Prevalence of transmitted HIV-1 antiretroviral resistance among patients initiating antiretroviral therapy in Brazil: a surveillance study using dried blood spots.

INTRODUCTION: In Brazil, the use of antiretrovirals is widespread: more than 260,000 individuals are currently undergoing treatment. We conducted a survey targeting antiretroviral-naïve individuals who were initiating antiretroviral therapy (ART) according to local guidelines. This survey covered five Brazilian regions. METHODS: The HIV Threshold Survey methodology (HIV-THS) of the World Health Organization was utilized, and subjects were selected from seven highly populated cities representative of all Brazilian macro-regions. Dried blood spots (DBS) were collected on SS903 collection cards and were transported by regular mail at room temperature to a single central laboratory for genotyping. RESULTS: We analysed samples from 329 individuals initiating highly active antiretroviral therapy (HAART), 39 (11.8%) of whom were harbouring transmitted drug resistance (TDR). The mean CD4+ T cell count was 253 cells/µL, and the mean viral load was 142,044 copies/mL. The regional prevalence of resistance was 17.0% in the Northeast, 12.8% in the Southeast, 10.6% in the Central region, 8.5% in the North and 8.5% in the South. The inhibitor-specific TDR prevalence was 6.9% for nucleoside reverse transcriptase inhibitors, 4.9% for non-nucleoside reverse transcriptase inhibitors and 3.9% for protease inhibitors; 3.6% of individuals presented resistance to more than one class of inhibitors. Overall, there were trends towards higher prevalences of subtype C towards the South and subtype F towards the North. Of the DBS samples collected, 9.3% failed to provide reliable results. DISCUSSION: We identified variable TDR prevalence, ranging from intermediate to high levels, among individuals in whom HIV disease progressed, thus implying that resistance testing before initiating ART could be effective in Brazil. Our results also indicate that the use of DBS might be especially valuable for providing access to testing in resource-limited and remote settings.

Vicriviroc plus optimized background therapy for treatment-experienced subjects with CCR5 HIV-1 infection: final results of two randomized phase III trials.

BACKGROUND: Vicriviroc, a novel HIV CCR5 antagonist, demonstrated significant efficacy and favorable tolerability in phase II trials in treatment-experienced subjects, supporting further evaluation in phase III studies. METHODS: Two identical double-blind, placebo (PBO)-controlled trials in CCR5-tropic HIV-infected subjects with documented resistance to two antiretroviral classes were conducted. Subjects were randomized to vicriviroc 30 mg QD (N = 571) or PBO (N = 286) with open-label optimized background therapy (OBT) containing ≥2 fully active antiretroviral drugs. The primary endpoint was percentage of subjects with <50 copies/mL HIV RNA at 48 weeks. It was analyzed in a logistic regression with treatment (vicriviroc + OBT/PBO + OBT), use of enfuvirtide in baseline OBT (yes/no), and baseline HIV RNA (≤100,000/>100,000 copies/mL) as covariates. In addition, a pre-planned analysis to examine other efficacy and safety endpoints was conducted. RESULTS: Baseline characteristics of the pooled mITT population (vicriviroc, n = 486; PBO, n = 235) included mean HIV RNA of 4.6 log(10) copies/mL and mean CD4 count of 257 cells/µL. Approximately 60% of subjects received ≥3 active drugs in the OBT. The percentage of subjects with <50 copies/mL HIV RNA was not significantly different between vicriviroc and PBO at week 48 (64% vs 62%, p = 0.6). However, in subjects receiving ≤2 active drugs in their OBT, the proportion achieving <50 copies/mL HIV RNA was higher in those receiving vicriviroc compared with PBO (70% vs 55%, p = 0.02). CONCLUSIONS: The studies failed to show significant efficacy gains when vicriviroc was added to OBT. However, given the efficacy results of earlier vicriviroc trials and other CCR5 antagonist, studies are needed to define the role of this class of drugs in the treatment of HIV. Clinical trial identifier: http://www.clinicaltrial.gov/: VICTOR-E3 (NCT00523211) and VICTOR-E4 (NCT00474370).

