Human Immunodeficiency Virus Infection

Introduction

• Infection with HIV occurs through three primary modes: sexual, parenteral, and perinatal. Sexual intercourse, primarily anal and vaginal intercourse, is the most common vehicle for transmission. The probability of HIV transmission from receptive anorectal intercourse is 0.5% to 3% per sexual contact and lower for receptive vaginal intercourse. Condom use reduces the risk of transmission by ~20-fold. Individuals with genital ulcers or sexually transmitted diseases, such as syphilis, chancroid, herpes, gonorrhea, Chlamydia, and trichomoniasis are at great risk for contracting HIV.
• The use of contaminated needles or other injection-related paraphernalia by drug abusers has been the main cause of parenteral transmissions of HIV.
• Healthcare workers have a small risk of occupationally acquiring HIV, mostly through accidental injury, most often percutaneous needlestick injury.
• Perinatal infection, or vertical transmission, is the most common cause of pediatric HIV infection. The risk of mother-to-child transmission is ~25% in the absence of breast-feeding or antiretroviral therapy. Breast-feeding can also transmit HIV.

Clinical Presentation and Diagnosis

• Clinical presentations of primary HIV infection vary, but patients often have a viral syndrome or mononucleosis-like illness with fever, pharyngitis, and adenopathy . Symptoms may last for 2 weeks.
• The probability of progression to AIDS is related to RNA viral load; in one study, 5-year mortality rates were 5% for those with a viral load less than 4530 and 49% for those greater than 36,270.
• Most children born with HIV are asymptomatic. On physical examination, they often present with unexplained physical signs such as lymphadenopathy, hepatomegaly, splenomegaly, failure to thrive, weight loss or unexplained low birth weight, and fever of unknown origin. Laboratory findings include anemia, hypergammaglobulinemia, altered mononuclear cell function, and altered T-cell subset ratios. The normal range for CD4 cell counts in children is much different than for adults .
• Clinical presentations of the opportunistic infections are presented in Infectious Complications of HIV below.
• The preferred method for diagnosing HIV is an enzyme-linked immunosorbent assay, which detects antibodies against HIV-1 and is both highly sensitive and specific. False-positives can occur in multiparous women; in recent recipients of hepatitis B, HIV, influenza, or rabies vaccine; following multiple blood transfusions; and in those with liver disease or renal failure or undergoing chronic hemodialysis. False-negatives may occur if the patient is newly infected and the test is performed before antibody production is adequate. The minimum time to develop antibodies is 3 to 4 weeks from initial exposure.
• Positive enzyme-linked immunosorbent assays are repeated in duplicate and if one or both tests are reactive, a confirmatory test is performed for final diagnosis. Western blot assay is the most commonly used confirmatory test, although an indirect immunofluorescence assay is available.
• The viral load test quantifies viremia by measuring the amount of viral RNA. There are several methods used for determining the amount of HIV RNA: reverse transcriptase–coupled polymerase chain reaction, branched DNA, and nucleic acid sequence–based assay. Each assay has its own lower limit of sensitivity, and results can vary from one assay method to the other; therefore, it is recommended that the same assay method be used consistently within patients.
• Viral load can be used as a prognostic factor to monitor disease progression and the effects of treatment.
• The number of CD4 lymphocytes in the blood is a surrogate marker of disease progression. The normal adult CD4 lymphocyte count ranges between 500 and 1600 cells/mm3 (500 and 1600 × 106 /L), or 40% to 70% of all lymphocytes.

Treatment

• Goal of Treatment: The central goal of antiretroviral therapy is to decrease morbidity and mortality, improve quality of life, restore and preserve immune function, and prevent further transmission through maximum suppression of HIV replication (HIV RNA level that is undetectable).
• Current recommendations for initial treatment of HIV infection advocate a minimum of three active antiretroviral agents: tenofovir disoproxil fumarate plus emtricitabine witheither a ritonavir-enhancedPI(darunaviror atazanavir),theNNRTI efavirenz, or the InSTI, raltegravir.
• Ritonavir is a potent inhibitor of cytochrome P450 enzyme 3A and is used to reduce clearance of other PIs. Rifampin may substantially reduce the concentrations of PIs and is contraindicated with the use of most PIs. Saint John’s wort is a potent inducer of metabolism and is contraindicated with PIs, NNRTIs, and maraviroc.