Pretreatment HIV Drug Resistance Among Adults Initiating or Re-Initiating First-Line Antiretroviral Therapy in Zimbabwe: Fast-Tracking the Transition to Dolutegravir-Based First-Line Regimens?

Kouamou, Vinie; Mavetera, Justice; Manasa, Justen; Ndhlovu, Chiratidzo E.; Katzenstein, David; McGregor, A M

doi:10.1089/aid.2020.0242

Cited by 10 publications

(11 citation statements)

References 34 publications

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“…Although the biological and behavioral explanations for these observations were not well defined, this observation is a warning for national programmes and may have multiple public health implications for many LMICs including Zimbabwe, which are switching to DTG-based ART. As we have recently reported, high levels of PDR (31%) and NNRTI (29%) and NNRTI (EFV/NVP; 17%) drug resistance were observed amongst adults initiating or reinitiating first-line ART in Zimbabwe [10]. These people were very likely initiated or re-initiated on a first-line ART regimen containing DTG.…”

mentioning

confidence: 69%

“…In a cross-sectional study conducted between October 2018 and February 2020 among adults (≥ 18 years old) initiating or re-initiating first-line ART at Parirenyatwa Hospital HIV ART treatment clinic, a tertiary level setting, in Harare, Zimbabwe; we showed that among 120 participants enrolled in the study, any PDR was present in 31% (95% CI: 22.5-39.6) and PDR to any NNRTIs and to [efavirenz/nevirapine (EFV/NVP)] was found in 29% and 17%, respectively [10]. These findings provide evidence of a considerable annual rise in PDR in Zimbabwe driven primarily by NNRTI-resistance.…”

mentioning

confidence: 91%

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High Levels of Pre-Treatment HIV Drug Resistance in Zimbabwe: Is this a Threat to HIV/AIDS Control?

2021

J AIDS HIV Treat

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confidence: 69%

mentioning

confidence: 91%

High Levels of Pre-Treatment HIV Drug Resistance in Zimbabwe: Is this a Threat to HIV/AIDS Control?

2021

J AIDS HIV Treat

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“…However, NNRTI pretreatment resistance likely played a more significant role in the last decade [24–27]. Second-line virologic failure (DTG or ATV/r) may more likely be related to poor treatment compliance based on literature showing almost no pretreatment or transmitted drug resistance among protease inhibitor- and INSTI-naïve PLWH in Zimbabwe and the demonstrated efficacy of both DTG and protease inhibitors with suboptimal NRTI backbones [15,25,28–30]. In addition, a longer duration of ART is associated with a higher likelihood of treatment failure [31,32].…”

Section: Discussionmentioning

confidence: 99%

Virologic outcomes on dolutegravir-, atazanavir-, or efavirenz-based ART in urban Zimbabwe: A longitudinal study

Shamu,

Egger,

Mudzviti

et al. 2023

Preprint

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There are few data from sub-Saharan Africa on the virologic outcomes associated with second-line ART based on protease inhibitors or dolutegravir (DTG). We compared viral load (VL) suppression among people living with HIV (PLWH) on atazanavir (ATV/r)- or dolutegravir (DTG)-based second-line ART with PLWH on efavirenz (EFV)-based first-line ART. We analyzed data from the electronic medical records system of Newlands Clinic in Harare, Zimbabwe. We included patients aged >=12 years when commencing first-line EFV-based ART or switching to second-line DTG- or ATV/r-based ART with >=24 weeks follow-up after start or switch. We computed suppression rates (HIV VL <50 copies/mL) at weeks 12, 24, 48, 72, and 96 and estimated the probability of VL suppression by treatment regimen, time since start/switch of ART, sex, age, and CD4 cell count (at start/switch) using logistic regression in a Bayesian framework. We included 7013 VL measurements of 1049 PLWH (61% female) initiating first-line ART and 1114 patients (58% female) switching to second-line ART. Among those switching, 872 (78.3%) were switched to ATV/r and 242 (21.7%) to DTG. VL suppression was lower in second-line ART patients than first-line ART patients, except at week 12, when those on DTG showed higher suppression than those on EFV (aOR 2.10, 95%-credible interval [CrI] 1.48-3.00) and ATV/r-based regimens (aOR 1.87, 95%-CrI 1.32-2.71). In weeks >=48, first-line patients had around 3 times the odds of VL suppression compared to second-line patients. There was no evidence of a difference between DTG and ATV/r for follow-up times >24 weeks in PLWH on second-line. Second-line ART patients had lower VL suppression rates than those receiving first-line ART, and there was no difference in suppression between DTG- and ATV/r-based second-line ART >6 months after switching. Virologic monitoring and adherence support remain essential to prevent second-line treatment failure in settings with limited treatment options.

