Impact of previous virological treatment failures and adherence on the outcome of antiretroviral therapy in 2007

Abstract

Background: Combination antiretroviral treatment (cART) has been very successful, especially among selected patients in clinical trials. The aim of this study was to describe outcomes of cART on the population level in a large national cohort.

Methods: Characteristics of participants of the Swiss HIV Cohort Study on stable cART at two semiannual visits in 2007 were analyzed with respect to era of treatment initiation, number of previous virologically failed regimens and self reported adherence. Starting ART in the mono/dual era before HIV-1 RNA assays became available was counted as one failed regimen. Logistic regression was used to identify risk factors for virological failure between the two consecutive visits.

Results: Of 4541 patients 31.2% and 68.8% had initiated therapy in the mono/dual and cART era, respectively, and been on treatment for a median of 11.7 vs. 5.7 years. At visit 1 in 2007, the mean number of previous failed regimens was 3.2 vs. 0.5 and the viral load was undetectable (<50 copies/ml) in 84.6% vs. 89.1% of the participants, respectively. Adjusted odds ratios of a detectable viral load at visit 2 for participants from the mono/dual era with a history of 2 and 3, 4, >4 previous failures compared to 1 were 0.9 (95% CI 0.4-1.7), 0.8 (0.4-1.6), 1.6 (0.8-3.2), 3.3 (1.7-6.6) respectively, and 2.3 (1.1-4.8) for >2 missed cART doses during the last month, compared to perfect adherence. From the cART era, odds ratios with a history of 1, 2 and >2 previous failures compared to none were 1.8 (95% CI 1.3-2.5), 2.8 (1.7-4.5) and 7.8 (4.5-13.5), respectively, and 2.8 (1.6-4.8) for >2 missed cART doses during the last month, compared to perfect adherence.

Conclusions: A higher number of previous virologically failed regimens, and imperfect adherence to therapy were independent predictors of imminent virological failure.

Figure 1. The patient disposition for this study is based upon all patients seen in the Swiss HIV Cohort Study during 2007.

Figure 2. Distribution of viral loads and CD4 cell counts at first follow-up visit in 2007 (visit 1) according to the number of previous virologically failed regimens.

The upper panels show HIV-1 RNA counts for patients who started therapy in the mono/dual era (A) and in the cART era (B). Lower panels show CD4 cell counts for patients from the mono/dual era (C) and for patients from the cART era (D), respectively. By definition all patients from the mono/dual era failed at least one regimen.

Figure 3. Virological course between the first follow-up visit in 2007 (visit 1) and the next semi-annual follow-up cohort visit (visit 2).

Viral loads patterns are shown in the upper panels: (A) patients from the mono/dual ART era; (B) patients from the cART era.

Figure 4. Factors associated with HIV-1 RNA >50 copies/ml at visit 2.

Odds ratios from uni- and multivariable logistic regressions are shown with 95% confidence intervals. Panel A includes patients who initiated ART the mono/dual era, and panel B those who initiated ART in the cART era. Multivariable models were also adjusted for age, sex, transmission risk group, HCV co-infection, total duration of ART therapy, maximum viral load ever and CD4 cell count at the first visit in 2007 (all p-values >0.05).