Detection of IgG antibody to envelope components (gp120 and its subunits) is the most commonly used marker of infection with HIV. The routine tests are based on ELISA techniques which may be confirmed with Western blot assays. Up to 3 months may elapse from initial infection to antibody production (the window period). These antibodies have no protective function. As with all IgG antibodies they cross the placenta. All babies born to HIV -infected women will thus have the antibodyat birth. In this situation HN antibody is not a reliable marker of active infection and in uninfected babies will be lost gradually over the first 18 months of life. HIV antibody testing should be carried out only after full discussion of the implications with the patient and with the patient’s express consent.Additional viral antigens and host antibodies can be detected in blood.
VIRAL p24 ANTIGEN is detectable shortly after infection but has usually disappeared by 8-10 weeks after exposure. It can be a useful marker in individuals who have recently been infected and have not yet had time to mount an antibody response. It may reappear at low levels intermittently during the asymptomatic phase and also as infection progresses in some people, in whom it can be used as a surrogate marker of viral activity.
IGG ANTIBODY TO can be detected from the earliest weeks of infection and through the asymptomatic phase. It is often lost as disease progresses.
ISOLATION OF VIRUS IN CULTURE AND DETECTION BY POLYMERASE CHAIN REACTION are specialized techniques available in some laboratories which may aid diagnosis.
Investigation and management
History and examination will provide a basis for the clinical staging of infection and give insight into the patient’s approach and particular circumstances. Baseline investigations will depend on the clinical setting but for an asymptomatic person are shown in Practical box l.l. The aims of management are to maintain health, avoid transmission of HIV and provide appropriate palliative support. Confidentiality must be strictly adhered to and psychological support must be readily available for the patient, family, friends and carers. Dietary assessment and advice should be freely accessible. Clear advice on reducing the risk of transmission must be provided and future sexual practices discussed. Informtion needs to be available for people to make informed choices about childbearing. The implications for existing family members should be considered. General health promotion advice on smoking, drug misuse and exercise is important.
Treatment strategies for specific conditions are discussed in the appropriate sections above. Various events in the HIV life-cycle have been identified as potential targets for antiretroviral therapy. Antagonists of reverse transcriptase are so far the most developed.
ZIDOVUDINE (3-AZIDO-3-DEOXYTHYMIDINE, AZT)
is an analogue of thymidine which inhibits reverse transcriptase and also acts as a DNA chain terminator. It is now widely used in the developed world in patients with symptomatic HIV disease (CDC Group IV). Studies have shown a survival advantage in people with AIDS taking AZT and a reduction in opportunistic infections. Constitutional symptoms may be ameliorated. Neurological disease may improve. A transient rise in CD4 lymphocytes and a fall in P24 antigen levels are seen on treatment.Clinical and survival benefits of AZT in HIV-positive asymptomatic patients still have to be conclusively demonstrated. Side-effects include headache, nausea, abdominal discomfort and insomnia, all of which may resolve after several weeks on AZT. The most common toxicity is bone marrow suppression, particularly megaloblasticchange and suppression of the red cell line. Neutropenia also occurs. Myopathy may occur after long-term use. Adverse reactions are more frequent and severe in patients with more advanced disease and are to some extent dose dependent. In vitro resistance of HIV to AZT may be seen after 6 months on treatment but its clinical significance is not clear. Dose regimens range from 500 to 1000 mg daily in divided doses.
DIDEOXYINOSINE (DDI) AND DIDEOXYCYTIDINE
(DDC) are also inhibitors of reverse transcriptase. They are less well evaluated than AZT. Side-effects include acute pancreatitis and peripheral neuropathy, but bonemarrow toxicity is rare. As a result they may be used as second line therapy in patients who cannot tolerate AZT.
OTHER DRUGS include non-nucleoside reverse transcriptase inhibitors and agents that act at other sites in the HIV replication cycle, e.g. protease inhibitors. These compounds are currently undergoing therapeutic trialsbut are not yet commercially available. Drugs used in combinations are also being evaluated. Prevention and control The development of an effective vaccine against HIV is being pursued but is not a realistic prospect in the near future. Changing behaviour is notoriously difficult, especially in areas that carry as many taboos as HIV and AIDS. It is however the main tool available for prevention of infection. Education programmes providing factual knowledge and strategies to avoid infection are fundamental to the process. The use of condoms has been shown to reduce the spread of HIV infection in discordant couples and their use has been strongly promoted. Control of other STOs is crucial in view of their potential role in enhancing HIV transmission. Access to clean needles and syringes to prevent sharing amongst drug users is important, as are programmes to reduce injecting drug use. Screening of blood products has reduced iatrogenic infection in developed countries but is expensive and not globally available. The need for blood transfusion in developing countries could be reduced by improved control of conditions such as malaria and hookworm, which lead to anaemia. Partner notification schemes are in various stages of development worldwide but are controversial. Availability and accessibility of confidential HIV testing is important and provides an opportunity for individual health education and risk reduction to be discussed.