Characterization of virologic failure after an initially successful 48-week course of antiretroviral therapy in HIV/AIDS outpatients treated in Santos, Brazil.

We characterized the virologic failure after an initially successful 48-week course of antiretroviral therapy among HIV/AIDS patients in a retrospective cohort study involving patients from Santos, Brazil. Patients with plasma HIV RNA below 500 copies/mL for 48 weeks were included. Variables analyzed included gender, age, level of education, marital status, mode of HIV acquisition, viral load, and CD4 cell count upon admission. There were 4,909 patients registered with the clinic, of which 669 patients met all the inclusion criteria (41.6% female and 58.4% male). Only 27.5% of the patients maintained undetectable viral loads during up to one year of follow-up. After 48 weeks, virologic failure occurred earlier in females and in patients first treated with an antiretroviral regimen other than highly active antiretroviral therapy. Patients who were married or had a steady partner experienced virologic failure later than did those who were separated or widowed. The percentage of public health clinic patients who maintain undetectable viral loads for a period of over a year is much lower than that observed among patients enrolled in clinical trials. Females, individuals in unstable relationships, single individuals and widowed individuals should be given special attention in order to improve durability of viral suppression.

Characterization of virologic failure after an initially successful 48-week course of antiretroviral therapy in HIV/AIDS outpatients treated in Santos, Brazil

We characterized the virologic failure after an initially successful 48-week course of antiretroviral therapy among HIV/AIDS patients in a retrospective cohort study involving patients from Santos, Brazil. Patients with plasma HIV RNA below 500 copies/mL for 48 weeks were included. Variables analyzed included gender, age, level of education, marital status, mode of HIV acquisition, viral load, and CD4 cell count upon admission. There were 4,909 patients registered with the clinic, of which 669 patients met all the inclusion criteria (41.6 percent female and 58.4 percent male). Only 27.5 percent of the patients maintained undetectable viral loads during up to one year of follow-up. After 48 weeks, virologic failure occurred earlier in females and in patients first treated with an antiretroviral regimen other than highly active antiretroviral therapy. Patients who were married or had a steady partner experienced virologic failure later than did those who were separated or widowed. The percentage of public health clinic patients who maintain undetectable viral loads for a period of over a year is much lower than that observed among patients enrolled in clinical trials. Females, individuals in unstable relationships, single individuals and widowed individuals should be given special attention in order to improve durability of viral suppression.

Identification of two HIV type 1 circulating recombinant forms in Brazil.

Recombination is an important way to generate genetic diversity. Accumulation of HIV-1 full-length genomes in databases demonstrated that recombination is pervasive in viral strains collected globally. Recombinant forms achieving epidemiological relevance are termed circulating recombinant forms (CRFs). CRF12_BF was up to now the only CRF described in South America. The objective was to identify the first CRF in Brazil conducting full genome analysis of samples sharing the same partial genome recombinant structure. Ten samples obtained from individuals residing in Santos, Brazil, sharing the same recombination pattern based on partial genome sequence data, were selected from a larger group to undergo full length genome analysis. Near full length genomes were assembled from overlapping fragments. Mosaic genomes were evaluated by Bootscan, alignment inspection, and phylogenetic analysis using neighbor joining and maximum likelihood. Full genomes were also analyzed by split decomposition. We were able to identify five mosaic genomes. Two of these structures were represented by at least three samples derived from epidemiologically unlinked individuals. These structures were named CRF28_BF and CRF29_BF and are the second and third CRFs composed exclusively by subtypes B and F as well as the second and third CRFs encountered in South America. Other recombinant forms studied here resembled CRF28_BF and CRF29_BF. Our results suggest that a diverse population of related recombinants, including CRFs may play an important part in the Brazilian and South American epidemic.