Virologic failure following persistent low-level viremia in a cohort of HIV-positive patients: results from 12 years of observation.

BACKGROUND: The current goal of antiretroviral therapy (ART) is to maintain a suppressed human immunodeficiency virus (HIV) viral load below limits of assay detection. When viral loads remain in low-level viremia (LLV), especially between 50 and 200 copies/mL, the best management and clinical consequences remain unknown. Our objective was to study the long-term impact of persistent LLV on the subsequent risk of virologic failure in a cohort of people living with HIV in Montreal, Canada. METHODS: We compared the cumulative incidence of subsequent virologic failure (defined as an HIV RNA viral load of >1000 copies/mL) in patients receiving ART for at least 12 months by following 4 persistence categories (<50, 50-199, 200-499, and 500-999 copies/mL) for 6, 9, or 12 months, using Kaplan-Meier analysis. The association between subsequent virologic failure and persistence status were estimated using a Cox proportional hazards model. RESULTS: The cumulative incidence of virologic failure 1 year after having maintained a LLV for 6 months was 22.7% (95% confidence interval [CI], 14.9-33.6) for 50-199 copies/mL, 24.2% (95% CI, 14.5-38.6) for 200-499 copies/mL, and 58.9% (95% CI, 43.1-75.2) for 500-999 copies/mL, compared with 6.6% (95% CI, 5.3-8.2) for an undetectable HIV RNA viral load. Even after adjustment for potential confounders, a persistent LLV of 50-199 copies/mL for 6 months doubled the risk of virologic failure (hazard ratio, 2.22; 95% CI, 1.60-3.09), compared with undetectable viral loads for the same duration. Similar results have been found for persistent LLV of 9 or 12 months. CONCLUSIONS: In this cohort, all categories of persistent LLV between 50 and 999 copies/mL were associated with an increased risk of virologic failure. The results shed new light for the management of patients with LLV, especially with regard to LLV of 50-199 copies/mL.

Atazanavir and other determinants of hyperbilirubinemia in a cohort of 1150 HIV-positive patients: results from 9 years of follow-up.

Hyperbilirubinemia is common among patients exposed to atazanavir (ATV), but its long-term significance is not well documented. The objective was to analyze hyperbilirubinemia (incidence, regression, determinants, and outcome) among 1150 HIV-positive patients followed-up in a prospective cohort between 2003 and 2012. Cumulative incidence of hyperbilirubinemia grades 3-4 and its probability of regression were estimated using Kaplan-Meier method. Cox proportional hazards model was used to study the determinants. Generalized estimating equation (GEE) regression was used to evaluate the association between hyperbilirubinemia grades 3-4 and adverse health outcome. Eight years cumulative incidence of hyperbilirubinemia was 83.6% (95% CI:79.0-87.7) and 6.6% (95% CI:4.7-9.2) among ATV users and non-users, respectively. This clinical outcome fluctuated considerably, as most patients exposed to ATV (91%) regressed, transiently, to lower grade at some point during follow-up. Determinants were atazanavir (HR=147.90, 95% CI: 33.64-604.18), ritonavir (HR=5.18, 95% CI:2.33-11.48), zidovudine (HR=2.62, 95% CI:1.07-6.46), and age (HR=1.04 95% CI:1.01-1.08). Alcohol consumption and others non-antiretroviral medications including hepatotoxic and recreational drugs were not available for analyses. Incidence of hyperbilirubinemia was very high among ATV users and, although regression to lower grade was frequent in the clinical follow-up of these patients, this was usually transient as the mean level of bilirubin stayed at a relatively high level. Importantly, long-term hyperbilirubinemia was not associated with adverse health outcome.

Association between tenofovir exposure and reduced kidney function in a cohort of HIV-positive patients: results from 10 years of follow-up.

BACKGROUND: Some studies have shown that tenofovir disoproxil fumarate (TDF), a drug widely used in highly active antiretroviral therapy, is associated with kidney dysfunction, but the magnitude of the effect and its clinical impact is still being debated. Our objective was to evaluate the association between long-term TDF exposure and kidney dysfunction in a cohort of 1043 human immunodeficiency virus-positive patients followed up for 10 years and to quantify the loss in estimated glomerular filtration rate (eGFR) in patients exposed to TDF in comparison with those exposed to other antiretroviral therapies. METHODS: Adjusted hazard ratios (HR) and odds ratios (OR) for the association between TDF and kidney dysfunction (defined as eGFR <90 mL/min/1.73 m(2)) were calculated using the Cox proportional hazards model and generalized estimating equations. Mean loss in eGFR attributable to TDF by cumulative years of exposure was estimated using linear regressions. RESULTS: Tenofovir exposure increased the risk of kidney dysfunction by 63% (HR, 1.63; 95% confidence interval, 1.26-2.10). The cumulative eGFR loss directly attributable to TDF after 1, 2, 3, and 4 years of TDF exposure was -3.05 (P = .017), -4.05 (P = .000), -2.42 (P = .023), and -3.09 mL/min/1.73 m(2) (P = .119), respectively, which shows that most of the loss occurred during the first years of exposure. CONCLUSIONS: In this cohort, TDF exposure was associated with reduced kidney function, but the loss in eGFR attributable to TDF is relatively mild in a long-term perspective.