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86 HIV INFECTION AND AIDS

86 HIV INFECTION AND AIDS
Harrison’s Manual of Medicine

86

HIV INFECTION AND AIDS

Definition
Etiology
Epidemiology
Pathophysiology and Immunopathogenesis
Immune Abnormalities in HIV Disease
Immune Response to HIV Infection
Diagnosis of HIV Infection
Laboratory Monitoring of Patients with HIV Infection
Clinical Manifestations of HIV Infection
HIV and the Health Care Worker
Vaccines
Prevention
Bibliography
Definition
AIDS was originally defined empirically by the Centers for Disease Control and Prevention (CDC) as “the presence of a reliably diagnosed disease that is at least moderately indicative of an underlying defect in cell-mediated immunity.” Following the recognition of the causative virus, HIV (formerly called HTLV- III/LAV), and the development of sensitive and specific tests for HIV infection, the definition of AIDS has undergone substantial revision. The current surveillance definition categorizes HIV-infected persons on the basis of clinical conditions associated with HIV infection and CD4+ T lymphocyte counts (Tables 309-1 and 309-2, p. 1852 and p. 1853, respectively, in HPIM-15). From a practical standpoint, the clinician should view HIV infection as a spectrum of disorders ranging from primary infection, with or without the acute HIV syndrome, to the asymptomatic infected state to advanced disease.
Etiology
AIDS is caused by infection with the human retroviruses HIV-1 or -2. HIV-1 is the most common cause worldwide; HIV-2 has about 40% sequence homology with HIV-1, is more closely related to simian immunodeficiency viruses, and has been identified predominantly in western Africa. HIV-2 infection has now, however, been reported in Europe, South America, Canada, and the United States. These viruses are passed through sexual contact; through contact with blood, blood products, or other bodily fluids (as in drug abusers who share contaminated intravenous needles); intrapartum or perinatally from mother to infant; or via breast milk. There is no evidence that the virus can be passed through casual or family contact or by insects such as mosquitoes. There is a definite, though small, occupational risk of infection for health care workers and laboratory personnel who work with HIV-infected specimens. The risk of transmission of HIV from an infected health care worker to his or her pts through invasive procedures is extremely low.
Epidemiology
By July 1, 1999, >702,745 cumulative cases of AIDS had been reported in the U.S.; ~60% of those had died. However, the death rate from AIDS has decreased substantially in the past 4 years primarily due to the increased use of potent antiretroviral drugs. It has been estimated that there are between 650,000 and 900,000 HIV-infected people in the U.S. Major risk groups continue to be men who have had sex with men and men and women injection drug users (IDUs); however, the number of cases that are transmitted heterosexually, particularly among women, is increasing rapidly (see Table 309-4; Figs. 309-12, p. 1861, and 309-13, p. 1862, in HPIM-15). These women also transmit the infection to their children. As the majority of IDU-associated cases are among inner-city minority populations, the burden of HIV infection and AIDS falls increasingly and disproportionately on minorities, especially in the cities of the Northeast and Southeast U.S. Cases of AIDS are still being found among individuals who have received contaminated blood products in the past, although the risk of acquiring new infection through this route is extremely small in the U.S. HIV infection/AIDS is a global pandemic, especially in developing countries. The current estimate of the number of cases of HIV infection worldwide is ~34 million, two-thirds of whom are in sub-Saharan Africa; 46% of cases are in women (Fig. 309-10, p. 1859, in HPIM-15).
Pathophysiology and Immunopathogenesis
The hallmark of HIV disease is a profound immunodeficiency resulting from a progressive quantitative and qualitative deficiency of the subset of T lymphocytes referred to as helper or inducer T cells. This subset of T cells is defined phenotypically by the expression on the cell surface of the CD4 molecule, which serves as the primary cellular receptor for HIV. A coreceptor must be present with CD4 for efficient entry of HIV-1 into target cells. The two major coreceptors for HIV-1 are CCR5 and CXCR4. Both of these receptors belong to the seven-transmembrane-domain G protein–coupled family of receptors. Although the CD4+ T lymphocyte and CD4+ monocyte lineage are the principal cellular targets of HIV, virtually any cell that expresses CD4 along with one of the coreceptors can potentially be infected by HIV.
