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

Abstract

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.

Virologic Response among Key Populations Living With HIV following a Switch to Dolutegravir-Based Regimen in Southern Nigeria

“…Our findings are consistent with previous studies that have assessed and demonstrated the efficacy of dolutegravir-based regimen in the treatment of PLWH [15][16][17]. A large retrospective cohort study in Brazil using program level data also shows viral suppression by 12 months was 84.0 percent with TLE and 90.5% with TLD.…”

Differences in HIV Markers between Infected Individuals Treated with Different ART Regimens: Implications for the Persistence of Viral Reservoirs

“…Some studies reported that INSTI-based regimens are associated with lower RV than other regimens. Pascom et al performed a very large study that compared cumulative viremia during the first 12 months of ART in 112,243 individuals [155]. INSTI-based regimens were associated with significantly lower cumulative RV compared to both PI-based and NNRTI-based regimens.…”

Heterogeneities of the impact of public health policies on HIV/AIDS indicators in Brazil according to sociodemographic factors: A real‐life study

“…ART is available exclusively through the public health system to registered persons. Data concerning CD4+ T cell counts and HIV viral load are available for persons undertaking laboratory testing in the public health system, comprising $84% of all PLHIV who are registered in care [19].…”

“…The database includes information from all PLHIV in Brazil who are registered in care; this corresponds roughly to the totality of diagnosed PLHIV, since ART is available exclusively through the public health system to registered persons. Data concerning CD4+ T cell counts and HIV viral load are available for persons undertaking laboratory testing in the public health system, comprising ~84% of all PLHIV who are registered in care [19].…”

“…Regimens containing INSTIs have been more effective in reducing HIV viral load, increasing CD4+ T cell counts, and have been associated with lower rates of adverse events and treatment discontinuation compared with regimens using non-nucleoside reverse transcriptase inhibitors or protease inhibitors [15][16][17][18][19]. Since 2017, Brazilian guidelines have recommended dolutegravir for PLHIV >12 years old and raltegravir for PLHIV between the ages of 2 and 12 years old as part of first-line ART regimens, replacing the previous recommendation of efavirenz or protease inhibitors as part of preferred regimens [20].…”