Browsing by Author "Jawed, Bilal"

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    1270. HIV Drug Resistance and Viral Outcomes after 2nd-line Antiretroviral Failure in Kenya
    (Oxford University Press, 2022) Ali, Shamim M.; Humphrey, John; Novitsky, Vladimir; Sang, Edwin; DeLong, Allison; Jawed, Bilal; Kemboi, Emmanuel; Goodrich, Suzanne; Gardner, Adrian; Hogan, Joseph W.; Kantor, Rami; Medicine, School of Medicine
    Background: Program data on HIV drug resistance and clinical outcomes after 2nd-line antiretroviral therapy (ART) failure in resource-limited settings are limited, yet can inform care, particularly with better ART access and options. Methods: We examined resistance upon 2nd-line failure and subsequent viral outcomes at the Academic Model Providing Access to Healthcare (AMPATH) in Kenya. Charts of people with genotypes upon 2nd-line failure up to 6/2021 were reviewed; and associations with viral suppression (< 1000 copies/mL) closest to 12 months post-genotyping were determined using bi- and multivariate analyses, adjusting for age, sex, time on ART, switch to 3rd-line (darunavir-, dolutegravir-, and/or raltegravir-based ART), and any resistance to regimens upon viral load (VL) testing. Results: Of 194 participants (53% female; median age 41 years; median 3.3 and 4.1 years on 1st- and 2nd-line), 60% were on lopinavir/ritonavir and 40% on atazanavir/ritonavir-based regimens. Overall, 178 (92%) had any resistance: 19% mono-, 40% dual-, 41% triple-class; 79% to NRTIs; 81% NNRTIs; and 43% PIs - 33% of those on lopinavir/ritonavir; 58% on atazanavir/ritonavir (p< 0.001); 24% with intermediate-high predicted resistance to darunavir/ritonavir (12 upon LPV/ritonavir, and 8 upon atazanavir/ritonavir failure; p=0.98). Of 140/194 people with post-genotype VLs, 55% stayed on 2nd-line, and 45% switched to 3rd-line. Of those 140, 72% virally suppressed (89% who switched to 3rd-line; 58% who didn't), and 75% had any resistance to their regimen at post-genotype VL (90% who switched to 3rd-line; 62% who didn't). In bivariate analysis, suppression was associated with switching to 3rd-line, and with resistance upon VL testing (Table). In multivariate analysis, suppression remained more likely among those who switched to 3rd-line, and association with resistance was less pronounced. Conclusion: In a large Kenyan HIV program, high resistance upon 2nd-line failure, high failure rates, and suppression association with 3rd-line switch suggest the need for dedicated management of this vulnerable population. Potential association between resistance and better viral outcomes, similar to reports upon 1st-line failure, needs further data and suggests significance of inadequate adherence.
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    HIV drug resistance, early treatment outcomes and impact of guidelines compliance after protease inhibitor‐based second‐line failure in a dedicated resistance clinic in western Kenya: a retrospective cohort study
    (Wiley, 2025) Humphrey, John M.; Ali, Shamim M.; DeLong, Allison; Novitsky, Vlad; Sang, Edwin; Jawed, Bilal; Kemboi, Emmanuel; Ngetich, Celia; Goodrich, Suzanne; Gardner, Adrian; Hogan, Joseph W.; Kantor, Rami; Medicine, School of Medicine
    Introduction: Data on drug resistance, viral outcomes and guidelines compliance following protease inhibitor (PI)-based second-line failure in low- and middle-income countries are limited, particularly in the era of dolutegravir-containing antiretroviral therapy (ART). Methods: We conducted a retrospective cohort study of people living with HIV (PLWH) ≥3 years old with second-line viral failure (VF, ≥1000 copies/ml) at the Academic Model Providing Access to Healthcare from 2011 to 2021. We assessed resistance prevalence and patterns at second-line VF, stratified by PI (atazanavir/ritonavir or lopinavir/ritonavir), and examined correlations of resistance and treatment strategies with VF at 6-18 months post-genotype. Analyses employed inverse probability weighting, adjusting for calendar year, age, gender, ART duration, PI at genotyping and class-specific resistance, and considered guidelines-supported versus unsupported strategies. Results: Of 187 participants (median age 41 years, 54% female, 41% on atazanavir/ritonavir, 59% on lopinavir/ritonavir-based ART), 91% had any resistance (NRTI 79%, NNRTI 80%, major PI 37%, dual-class 36%, triple-class 37%). Predicted resistance to third-line options was 67% for etravirine or rilpivirine and 10% for darunavir/ritonavir. Despite higher resistance detected on atazanavir/ritonavir versus lopinavir/ritonavir, predicted darunavir/ritonavir resistance was similar. At median 9 months post-genotype, 95% of 173 participants with available data were on a guidelines-supported regimen (55% second-line; 45% third-line, 86% dolutegravir-based), of whom 28% had post-genotype VF. Of the 5% not on guidelines-supported regimens, 71% had post-genotype VF. Adjusted odds of VF were higher for guidelines-unsupported versus supported regimens (OR = 4.52; 95% CI 1.02-26.24), and odds of VF were 97% lower for those on third-line versus second-line (OR = 0.07; 95% CI 0.02-0.20). Conclusions: We found high levels of drug resistance and early VF following PI-based second-line failure in Kenya. Treatment guidelines compliance and switches to third-line, even within guidelines recommendations, improved early viral outcomes. Findings highlight the vulnerability of PLWH with advanced ART experience and resistance profiles, and the importance of following guidelines and improving access to third-line and drug resistance testing, particularly in the new ART era.