Prevalence of HIV Drug Resistance Before and 1 Year After Treatment Initiation in 4 Sites in the Malawi Antiretroviral Treatment Program

Wadonda-Kabondo, Nellie; Bennett, Diane; Oosterhout, Joep J. van; Moyo, Kundai; Hosseinipour, Mina C.; DeVos, Josh; Zhou, Zhansong; Aberle‐Grasse, John; Warne, Thomas R.; Mtika, Clement; Chilima, Ben; Banda, Richard; Pasulani, Olesi; Porter, Carol Q.; Phiri, Sam; Jahn, Andreas; Kamwendo, Debbie; Jordan, Michael R.; Kabuluzi, Storn; Chimbwandira, Frank; Kagoli, Mathew; Matatiyo, Blackson; Demby, Austin; Yang, Chunfu

doi:10.1093/cid/cir987

Cited by 15 publications

(19 citation statements)

References 24 publications

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“…Of the 48 independent cohorts, 31 reported results from the overall cohort [24, 62, 64–92], while 17 reported results from two different groups within the cohort [59, 93–108], although for two of these studies, only one group was considered in our meta-analysis due to sample size restriction [100, 107]. This gave 63 distinct populations.…”

Section: Resultsmentioning

confidence: 99%

Virological success after 12 and 24 months of antiretroviral therapy in sub-Saharan Africa: Comparing results of trials, cohorts and cross-sectional studies using a systematic review and meta-analysis

et al. 2017

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BackgroundUNAIDS recently defined the 90-90-90 target as a way to end the HIV epidemic. However, the proportion of virological success following antiretroviral therapy (ART) may not be as high as the anticipated 90%, and may in fact be highly heterogeneous. We aimed to describe the proportion of virological success in sub-Saharan Africa and to identify factors associated with the proportion of virological success.MethodsWe performed a systematic review and meta-analysis focusing on the proportion of patients in sub-Saharan Africa who demonstrate virological success at 12 and 24 months since ART initiation, as well as at 6 and 36 months, where possible. Programme factors associated with the proportion of virological success were identified using meta-regression. Analyses were conducted using both on-treatment (OT) and intention-to-treat (ITT) approaches.ResultsEighty-five articles were included in the meta-analysis, corresponding to 125 independent study populations. Using an on-treatment approach, the proportions (95% confidence interval (CI)) of virological success at 12 (n = 64) and at 24 (n = 32) months since ART initiation were 87.7% (81.3–91.0) and 83.7% (79.8–87.6), respectively. Univariate analysis indicated that the proportion of virological success was not different by study design. Multivariate analysis at 24 months showed that the proportion of virological success was significantly larger in studies conducted in public sector sites than in other sites (p = 0.045). Using an ITT approach, the proportions (95% CI) of virological success at 12 (n = 50) and at 24 (n = 20) months were 65.4% (61.8–69.1) and 56.8% (51.3–62.4), respectively. At 12 months, multivariate analysis showed that the proportion of success was significantly lower in cohort studies than in trials (63.0% vs. 71.1%; p = 0.017). At 24 months, univariate analysis demonstrated that the proportion of success was also lower in cohorts.DiscussionRegardless of the time following ART initiation, and of the threshold, proportions of virological success were highly variable. Evidence from this review suggests that the new international target of 90% of patients controlled is not yet being achieved, and that in order to improve the virological outcome, efforts should be made to improve retention in care.

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Section: Resultsmentioning

confidence: 99%

Virological success after 12 and 24 months of antiretroviral therapy in sub-Saharan Africa: Comparing results of trials, cohorts and cross-sectional studies using a systematic review and meta-analysis

et al. 2017

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Section: Introductionmentioning

confidence: 87%

“…A prior survey in Malawi found high virological suppression at 12 months (91%) 7,8 . However, the estimated prevalence of pre-treatment HIV resistance ranged from 2.8 and 6.5% 7 which accounted for 37.5% of the detected resistance at 12 months. A more recent report from Malawi suggests that between 5-15% of pregnant women have transmitted HIV drug resistance using the WHO threshold survey (personal communication, Nellie Wadonda Kabondo), predominantly to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of drugs which forms the back bone of the most popular first line therapy worldwide 9 .…”

Section: Introductionmentioning

confidence: 87%

Viral Suppression and HIV Drug Resistance at 6 Months Among Women in Malawi's Option B+ Program: Results From the PURE Malawi Study

