Incidence and Predictors of Virologic Failure of Antiretroviral Triple-Drug Therapy in a Community-Based Cohort

Abstract

Highly active antiretroviral therapy fails to reach its recommended goal of sustained suppression of viral replication in a substantial proportion of patients. We analyzed incidence and predictors of virologic failure of the first regimen of a triple-drug combination therapy, including a protease inhibitor and two nucleoside analog reverse transcriptase inhibitors (NRTIs), in 274 HIV-infected patients. Long-term virologic response to combination therapy including salvage regimens was assessed 2.5 years after treatment initiation. During an initial observation period of up to 1.8 years (median, 0.8 years) 152 patients (55%) experienced sustained suppression of HIV-1 RNA to <500 copies/ml. Failure to reduce viral load to <500 copies/ml within 6 months (initial failure) was observed in 51 patients (19%). Independent risk factors for initial failure included higher baseline viral load; addition of a protease inhibitor to an unchanged NRTI regimen; use of saquinavir hard-gel capsules; and longer duration of prior NRTI treatment. Within a median of 7 months viral load rebound above 500 copies/ml occurred in 71 of 223 patients (32%) whose viral load had initially decreased below this threshold. In proportional hazard analysis none of the potential risk factors was significantly associated with viral load rebound. However, in 40 patients (56%) with viral load rebound, incomplete adherence to therapy or treatment interruptions preceded the rebound. Virologic outcome after 2.5 years correlated with initial response to the first regimen: viral load was <500 copies/ml in 88, 55, and 21% of patients with sustained suppression, viral load rebound, and initial failure, respectively.

Residual HIV-RNA Levels Persist for Up to 2.5 Years in Peripheral Blood Mononuclear Cells of Patients on Potent Antiretroviral Therapy

“…26 Comparison of HIV-1 RNA levels from the different compartments revealed that virological response in plasma mirrored response in PBMC with rem arkable accuracy. The rational for having defined virological response in our patients by the ratio of baseline and nadir HIV-1 RNA levels 13 was based on observation s that found "high baseline" [27][28][29] and "high nadir levels" 3 0,31 of plasma virem ia to be predictors for virological failure of antiretrovir al therapy. Reminiscent of the correlation of virological responses, PBMC HIV-1 RNA levels were also directly correlated with viral RNA levels in plasma at baseline and throughout the whole observation period.…”

Estimating the impact of alcohol consumption on survival for HIV+ individuals

“…In a cohort of Swiss HIV patients, lapses in adherence preceded more than half of all therapy failures. (Paris et al, 1999) Because the adherence reductions induced by alcohol consumption may decrease survival, it is possible that HIV clinical guidelines should place a greater emphasis on screening for alcohol use disorders and facilitating access to alcohol cessation interventions.…”

History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change*

“…This proportion has increased in recent years [11][12][13]; however, viral replication is still not fully controlled in all patients at all times. Previous analyses have found that a patient is most likely to fail in the first few months after initial viral suppression [14], that increasing time with viral suppression decreases the risk of rebound [15,16], and that treatment interruptions with detectable viral load [17] increase the risk of rebound, as does pre-cART exposure to nucleoside reverse transcriptase inhibitor (NRTI) regimens [15,18]. Additionally, low CD4 cell counts, high viral load, a slow virological response to cART and prior AIDS diagnosis were linked to lack of durable viral load undetectability [19,20].…”