Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2012
Frequent emergence of N348I in HIV-1 subtype C reverse transcriptase with failure of initial therapy reduces susceptibility to reverse-transcriptase inhibitors.
Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Acquired HIV drug resistance mutations on first-line antiretroviral therapy in Southern Africa: Systematic review and Bayesian evidence synthesis.Journal of clinical epidemiology · 2022Pooled it
- Brief Report: HIV Drug Resistance Assessment Among Women Who Seroconverted During the MTN-025/HOPE Open-Label Extension Dapivirine Vaginal Ring Trial.Journal of acquired immune deficiency syndromes (1999) · 2024Trial
- HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial.Journal of the International AIDS Society · 2021Trial
- Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda.The Journal of antimicrobial chemotherapy · 2014Trial
- Reverse Transcriptase Connection and RNase H Domain Variation in HIV-1 Subtype C Among Individuals with Virologic Failure in Botswana.Biomedicines · 2026Article
- New antiretroviral inhibitors and HIV-1 drug resistance: more focus on 90% HIV-1 isolates?FEMS microbiology reviews · 2023Review
- How could HIV-1 drug resistance impact preexposure prophylaxis for HIV prevention?Current opinion in HIV and AIDS · 2022Review
- 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.BMC infectious diseases · 2017Article
- High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa.AIDS research and therapy · 2017Article
- Article
- Identification of Novel Resistance-Related Polymorphisms in HIV-1 Subtype C RT Connection and RNase H Domains from Patients Under Virological Failure in Brazil.AIDS research and human retroviruses · 2017Article
- Frequent Cross-Resistance to Dapivirine in HIV-1 Subtype C-Infected Individuals after First-Line Antiretroviral Therapy Failure in South Africa.Antimicrobial agents and chemotherapy · 2017Article
- A novel mutation, D404N, in the connection subdomain of reverse transcriptase of HIV-1 CRF08_BC subtype confers cross-resistance to NNRTIs.The Journal of antimicrobial chemotherapy · 2015Article
- Data-intensive analysis of HIV mutations.BMC bioinformatics · 2015Article
- Impact of drug resistance-associated amino acid changes in HIV-1 subtype C on susceptibility to newer nonnucleoside reverse transcriptase inhibitors.Antimicrobial agents and chemotherapy · 2015Article
- Subtype-independent near full-length HIV-1 genome sequencing and assembly to be used in large molecular epidemiological studies and clinical management.Journal of the International AIDS Society · 2015Article
- Resistance to reverse transcriptase inhibitors used in the treatment and prevention of HIV-1 infection.Future microbiology · 2015Review
- Compensatory role of double mutation N348I/M184V on nevirapine binding landscape: insight from molecular dynamics simulation.The protein journal · 2014Article
- Drug resistance in non-B subtype HIV-1: impact of HIV-1 reverse transcriptase inhibitors.Viruses · 2014Review
- The emerging profile of cross-resistance among the nonnucleoside HIV-1 reverse transcriptase inhibitors.Viruses · 2014Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundIt is not known how often mutations in the connection and ribonuclease H domains of reverse transcriptase (RT) emerge with failure of first-line antiretroviral therapy (ART) in subtype C human immunodeficiency virus type 1 (HIV-1) infection and how these mutations affect susceptibility to other antiretrovirals.
methodsWe compared full-length RT sequences in plasma obtained before therapy and at virologic failure of initial ART among 63 participants with subtype C HIV-1 infection enrolled in the Comprehensive International Program of Research on AIDS in South Africa (CIPRA-SA) study. Recombinant viruses containing full-length plasma-derived RT sequences from participants with N348I at virologic failure were assayed for drug susceptibility.
resultsY181C and M184V mutations in the RT polymerase domain were associated with failure of stavudine-lamivudine-nevirapine (d4T/3TC/NVP; P < .01), and K103N, V106M, and M184V with failure of d4T/3TC/efavirenz (EFV; P < .01). N348I in the RT connection domain emerged in 45% (P = .002) and 12% (P = .06) of participants receiving failing regimens containing NVP or EFV, respectively. Longitudinal analyses revealed that nonnucleoside RT inhibitor resistance mutations in the polymerase domain generally appeared first. N348I emerged at the same time, or after, M184V. N348I in the context of polymerase domain mutations reduced susceptibility to NVP (8.9-13-fold), EFV (4-56-fold), etravirine (ETV; 1.9-4.7-fold) and decreased hypersusceptibility to zidovudine (AZT; 1.4-2.2-fold).
conclusionsN348I emerges frequently with virologic failure of first-line ART in subtype C HIV-1 infection and reduces susceptibility to NVP, EFV, ETV, and AZT. Additional studies are warranted to characterize the effects of N348I on virologic response to second- and third-line regimens in resource-limited settings where subtype C predominates.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.