ABSTRACT
OBJECTIVE: Compare the initial phases of virologic decay when acute/early and advanced HIV-infected adults are administered the same treatment regimen. DESIGN: Mathematical modeling of a previously completed prospective treatment pilot study involving treatment-naive patients with early and advanced immunosuppression. METHODS: We analyzed data from a treatment protocol in which 18 individuals with acute or recent HIV-1 seroconversion and six patients with advanced AIDS were administered the same four-drug antiretroviral regimen. Initial treatment responses were compared by fitting a mathematical model to frequent viral load measurements in order to calculate the first and second phase kinetics of viral clearance, and also by comparing viral load suppression over 24 weeks. Patients were also comprehensively compared in terms of protease inhibitor drug levels, HIV-specific immune responses at baseline, and the presence of drug resistance-conferring mutations. RESULTS: There was no statistically meaningful difference in first phase clearance of comparable high-level viremia in the two groups, whether protease inhibitor levels were inserted into the model or 100% antiviral drug effectiveness was assumed. In contrast, acute/early patients had inferior sustained responses than advanced patients, reflecting erratic adherence. CONCLUSIONS: Despite many years of intervening immune destruction, the initial virologic decay on therapy appears to be the same at the extremes of the HIV disease spectrum.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV-1/drug effects , Acquired Immunodeficiency Syndrome/drug therapy , Acquired Immunodeficiency Syndrome/immunology , Acquired Immunodeficiency Syndrome/virology , Acute Disease , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , Drug Resistance, Viral/genetics , Follow-Up Studies , HIV Infections/immunology , HIV Infections/virology , HIV Protease Inhibitors/blood , HIV Protease Inhibitors/therapeutic use , HIV-1/genetics , HIV-1/isolation & purification , Humans , Mutation , RNA, Viral/blood , T-Lymphocytes/immunology , Treatment Outcome , Viral LoadABSTRACT
We determined the abilities of 10 technologies to detect and quantify a common drug-resistant mutant of human immunodeficiency virus type 1 (lysine to asparagine at codon 103 of the reverse transcriptase) using a blinded test panel containing mutant-wild-type mixtures ranging from 0.01% to 100% mutant. Two technologies, allele-specific reverse transcriptase PCR and a Ty1HRT yeast system, could quantify the mutant down to 0.1 to 0.4%. These technologies should help define the impact of low-frequency drug-resistant mutants on response to antiretroviral therapy.
Subject(s)
Drug Resistance, Viral/genetics , HIV-1/drug effects , HIV-1/genetics , Molecular Diagnostic Techniques , Mutation , Virology/methods , Anti-HIV Agents/pharmacology , HIV Reverse Transcriptase/genetics , HIV-1/isolation & purification , Humans , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and SpecificityABSTRACT
Zidovudine (ZDV) and stavudine (d4T) select for the same set of thymidine analogue resistance mutations (TAMs). To compare the rate at which TAMs emerge, genotypic analysis of HIV-1 was performed on serial plasma samples from treatment-naive subjects randomly assigned to receive ZDV or d4T in combination with lamivudine. After 72 weeks of follow-up, TAMs were detected in samples from 50% of ZDV-treated subjects and 45% of d4T-treated subjects (P = 0.79). The frequency of K70R and T215Y or F mutations was similar in both groups, although M41L was observed more frequently in samples from ZDV-treated subjects. This randomized study shows that TAMs accumulate at similar rates during treatment with ZDV or d4T, but the specific pattern of mutations may differ somewhat in patients treated with these thymidine analogues.