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“…Concerns that such resistance, especially to non-nucleoside reverse transcriptase inhibitors (NNRTIs), could compromise the effectiveness of antiretroviral therapy (ART) led the WHO to update ART treatment recommendations in 2019, designating dolutegravir-based ART as preferred in first-line and second-line regimens [3]. However, some individuals may not tolerate dolutegravir, and efavirenz combined with two NRTI remains a recommended alternative regimen for adolescents and adults living with HIV and initiating ART treatment; [3] indeed, in some countries efavirenz-based ART remains the most prevalent ART regimen [4]. As ART regimens are prescribed for an individual's lifetime, and few regimens exist without cross-resistance, understanding the effects of pre-treatment HIV variants resistant to NRTIs and NNRTIs remains relevant in the age of dolutegravir.…”

Section: Introductionmentioning

confidence: 99%

Low-frequency pre-treatment HIV drug resistance: effects on 2-year outcome of first-line efavirenz-based antiretroviral therapy

Milne¹,

Beck²,

Levine³

et al. 2022

Aids

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Objective(s): Assess the impact of pre-treatment high-frequency and low-frequency drug-resistant HIV variants on long-term outcomes of first-line efavirenz-based antiretroviral therapy (ART). Design: Prospective observational study. Methods: Participants’ pre-treatment plasma RNA had two sections of HIV pol encoding reverse transcriptase sequenced (Illumina, MiSeq) using unique molecular identifiers to detect wild-type (pre-treatment drug-resistant variants less than 1% of viral quasispecies), low-frequency (1–9%) or high-frequency drug-resistant variants (10–100%). Associations between pre-treatment drug resistance and virologic outcomes over 24 months of efavirenz-based ART were assessed for the number and frequency of mutations by drug class and other resistance parameters. Results: Virologic failure was detected in 30 of 352 (9%) and pre-treatment drug-resistant variants were detected in the viral quasispecies of 31 of 352 (9%) participants prescribed efavirenz-based ART. Survival analyses revealed statistically significant associations between pre-treatment drug resistance at low (P < 0.0001) and high (P < 0.001) frequencies, at oligonucleotide ligation assay (OLA) (P < 0.00001) and non-OLA (P < 0.01) codons, to a single-antiretroviral class (P < 0.00001), and a shorter time to virologic failure of efavirenz-based ART. Regression analyses detected independent effects across resistance categories, including both low-frequency (P < 0.01) and high-frequency (P < 0.001) drug-resistant variants. Conclusion: We observed that pre-treatment HIV drug resistance detected at low frequencies increased the risk of virologic failure over 24 months of efavirenz-based ART, but that most failures, regardless of drug-resistant variants’ frequencies, were detected within a year of ART initiation. These observations suggest that when efavirenz-based ART is prescribed, screening for pre-treatment drug resistance by an assay capable of detecting low-frequency variants, including OLA, may guide clinicians to prescribe more effective ART.

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Pretreatment HIV Drug Resistance Among Adults Initiating or Re-Initiating First-Line Antiretroviral Therapy in Zimbabwe: Fast-Tracking the Transition to Dolutegravir-Based First-Line Regimens?

Cited by 10 publications

References 34 publications

High Levels of Pre-Treatment HIV Drug Resistance in Zimbabwe: Is this a Threat to HIV/AIDS Control?

High Levels of Pre-Treatment HIV Drug Resistance in Zimbabwe: Is this a Threat to HIV/AIDS Control?

Virologic outcomes on dolutegravir-, atazanavir-, or efavirenz-based ART in urban Zimbabwe: A longitudinal study

Low-frequency pre-treatment HIV drug resistance: effects on 2-year outcome of first-line efavirenz-based antiretroviral therapy

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