Second-line HIV treatment failure in sub-Saharan Africa: A systematic review and meta-analysis

Edessa, Dumessa; Sisay, Mekonnen; Asefa, Fekede

doi:10.1371/journal.pone.0220159

Cited by 48 publications

(68 citation statements)

References 93 publications

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“…The overall incidence of second-line treatment failure in this study was similar with studies conducted in African and Asian countries [18][19][20]. However, the incidence of the treatment failure of this study was lower as compared to the study conducted in South Africa, other studies from African and Asian patients, Amhara region, Ethiopia (9.86 per 100 PYs) and systematic analysis (15.0 per 100 PYs) [17,[21][22][23]. The cumulative incidence of this study is however higher compared to the study conducted in the north western Ethiopia (61.7/1000 PYs) [16].…”

Section: Plos Onesupporting

confidence: 82%

Incidence and factors associated with treatment failure among HIV infected adolescent and adult patients on second-line antiretroviral therapy in public hospitals of Northern Ethiopia: Multicenter retrospective study

Haftu¹,

Desta

Bezabih

et al. 2020

PLoS ONE

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Background This study aimed to determine the incidence and factors associated with treatment failure among HIV infected adolescent and adult patients on second-line antiretroviral therapy (ART) in public hospitals of Northern Ethiopia. Methods A retrospective study was conducted from September 1, 2007 to July 30, 2017 on 227 patients. The data were extracted using a retrieval checklist from the patient's charts. The incidence rate of treatment failure was calculated using Kaplan-Meier methods and Cox proportional hazard model was used to assess factors associated with treatment failure. Result The study subjects were followed for a total observation of 788.58 person-years with a median follow-up period of 35 (IQR: 17-60) months after switching to second-line ART. About 57 (25.11%) patients developed treatment failure, out of which, 32 (56.14%) occurred during the first two years. The overall incidence of second-line treatment failure was 72.3 per 1000 person years (95%CI: 55.75-93.71) of observation. The Kaplan-Meier estimates of cumulative treatment failure after 1, 2, and around 10 years of follow-up were 12.31%

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Section: Plos Onesupporting

confidence: 82%

Incidence and factors associated with treatment failure among HIV infected adolescent and adult patients on second-line antiretroviral therapy in public hospitals of Northern Ethiopia: Multicenter retrospective study

Haftu¹,

Desta

Bezabih

et al. 2020

PLoS ONE

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“…Although DRMs were common after first-line ART failure, switching to second-line bPI-based ART demonstrated suppression to <1,000 copies/mL in 53/60 (88%), consistent with studies among HIV-infected children and adults where VS in response to second-line regimens range from 70% to 95% after 48 weeks of follow-up. [33][34][35][36][37][38][39] We observed that overall, first-line ART failures who changed to a new NRTI were more likely to achieve VS on secondline regimens compared to those who continued on the same NRTI ( p = .031) (Fisher's exact test). Genotyping before the switch to second-line regimens demonstrated M184V (72%) and K65R (41%) at first-line ART failure.…”

Section: Discussionmentioning

confidence: 99%

“…High rates of VS similar to those reported in other studies provide reassurance of effective VS on a PI-based second-line ART. [35][36][37] However, when the NRTI backbone is not optimized after failure of firstline ART, concern is raised about the durability of second-line treatment, particularly with ATV/r as the sole active agent in a population where many decades of continued treatment are anticipated. The costs, long-term adherence to bPIs, together with the increasing prevalence of NNRTI DRMs support the recent recommendations to adopt Integrase Strand Transfer Inhibitors such as dolutegravir (DTG).…”

Section: Discussionmentioning

confidence: 99%

Drug Resistance Among Adolescents and Young Adults with Virologic Failure of First-Line Antiretroviral Therapy and Response to Second-Line Treatment

