Treatment with indinavir, zidovudine, and lamivudine as compared with zidovudine and lamivudine alone significantly slows the progression of HIV-1 disease in patients with 200 CD4 cells or fewer per cubic millimeter and prior exposure to zidovudine.
A sensitive and specific polymerase chain reaction (PCR)-based assay was developed for four mutations in the reverse transcriptase gene of human immunodeficiency virus type 1 that have been associated with zidovudine resistance. These mutations were correlated in 366 specimens with zidovudine chemotherapy and resistance. Mutations at these four codons were detected only after zidovudine therapy. The usual sequence of appearance of mutations was codons 215, 70, 67, and 219, although individual variations occurred. The degree of resistance was proportional to the number of mutations present, although variable susceptibilities with identical patterns of mutations suggested the likelihood that additional mutations contribute to resistance. The existence of both phenotypic and genotypic mixtures was documented as was the occasional selection of subpopulations with passage of virus in vitro. The many complexities of zidovudine resistance render the assay of limited use for application to individual patients; however, it could prove useful for correlating disease or therapy with the emergence of resistance.
Differences in pretreatment characteristics and on study experiences were demonstrated between women and men enrolled in this clinical trial. The suggestion of a gender difference in response to ZDV monotherapy by antiretroviral-naive study subjects and the lower baseline values for HIV RNA in women compared with those in men provides evidence for gender differences in the relationship between virus replication, CD4+ decline, and responses to nucleoside analogue therapy.
In asymptomatic, HIV-infected adults with 500 or more CD4 cells per cubic millimeter, treatment with zidovudine slows the decline in the CD4 cell count but does not significantly prolong either AIDS-free or overall survival. These results do not encourage the routine use of zidovudine monotherapy in this population.
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