Sexual Health and Genital Medicine in Clinical Practice

Chapter 20. Human Immunodeficiency Virus (HIV) Infection

In the UK, GU medicine physicians provide much of the outpatient care, and in some hospitals also the in-patient care, for patients with HIV infection. The diagnosis still carries a certain stigma and may bring to the forefront emotions regarding past sexual relationships, sexuality, or drug abuse. In the 1980s, AIDS received a tremendous amount of hype by "medical" journalists and social commentators but with advances in our knowledge of the disease and developments in treatment, HIV infection should now probably be better viewed as a chronic illness. Primary care practitioners are playing more of a role in managing patients with HIV infection, particularly during the pre-treatment years. However, once the disease progresses and highly active antiretroviral treatment (HAART) is considered necessary, specialist input should be sought. Inappropriate drug combinations can seriously limit future treatment strategies through the development of drug resistance, and choosing the right therapy for an individual patient is not always a straightforward matter. This chapter deals with just a few of the important issues regarding HIV antibody testing and patient management.

20.1 HIV ANTIBODY TESTING

(1) Many people request an HIV antibody test for "peace of mind". They may be entering a new sexual relationship and wish to clear up a nagging doubt about a previous partner. It is important to try and assess the degree of risk: Has there been previous sexual contact with bisexual or homosexual men, injecting drug users, or persons from "highrisk" areas of the world? Of course one can never be certain about the behavioral history of their previous partners and so direct questioning only provides a rough guide to the true risk. Although an unexpected positive result occasionally turns up, more commonly there is a clue from the history. Remember that injecting users who deny ever sharing needles and syringes ("works") may have been exposed to HIV from their sexual partners who do share needles.

(2) Following infection with HIV, there is a delay of between 3 and 6 months before antibodies become detectable on serology. This "window period" needs to be explained to the patient and testing possibly delayed until sufficient time has elapsed after potential exposure. For this reason, testing is usually performed at 3 months after exposure. This may be repeated at 6 months in individuals who report known HIV exposure or have received post exposure prophylaxis with anti-retrovirals. Seroconversion after 6 months has been reported but is considered a rare event. Improved antibody detection tests and PCR have lessened the interval to detect infection and should be discussed with your local laboratory in cases where there is confirmed exposure to HIV.

(3) The "HIV antibody test" has become much more of a routine investigation and should be considered as such; however, a positive result does carry implications. It is therefore wise that the test is discussed, covering the points mentioned above, and the reason for testing explained in cases where HIV is on the list of differential diagnoses in a symptomatic patient.

(4) Although needle-stick injuries are more common in the hospital setting, occasionally the GP will be consulted following an injury in the community or in the surgery. The risk of acquiring HIV from a needle-stick injury from an infected-patient not taking anti-retrovivals is approximately 3%. The risk of transmission following an injury from a needle of "unknown origin" is obviously less. The risk of acquiring hepatitis B following a needle-stick injury from an "e antigen" positive patient is 30% and the risk of hepatitis C infection from a needle-stick injury is approximately 3%. If the injury were sustained by a doctor or nurse from a patient in the surgery, direct questioning will help to determine the risk of infection, although bear in mind that questions regarding sexuality and drug use may not always be answered honestly and that some infected patients give no history of "risk contact" If there is concern, ask the patient whether they would consent to being tested for HIV, hepatitis B and, if intravenous drug misuse is suspected, hepatitis C infection. If consent is denied and there is a definite risk of infection, consider a booster dose of hepatitis B vaccine, assuming that the healthcare worker has been previously vaccinated and that antibody levels are unknown. HIV serology should be performed at 3 and 6 months and condoms used during this time.

Specific hepatitis B immunoglobulin (HBIG) in addition to hepatitis B vaccination should be considered for patients sustaining a needle-stick injury in the community. A careful evaluation is required in each case to determine the true risk and whether prophylaxis is needed. If in doubt, err on the side of caution. HBIG should be given preferably within 48 hours and not later than a week after exposure at a dose of 200 IU for children of 0-4 years, 300 IU for children of 5-9 years and 500 IU for adults and children over 10 years. HIV serology should be performed at 3 and 6 months (see page 128 regarding earlier detection). Discussion with your local Public Health Laboratory is advisable; they may already have guidelines for the management of needle-stick injuries in general practice.

(5) Post exposure prophylaxis (PEP) should be strongly considered if there is needle-stick injury involving HIV infected blood, as does occasionally happen in the clinical setting. Three drugs are administered as soon as possible after the injury (ideally within 24 hours) although some practitioners will consider PEP up to two weeks after exposure. PEP is usually continued for 4-6 weeks. Prophylaxis post sexual exposure is also now considered worthwhile, the common scenario being a condom split or slippage in a discordant relationship (i.e. one partner HIV positive and the other negative). The decision to start PEP is not always straightforward (e.g. has the HIV infected person drug resistant virus, is the viral load undetectable, as is usually the case when on treatment, or is it very high, etc.) and specialist advice should be sought.

