Comparative effectiveness of first-line antiretroviral therapy: results from a large real-world cohort after the implementation of dolutegravir.

OBJECTIVE: We aimed to assess the effectiveness of first-line antiretroviral therapy (ART) regimens in achieving viral suppression at 12 months, from 2014 to 2017 in Brazil. DESIGN: A retrospective cohort study utilizing programmatic data from the Brazilian HIV Program. METHODS: Adults (aged 15-80 years) who started ART from January 2014 to July 2017 and had a viral load 365 (±90) days after treatment initiation were included. Associations with achieving viral suppression (<50 copies/ml) at 365 (±90) days were assessed using logistic regression. Our main study variable was ART regimen, and covariates included year of ART initiation, sex/exposure group, age, education, race, region, baseline CD4 and viral load counts, and adherence measured by pharmacy refill data. We performed both intent-to-treat and per-protocol analogous analyses. RESULTS: Out of 107 647 ART-naive patients, 71.5% initiated with tenofovir/lamivudine/efavirenz (TLE) and 10.5% with tenofovir/lamivudine/dolutegravir (TLD). Median age and CD4 cell counts were 34 [interquartile range (IQR) 26-46] and 379 cells/µl (IQR 190-568), respectively; 68.0% were men. Viral suppression by 12 months was 84.0% [95% confidence interval (95% CI) 83.7-84.2] with TLE and 90.5% (95% CI 90.0-91.0) with TLD, and below 80% for protease-inhibitor-based regimens. In the multivariable intent-to-treat-analogous analysis, controlling for cofactors related to viral suppression including adherence, the adjusted odds ratio (aOR) for TLD's viral suppression relative to TLE was 1.56 (95% CI 1.40-1.75). Findings were robust to secondary per-protocol analogous and sensitivity analysis. CONCLUSION: Our results showed the superiority of dolutegravir- over efavirenz- and protease-inhibitor-based regimens in suppressing viral replication in a real-word cohort of HIV-positive adults. This superiority was not driven by higher levels of adherence with dolutegravir-based regimens.

Determinants of survival of people living with HIV/AIDS on antiretroviral therapy in Brazil 2006-2015.

BACKGROUND: We compared AIDS-related mortality rates in people living with HIV (PLHIV) starting antiretroviral therapy (ART) in Brazil during 2006-2015 and examined associated risk factors . METHODS: Data on ART use in PLHIV and AIDS mortality in Brazil was analysed with piecewise constant exponential models. Mortality rates and hazard ratios were estimated for 0-6, 6-12, 13-24, 25-36 and > 36 months of ART use and adjusted for region, age, sex, baseline CD4 cell count and calendar year of ART initiation. An additional analysis restricted to those with data on risk group was also performed. RESULTS: 269,076 individuals were included in the analysis, 165,643 (62%) males and 103,433 (38%) females, with 1,783,305 person-years of follow-up time. 21,749 AIDS deaths were reported and 8898 deaths occurred in the first year of ART. The risk of death in the first six months decreased with early ART initiation; those starting treatment early with CD4 > 500 cells per µL had a hazard ratio of 0.06 (95% CI 0.05-0.07) compared with CD4 < 200 cells per µL. Older age, male sex, intravenous drug use and starting treatment in earlier calendar years were associated with higher mortality rates. People living in the North, Northeast and South of Brazil experienced significantly higher AIDS mortality rates than those in the Southeast (HR 1.44, [95% CI 1.35-1.54], 1.10 [1.05-1.16] and 1.22 [1.17-1.28] respectively). CONCLUSIONS: Early treatment is likely to have contributed to the improved survival in PLHIV on ART, with the greatest benefits observed in women, younger age-groups and those living in the North.

Estimating HIV incidence from surveillance data indicates a second wave of infections in Brazil.

Emerging evidence suggests that HIV incidence rates in Brazil, particularly among men, may be rising. Here we use Brazil's integrated health systems data to develop a mathematical model, reproducing the complex surveillance systems and providing estimates of HIV incidence, number of people living with HIV (PLHIV), reporting rates and ART initiation rates. An age-structured deterministic model with a flexible spline was used to describe the natural history of HIV along with reporting and treatment rates. Individual-level surveillance data for 1,077,295 cases (HIV/AIDS diagnoses, ART dispensations, CD4 counts and HIV/AIDS-related deaths) were used to calibrate the model using Bayesian inference. The results showed a second wave of infections occurring after 2001 and 56,000 (95% Credible Interval 43,000-71,000) new infections in 2015, 37,000 (95% CrI 28,000-54,000) infections in men and 16,000 (95% CrI 10,000-23,000) in women. The estimated number of PLHIV by end-2015 was 838,000 (95% CrI 675,000-1,083,000), with 80% (95% CrI 62-98%) of those individuals reported to the Ministry of Health. Women were more likely to be diagnosed and reported than men; 86.8% of infected women had been reported compared with 75.7% of men. Likewise, ART initiation rates for women were higher than those for men. The second wave contradicts previous estimates of HIV incidence trends in Brazil and there were persistent differences in the rates of accessing care between men and women. Nevertheless, the Brazilian HIV program has achieved high rates of detection and treatment, making considerable progress over the past ten years.

Sociodemographic determinants of attrition in the HIV continuum of care in Brazil, in 2016.

The aim of this study was to identify sociodemographic factors associated with attrition in the 3 steps of the HIV continuum of care related to the 90-90-90 targets - access to diagnosis, treatment initiation, and virologic suppression, in Brazilian adults (15 years or older), in 2016.Programmatic data were obtained from 2 information systems from the Brazilian Ministry of Health, which register all antiretroviral therapy (ART) dispensations and all CD4 and viral load counts (VL) performed within the country's public health system. The 3 attrition indicators were late presentation to care, defined as a first CD4 count <350 cells/mm among ART-naive individuals who performed a first CD4 count in 2016; not being on ART, defined as having no recorded dispensation within the last 100 days of the year, among those who were linked to care in 2016; and not being virologically suppressed, defined as having the last recorded VL >200 copies/mL in 2016, among those with a recorded VL count who were on treatment for at least 6 months. Association of sociodemographic factors with these indicators was analyzed by unconditional logistic regression analysis.Lower educational level and black/brown/indigenous race/color were associated with worse outcomes in the 3 indicators. Environmental indicators, namely the region, size, and social vulnerability index of the municipality of residence, also played an important role in the models. Younger age was strongly associated with not being on ART and not showing virological suppression.Our findings help identify the barriers in the different stages of the HIV continuum of care, which need to be addressed in order to progress toward the achievement of the 90-90-90 targets.