Comparison of cumulative viraemia following treatment initiation with different antiretroviral regimens: a real-life study in Brazil.

INTRODUCTION: The relative efficacy of different antiretroviral (ART) regimens has been extensively evaluated in the context of clinical trials, using HIV viral load (VL) measurements at pre-specified timepoints after ART onset. However, data from real-life studies using combined longitudinal measurements of cumulative viraemia are scarce. This study aimed to address the independent effect of different ART regimens on HIV cumulative viraemia over the first 12 months after treatment initiation, using programmatic data from the Ministry of Health of Brazil. METHODS: Retrospective cohort study analysing cumulative viraemia under the most frequently used ART regimens in Brazil (tenofovir, lamivudine and dolutegravir (regimen 1); tenofovir, lamivudine and efavirenz (regimen 2); tenofovir, lamivudine and ritonavir-boosted atazanavir (regimen 3)). RESULTS AND DISCUSSION: We included 112,243 patients >12 years old who received their first ART prescription between January 2014 and August 2017. Univariate analysis indicated that cumulative viraemia was significantly lower in patients receiving regimen 1 as compared with those receiving regimens 2 or 3 (p<0.0001 for both pairwise comparisons). In a multivariable analysis adjusted for age, sex, baseline T CD4+ counts and baseline HIV VL, ART regimen persisted with statistically significant effect on 12-month cumulative viraemia. The model predicted a 45-unit increase in log10 copy-days/mL cumulative viraemia for regimen 2 as compared with regimen 1, and a 70-unit increase in log10 copy-days/mL cumulative viraemia for regimen 3 as compared with regimen 1 (95%CI 41 to 49 and 61 to 79 respectively; p<0.001 for both comparisons). In models restricted to youths (13 to 24 years old) and female patients, ART regimen had similar effects. ART regimen with dolutegravir in association with a tenofovir-lamivudine backbone was superior to regimens containing efavirenz or boosted atazanavir in reducing HIV VL, as shown by cumulative viraemia over the first 12 months after treatment initiation. The superiority persisted even after adjusting the analysis for potential confounders. CONCLUSIONS: Our findings could bring direct benefits to patients as suggested by lower viral replication during treatment, lower risk of HIV transmission, and a potential reduction in resistance mutations in the initial 12 months under ART.

Brazilian network for HIV Drug Resistance Surveillance (HIV-BresNet): a survey of treatment-naive individuals.

INTRODUCTION: In Brazil, more than 487,450 individuals are currently undergoing antiretroviral treatment. In order to monitor the transmission of drug-resistant strains and HIV subtype distribution in the country, this work aimed to estimate its prevalence and to characterize the nationwide pretreatment drug resistance in individuals recently diagnosed with HIV between 2013 and 2015. METHODS: The HIV threshold survey methodology (HIV-THS, WHO) targeting antiretroviral-naive individuals with recent HIV diagnosis was utilized, and subjects were selected from 51 highly populated cities in all five Brazilian macroregions. The HIV pol genotypic test was performed by genomic sequencing. RESULTS: We analysed samples from 1568 antiretroviral-naive individuals recently diagnosed with HIV, and the overall transmitted drug resistance (TDR) prevalence was 9.5% (150 sequences). The regional prevalence of resistance according to Brazilian geographical regions was 9.4% in the northeast, 11.2% in the southeast, 6.8% in the central region, 10.2% in the north and 8.8% in the south. The inhibitor-specific TDR prevalence was 3.6% for nucleoside reverse transcriptase inhibitors (NRTIs), 5.8% for non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 1.6% for protease inhibitors (PIs); 1.0% of individuals presented resistance to more than one class of inhibitors. Overall, subtype B was more prevalent in every region except for the southern, where subtype C prevails. CONCLUSIONS: To the best of our knowledge, this is the first TDR study conducted in Brazil with nationwide representative sampling. The TDR prevalence revealed a moderate rate in the five Brazilian geographical regions, although some cities presented higher TDR prevalence rates, reaching 14% in São Paulo, for example. These results further illustrate the importance of surveillance studies for designing future strategies in primary antiretroviral therapy, aiming to mitigate TDR, as well as for predicting future trends in other regions of the globe where mass antiretroviral (ARV) treatment was implemented.