Abstract
ObjectivesSwitching to second-line antiretroviral therapy (ART) largely depends on careful clinical assessment and access to biological measurements. We performed a systematic review and meta-analysis to estimate the incidence of switching to second-line ART in sub-Saharan Africa and its main programmatic determinants.MethodsWe searched 2 databases for studies reporting the incidence rate of switching to second-line ART in adults living in sub-Saharan Africa. Data on the incidence rate of switching were pooled, and random-effect models were used to evaluate the effect of factors measured at the programme level on this incidence rate.ResultsNine studies (157,340 patients) in 21 countries were included in the meta-analysis. All studies considered patients under first-line ART and conditions to initiate ART were similar across studies. Overall, 3,736 (2.4%) patients switched to second-line ART. Incidence rate of switch was in mean 2.65 per 100 person-years (PY) (95% confidence interval: 2.01–3.30); it ranged from 0.42 to 4.88 per 100 PY and from 0 to 4.80 per 100 PY in programmes with and without viral load monitoring, respectively. No factors measured at the programme level were associated with the incidence rate of switching to second-line ART.ConclusionThe low incidence rate of switching to second-line ART suggests that the monitoring of patients under ART is challenging and that access to second-line ART is ineffective; efforts should be made to increase access to second-line ART to those in need by providing monitoring tools, education and training, as well as a more convenient regimen.
Highlights
The number of patients on antiretroviral therapy (ART) has dramatically increased by more than 26-fold between 2003 and 2011 in resource-limited settings [1], where ART has been proven to be as successful as in developed countries with regards to clinical, immunological or virological outcomes [2,3,4,5]
We included studies without condition on a minimum patient’s follow-up on ART; i.e. we considered studies which enrolled patients without condition on their minimum duration of follow-up as well as studies which only enrolled patients who had reached a minimum duration of follow-up
Regarding the nucleoside reverse transcriptase inhibitor (NNRTI), a majority of patients received tenofovir (TDF) in the DART trial [19], efavirenz (EFV) in two studies [16,23] and nevirapine (NVP) in the remaining studies [8,17,18,20,21,22,23] Second-line ART was defined as a protease inhibitor (PI) introduction in the ART regimen, but in four studies, the modification of at least one nucleoside reverse transcriptase inhibitor (NRTI) molecule was required [17,20,22,23]
Summary
The number of patients on antiretroviral therapy (ART) has dramatically increased by more than 26-fold between 2003 and 2011 in resource-limited settings [1], where ART has been proven to be as successful as in developed countries with regards to clinical, immunological or virological outcomes [2,3,4,5]. A first ART (first-line) may fail, and tools to detect therapeutic failure differ between countries; viral load testing is the gold standard to inform the switching decision to a more successful regimen in wealthy countries [2]. If clinical trials failed to demonstrate that viral load monitoring translated to survival gain [8], it remains that in the absence of routine viral load, detection of treatment failure and the subsequent switch to second-line ART usually occurred late. HIV transmission is more likely to occur due to on-going viral replication
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