PRIMARY INFECTION   Following initial transmission, the virus infects CD4+ cells, probably T lymphocytes, monocytes, or bone marrow–derived dendritic cells. Both during this initial stage and later in infection, the lymphoid system is a major site for the establishment and propagation of HIV infection. Initially, lymph node architecture is preserved, but ultimately it is completely disrupted and the efficiency of the node in trapping virions declines, leading to equilibration of the viral burden between peripheral blood cells and lymph node cells.
Most pts undergo a viremic stage during primary infection, in some pts this is associated with the “acute retroviral syndrome,” a mononucleosis-like illness. This phase is important in disseminating virus to lymphoid and other organs throughout the body, and it is ultimately contained partially by the development of an HIV-specific immune response and the trapping of virions in lymphoid tissue.
ESTABLISHMENT OF CHRONIC AND PERSISTENT INFECTION   Despite the robust immune response that is mounted following primary infection, the virus, with very few exceptions, is not cleared from the body. Instead, a chronic infection develops that persists for a median time of 10 years before the patient becomes clinically ill. During this period of clinical latency, the number of CD4+ T cells gradually declines but few, if any, clinical findings are evident; however, active viral replication can almost always be detected by measurable plasma viremia and the demonstration of virus replication in lymphoid tissue. The level of steady-state viremia (referred to as the viral set point) at approximately 1 year postinfection has important prognostic implications for the progression of HIV disease; individuals with a low viral set point at 6 months to 1 year after infection progress to AIDS more slowly than those whose set point is very high at this time.
ADVANCED HIV DISEASE   After some period of time (often years), CD4+ T cell counts will fall below some critical level (~200/µL) and pts become highly susceptible to opportunistic disease. However, control of plasma viremia by effective antiretroviral therapy, even in individuals with extremely low CD4+ T cell counts, has increased survival in these pts despite the fact that their CD4+ T cell counts may not increase significantly as a result of therapy.
Immune Abnormalities in HIV Disease
A broad range of immune abnormalities has been documented in HIV-infected pts. These include both quantitative and qualitative defects in lymphocyte, monocyte/macrophage, and natural killer (NK) cell function, as well as the development of autoimmune phenomena.
Immune Response to HIV Infection
Both humoral and cellular immune responses to HIV develop soon after primary infection (see summary in Table 309-8, and Fig. 309-21, p. 1875, in HPIM-15). Humoral responses include antibodies with HIV binding and neutralizing activity, as well as antibodies participating in antibody-dependent cellular cytotoxicity (ADCC). Cellular immune responses include the generation of HIV-specific CD4+ and CD8+ T lymphocytes, as well as NK cells and mononuclear cells mediating ADCC. CD8+ T lymphocytes may also suppress HIV replication in a noncytolytic, non-MHC restricted manner. This effect is mediated by soluble factors such as the b-chemokines RANTES, MIP-1a, and MIP-1b as well as other as-yet-unidentified factors secreted by CD8+ T lymphocytes.
Diagnosis of HIV Infection
Laboratory diagnosis of HIV infection depends on the demonstration of anti- HIV antibodies and/or the detection of HIV or one of its components.
The standard screening test for HIV infection is the detection of anti-HIV antibodies using an enzyme immunoassay (EIA). This test is highly sensitive (>99.5%) and is quite specific. Most commercial EIA kits are able to detect antibodies to both HIV-1 and -2. Western blot is the most commonly used confirmatory test and detects antibodies to HIV antigens of specific molecular weights. Antibodies to HIV begin to appear within 2 weeks of infection, and the period of time between initial infection and the development of detectable antibodies is rarely >3 months. The HIV p24 antigen can be measured using a capture assay, an EIA-type assay. Plasma p24 antigen levels rise during the first few weeks following infection, prior to the appearance of anti-HIV antibodies. A guideline for the use of these serologic tests in the diagnosis of HIV infection is depicted in Fig. 86-1.

