HIV Disease and AIDS

HUMAN IMMUNODEFICIENCY VIRUS

Human immunodeficiency virus (HIV) is a cytopathic retrovirus that kills the cells it infects.
It targets the T-helper (CD4) lymphocytes and depletes them.
This depletion creates a profound defect in cellular immunity, leaving the infected individual susceptible to opportunistic pathogens and tumors.
The natural history of HIV infection is divided into stages based on CD4 cell counts and clinical manifestations.
The average CD4 count in the peripheral blood of healthy individuals is 800 to 1,000/mm³, but most laboratories use a normal range of 450 to 1,400/mm³.
The first stage is the acute retroviral syndrome, which usually occurs 2 to 4 weeks after an exposure.
It has a clinical presentation similar to infectious mononucleosis. Common features are fever, adenopathy, hepatosplenomegaly, sore throat, myalgias, and leukopenia with atypical lymphocytes.
A high-grade viremia with a transient decrease in CD4 cell count is also present.
This is followed by a spontaneous recovery in 1 to 3 weeks.
Stage two involves a seroconversion, which usually occurs 1 to 3 months after viral transmission.
During this phase, there is an interplay of the cytotoxic T-cell response (responsible for the destruction of HIV-infected CD4 cells), humeral immunity, and cytokine release that reduces the viral load and returns the CD4 cell count to levels near, but not equal to, those that predated infection.
The third stage is an asymptomatic infection in which the CD4 count may be greater than or equal to 500 to 200/mm³.
The patient may have no symptoms or may have a generalized lymphadenopathy, but in this stage has developed a gradual decrease in CD4 counts.
The average decline is 30 to 60/mm³/y for 5 to 8 years, followed by an accelerated decline over the 2 years preceding an opportunistic and/or acquired immunodeficiency syndrome (AIDS)-defining infection.
However, the rate of decline in CD4 counts and the rate of progression to full-blown AIDS are variable.
The fourth stage involves an early symptomatic HIV infection in which the CD4 count is 100 to 300/mm³.

Those with CD4 counts greater than 200/mm³ are susceptible to the same pathogens that infect immunocompetent hosts, while those with CD4 counts less than 200/mm³ are vulnerable to major complications such as bacterial pneumonia, vaginal candidiasis, thrush, oral hairy leukoplakia, shingles, idiopathic thrombocytopenic purpura, and pulmonary tuberculosis.

Table 34-1 Positive HIV Serology with Any of the Following

Candidiasis, esophageal, or pulmonary

Cervical cancer

Coccidioidomycosis

Cryptosporidiosis with diarrhea >1 mo

Cytomegalovirus

Histoplasmosis

Kaposi sarcoma

Lymphoma

Mycobacterium avium infection

Mycobacterium kansasii infection

Mycobacterium tuberculosis infection

Pneumocystis carinii pneumonia

Pneumonia, recurrent bacterial

Progressive multifocal leukoencephalopathy

Salmonellosis, recurrent

Toxoplasmosis

The fifth stage involves a late symptomatic infection in which the CD4 count is less than 200/mm³.
This phase is characterized by a low CD4 cell count and/or the AIDS-defining illnesses (see Table 34-1) and represents the transition from HIV infection to the development of the AIDS.

EPIDEMIOLOGY

Worldwide more than 33.4 million people are HIV-positive, and in 2006, there were more than 1.1 million individuals living with HIV in the United States.
Approximately 56,000 new cases are diagnosed each year in the United States.
With improvements in antiretroviral therapy, the mortality and morbidity from AIDS are decreasing faster than the incidence of AIDS.
Highly active antiretroviral therapy (HAART) allows people to live longer and healthier lives with HIV, a terminal disease, but it does not prevent HIV infection.
Prevention of HIV disease remains crucial in stopping this epidemic.
Initially, the majority of US cases occurred in homosexual men, but today, the rate of HIV infection within the heterosexual community exceeds that seen in most homosexual communities.
Minorities and socioeconomically disadvantaged groups continue to have a disproportionate number of cases and spread of HIV infection.
The proportion of women infected with HIV is increasing, especially among women of reproductive age.
Women currently comprise 22% of adult AIDS cases in the United States.
Behavior or risks associated with a greater likelihood of acquiring HIV include male homosexuality or bisexuality, intravenous drug abuse, prostitution, heterosexual exposure to a partner at risk, a large number of sexual partners, a history of receiving blood products before 1985, and being born to an HIV-infected mother.

