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


Of 110 654 PLHIV who met the inclusion criteria, 3007 (2.7%) had an undetectable baseline viral load and were excluded, resulting in 107 647 included in the analysis. Regarding initial regimen, 71.5% started on TLE and 10.5% on TLD (Table 1). Four other regimens had at at least 1000 individuals, including one efavirenz-based and three based on ritonavir-boosted protease inhibitors. Median baseline CD4+ cell count, log10viral load and age were, respectively, 379 cells/μl (IQR 190–568), 4.61 copies/ml (IQR 3.98–5.18) and 34 years (IQR 26–43). Over two-thirds (68.1%) were men. Median time to assessment of the outcome viral load was 371 days (IQR 328–412).

Protease-inhibitor-based regimens were used more often in women than men, especially 3TC+AZT+LPV/r, which was the regimen recommended for pregnant women in 2014 and 2015. There were no large differences in ART regimens across other characteristics, including demographics, baseline CD4+ cell count and baseline viral load.

By regimen, the proportion of patients virally suppressed at 12 months ranged from 71.0% with 3TC+AZT+LPV/r to 90.5% with TLD (Table 2). In multivariable analysis, TLD was significantly associated with higher viral suppression at 12 months compared with TLE (aOR 1.56, 95% CI 1.40–1.75), after controlling for other factors, including baseline CD4, viral load and adherence. All other regimens were significantly inferior to TLE, with protease-inhibitor-containing regimens presenting the worst outcomes, especially regimens containing lopinavir (aORs 0.65, 95% CI 0.60–0.70 and 0.67, 95% CI 0.60–0.76).

Race/colour was not retained in the multivariable model due to nonsignificance, while the effects of year of ART initiation, education and region were attenuated. With respect to sex/exposure, MSM had higher odds of viral suppression than heterosexual men (aOR 1.22, 95% CI 1.15–1.30), followed by heterosexual women (aOR 1.18, 95% CI 1.11–1.26).

In the per-protocol analogous analysis, we excluded 2044 (1.9%) PLHIV who switched regimens and 62 974 (58.5%) with adherences less than 95% or more than 105%, resulting in 42 629 individuals included. In this model, race, year of ART initiation and age were not retained. The aOR for TLD achieving viral suppression by 12 months compared with TLE was higher (aOR 1.75, 95% CI 1.52–2.02). For 3TC+AZT+EFZ and 3TC+AZT+LPV/r, there was no statistically significant difference in achieving suppression compared with TLE. In the per-protocol analysis, aORs were similar to the intent-to-treat analysis for 3TC+TDF+ATV/r and 3TC+TDF+LPV/r.

The sensitivity analysis excluding patients with missing baseline CD4+ cell count and who started TLE during the periods of specific recommendations did not show any substantial differences in aORs compared with the full intent-to-treat analysis.