infection worldwide is heterosexual sex and, with the great majority of the affected population being in their reproductive years, vertical transmission is an increasing problem. Proper use of condoms is known to greatly reduce the risk of transmission (Heikinheimo and Lähteenmäki 2009). Male-to-female transmission is more efficient than female-to-male transmission, with the mucous membrane of the vagina being more permeable and the surface area being greater, although a partner receptive to anal intercourse is at greatest risk. It is difficult to quantify the risk of sexual transmission ‘per act’ as a constellation of factors are involved, although higher levels of viral load and intercurrent sexually transmitted infection (Wasserheit 1992), particularly ulcerative conditions, in either partner make transmission more likely. Use of barrier methods should also be encouraged in concordant HIV-positive couples to reduce the risk of transmission of resistant virus.

Although transmission of HIV between women who have sex with women (Monzon and Capellan 1987) is very rare, cases have occurred. Use of dental dams (latex barriers) should be encouraged to reduce oral contact with vaginal secretions, and shared sex toys should be cleaned appropriately. Salivary hypotonicity is thought to inactivate HIV-infected lymphocytes, and hence salivary transmission is almost certainly very rare. Oral sex, although less risky than vaginal or anal sex, may result in transmission and this may, in part, be the result of the isotonic nature of seminal fluid overcoming the inactivation of infected cells by hypotonic saliva.

In 2007, approximately 370,000 children under 15 years of age became infected with HIV, mainly through mother-to-child transmission (MTCT). Approximately 90% of infections due to MTCT occurred in Africa where AIDS is beginning to reverse decades of steady progress in child survival. In high-income countries, MTCT has been virtually eliminated thanks to effective voluntary testing and counselling, access to antiretroviral therapy, safe delivery practices, and the widespread availability and safe use of breast-milk substitutes.

HIV testing

HIV testing should be performed with the woman’s consent, and needs only a pretest discussion and consent by a trained healthcare worker. Medical care and support for those diagnosed HIV positive should be arranged immediately after diagnosis. As with all medical care, patient confidentiality should be respected.

There are two methods in routine practice for testing for HIV: screening assay, where blood is sent to the laboratory for testing, or a rapid point of care test (UK National Guidelines for HIV Testing 2008). The recommended first-line assay is one which tests for HIV antibody and p24 antigen simultaneously. These are termed ‘fourth-generation assays’ and have the advantage of reducing the time between the infection and testing HIV positive to 1 month; this is 1–2 weeks earlier than with sensitive third-generation (antibody-only detection) assays. HIV RNA quantitative assays (viral load tests) are not recommended as screening assays because of the possibility of false-positive results, and because they only have a marginal advantage over the fourth-generation assays for the detection of primary infection. Laboratories undertaking screening tests should be able to confirm antibody and antigen/RNA. There is a requirement for three independent assays able to distinguish HIV-1 from HIV-2. These tests could be provided within the primary testing laboratory or by a referral laboratory. All new HIV diagnoses should be made following appropriate confirmatory assays and testing a second sample. Testing including confirmation should follow the standards laid out by the Health Protection Agency (2007).

Point of care tests offer the advantage of a result from either a finger prick or a mouth swab sample within minutes. They have advantages of ease of use when venepuncture is not possible (e.g. outside conventional healthcare settings) and where a delay in obtaining results is a disadvantage, but these must be weighed against the disadvantages of a test which has reduced specificity and reduced sensitivity compared with current fourth-generation assays. Point of care tests are therefore recommended in the following settings:

• clinical settings where rapid turnaround of testing results is desirable;

• community testing sites;

• urgent source testing in cases of exposure incidents; and

• circumstances where venepuncture is refused.

Although a cure for HIV remains elusive, the advent of effective treatment has resulted in a significantly more optimistic outlook for infected patients. There are clear advantages to knowledge of HIV status, not only in terms of accessing medical monitoring and treatment but also regarding protection of sexual partners and reduction of risk of MTCT. Antenatal testing, previously only offered to women deemed at high risk of infection, is now offered universally as part of routine investigations offered to women in early pregnancy (see below).