Kouamou

Varyani

Shamu³

et al. 2020

AIDS Research and Human Retroviruses

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Barriers to sustainable virologic suppression (VS) of HIV-infected adolescents and young adults include drug resistance mutations (DRMs) and limited treatment options, which may impact the outcome of second-line antiretroviral therapy (ART). We sequenced plasma viral RNA from 74 adolescents and young adults (16-24 years) failing first-line ART at Newlands Clinic, Zimbabwe between October 2015 and December 2016. We evaluated first-line nucleoside reverse transcriptase inhibitor (NRTI) susceptibility scores to first-and second-line regimens. Boosted protease inhibitor (bPI)-based ART was provided and viral load (VL) monitored for ‡48 weeks. Fisher's exact test was used to evaluate factors associated with VS on second-line regimens, defined as VL <1,000 copies/mL (VS 1,000 ) or <50 copies/mL (VS 50 ). The 74 participants on first-line ART had a median [interquartile range (IQR)] age of 18 (16-21) years and 42 (57%) were female. The mean (-standard deviation) duration on ART was 5.5 (-3.06) years and the median (IQR) log 10 VL was 4.26 (3.78-4.83) copies/mL. After switching to a second-line PI regimen, 88% suppressed to <1,000 copies/mL and 76% to <50 copies/mL at ‡48 weeks. A new NRTI was associated with increased VS 50 ( p = .031). These 74 adolescents and young adults failing first-line ART demonstrated high levels (97%) of DRMs, despite enhanced adherence counseling. Switching to new NRTIs in second-line improved VS. With the widespread adoption of generic dolutegravir, lamivudine and tenofovir combinations in Africa, genotyping to determine NRTI susceptibility, may be warranted.

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“…If inadequately treated, children progress much faster to AIDS and death [8][9][10]. As children's initial ART regimens are often their best opportunity for effective, tolerable treatment, optimizing the time on a successful initial regimen may result in greater long-term effectiveness of ART and more lifetime treatment options [11]. Analyzing longitudinal relationships between pediatric ART regimens and time to treatment disruption allows identification of initial ART regimens that pose greater challenges to maintaining optimal, continuous ART.…”

Section: Introductionmentioning

confidence: 99%

Time to treatment disruption in children with HIV-1 randomized to initial antiretroviral therapy with protease inhibitors versus non-nucleoside reverse transcriptase inhibitors

et al. 2020

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Background Choice of initial antiretroviral therapy regimen may help children with HIV maintain optimal, continuous therapy. We assessed treatment-naïve children for differences in time to treatment disruption across randomly-assigned protease inhibitor versus non-nucleoside reverse transcriptase inhibitor-based initial antiretroviral therapy. Methods We performed a secondary analysis of a multicenter phase 2/3, randomized, open-label trial in Europe, North and South America from 2002 to 2009. Children aged 31 days to <18 years, who were living with HIV-1 and treatment-naive, were randomized to antiretroviral therapy with two nucleoside reverse transcriptase inhibitors plus a protease inhibitor or non-nucleoside reverse transcriptase inhibitor. Time to first documented treatment disruption to any component of antiretroviral therapy, derived from treatment records and adherence questionnaires, was analyzed using Kaplan-Meier estimators and Cox proportional hazards models. Results The modified intention-to-treat analysis included 263 participants. Seventy-two percent (n = 190) of participants experienced at least one treatment disruption during study. At 4 years, treatment disruption probabilities were 70% (protease inhibitor) vs. 63% (non-nucleoside reverse transcriptase inhibitor). The unadjusted hazard ratio (HR) for treatment disruptions comparing protease inhibitor vs. non-nucleoside reverse transcriptase inhibitor-based regimens was 1.19, 95% confidence interval [CI] 0.88–1.61 (adjusted HR 1.24, 95% CI 0.91–1.68). By study end, treatment disruption probabilities converged (protease inhibitor 81%, non-nucleoside reverse transcriptase inhibitor 84%) with unadjusted HR 1.11, 95% CI 0.84–1.48 (adjusted HR 1.13, 95% CI 0.84–1.50). Reported reasons for treatment disruptions suggested that participants on protease inhibitors experienced greater tolerability problems. Conclusions Children had similar time to treatment disruption for initial protease inhibitor and non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy, despite greater reported tolerability problems with protease inhibitor regimens. Initial pediatric antiretroviral therapy with either a protease inhibitor or non-nucleoside reverse transcriptase inhibitor may be acceptable for maintaining optimal, continuous therapy.

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Second-line HIV treatment failure in sub-Saharan Africa: A systematic review and meta-analysis

Cited by 48 publications

References 93 publications

Incidence and factors associated with treatment failure among HIV infected adolescent and adult patients on second-line antiretroviral therapy in public hospitals of Northern Ethiopia: Multicenter retrospective study

Incidence and factors associated with treatment failure among HIV infected adolescent and adult patients on second-line antiretroviral therapy in public hospitals of Northern Ethiopia: Multicenter retrospective study

Drug Resistance Among Adolescents and Young Adults with Virologic Failure of First-Line Antiretroviral Therapy and Response to Second-Line Treatment

Time to treatment disruption in children with HIV-1 randomized to initial antiretroviral therapy with protease inhibitors versus non-nucleoside reverse transcriptase inhibitors

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