Switching to second-line antiretroviral therapy in resource-limited settings: comparison of programmes with and without viral load monitoring

Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.
AIDS (London, England) (Impact Factor: 6.56). 07/2009; 23(14):1867-74. DOI: 10.1097/QAD.0b013e32832e05b2
Source: PubMed

ABSTRACT In high-income countries, viral load is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. Viral load monitoring is not generally available in resource-limited settings. We examined switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor-based regimens in Africa, South America and Asia.
Multicohort study of 17 ART programmes. All sites monitored CD4 cell count and had access to second-line ART and 10 sites monitored viral load. We compared times to switching, CD4 cell counts at switching and obtained adjusted hazard ratios for switching (aHRs) with 95% confidence intervals (CIs) from random-effects Weibull models.
A total of 20 113 patients, including 6369 (31.7%) patients from 10 programmes with access to viral load monitoring, were analysed; 576 patients (2.9%) switched. Low CD4 cell counts at ART initiation were associated with switching in all programmes. Median time to switching was 16.3 months [interquartile range (IQR) 10.1-26.6] in programmes with viral load monitoring and 21.8 months (IQR 14.0-21.8) in programmes without viral load monitoring (P < 0.001). Median CD4 cell counts at switching were 161 cells/microl (IQR 77-265) in programmes with viral load monitoring and 102 cells/microl (44-181) in programmes without viral load monitoring (P < 0.001). Switching was more common in programmes with viral load monitoring during months 7-18 after starting ART (aHR 1.38; 95% CI 0.97-1.98), similar during months 19-30 (aHR 0.97; 95% CI 0.58-1.60) and less common during months 31-42 (aHR 0.29; 95% CI 0.11-0.79).
In resource-limited settings, switching to second-line regimens tends to occur earlier and at higher CD4 cell counts in ART programmes with viral load monitoring compared with programmes without viral load monitoring.

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Available from: Mar Pujades-Rodríguez, Aug 16, 2015
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    • "However, several studies portray limited correlation between such parameters and virological failure [3] [4] [5]. Furthermore, recently it has been shown that virological monitoring results in switching treatment earlier and at higher CD4 counts [6]. Ndlovu Medical Centre (NMC) is located in rural South Africa. "
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    ABSTRACT: Objective. To define the long-term (2–4 years) clinical and virological outcome of an antiretroviral treatment (ART) programme in rural South Africa. Methods. We performed a retrospective observational cohort study, including 735 patients who initiated ART. Biannual monitoring, including HIV-RNA testing, was performed. Primary endpoint was patient retention; virological suppression (HIV-RNA < 50 copies/mL) and failure (HIV-RNA > 1000 copies/mL) were secondary endpoints. Moreover, possible predictors of treatment failure were analyzed. Results. 63% of patients (466/735) have a fully suppressed HIV-RNA, a median of three years after treatment initiation. Early mortality was high: 14% died within 3 months after treatment start. 16% of patients experienced virological failure, but only 4% was switched to second-line ART. Male gender and a low performance score were associated with treatment failure; immunological failure was a poor predictor of virological failure. Conclusions. An “all or nothing” phenomenon was observed in this rural South African ART programme: high early attrition, but good virological control in those remaining in care. Continued efforts are needed to enrol patients earlier. Furthermore, the observed viro-immunological dissociation emphasises the need to make HIV-RNA testing more widely available.
    AIDS research and treatment 01/2011; 2011(2090-1240):434375. DOI:10.1155/2011/434375
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    • "We have recently shown that patients on ART in resource-limited settings were switched earlier and at higher CD4 cell counts in programmes with access to viral load monitoring than in programmes without (Keiser et al. 2009b). The sensitivity and positive predictive value of the immunological WHO criteria for virological treatment failure is poor, both in low-income (Keiser et al. 2009a; Mee et al. 2008; Bisson et al. 2006) and high-income countries (Moore et al. 2006). "
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    ABSTRACT: To assess the outcome of patients who experienced treatment failure with antiretrovirals in sub-Saharan Africa. Analysis of 11 antiretroviral therapy (ART) programmes in sub-Saharan Africa. World Health Organization (WHO) criteria were used to define treatment failure. All ART-naive patients aged >or=16 who started with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen and had at least 6 months of follow-up were eligible. For each patient who switched to a second-line regimen, 10 matched patients who remained on a non-failing first-line regimen were selected. Time was measured from the time of switching, from the corresponding time in matched patients, or from the time of treatment failure in patients who remained on a failing regimen. Mortality was analysed using Kaplan-Meier curves and random-effects Cox models. Of 16 591 adult patients starting ART, 382 patients (2.3%) switched to a second-line regimen. Another 323 patients (1.9%) did not switch despite developing immunological or virological failure. Cumulative mortality at 1 year was 4.2% (95% CI 2.2-7.8%) in patients who switched to a second-line regimen and 11.7% (7.3%-18.5%) in patients who remained on a failing first-line regimen, compared to 2.2% (1.6-3.0%) in patients on a non-failing first-line regimen (P < 0.0001). Differences in mortality were not explained by nadir CD4 cell count, age or differential loss to follow up. Many patients who meet criteria for treatment failure do not switch to a second-line regimen and die. There is an urgent need to clarify the reasons why in sub-Saharan Africa many patients remain on failing first-line ART.
    Tropical Medicine & International Health 12/2009; 15(2):251-8. DOI:10.1111/j.1365-3156.2009.02445.x · 2.30 Impact Factor
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    • "It appeared that clinicians were less confident if they had to base their decision of switching to second-line on CD4 counts only [16]. This conservative attitude needs to be addressed by training activities aiming at strengthening physicians' prescription abilities but also by facilitating access to VL, in particular for patients with insufficient immune response [17]. "
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