Comparative Effectiveness of First-Line Antiretroviral Therapy

Results From a Large Real-World Cohort After the Implementation of Dolutegravir

Mariana Veloso Meireles; Ana Roberta P. Pascom; Elisabeth C. Duarte; Willi McFarland


AIDS. 2019;33(10):1663-1668. 

In This Article

Abstract and Introduction


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.


Recommended initial antiretroviral therapy (ART) primarily consists of two nucleoside reverse transcriptase inhibitors (NRTIs) and a third agent from a different class. Integrase strand transfer inhibitors (INSTIs) are increasingly used as the third agent in treatment guidelines, with dolutegravir (DTG) often being the preferred drug.[1–4] Clinical trials show greater efficacy, tolerability and safety for DTG than efavirenz (EFV), a nonnucleoside reverse transcriptase inhibitor (NNRTI),[5–7] and to darunavir (DRV) and atazanavir (ATV), protease inhibitors.[8,9] Meta-analyses have provided indirect evidence of the superiority of DTG compared with other commonly used antiretroviral agents.[10–12]

In Brazil, access to free ART is guaranteed by law[13] and there are currently more than 550 000 people living with HIV (PLHIV) on treatment.[14] In 2017, the Ministry of Health of Brazil (BMoH) implemented tenofovir-lamivudine-dolutegravir (TLD) as the preferred first-line ART regimen,[3] replacing tenofovir-lamivudine-efavirenz (TLE), which was recommended from December 2013 to December 2016[15] (Figure 1).

Figure 1.

Summary of recent adult antiretroviral therapy recommendations in Brazil, 2014–2017.

Most evidence on the efficacy of antiretroviral drugs comes from clinical trials in controlled settings with restricted inclusion criteria. In this study, we compare the observed effectiveness (assessed by achieving viral suppression by 12 months after initiation) of different ART regimens in a real-life setting using programmatic data from adults who started ART from 2014 to 2017 in Brazil.