FIGURE 86-1. Algorithm for the use of serologic tests in the diagnosis of HIV-1 or HIV-2 infection. * Stable indeterminate western blot 4 to 6 weeks later makes HIV infection unlikely. However, it should be repeated twice at 3-month intervals to rule out HIV infection. Alternatively, one may test for HIV-1 p24 antigen on HIV RNA.

HIV can be cultured directly from tissue, peripheral blood cells, or plasma, but this is most commonly done in a research setting. HIV genetic material can be detected using RT-PCR. This is a useful test in pts with a positive or indeterminate EIA and an indeterminate western blot or in pts in whom serologic testing may be unreliable (such as those with hypogammaglobulinemia).
Laboratory Monitoring of Patients with HIV Infection
Measurement of the CD4+ T cell count and level of plasma HIV RNA are important parts of the routine evaluation and monitoring of HIV-infected individuals. The CD4+ T cell count is a generally accepted indicator of the immunologic competence of the pt with HIV infection, and there is a close relationship between the CD4+ T cell count and the clinical manifestations of AIDS (Fig. 309-26, p. 1879, in HPIM-15). Pts with CD4+ T cell counts below <200/ µL are at high risk of infection with Pneumocystis carinii, while pts with CD4+ T cell counts below <50/µL are at high risk for developing CMV disease and infection with Mycobacterium avium-intracellulare. While the CD4+ T cell count provides information on the current immunologic status of the pt, the HIV RNA level predicts what will happen to the CD4+ T cell count in the near future and hence predicts the clinical prognosis. Measurements of plasma HIV RNA levels should be made at the time of HIV diagnosis and every 3–4 months thereafter in the untreated pt. Measurement of plasma HIV RNA is also useful in making therapeutic decisions about antiretroviral therapy. A level of HIV RNA >20,000 copies/mL is felt by many experts to be an indication for initiation of antiretroviral therapy regardless of the CD4+ T cell count (see below). Following the initiation of therapy or any change in therapy, HIV RNA levels should be monitored approximately every 4 weeks until the effectiveness of the therapeutic regimen is determined by the development of a new steady-state level of HIV RNA. During therapy, levels of HIV RNA should be monitored every 3–4 months to evaluate the continuing effectiveness of therapy.
The sensitivity of an individual’s HIV virus(es) to different antiretroviral agents can be tested by either genotypic or phenotypic assays. The clinical value of HIV resistance testing is still under investigation.
Clinical Manifestations of HIV Infection
A complete discussion is beyond the scope of this chapter. The major clinical features of the various stages of HIV infection are summarized below (see also Chap. 309, HPIM-15).
ACUTE HIV (RETROVIRAL) SYNDROME   Approximately 50 to 70% of infected individuals experience an acute syndrome following primary infection. Acute syndrome follows infection by 3 to 6 weeks. Characterized by fevers, rigors, arthralgias, myalgias, maculopapular rash, urticaria, abdominal cramps, diarrhea, and aseptic meningitis; lasts 1 to 2 weeks and resolves spontaneously as immune response to HIV develops. Most pts will then enter a phase of clinical latency, although an occasional pt will experience progressive immunologic and clinical deterioration.
ASYMPTOMATIC INFECTION   Length of time between infection and development of disease varies greatly, but the median is estimated to be 10 years. HIV disease with active viral replication usually progresses during this asymptomatic period, and CD4+ T cell counts fall. The rate of disease progression is directly correlated with plasma HIV RNA levels. Pts with high levels of HIV RNA progress to symptomatic disease faster than do those with low levels of HIV RNA.
SYMPTOMATIC DISEASE   Symptoms of HIV disease can develop at any time during the course of HIV infection. In general, the spectrum of illness changes as the CD4+ T cell count declines. The more severe and life-threatening complications of HIV infection occur in patients with a CD4+ T cell count <200/µl. Approximately 80% of the deaths among AIDS pts are a direct result of infection other than HIV, with bacterial infections heading the list. Overall, the clinical spectrum of HIV disease is constantly changing as pts live longer and new and better approaches to treatment and prophylaxis of opportunistic infections are developed. The key element to treating symptomatic complications of HIV disease, whether primary or secondary, is achieving good control of HIV replication through the use of combination antiretroviral therapy and instituting primary and secondary prophylaxis as indicated. Major clinical syndromes seen in the symptomatic stage of HIV infection are summarized below.

