Different tissues or body fluids in which human immunodeficiency virus type 1 (HIV-1) can reside may contain viruses with distinct characteristics. Sixteen HIV-1-infected patients receiving zidovudine or didanosine were studied cross-sectionally and 1 patient who switched from zidovudine to didanosine was followed sequentially to determine if drug resistance mutations within the HIV-1 pol gene at codons 74 and 215 differed depending on the compartment from which the gene was isolated (plasma, seminal fluid, peripheral blood mononuclear cells, or seminal nonspermatozoal mononuclear cells). Cell-free virus in plasma and semen developed detectable mutations first, followed by proviral DNA in seminal nonspermatozoal and peripheral blood mononuclear cells. Study of the appearance of HIV-1 mutations in various compartments may help elucidate how the populations and dynamics of the virus differ throughout the body and determine whether seminal cell-free virus or provirus is the major sexually transmitted form.
Among patients infected with HIV who had advanced disease and were switched from zidovudine to didanosine therapy, more than one half developed the didanosine resistance mutation at codon 74 by 24 weeks of didanosine therapy. Patients who developed the codon 74 mutation had a greater decline in CD4+ T cells after the development of the mutation and had a greater serum virus burden than did patients without the codon 74 mutation.
Major recent advances in HIV diagnosis include rapid screening serological tests that yield results on the same day of testing, new serological tests that detect infection with a wide variety of different HIV infections including HIV-1 group O and HIV-2, qualitative gene amplification tests (e.g.) that help confirm infection in persons with indeterminate serology, and quantitative gene amplification tests that detect low levels of plasma viremia (>50 virions/ml) and provide prognostic data essential for patient management. Major advances in treatment include the development of drug combinations that completely block HIV replication in a large proportion of adherent previously untreated HIV-infected persons, the demonstration that antiretroviral treatment, under some circumstances, prevents transmission - during pregnancy and following occupational exposure, and the development of sophisticated assays for assessing the drug susceptibility of clinical HIV isolates. Ongoing clinical trials will help clinicians choose the optimal treatment for both previously treated and untreated patients.
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