TRANSMISSION

The HIV virus is concentrated in cells, which makes cellular fluids more infectious than acellular fluids.
Highly cellular fluids include blood, semen, pleuroperitoneal fluids, cerebrospinal fluid (CSF), amniotic fluid, breast milk, and vaginal secretions.
Urine, sweat, saliva, and tears do not transmit HIV.
The greater the viral load, the more infectious; thus, exposure to body fluids during periods of high viremia as seen in seroconversion and advanced disease carry the greatest risk of transmission.
HIV is most frequently transmitted through unprotected sexual intercourse, and that risk increases in the presence of mucosal disruption seen with sexually transmitted diseases, especially chancroid.
High-risk sexual behaviors include anal intercourse and intercourse during menses.
Transmission during oral intercourse with ejaculation has been reported.
Parenteral transmission occurs with needle sharing among intravenous drug abusers, via blood transfusion with HIV-infected blood without detectable antibodies (risk 1 in 40,000-250,000), or transfer of the virus by a HIV contaminated needle-stick (risk 0.3%-0.4% per exposure).
Vertical transmission from an HIV-infected mother to her infant occurs in 13% to 39% of deliveries.
Breast-feeding also poses a risk of transmission up to 29% and is discouraged in women with HIV.
The risk of HIV seroconversion after a needle-stick injury when the source patient has known HIV disease is 0.3% to 0.4%.
However, that risk is influenced by the depth of penetration, gauge of the needle, amount of blood injected, and the viral load of the source patient.
The likelihood of mucocutaneous transmission of HIV is less than 0.09% and is influenced by the cellularity and viral load of splashed fluid, and the fluid’s contact time.
Early prophylaxis after HIV exposure may reduce the risk of HIV seroconversion by as much as 81% and should be recommended or offered to all high-risk parenteral exposures (see Tables 34-2 and 34-3).
Chemoprophylaxis is effective, but not absolute.
The current recommendations from the CDC for HIV postexposure prophylaxis (PEP) is a 4-week regimen of two drugs (zidovudine [ZDV] and lamivudine [3TC]; 3TC and stavudine [d4T]; or didanosine [ddI] and d4T) for most HIV exposures and an expanded regimen that includes the addition of a third drug for HIV exposures of increased risk for transmission (see Tables 34-2, 34-3 and 34-4).
When the source person’s virus is known or suspected to be resistant to one or more of the drugs considered for the PEP regimen, the selection of drugs to which the source person’s virus is unlikely to be resistant is recommended. This means when selecting a PEP regimen, choose at least two antiviral drugs that the source patient is not taking and add a third drug if needed to ensure two new drugs.
When there is a delayed exposure report, unknown source person, pregnancy in the exposed person, resistance of the source virus to antiretroviral agents, or toxicity of the PEP regimen, then consultation with local experts or the National Clinicians’ Post-Exposure Prophylaxis Hotline is advised (see Table 34-5).

Table 34-2 Recommended HIV Postexposure for Percutaneous Injuries

Infection Status of Source
Exposure Type	HIV-Positive Class 1^a	HIV-Positive Class 2^a	Source or Unknown HIV Status^b	Unknown Source^c	HIV-Negative
Less severe	Recommend basic two-drug PEP.	Recommend expanded three-drug PEP.	Generally, no PEP warranted; however, consider basic twodrug PEP^d for source with HIV risk factors.^e	Generally, no PEP warranted; however, consider basic two-drug PEP^d in settings where exposure to HIV-infected persons is likely.	No PEP warranted.
More severe^f	Recommended expanded three-drug PEP.	Recommend expanded three-drug PEP.	Generally, no PEP warranted; however, consider basic two-drug PEP^d for source with HIV risk factors.^e	Generally, no PEP warranted; however, consider basic two-drug PEP^d in settings where exposure to HIV-infected person is likely.	No PEP warranted.
^aHIV-positive, Class 1, asymptomatic HIV infection or known low viral load (e.g., <1,500 RNA copies/mL); HIV-positive, Class 2, symptomatic HIV infection, AIDS, acute seroconversion, or known high viral load. If drug resistance is a concern, obtain expert consultation. Initiation of postexposure prophylaxis (PEP) should not be delayed pending expert consultation, and, because expert consultation alone cannot substitute for face-to-face counseling, resources should be available to provide immediate evaluation and follow-up care for all exposures. ^bSource of unknown HIV status (e.g., deceased source person with no samples available for HIV testing). ^cUnknown source (e.g., solid needle and superficial injury). ^dThe designation “consider PEP” indicates that PEP is optional and should be based on an individualized decision between the exposed person and the treating clinician. ^eIf PEP is offered and taken and the source is later determined to be HIV-negative, PEP should be discontinued. ^fMore severe (e.g., large-bore hollow needle, deep puncture, visible blood on device, or needle used in patient’s artery or vein).