Persistent generalized lymphadenopathy: Palpable adenopathy at two or more extrainguinal sites that persists for >3 months without explanation other than HIV infection. Many pts will go on to disease progression.

Constitutional symptoms: Fever persisting for more than 1 month, involuntary weight loss of more than 10% of baseline, diarrhea for longer than 1 month in absence of explainable cause.

Neurologic disease: Most common is HIV encephalopathy (AIDS dementia complex); other neurologic complications include opportunistic infections, primary CNS lymphoma, CNS Kaposi’s sarcoma, aseptic meningitis, myelopathy, peripheral neuropathy and myopathy.

Secondary infectious diseases: P. carinii pneumonia is most common opportunistic infection, occurring in approximately ~80% of individuals during the course of their illness. Other common pathogens include CMV (chorioretinitis, colitis, pneumonitis, adrenalitis), Candida albicans (oral thrush, esophagitis), M. avium-intracellulare (localized or disseminated infection), M. tuberculosis, Cryptococcus neoformans (meningitis, disseminated disease), Toxoplasma gondii (encephalitis, intracerebral mass lesion), herpes simplex virus (severe mucocutaneous lesions, esophagitis), diarrhea due to Cryptosporidium spp. or Isospora belli, bacterial pathogens (especially in pediatric cases).

Secondary neoplasms: Kaposi’s sarcoma (cutaneous and visceral, more fulminant course than in non-HIV-infected pts), lymphoid neoplasms (especially B cell lymphomas of brain, marrow, GI tract).

Other diseases: A variety of organ-specific syndromes can be seen in HIV- infected pts, either as primary manifestations of the HIV infection or as complications of treatment.

