HIV-1 Drug Resistance In Patients Research Articles

HIV1 drug resistance among patients experiencing first-line treatment failure in Ethiopia: protocol for a systematic review and meta-analysis

BackgroundThe emergence of HIV drug resistance presents a substantial challenge. Current antiretroviral treatments, along with current classes, face the danger of becoming partially or entirely inactive. As a result, alternative treatment regimens are limited, and treatment choices are complicated. According to the recommendation of the WHO, nations should consider changing their first-line ART regimen if HIV drug resistance exceeds 10%. In spite of the fact that a number of primary studies have been performed on HIV drug resistance in Ethiopia, their pooled prevalence rate has not been determined in a systematic review and meta-analysis, which may provide stronger evidence. Therefore, the objective of this systematic review and meta-analysis will be to estimate the pooled prevalence rate of HIV1 drug resistance in patients with first-line treatment failure in Ethiopia.MethodsPrimary studies will be identified from PubMed/MEDLINE, Scopus, Embase, Web of Science Core Collection, and Google Scholar. The period of search will be from 01 April to 30 June 2024. Studies identified through the search strategies will first be screened by titles and abstracts. Included studies meeting established criteria will be evaluated for risk of bias using the JBI checklist. Data will be extracted, and the pooled prevalence rate of HIV drug resistance will be computed using STATA 14 software. Random effect models will be used when heterogeneity is suspected. The I2 statistic and its corresponding P value will be checked to distinguish heterogeneity. Additionally, publication bias and heterogeneity will be checked using visual funnel plots, Egger’s test, trim-and-fill tests, meta-regression, and subgroup analysis. To present and synthesize the results, narrative synthesis will be performed to describe study characteristics and findings, and forest plots will be used to visually represent effect sizes and confidence intervals from individual studies.DiscussionEstimating the pooled prevalence rate of HIV drug resistance through a systematic review and meta-analysis improves the reliability of the evidence, the availability of effective HIV treatment options, and the ability to assist in making decisions for both clinical practice and public health policy in Ethiopia.Systematic review registrationPROSPERO CRD42024533975.

1271. HIV-1 Drug Resistance in Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Rhode Island, USA

Abstract Background Integrase Strand Transfer Inhibitors (INSTIs) are the most common antiretroviral therapy (ART) anchor drugs. Despite reassuring clinical trial data, real-life extent and characteristics of resistance at failure of INSTI-based regimens are unclear and can inform care. Methods We investigated drug resistance upon failure of INSTI-based regimens at the largest HIV program in Rhode Island (RI), caring for > 80% of the state’s people with HIV. Eligible patients had full ART history, were on INSTI-based regimens, and had available protease-reverse transcriptase-integrase sequences from clinical care. Resistance interpretation was done with Stanford Database tools. Results Of 1,169 eligible patients (55% of clinic population), 102 (9%) were failing INSTI-based regimens; mean age at genotyping 39 years, CD4 377 cells/µL, and 11 years on ART; 67% male; 53% white, 44% Black, 63% non-Hispanic; 58% US born; with prior exposure to 8 drugs and 4 regimens. Of these 102, 55% were on 1st-generation INSTI (41% elvitegravir (EVG); 14% raltegravir (RAL)), and 45% on 2nd-generation INSTI (23% bictegravir (BIC); 22% dolutegravir (DTG)); most (73%) with only 2 NRTIs. Overall, 57% had any intermediate-high level predicted resistance (55% on 1st-, 45% on 2nd-generation INSTI); NRTI 37%; NNRTI 40%; PI 3%; INSTI 22% (EVG 22%, RAL 21%, DTG/BIC/cabotegravir 8% each). Common INSTI mutations were N155H (n=7); E92Q, Q148H/R, S147G (5 each); T66I/K, E138A/K/T (4 each); G140A/S (3), R263K (2), Y143R (1). Multi (≥ 3) class resistance occurred in 12%, a third of whom had intermediate-high resistance to all five INSTIs (50% on 1st-, 50% on 2nd-generation). Resistance trends were stable over 2014-2021, and 2nd-generation INSTI resistance was only seen in those with prior exposure to 1st-generation INSTI. Conclusion At the largest RI HIV clinic, 9% of eligible patients were failing INSTI-based regimens, most with clinically relevant resistance that was stable over time, and 1% had multi-class resistance including some to all available INSTIs. Though low resistance levels to 2nd-generation INSTIs are encouraging, they exist; and continued ADR monitoring is important, particularly with increasing incorporation of INSTIs in HIV treatment and prevention and use of 2-drug regimens. Disclosures All Authors: No reported disclosures.

