Memorias do Instituto Oswaldo Cruz · 2026
Determinants of HIV-1 virologic suppression in HIV-associated tuberculosis in Brazil.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Ridolfi Felipe, Amorim Gustavo, Haas David W, Arriaga Maria, Staats Cody, Cordeiro-Santos Marcelo, Kritski Afrânio L, Figueiredo Marina C, Andrade Bruno B, Sterling Timothy R, Rolla Valeria C, Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil Consortium, Benjamin Aline, Sant'Anna Flavia M, Oliveira Jamile Garcia de, Marin João, Rezende Adriana, Carvalho Anna Cristina, Rocha Michael, Nogueira Betânia, Brito Alexandra, Spener Renata, Turner Megan
Аннотация
BACKGROUND: Tuberculosis/human immunodeficiency virus (TB/HIV) coinfection is associated with advanced HIV disease and variable responses to antiretroviral therapy (ART).
OBJECTIVES: We examined whether baseline HIV severity markers, ART regimes, or human genetic variants influenced HIV-1 virologic suppression in HIV-associated TB.
METHODS: We included TB/HIV participants from Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil study, who received standard TB therapy and antiretroviral treatment. The primary endpoint was HIV-1 virologic suppression (≤ 1,000 copies/mL); Baseline characteristics, viral load (VL), CD4 cell count, timing of ART initiation, and ART regimens were included. We genotyped UGT1A1 (rs887829; integrase strand transfer inhibitor-related) and CYP2B6 [rs3745274, rs28399499, rs4803419; efavirenz (EFZ)-related]; all have defined normal, intermediate, and slow genotypes. Genotyping was performed by MassARRAY iPLEX Gold; Kaplan-Meier curves compared time-to-suppression with log-rank tests; Cox proportional hazards models estimated hazard ratios.
FINDINGS: Among 194 participants, 68% (n = 132) achieved virologic suppression (≤ 1,000 copies/mL). Median time-to-suppression: 84 days [95% confidence interval (CI): 42-125]. Participants with higher baseline viral load (BVL) (≥ 5 log10 copies/mL) had delayed suppression compared with those with lower VL (< 5 log10; log-rank χ² = 75.9; p < 0.001). Individuals with CD4 ≤ 200 cells/µL suppressed more slowly than those with CD4 > 200 cells/µL (log-rank χ² = 29.6; p < 0.001). Participants starting ART before TB treatment achieved suppression faster than ART-naïve individuals (32 vs. 147 days; log-rank χ² = 48.5; p < 0.001). Higher BVL was associated with reduced hazard of suppression [adjusted hazard ratio (aHR) = 0.67; 95% CI: 0.61-0.75], while higher baseline CD4 count increased the hazard of suppression (per 100 cells/µL: aHR = 1.11; 95% CI: 1.01-1.21). ART-naïve status was associated with lower hazard of suppression in univariate analysis (Hazard Ratio = 0.51; 95% CI: 0.36-0.72) but not after adjustment. ART regimen class and pharmacogenetic metabolizer profiles were not significantly associated with virologic suppression.
MAIN CONCLUSIONS: BVL and CD4 count were the strongest determinants of virologic suppression in TB/HIV patients. Suppression rates were low, and neither ART regimen nor pharmacogenetic profiles significantly influenced the likelihood of suppression.
OBJECTIVES: We examined whether baseline HIV severity markers, ART regimes, or human genetic variants influenced HIV-1 virologic suppression in HIV-associated TB.
METHODS: We included TB/HIV participants from Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil study, who received standard TB therapy and antiretroviral treatment. The primary endpoint was HIV-1 virologic suppression (≤ 1,000 copies/mL); Baseline characteristics, viral load (VL), CD4 cell count, timing of ART initiation, and ART regimens were included. We genotyped UGT1A1 (rs887829; integrase strand transfer inhibitor-related) and CYP2B6 [rs3745274, rs28399499, rs4803419; efavirenz (EFZ)-related]; all have defined normal, intermediate, and slow genotypes. Genotyping was performed by MassARRAY iPLEX Gold; Kaplan-Meier curves compared time-to-suppression with log-rank tests; Cox proportional hazards models estimated hazard ratios.
FINDINGS: Among 194 participants, 68% (n = 132) achieved virologic suppression (≤ 1,000 copies/mL). Median time-to-suppression: 84 days [95% confidence interval (CI): 42-125]. Participants with higher baseline viral load (BVL) (≥ 5 log10 copies/mL) had delayed suppression compared with those with lower VL (< 5 log10; log-rank χ² = 75.9; p < 0.001). Individuals with CD4 ≤ 200 cells/µL suppressed more slowly than those with CD4 > 200 cells/µL (log-rank χ² = 29.6; p < 0.001). Participants starting ART before TB treatment achieved suppression faster than ART-naïve individuals (32 vs. 147 days; log-rank χ² = 48.5; p < 0.001). Higher BVL was associated with reduced hazard of suppression [adjusted hazard ratio (aHR) = 0.67; 95% CI: 0.61-0.75], while higher baseline CD4 count increased the hazard of suppression (per 100 cells/µL: aHR = 1.11; 95% CI: 1.01-1.21). ART-naïve status was associated with lower hazard of suppression in univariate analysis (Hazard Ratio = 0.51; 95% CI: 0.36-0.72) but not after adjustment. ART regimen class and pharmacogenetic metabolizer profiles were not significantly associated with virologic suppression.
MAIN CONCLUSIONS: BVL and CD4 count were the strongest determinants of virologic suppression in TB/HIV patients. Suppression rates were low, and neither ART regimen nor pharmacogenetic profiles significantly influenced the likelihood of suppression.