TREATMENT (See Chap. 309, HPIM-15)
General principles of pt management include counseling, psychosocial support, and screening for infections and require comprehensive knowledge of the disease processes associated with HIV infection.
Antiretroviral Therapy (See Table 309-21 p. 1901, in HPIM-15)
The cornerstone of medical management of HIV infection is combination antiretroviral therapy, or HAART. Suppression of HIV replication is an important component in prolonging life as well as in improving the quality of life of pts with HIV infection. However, several important questions related to the treatment of HIV disease lack definitive answers. Among them are questions of when antiretroviral therapy should be started, what is the best HAART regimen, when should a given regimen be changed, and what drugs in a regimen should be changed when a change is made. The drugs that are currently licensed for the treatment of HIV infection are listed below. These drugs fall into two main categories: those that inhibit the viral reverse transcriptase enzyme and those that inhibit the viral protease enzyme. There are numerous drug-drug interactions that must be taken into consideration when using these medications (Table 309-22, p. 1994, in HPIM-15). One of the main problems that has been encountered with the widespread use of HAART regimens has been a syndrome of hyperlipidemia and fat distribution often referred to as lipodystrophy syndrome (Chap. 309, HPIM-15).
Nucleoside Analogues These should only be used in combination with other antiretroviral agents. The most common usage is together with another nucleoside analogue and a protease inhibitor (see below). Zidovudine (AZT, 3′-azido-2′,3′-dideoxythymidine) is the prototype of these agents. The only indication for zidovudine monotherapy is the prophylaxis of maternal-fetal transmission of HIV when the mother herself does not require antiretroviral therapy based on the stage of her disease. Major toxicities are due to bone marrow suppression, especially anemia. Other toxicities include myopathy, cardiomyopathy, and lactic acidosis associated with hepatic steatosis. Standard dose is 200 mg 3 times daily.
Didanosine (ddI, 2′,3′-dideoxyinosine) is the second drug to be approved for anti-HIV therapy. Major toxicities include painful sensory peripheral neuropathy and pancreatitis. Standard dose is 200 mg bid, for pts weighing >60 kg; 125 mg bid, for pts <60 kg.
Zalcitabine (ddC, 2′,3′-dideoxycytidine) has toxicities similar to didanosine, although pancreatitis is not seen as frequently. Standard dose is 0.75 mg tid.
Stavudine (d4T, 2′,3′-didehydro-3′-deoxythymidine) is antagonistic with zidovudine in vitro and possibly in vivo; hence, this combination should be avoided. The standard dose of stavudine is 40 mg bid, for pts weighing >60 kg; 30 mg bid, for pts <60 kg. Peripheral neuropathy is the predominant toxicity seen with this drug.
The combination of lamivudine (3TC, 2′,3′-dideoxy-3′-thiacytidine), and zidovudine in vitro is the most potent nucleoside combination studied to date. The standard dose of lamivudine is 150 mg bid. Lamivudine is available either alone or in combination with zidovudine (Combivir). Although the main toxicities of lamivudine are peripheral neuropathy and pancreatitis, it is among the best tolerated of the nucleoside analogues.
Abacavir {(1S,cis)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2- cyclopentene-1-methanol sulfate} is a synthetic analogue of the nucleoside guanosine. It is licensed to be used in combination with other antiretroviral drugs for the treatment of HIV infection. Hypersensitivity reactions have been reported in ~5% of pts treated with abacavir, and pts developing signs or symptoms such as fever, skin rash, fatigue, and GI symptoms should discontinue the drug and not restart it. Fatal hypersensitivity reactions have been reported with rechallange. Abacavir is available either alone or in a fixed- dose combination with zidovudine and lamivudine (Trizivir).
Nonnucleoside Reverse Transcriptase Inhibitors These agents interfere with the function of HIV-1 reverse transcriptase by binding to regions outside the active site and causing conformational changes in the enzyme that render it inactive. These agents are very potent; however, when they are used as monotherapy, they induce rapid emergence of drug-resistant mutants. Three members of this class, nevirapine, delavirdine, and efavirenz are currently available for clinical use. These drugs are licensed for use in combination with other antiretrovirals. The main toxicities of these drugs are maculopapular rash and elevations in hepatic enzymes levels. While it is possible to treat through the rash, it is important to be sure that one is not dealing with more severe eruptions (such as Stevens-Johnson syndrome), which are characterized by mucosal involvement, significant fever, or painful lesions with desquamation. Efavirenz therapy may be associated with CNS symptoms such as light-headedness, dizziness, or vivid dreams. These symptoms tend to abate after several weeks of therapy. The usual dose of delavirdine is 400 mg tid; for nevirapine it is 200 mg/d for 1 week, then 200 mg bid; for efavirenz it is 600 mg once a day at bedtime.
Protease Inhibitors These drugs are potent and selective inhibitors of the HIV-1 protease enzyme and are active in the nanomolar range. Unfortunately, as in the case of the nonnucleoside reverse transcriptase inhibitors, this potency is accompanied by the rapid emergence of resistant isolates when these drugs are used as monotherapy. Thus, the protease inhibitors should be used only in combination with other antiretroviral drugs.
