BackgroundThe genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate.Methods and FindingsTo assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of mutations in protease and reverse transcriptase, a binomial response model using subtype and treatment as explanatory variables was used to analyze a large compiled dataset of non-subtype-B HIV-1 sequences. Non-subtype-B sequences from 3,686 persons with well characterized antiretroviral treatment histories were analyzed in comparison to subtype B sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A, 1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG. Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B isolate, and 44 (80%) of these mutations were significantly associated with antiretroviral treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated with antiretroviral therapy in at least one non-B subtype, 61 were also associated with antiretroviral therapy in subtype B isolates.ConclusionGlobal surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations.

Brazil has a low prevalence of drug-resistant strains circulating among recently diagnosed individuals. However, there was an increase in these rates compared with similar studies performed with samples collected in Brazil from 1996 to 1998. Continued surveys are required to detect trends in these rates, but routine genotypic testing in the drug-naive population prior to antiretroviral initiation is not required in Brazil.

Introduction of subtype C of HIV-1 in Brazil was likely a single event of one or a mixture of similarly related strains. Recombination between subtype C and B viruses is an ongoing process in the country. Primary and secondary drug resistance mutations were observed, although some of the secondary mutations could be associated with subtype C molecular signatures. Subtype-specific polymorphisms of PR and RT sequences found in this subtype C Brazilian variant might influence this emergence and have an impact on HIV treatment and on vaccine development in the country.

HIVseq allows users to examine protease and RT mutations within the context of previously published sequences of these genes. The publication of additional non-B protease and RT sequences from persons with well-characterized treatment histories, however, will be required to perform the same types of analysis possible with the much larger number of subtype B sequences.

The objective of this study was to assess if a simple evaluation, adherence to antiretroviral therapy, would correlate to clinical and laboratory outcomes. We followed an open cohort of patients from a public teaching hospital AIDS outpatient clinic. Patients were categorized according to adherence as: regular (Reg), optimal, all doses all days, tolerating only irregular timing (+/- 2 hours) of intake; quasi-regular (qReg), those missing up to four doses or 1 full day during a month; irregular (Irreg), all other irregular regimens, and ignored (Ign), those without information. The results from a simple questionnaire were compared to CD4+ cell counts and human immunodeficiency virus type 1 (HIV-1) RNA plasma viremia. One hundred eighty-two HIV-1-infected patients (126 males, 69%; 56 females, 31%) were analyzed. Information on adherence was available for 168 (90%). Reg adherence was reported by 75 (41%) patients, qReg adherence by 35 (19%), and Irreg by 53 (29%) of patients. The main reasons for nonadherence were forgetfulness, intolerance, use of alcohol, and misunderstanding of prescription. A significant increase of CD4+ T-cell counts and absolute gain were only observed among Reg and qReg users (p < 0.001). The median viral RNA load log10 decreases were -1.68, -1.45, -0.9 log, respectively, for Reg, qReg, and Irreg patients (p = 0.043, Kruskal-Wallis). Development of and death from AIDS occurred almost exclusively among those with Ign or Irreg adherence. Previous use of antiretroviral therapy may have had an impact in treatment response. Individuals who were treatment-naive were more likely to be Reg users (41%). Although more refined methods to assess adherence should be implemented when available, the inability to do so should not prevent simple, albeit subjective measurements that also correlate with favorable outcome. Mechanisms to improve adherence should be considered an integral part of antiretroviral therapy.