(6) Insurance companies used to ask new clients to state whether they had previously had an HIV antibody test or considered themselves at potential risk of acquiring HIV, whereas now they should only inquire whether there has been a previous positive test for HIV. Having previously been tested negative for HIV should no longer cause difficulties when applying for life insurance.

(7) Some "HIV-workers" have suggested that HIV pretest counseling should be performed only by experienced counselors within departments of GU medicine or by specialized testing centers. This is a rather extreme and outdated view. There is no reason why HIV antibody testing should not be performed in general practice; however, there are a few points worth considering. First, for reasons of confidentiality, many patients prefer not to have a record of HIV antibody testing in their general practice notes. If the result proves positive then of course it is important that the general practitioner is aware of the diagnosis. Secondly, patients with possible risk

factors for infection may be better assessed and tested in the GU medicine setting where full support and information can be provided if the result is positive. Thirdly, if an individual is concerned about possible sexual exposure to HIV then it is wise to check for other sexually transmitted infections, such as Chlamydia, which are far more common than HIV.

(8) Many GU medicine clinics now run "fast service" HIV antibody testing that provides results within 24 hours. This is ideal for the anxious patient who is deterred from testing because of a several day wait for results.

20.2 CLINICAL FEATURES AND MANAGEMENT

20.2.1 Seroconversion Illness

Over 50% of patients report a "flulike" or "glandular-fever like" illness at the time of seroconversion (i.e. about 2-6 months after infection).

20.2.2 Persistent Generalized Lymphadenopathy

After a variable period of time a number of patients develop cervical and axillary lymphadenopathy. This is usually painless and the glands affected are usually > 1 cm in diameter. Lymphadenopathy is of no prognostic significance.

20.2.3 Constitutional Symptoms

Most patients with HIV remain asymptomatic for a number of years. During this time the virus is replicating in the lymphoid tissue and other body sites and although the CD4 or T-helper lymphocytes are being destroyed, the immune system is sufficiently robust to maintain normal lymphocyte levels. After a period of usually some years, the immune system shows signs of deterioration and the CD4 lymphocyte count falls. This is sometimes associated with the development of constitutional symptoms such as loss of weight, night sweats, diarrhea, and profound lethargy. It is important to remember, however, that many patients with low CD4 cell counts are asymptomatic. Symptoms of constitutional HIV disease improve with antiretroviral medication.

20.2.4 Acquired Immunodeficiency Syndrome (AIDS)

This is an emotive and not particularly helpful term clinically. A diagnosis of AIDS indicates marked immunosuppression and a number of clinical conditions (‘indicator disease') will place the patient in the diagnostic category of AIDS. In addition, all persons with a CD4 lymphocyte count <200x106/l irrespective of the presence or absence of an ‘indicatior disease' are now classified as having AIDS. However, it is important to reassure the patient that HARRT will often lead to dramatic clinical improvement, although this obviously will depend upon the severity of the AIDS defining illness. A small subgroup of patients with HIV remains clinically well for many years, which is probably the result of infection with a less virulent strain of virus. AIDS defining conditions are listed in Table 20.1.

Table 20.1. AIDS Defining Conditions (1993 classification).

20.2.5 Important Management Points

(1) Clinical review every 3-6 months is advisable. When patients are well the fewer visits to the clinic the better as it often serves as an unhappy reminder of their diagnosis. A great deal of psychological support, however, may be required for the patient and, in many cases, sexual partners and the immediate family. This is particularly important at the time of diagnosis and during the early months after diagnosis.

(2) Issues which should be addressed and discussed include the following:

(a) Need to notify sexual or “works-sharing" partners. This is an important issue that requires careful discussion. Partner notification is one of the many tasks performed by the GU medicine clinic health adviser and should be considered when a patient is reluctant to contact a previous partner directly. Most patients, however, fully appreciate the need to inform previous contacts and take on this responsibility.

(b) How to avoid passing on the infection (i.e. what sexual practices are safe or unsafe; safe-injecting practices). Condoms provide an adequate barrier to HIV; however, problems arise when they are not used consistently or when they split or slip off the penis. Extra strong condoms are available for anal intercourse, although these may occasionally tear, and remember to advise the use of water-based rather than oil-based lubricants (see Chapter 12).

There is a small but definite risk of transmitting HIV through oral sex; advise the use of a dental dam (a thin latex square) or flavored condoms.

Practices which may draw blood, such as biting or scratching, should be avoided.

Kissing, mutual masturbation, and body-rubbing are considered safe. Injecting drug users should avoid sharing contaminated needles, spoons, and syringes ("works") and many pharmacists and drug agencies now run needle-exchange schemes. Boiling used syringes and needles is a less safe alternative. Flushing "works" with bleach reduces levels of active virus but is unreliable and should only be considered when there is no reasonable alternative. Full-strength household bleach is required with a minimum contact time of 30 seconds.

