Browsing by Author "Warrier R"

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Evolution of HIV-1 drug resistance after virological failure of first-line antiretroviral therapy in Lusaka, Zambia.
(2019) Hudson FP; Mulenga L; Westfall AO; Warrier R; Mweemba A; Saag MS; Stringer JS; Eron JJ; Chi BH; Department of Internal Medicine, University of Texas at Austin, Austin, TX, USA.; UNC Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA.; Department of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; School of Medicine, University of Zambia, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: HIV viral load (VL) and resistance testing are limited in sub-Saharan Africa, so individuals may have prolonged time on failing first-line antiretroviral therapy (ART). Our objective was to describe the evolution of drug resistance mutations among adults failing first-line ART in Zambia. METHODS: We analysed data from a trial of VL monitoring in Lusaka, Zambia. From 2006 to 2011, 12 randomized sites provided either routine VL monitoring (intervention) or discretionary (control) after ART initiation. Samples were collected prospectively following the same schedule in each arm but analysed retrospectively in the control group. For those with virological failure (VF; >400 copies/ml), HIV genotyping was performed retrospectively on baseline (BL) and on all subsequent specimens until censored due to study completion, withdrawal or death. RESULTS: Of 1,973 enrollees, 165 (8.4%) developed VF. 464 genotype results were available including 132 (80%) at BL, 116 (70%) at VF and 125 (76%) had at least one result between VF and censoring. Major nucleoside reverse transcriptase inhibitor (NRTI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations increased from 26% (BL) to 82% (VF) to 89% at last genotype (LG). M184 mutations increased from 2% to 59% to 71%; K65R from 2% to 11% to 13%; 2 or more thymidine analogue mutations from 1% to 3% to 12%. Among those on a failing tenofovir disoproxil fumarate (TDF)-based regimen, TDF resistance increased from 42% to 58%. CONCLUSIONS: We found substantial resistance to NRTIs and NNRTIs at VF with incremental increases after VF while still on a failing first-line ART; this resistance may compromise attainment of the UNAIDS 90-90-90 goals.
Intrapartum tenofovir and emtricitabine reduces low-concentration drug resistance selected by single-dose nevirapine for perinatal HIV prevention.
(2009-Nov) Chi BH; Ellis GM; Chintu N; Cantrell RA; Sinkala M; Aldrovandi GM; Warrier R; Mbewe F; Nakamura K; Stringer EM; Frenkel LM; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
A single dose of tenofovir/emtricitabine (TDF/FTC) during labor significantly reduces peripartum nevirapine-associated viral drug resistance when measured by consensus HIV sequencing. It is unknown whether this effect extends to HIV subpopulations of <25-50%. We conducted a randomized trial of single-dose TDF/FTC added to peripartum nevirapine to reduce drug resistance associated with nonnucleoside reverse transcriptase inhibitors (NNRTIs). To detect mutations for NNRTIs comprising > or = 2% of the viral population, we used an oligonucleotide ligation assay (OLA) at codons 103, 106, 181, and 190 of HIV reverse transcriptase. To assess development of drug resistance mutations to our study intervention, OLA was also performed at codons 65 and 184. Among the 328 women included in the 2-week analysis, those receiving TDF/FTC were less likely to have NNRTI resistance by OLA (RR = 0.40, 95% CI = 0.21-0.77). A similar trend was observed among the 315 women included in the 6-week analysis (RR = 0.45, 95% CI = 0.31-0.66). Only two (1%) specimens had detectable K65R by OLA. Both were at 6 weeks postpartum; one was detected in the intervention arm and one in the control arm (p = 0.96). M184V was not detected. The ability of single-dose TDF/FTC to protect against peripartum NVP-induced NNRTI resistance extends to minority populations. This efficacy is achieved without significant selection of TDF- or FTC-resistant viruses.
The integration of tuberculosis and HIV testing on GeneXpert can substantially improve access and same-day diagnosis and benefit tuberculosis programmes: A diagnostic network optimization analysis in Zambia.
(2023) Girdwood S; Pandey M; Machila T; Warrier R; Gautam J; Mukumbwa-Mwenechanya M; Benade M; Nichols K; Shibemba L; Mwewa J; Mzyece J; Lungu P; Albert H; Nichols B; Choonga P; Department of Internal Medicine, Health Economics and Epidemiology Research Office, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Department of Medical Microbiology, Amsterdam University Medical Center, Amsterdam, The Netherlands.; FIND, Geneva, Switzerland.; Ministry of Health, Lusaka, Zambia.; National TB and Leprosy Programme, Ministry of Health, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; FIND, Cape Town, South Africa.; Department of Global Health, Boston University School of Public Health, Boston, MA, United States of America.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Diagnostic network optimization (DNO), a geospatial optimization technique, can improve access to diagnostics and reduce costs through informing policy-makers' decisions on diagnostic network changes. In Zambia, viral load (VL) testing and early infant diagnosis (EID) for HIV has been performed at centralized laboratories, whilst the TB-programme utilizes a decentralized network of GeneXpert platforms. Recently, the World Health Organization (WHO) has recommended point-of-care (POC) EID/VL to increase timely diagnosis. This analysis modelled the impact of integrating EID/VL testing for children and pregnant/breastfeeding-women (priority-HIV) with TB on GeneXpert in Zambia. Using OptiDx, we established the baseline diagnostic network using inputs for testing demand (October 2019-September 2020), referrals, testing sites, testing platforms, and costs for HIV/TB testing (transport, test, device) respectively in Zambia. Next, we integrated priority-HIV testing on GeneXpert platforms, historically only utilized by the TB-programme. 228,265 TB tests were conducted on GeneXpert devices and 167,458 (99%) of priority-HIV tests on centralized devices at baseline, of which 10% were tested onsite at the site of sample collection. With integration, the average distance travelled by priority-HIV tests decreased 10-fold (98km to 10km) and the proportion tested onsite increased (10% to 48%). 52% of EID tests are likely to be processed within the same-day from a baseline of zero. There were also benefits to the TB-programme: the average distance travelled/specimen decreased (11km to 7km), alongside potential savings in GeneXpert device-operating costs (30%) through cost-sharing with the HIV-programme. The total cost of the combined testing programmes reduced marginally by 1% through integration/optimization. DNO can be used to strategically leverage existing capacity to achieve the WHO's recommendation regarding POC VL/EID testing. Through DNO of the Zambian network, we have shown that TB/HIV testing integration can improve the performance of the diagnostic network and increase the proportion of specimens tested closer to the patient whilst not increasing costs.