HIV AIDS : Definition, Diagnosis, Pathophysiology, Treatment

Sunday, May 25th 2014. | Disease
HIV AIDS Pathophysiology
Infection with HIV occurs through three primary modes: sexual, parenteral, and perinatal. Sexual intercourse, primarily receptive anal and vaginal intercourse, is the most common vehicle for transmission. The probability of HIV transmission from receptive anorectal intercourse is 0.1% to 3% per sexual contact and 0.1% to 0.2% per sexual contact for receptive vaginal intercourse. In general, the risk is increased when the index partner is in an advanced stage of disease. Persons at higher risk for heterosexual transmission include those with ulcerative sexually transmitted diseases, those with multiple sex partners, and sexual partners of intravenous drug users.
The use of contaminated needles or other injection-related paraphernalia by drug abusers has been the main cause of parenteral transmissions and currently accounts for one-fourth of AIDS cases reported in the United States.
Health care workers have a small risk of occupationally acquiring HIV, mostly through needlestick injury.
Perinatal infection, or vertical transmission, is the most common cause (greater than 90%) of pediatric HIV infection. The risk of mother-to-child transmission is approximately 25% in the absence of breast feeding or antiretroviral therapy. Breast feeding can also transmit HIV.
  • 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.
  • Probability of progression to AIDS is related to RNA viral load; in one study, 5-year progression rates to AIDS were 8%, 26%, 49%, and 62% for RNA copies per milliliter of less than 4530, 4531 to 13,020, 13,021 to 36,270, and greater than 36,270, respectively.
  • The classification scheme of the Centers for Disease Control and Prevention (CDC) divides HIV infection into a matrix of nine categories based on the CD4 cell count (see “Diagnosis” below) and clinical conditions.
  • 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 and 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.
  • The most commonly used screening method for HIV is an enzyme-linked immunosorbent assay (ELISA), 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 ELISAs 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.
  • 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 (RT-PCR), branched DNA (bDNA), and transcription-mediated amplification. 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/µL, or 40% to 70% of all lymphocytes.
  • Regular, periodic measurement of plasma HIV RNA levels and CD4 cell counts is necessary to determine the risk of disease progression in an HIV-infected individual and to determine when to initiate or modify antiretroviral treatment regimens.
  • Treatment decisions should be individualized by level of risk indicated by plasma HIV RNA levels and CD4 counts.
  • The use of potent combination antiretroviral therapy to suppress HIV replication to below the levels of detection of sensitive plasma HIV RNA assays limits the potential for selection of antiretroviral-resistant HIV variants, the major factor limiting the ability of antiretroviral drugs to inhibit virus replication and delay disease progression.
  • The most effective means to accomplish durable suppression of HIV replication is the simultaneous initiation of combinations of effective anti-HIV drugs with which the patient has not been previously treated and that are not cross resistant with antiretroviral agents with which the patient has been treated previously.
  • Each of the antiretroviral drugs used in combination therapy regimens should always be used according to optimum schedules and dosages.
  • Women should receive optimal antiretroviral therapy regardless of pregnancy status.
  • The same principles of antiretroviral therapy apply to both HIV-infected children and adults, although the treatment of HIV-infected children involves unique pharmacologic, virologic, and immunologic considerations.
  • Persons with acute primary HIV infections should be treated with combination antiretroviral therapy to suppress virus replication to levels below the limit of detection of sensitive plasma HIV RNA assays.
  • HIV-infected persons, even those with viral loads below detectable limits, should be considered infectious and should be counseled to avoid sexual and drug-use behaviors that are associated with transmission or acquisition of HIV and other infectious pathogens.
Antiretroviral Agents
  • Inhibiting viral replication with combination of potent antiretroviral therapy has been the most clinically successful strategy in the treatment of HIV infection. There have been three primary groups of drugs used: nucleoside and nonnucleoside reverse transcriptase inhibitors and protease inhibitors.
  • Reverse transcriptase inhibitors are of two types: those that are derivatives of purine- and pyrimidine-based nucleosides and nucleotides (NRTIs) and those that are not nucleoside or nucleotide based (NNRTIs).
  • Current recommendations for treating HIV infection advocate a minimum of three antiretroviral agents. The typical regimen consists of two nucleoside analogues with either a protease inhibitor (PI) or an NNRTI.
  • Significant drug interactions can occur with many antiretroviral agents:
  • Amprenavir, Efavirenz, tipranavir, and nevirapine are inducers of drug metabolism, whereas delavirdine and protease inhibitors inhibit drug metabolism.
  • Ritonavir is a potent inhibitor of cytochrome P4503A and is used to reduce clearance of other protease inhibitors.
  • Two NRTIs, zidovudine and stavudine, antagonize each other’s metabolism and should not be given together.
  • Rifampin may substantially reduce the concentrations of PIs
  • Saint John’s wort is a potent inducer of metabolism and is contraindicated with PIs and NNRTIs.
Therapy during pregnancy is warranted, particularly in light of the dramatic reduction in transmission seen with zidovudine monotherapy. In general, pregnant women should be treated similar to nonpregnant adults; if possible, zidovudine should be used for both mother and infant.
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