Hosseinipour¹,

Nelson

Trapence

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background In 2011, Malawi launched Option B+, a program of universal ART treatment for pregnant and lactating women to optimize maternal health and prevent pediatric HIV infection. For optimal outcomes, women need to achieve HIVRNA suppression. We report 6 month HIVRNA suppression and HIV drug resistance in the PURE study. Methods PURE study was a cluster-randomized controlled trial evaluating three strategies for promoting uptake and retention; Arm 1: Standard of Care, Arm 2: Facility Peer Support and Arm 3: Community Peer support. Pregnant and breastfeeding mothers were enrolled and followed according to Malawi ART guidelines. Dried blood spots for HIVRNA testing were collected at 6 months. Samples with ART failure (HIVRNA ≥1000 copies/ml) had resistance testing. We calculated odds ratios for ART failure using generalized estimating equations with a logit link and binomial distribution. Results We enrolled 1269 women across 21 sites in Southern and Central Malawi. Most enrolled while pregnant(86%) and were WHO Stage 1(95%). At 6 months, 950/1269 (75%) were retained; 833/950 (88%) had HIVRNA testing conducted and 699/833(84%) were suppressed. Among those with HIVRNA ≥1000 copies/ml with successful amplification (N=55, 41% of all VL> 1000 copies/ml), confirmed HIV resistance was found in 35% (19/55), primarily to the Non-nucleoside reverse transcriptase inhibitors(NNRTI) class of drugs. ART failure was associated with treatment default but not study arm, age, WHO stage, or breastfeeding status. Conclusions Virologic suppression at 6 months was <90% targets, but the observed confirmed resistance rates suggest adherence support should be the primary approach for early failure in Option B+.

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“…In this 2008 ART patient monitoring survey, 6.1% of the patients on ART for 12–15 months harboured drug resistant HIV. 22 The most common non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations were K103N (58.1%), Y181C (41.9%) and G190A (6.5%), and the most frequent nucleoside reverse transcriptase inhibitor (NRTI) mutation was M184V (61.3%). The DRMs conferring resistance against NNRTI at baseline were associated with DRMs detected at 12–15 months on ART.…”

Section: Introductionmentioning

confidence: 99%

Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy

Zhou

Tang

Zhang

et al. 2018

African Journal of Laboratory Medicine

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BackgroundMinority drug resistance mutations (DRMs) that are often missed by Sanger sequencing are clinically significant, as they can cause virologic failure in individuals treated with antiretroviral therapy (ART) drugs.ObjectiveThis study aimed to estimate the prevalence of minor DRMs among patients enrolled in a Malawi HIV drug resistance monitoring survey at baseline and at one year after initiation of ART.MethodsForty-one plasma specimens collected from HIV-1 subtype C-positive patients and seven clonal control samples were analysed using ultra-deep sequencing technology.ResultsDeep sequencing identified all 72 DRMs detected by Sanger sequencing at the level of ≥20% and 79 additional minority DRMs at the level of < 20% from the 41 Malawian clinical specimens. Overall, DRMs were detected in 85% of pre-ART and 90.5% of virologic failure patients by deep sequencing. Among pre-ART patients, deep sequencing identified a statistically significant higher prevalence of DRMs to nucleoside reverse transcriptase inhibitors (NRTIs) compared with Sanger sequencing. The difference was mainly due to the high prevalence of minority K65R and M184I mutations. Most virologic failure patients harboured DRMs against both NRTIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs). These minority DRMs contributed to the increased or enhanced virologic failures in these patients.ConclusionThe results revealed the presence of minority DRMs to NRTIs and NNRTIs in specimens collected at baseline and virologic failure time points. These minority DRMs not only increased resistance levels to NRTIs and NNRTIs for the prescribed ART, but also expanded resistance to additional major first-line ART drugs. This study suggested that drug resistance testing that uses more sensitive technologies, is needed in this setting.

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Prevalence of HIV Drug Resistance Before and 1 Year After Treatment Initiation in 4 Sites in the Malawi Antiretroviral Treatment Program

Cited by 15 publications

References 24 publications

Virological success after 12 and 24 months of antiretroviral therapy in sub-Saharan Africa: Comparing results of trials, cohorts and cross-sectional studies using a systematic review and meta-analysis

Virological success after 12 and 24 months of antiretroviral therapy in sub-Saharan Africa: Comparing results of trials, cohorts and cross-sectional studies using a systematic review and meta-analysis

Viral Suppression and HIV Drug Resistance at 6 Months Among Women in Malawi's Option B+ Program: Results From the PURE Malawi Study

Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy

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