Saquinavir was the first protease inhibitor licensed; it is one of the better tolerated protease inhibitors. Initially marketed as a hard gel (Invirase) with poor bioavailability, the current soft-gel formulation (Fortavase) provides good plasma levels of drug. HIV resistance to protease inhibitors is quite complex, but it seems that strains of HIV resistant to saquinavir are generally not resistant to either ritonavir or indinavir (see below), suggesting that combination therapy with different protease inhibitors may be of value. This must be approached with caution, since saquinavir is metabolized by the cytochrome P450 system and ritonavir therapy results in inhibition of the P450 system. Thus, the use of both drugs together has the potential to result in unpredictable increases in saquinavir levels. The usual dose of saquinavir is 600 mg q8h (Invirase) or 1200 mg tid (Fortovase).
Ritonavir is the first protease inhibitor for which clinical efficacy was demonstrated. Strains of HIV resistant to ritonavir are also resistant to indinavir. The main side effects of ritonavir are nausea, abdominal pain, diarrhea, and circumoral paresthesia. These side effects can be reduced somewhat by initiating therapy at 300 mg bid and then rapidly escalating the dose over 5 to 7 days to the full dose of 600 mg bid. Ritonavir has a high affinity for certain isoforms of cytochrome P450, and thus it can produce large increases in the plasma levels of drugs that are metabolized by this enzyme. Among the agents affected in this manner are saquinavir, macrolide antibiotics, terfenadine, astemizole, warfarin, ondansetron, rifampin, most calcium channel blockers, glucocorticoids, sedative-hypnotics (alprazolam, diazepam, flurazepam, midazolam, and triazolam), and analgesics (fentanyl citrate, hydrocodone, oxycodone, methadone). Great care should be taken when prescribing additional drugs to pts receiving ritonavir. The use of low doses of ritonavir (100–200 mg bid) to provide pharmacodynamic boosting of other antiretroviral agents has become a fairly common strategy in HIV therapy.
Indinavir was the third protease inhibitor licensed. The usual dose is 800 mg q8h (1000 mg q8h with nevirapine or efavirenz; 400–600 mg q8h with delavirdine). HIV isolates that are resistant to indinavir show cross-resistance to ritonavir and varying degrees of cross-resistance to saquinavir. The main side effects of indinavir are nephrolithiasis and asymptomatic indirect hyperbilirubinemia. Indinavir is also metabolized by cytochrome P450, and coadministration of indinavir with any of the antihistamines, sedative-hypnotics, and analgesics listed above should be avoided. Levels of indinavir are decreased during concurrent therapy with rifampin and nevirapine and increased during concurrent therapy with ketoconazole and delavirdine. Dosages of indinavir should be appropriately modified in these situations. Rifampin should not be administered concurrently with indinavir or the other currently available protease inhibitors. Concurrent administration of indinavir with rifabutin results in a twofold increase in rifabutin levels; thus, the rifabutin dose should be decreased by one-half if given with indinavir.
Nelfinavir was approved in 1997, and amprenavir was approved in 1999 for the treatment of adult or pediatric HIV infection when antiretroviral therapy is warranted. At present, limited clinical data are available for these drugs. GI side effects are associated with both agents. The usual dose of nelfinavir is 750 mg tid; the dose of amprenavir is 1200 mg (8 large capsules) bid; 1200 mg tid if given with nevirapine or efavirenz
Lopinavir/ritonavir (Kaletra) is a coformulation of lopinavir, an inhibitor of HIV protease that is metabolized by cytochrome P450, and low-dose ritonavir, which inhibits cytochrome P450 and boosts lopinavir levels. Based on controlled and uncontrolled trials that demonstrated decreases in plasma HIV RNA and increases in CD4+ T cell counts, this drug was approved in 2000 for use in combination with other antiretroviral agents. The side effect profile is similar to that of ritonavir and nelfinavir. The usual adult dose is 400 mg (lopinavir)/100 mg (ritonavir) bid.
Choice of Antiretroviral Treatment Strategy
The large number of available antiretroviral agents coupled with a relative paucity of clinical end-point studies make the subject of antiretroviral therapy one of the more controversial in the management of HIV-infected pts.
The principles of therapy for HIV infection have been articulated by a panel sponsored by the U.S. Department of Health and Human Services and the Henry J. Kaiser Family Foundation (Table 86-1). Treatment decisions must take into account the fact that one is dealing with a chronic infection and that complete eradication of HIV infection is probably not possible with currently available HAART regimens. Thus, immediate treatment of HIV infection upon diagnosis may not be prudent, and therapeutic decisions must take into account the balance between risks and benefits. At present a reasonable course of action is to initiate antiretroviral therapy in anyone with the acute HIV syndrome; pts with symptomatic disease; pts with asymptomatic infection and CD4+ counts <500/µl or with >20,000 copies/mL of HIV RNA. In addition, one may wish to administer a 4-week course of therapy to uninfected individuals immediately following a high-risk exposure to HIV (see below).