Accumulation of HIV-1 drug resistance in patients on a standard thymidine analogue-based first line antiretroviral therapy after virological failure: implications for the activity of next-line regimens from a longitudinal study in Mozambique

BackgroundWe describe the accumulation of HIV-1 drug resistance and its effect on the activity of next-line components in patients with virological failure (HIV-1 RNA >1000 copies/mL) after 1 year (t1) of first-line antiretroviral therapy (ART) not switching to second-line drugs for one additional year (t2) in low-middle income countries (LMIC).Methods and resultsWe selected 48 patients from the DREAM cohort (Maputo, Mozambique); their median pre-ART CD4+ cell count was 165 cells/μl. At t1 patients were receiving ART since a median of 12.2 months (mainly zidovudine/lamivudine/nevirapine), their median HIV RNA was 3.8 log10 copies/mL, 43 (89.6%) presented at least one resistance-associated mutation (RAM), most frequently for lamivudine/emtricitabine, nevirapine and efavirenz. Resistance to tenofovir, was 10% at 1 year and higher than 20% at 2 years, while projection at 3 years was >30%. At t2, 42 (89.4%) had a predicted low-level or higher resistance to at least 1 s-line drug. At t1, the frequency of RAM in patients with a lower adherence to pharmacy appointments (<95%) was significantly lower (12/20, 60% for NRTI and 14/20, 70% for NNRTI) than in those with a better adherence (26/28, 92.8% for NRTI and 25/28, 89.3% for NNRTI) (OR 0.12, 95% CI 0.02–0.63, p = 0.012 and OR 0.28, 95% CI 0.06–1.29, p = 0.103, respectively). Overall thymidine analogue mutations (TAMs) accumulation rate was 0.32/year, 0.50/year in the subgroup with HIV RNA >10,000 copies/mL; NNRTI RAM accumulation rate was 0.15/year, 0.40/year in the subgroup with HIV RNA >10,000 copies/mL.ConclusionsWhile the activity of NNRTIs is compromised early during failure, tenofovir and zidovudine activity are reduced more frequently after 1 year of documented virological failure of thymidine analogue-based first-line ART, with RAMs accumulating faster in patients with higher viral loads. The present observation may help informing decisions on when to switch to a second line ART in patients on virological failure in LMIC.

Study of HIV-1 drug resistance in patients receiving free antiretroviral therapy in China

To investigate the prevalence of drug-resistance mutations, resistance to antiretroviral drugs, and the subsequent virological response to therapy in treatment-naive and antiretroviral-treated patients infected with HIV/AIDS in Henan, China, a total of 431 plasma samples were collected in Queshan county between 2003 and 2004, from patients undergoing the antiretroviral regimen Zidovudine + Didanosine + Nevirapine (Azt+Ddi+Nvp). Personal information was collected by face to face interview. Viral load and genotypic drug resistance were tested. Drug resistance mutation data were obtained by analyzing patient-derived sequences through the HIVdb Program (http://hivdb.stanford.edu). Overall, 38.5% of treatment-naive patients had undetectable plasma viral load (VL), the rate significantly increased to 61.9% in 0 to 6 months treatment patients (mean 3 months) (P<0.005) but again significantly decrease to 38.6% in 6 to 12 months treatment patients (mean 9 months) (P<0.001) and 40.0% in patients receiving more than 12 months treatment (mean 16 months) (P<0.005). The prevalence of drug resistance in patients who had a detectable VL and available sequences were 7.0%, 48.6%, 70.8%, 72.3% in treatment-naive, 0 to 6 months treatment, 6 to 12 months treatment, and treatment for greater than 12 months patients, respectively. No mutation associated with resistance to Protease inhibitor (PI) was detected in this study. Nucleoside RT inhibitor (NRTI) mutations always emerged after non-nucleoside RT inhibitor (NNRTI) mutations, and were only found in patients treated for more than 6 months, with a frequency less than 5%, with the exception of mutation T215Y (12.8%, 6/47) which occurred in patients treated for more than 12 months. NNRTI mutations emerged quickly after therapy begun, and increased significantly in patients treated for more than 6 months (P<0.005), and the most frequent mutations were K103N, V106A, Y181C, G190A. There had been optimal viral suppression in patients undergoing treatment for less than 6 months in Queshan, Henan. The drug resistance strains were highly prevalent in antiretroviral-treated patients, and increased with the continuation of therapy, with many patients encountering virological failure after 6 months therapy.