Clinical outcomes with second-line dolutegravir in people with virological failure on first-line non-nucleoside reverse transcriptase inhibitor-based regimens in South Africa: a retrospective cohort study

IntroductionWe investigated the impact of increasing CD4 count eligibility for antiretroviral-therapy (ART) initiation on advanced HIV and tuberculosis (TB) prevalence and incidence among people living with HIV (PLHIV) in South Africa.MethodsWe conducted an interrupted time series analysis with de-identified data of PLHIV aged ≥15 initiating ART between April-2012 and February-2020 at 65 primary healthcare clinics in KwaZulu-Natal, South Africa. Outcomes included monthly proportions of new ART initiators presenting with advanced HIV (CD4 count <200 cells/µl) and TB disease. We created a cohort of monthly ART initiators without TB and evaluated the cumulative incidence of TB within 12 months follow-up. We used segmented binomial regression models to estimate relative risks (RR) of outcomes, allowing for a step and slope change after expanding the ART initiation CD4 count eligibility from <350 to <500 cells/µl in January- 2015 and following Universal-Test-and-Treat (UTT) implementation in September-2016.ResultsAmong 187,544 participants, median age was 32 (27-39), and 125,065 (66.7%) were female. After January-2015, risk of advanced HIV at initiation decreased by 24.5% (RR=0.745, 95%CI 0.690-0.800) and further reduced by 26.2% following UTT implementation (RR=0.738, 95%CI 0.688-0.788). Risk of TB at initiation also decreased by 28.7% after January-2015 (RR=0.713, 95%CI 0.644-0.782) and further decreased by 17.6% after UTT implementation (RR=0.824, 95%CI 0.703-0.945) but remained stable among initiators with advanced HIV. Among the incidence cohort, the risk of new TB decreased by 31.9% (RR=0.681, 95%CI 0.441-0.921) following UTT implementation. Among the incidence cohort with advanced HIV, there was weak evidence of a decrease in risk of new TB (RR=0.755, 95%CI 0.489-1.021), but it gradually decreased per month (slope change per month 9.7%, RR=0.903, 95%CI 0.872-0.934) following UTT implementation.ConclusionsOur data supports the added benefit of decreased TB co-burden with expanded ART access. Early diagnosis and immediate linkage to care should be prioritised among PLHIV.

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Three Year Outcomes after Programmatic Transitioning to Dolutegravir in the Context of Severe Civil Unrest in Haiti

Liautaud,

Chico,

Macius

et al. 2024

Preprint

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BackgroundDolutegravir (DTG) has been widely scaled-up worldwide. Data on long-term outcomes are limited.MethodsWe included all persons living with HIV (PLWH) ≥15 years of age who initiated or switched to DTG in Port-au-Prince, Haiti. We described treatment outcomes by pre-switch viral load and assessed predictors of virologic failure using multivariable logistic regression.FindingsA total of 10,354 PLWH initiated or switched to DTG from November 5, 2018 to March 21, 2021, and were included in the analyses. Of these, 2217 (21.4%) were ART-naïve and 8137 (78.6%) switched from an NNTRI-based regimen. Median follow-up time on DTG was 2.8 years (IQR: 2.3, 3.1). Among PLWH with ≥2 tests on DTG, 83.5% of ART-naïve, 93.1% with pre-switch suppression, 64.8% with pre-switch failure, and 90.2% without pre-switch viral load had <1000 copies/mL at latest test. Among treatment-experienced patients, predictors of HIV-1 RNA ≥1000 copies/mL at latest test included younger age (adjusted odds ratio [aOR]: 2.33 for ≤30 vs. ≥50 years), shorter pre-switch time on ART (aOR: 0.91; 95% CI: 0.89, 0.94/year), lower education (aOR: 1.31; 95% CI: 1.10, 1.55), and higher pre-switch viral load: (aOR: 7.00; 95% CI; 5.74, 8.54 for ≥10,000 vs. <1000 copies/mL).InterpretationVirologic outcomes on DTG-based regimens are outstanding for PLWH with pre-switch suppression, even in the context of severe civil unrest in Haiti. However, rates of persistent viremia are high among PLWH who experienced pre-switch failure; additional interventions are critically needed, including access to genotypic resistance testing and provision of alternative regimens as clinically-indicated.FundingNone

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Clinical outcomes with second-line dolutegravir in people with virological failure on first-line non-nucleoside reverse transcriptase inhibitor-based regimens in South Africa: a retrospective cohort study

Cited by 5 publications

References 22 publications

Dolutegravir for second-line antiretroviral therapy: the beat goes on

Dolutegravir for second-line antiretroviral therapy: the beat goes on

Impact of increasing CD4 count threshold eligibility for antiretroviral therapy initiation on advanced HIV disease and tuberculosis prevalence and incidence in South Africa: an interrupted time series analysis

Three Year Outcomes after Programmatic Transitioning to Dolutegravir in the Context of Severe Civil Unrest in Haiti

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