(c) Who should be informed or needs to know the diagnosis. Advise the patient to think carefully before telling others of the diagnosis. Employers and work colleagues rarely need to be informed.

(d) Healthy lifestyle. This involves getting enough rest, taking exercise as tolerated, reducing and eventually stopping smoking, eating a "healthy" diet, and reducing unnecessary stress. Some patients benefit from complementary medical care such as reflexology, aromatherapy, facial massage, and relaxation and visualization techniques.

(e) Pregnancy and the risk to the infant. Most mother to baby transmission occurs late in pregnancy or during delivery. Without treatment, transmission rates vary from 15 to 20% in Europe and are higher, in the region of 30%, in Africa. With treatment the risk of transmission may be reduced to less than 1%. An increased risk of transmission to the baby is associated with a high maternal viral load, low CD4 lymphocyte count, premature rupture of membranes, and vaginal delivery with a detectable viral load. It is current practice to advise taking antiretroviral treatment during the later stages of pregnancy, either as a single agent (zidovudine) or as a triple drug regimen. Vaginal delivery may be considered if the viral load is below 50/mm3, otherwise an elective cesarean section is recommended at 38 weeks. The baby will also usually be prescribed zidovudine syrup for 4-6 weeks. Breast-feeding carries an additional risk of transmission and should be advised against where there are safe alternatives. Breast-feeding, however, is still recommended in the developing world where the protection against infectious disease outweighs the risk of HIV transmission.

(f) What support is available. Support will be available at both local and national level. Information about local support groups is best obtained from your local GU medicine clinic.

(g) Immunization. BCG and yellow fever vaccination should be avoided. Live attenuated vaccines for measles, mumps, rubella, and polio may be given, although it should be noted that polio virus may be excreted for longer periods than in uninfected persons.

Although pneumococcal vaccination has been recommended for HIV-positive patients, clinical efficacy has not been proven.

Further information on vaccination in the UK may be obtained from the HMSO publication Immunisation against Infectious Disease.

(h) Clinical follow-up. The importance of clinical follow-up should be stressed and an emphasis placed on the role of drugs to prevent complications, slow disease progression, and restore immune function.

(3) Baseline investigations performed routinely after diagnosis include the following:

 Confirmatory HIV antibody test

 HIV mRNA level (also known as the "viral load")

 Viral genotyping (also known as "drug resistance testing" - infection with a partially resistant virus is now common and will influence which drugs to use when starting HAART)

 Full blood count

 T lymphocyte subsets (CD4 and CD8)

 Liver function tests

 Fasting lipids (a number of antiretroviral drugs raise lipid levels)

 Hepatitis B and C serology

 Syphilis serology

 Toxoplasma serology

 Cytomegalovirus serology

 Chest radiograph

 Weight

(4) The CD4 lymphocyte count, CD4 percentage and "viral load" should be measured on a regular basis as this provides some guide to immune status. Every six months is usually sufficient in the early stage of infection if the CD4 count is high. More frequent monitoring is required when the CD4 count or percentage starts to decline as the decision to start HAART will be determined by the rate of decline or the level reached. The risk of developing Pneumocystis carinii pneumonia (PCP) increases once the CD4 count falls below 200/mm3 and HAART should be started before this time. Most clinicians consider treatment as the count drops below 350/mm3 and moves toward, but before it reaches, 200/mm3. HAART would also be considered in symptomatic patients irrespective of the CD4 count. Prophylaxis against PCP is recommended for patients with CD4 counts below 200/mm3 (e.g. cotrimoxazole 960 mg orally three times a week).

(5) HAART involves the use of a combination of drugs that act at various stages of the HIV replicative cycle. Three drugs are usually used initially, occasionally four, and a number of formulations combine drugs in a single tablet or capsule, to aid compliance. There are roughly three groups of commonly used drugs: nucleoside analogue reverse transcriptase inhibitors (e.g. zidovudine, didanosine, lamivudine, emtricitabine, teno- fovir), non-nucleoside analogue reverse transcriptase inhibitors (e.g. efavirenz, nevirapine), and protease inhibitors (e.g. saquinavir, ritonavir, loprenavir/ritonavir, atazanavir/ritonovir, nelfinavir). As mentioned above, choosing the right combination for the individual patient is not always straightforward. Potential interactions with other medications, HIV drug resistance, patient lifestyle, other current medical problems (e.g. depression, anemia, hyperlipidemia) all need to be considered.

Figure 20.1. Oral candidiasis

(6) The "shared-care" approach with general practitioners involved in clinical management along with the hospital team is a useful model to adopt. A multidisciplinary team is often required with hospital doctors, GPs, social workers, counselors, dietitians, drug-workers, and district nurses working closely together. Most teams also have a designated "HIV liaison nurse" who plays a key role in coordinating care and oversees the smooth transition between hospital and the community.

Management of complications of HIV infection are summarized in Table 20.2.

(Continued)

Table 20.2. (Continued)

Figure 20.2. Kaposi's sarcoma



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