Table 86-1 Principles of Therapy of HIV Infection

When the decision to initiate therapy is made, the physician must decide which drugs to use in the initial regimen. The two options for initial therapy most commonly in use today are: two nucleoside analogues (one of which is usually lamivudine) combined with a protease inhibitor; or two nucleoside analogues and a nonnucleoside reverse transcriptase inhibitor. There are no clear data at present on which to base distinctions between these two approaches. Following the initiation of therapy, one should expect a 1-log (tenfold) reduction in plasma HIV RNA within 1–2 months and eventually a decline in plasma HIV RNA to <50 copies/mL. There should also be a rise in CD4+ T cell count of 100–150/µL. Many physicians feel that failure to achieve this endpoint is an indication for a change in therapy. Other reasons for changing therapy are listed in Table 86-2. When changing therapy because of treatment failure, it is important to attempt to provide a regimen with at least two new drugs. In the pt in whom a change is made for reasons of drug toxicity, a simple replacement of one drug is reasonable.

Table 86-2 Indications for Changing Antiretroviral Therapy in Patients with HIV Infectiona

Treatment of Secondary Infections and Neoplasms
Specific for each infection and neoplasm (Chap. 309, in HPIM-15).
Prophylaxis against Secondary Infections (Table 309-11, p. 1881, in HPIM-15) Primary prophylaxis is clearly indicated for P. carinii pneumonia (especially when CD4+ T cell counts fall below to <200 cells/µL), M. avium complex infections, and M. tuberculosis infections in pts with a positive PPD or anergy if at high risk of TB. Vaccination with pneumococcal polysaccharide and H. influenzae type b vaccines is recommended. Secondary prophylaxis, when available, is indicated for virtually every infection experienced by HIV-infected pts.

HIV and the Health Care Worker
There is a small but definite risk to health care workers of acquiring HIV infection via needle stick exposures, large mucosal surface exposures, or exposure of open wounds to HIV-infected secretions or blood products. The risk of HIV transmission after a skin puncture by an object contaminated with blood from a person with documented HIV infection is ~0.3%, compared to 20–30% risk for hepatitis B infection from a similar incident. The role of antiretroviral agents in postexposure prophylaxis is still controversial. However, a U.S. Public Health Service working group has recommended that chemoprophylaxis be given as soon as possible after occupational exposure. While the precise regimen remains a subject of debate, the U.S. Public Health Service guidelines recommend (1) a combination of two nucleoside analogue reverse transcriptase inhibitors given for 4 weeks for routine exposures, or (2) a combination of two nucleoside analogue reverse transcriptase inhibitors plus a protease inhibitor given for 4 weeks for high-risk or otherwise complicated exposures. Most clinicians administer the latter regimen in all cases in which a decision to treat is made. Regardless of which regimen is used, treatment should be initiated as soon as possible after exposure.
Prevention of exposure is the best strategy and includes following universal precautions and proper handling of needles and other potentially contaminated objects.
Transmission of TB is another potential risk for all health care workers, including those dealing with HIV-infected pts. All workers should know their PPD status, which should be checked yearly.
Vaccines
Development of a safe and effective HIV vaccine is the object of active investigation at present. Extensive animal work is ongoing, and clinical trials of candidate vaccines have begun in humans.
Prevention
Education, counseling, and behavior modification remain the cornerstones of HIV prevention efforts. While abstinence is an absolute way to prevent sexual transmission, other strategies include “safe sex” practices such as use of condoms together with the spermatocide nonoxynol-9. Avoidance of shared needle use by IDUs is critical. If possible, breast feeding should be avoided by HIV- positive women, as the virus can be transmitted to infants via this route.
Bibliography

For a more detailed discussion, see Fauci AS, Lane HC: Human Immunodeficiency Virus (HIV) Disease: AIDS and Related Disorders, Chap. 309, p. 1852, in HPIM-15.

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