Etravirine and Rilpivirine Drug Resistance Among HIV-1 Subtype C Infected Children Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens in South India

Migration is associated with HIV-1 vulnerability. Objectives: To identify long-term trends in HIV-1 molecular epidemiology and antiretroviral drug resistance (ARV) among migrants followed up in Portugal Methods: 5177 patients were included between 2001 and 2017. Rega, Scuel, Comet, and jPHMM algorithms were used for subtyping. Transmitted drug resistance (TDR) and Acquired drug resistance (ADR) were defined as the presence of surveillance drug resistance mutations (SDRMs) and as mutations of the IAS-USA 2015 algorithm, respectively. Statistical analyses were performed. Results: HIV-1 subtypes infecting migrants were consistent with the ones prevailing in their countries of origin. Over time, overall TDR significantly increased and specifically for Non-nucleoside reverse transcriptase inhibitor (NNRTIs) and Nucleoside reverse transcriptase inhibitor (NRTIs). TDR was higher in patients from Mozambique. Country of origin Mozambique and subtype B were independently associated with TDR. Overall, ADR significantly decreased over time and specifically for NRTIs and Protease Inhibitors (PIs). Age, subtype B, and viral load were independently associated with ADR. Conclusions: HIV-1 molecular epidemiology in migrants suggests high levels of connectivity with their country of origin. The increasing levels of TDR in migrants could indicate an increase also in their countries of origin, where more efficient surveillance should occur.

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Emergent HIV-1 Drug Resistance Mutations Were Not Present at Low-Frequency at Baseline in Non-Nucleoside Reverse Transcriptase Inhibitor-Treated Subjects in the STaR Study

Viruses ◽

10.3390/v7122943 ◽

2015 ◽

Vol 7 (12) ◽

pp. 6360-6370 ◽

Cited By ~ 12

Author(s):

Danielle Porter ◽

Martin Daeumer ◽

Alexander Thielen ◽

Silvia Chang ◽

Ross Martin ◽

...

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Nucleoside Reverse Transcriptase Inhibitor ◽

Low Frequency ◽

Transcriptase Inhibitor ◽

Resistance Mutations ◽

Drug Resistance Mutations ◽

Reverse Transcriptase Inhibitor ◽

Hiv 1

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P1913 Genotypic drug resistance mutations among HIV–1–infected patients failing an initial non–nucleoside reverse transcriptase inhibitor-based antiretroviral regimen in a resource-limited setting

International Journal of Antimicrobial Agents ◽

10.1016/s0924-8579(07)71752-1 ◽

2007 ◽

Vol 29 ◽

pp. S549

Author(s):

S. Sungkanuparph ◽

S. Kiertiburanakul ◽

K. Malathum ◽

N. Saekang ◽

W. Pairoj ◽

...

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Nucleoside Reverse Transcriptase Inhibitor ◽

Transcriptase Inhibitor ◽

Resistance Mutations ◽

Drug Resistance Mutations ◽

Resource Limited ◽

Reverse Transcriptase Inhibitor ◽

Hiv 1 ◽

Limited Setting

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Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals

Viruses ◽

10.3390/v9110330 ◽

2017 ◽

Vol 9 (11) ◽

pp. 330 ◽

Cited By ~ 2

Author(s):

Sinaye Ngcapu ◽

Kristof Theys ◽

Pieter Libin ◽

Vincent Marconi ◽

Henry Sunpath ◽

...

Keyword(s):

Reverse Transcriptase ◽

Nucleoside Reverse Transcriptase Inhibitor ◽

Transcriptase Inhibitor ◽

Rnase H ◽

Subtype C ◽

Reverse Transcriptase Inhibitor ◽

Hiv 1

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Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa

Antiviral Chemistry and Chemotherapy ◽

10.1177/2040206618762985 ◽

2018 ◽

Vol 26 ◽

pp. 204020661876298 ◽

Cited By ~ 5

Author(s):

Kerri J Penrose ◽

Chanson J Brumme ◽

Maritsa Scoulos-Hanson ◽

Kristen Hamanishi ◽

Kelley Gordon ◽

...

Keyword(s):

South Africa ◽

Antiretroviral Therapy ◽

Reverse Transcriptase ◽

Nucleoside Reverse Transcriptase Inhibitor ◽

Transcriptase Inhibitor ◽

Cross Resistance ◽

Subtype C ◽

First Line ◽

Reverse Transcriptase Inhibitor ◽

Hiv 1

Background Rilpivirine (TMC278LA) is a promising drug for pre-exposure prophylaxis of HIV-1 because of its sub-nanomolar potency and long-acting formulation; however, increasing transmission of non-nucleoside reverse transcriptase inhibitor-resistant HIV-1 with potential cross-resistance to rilpivirine could reduce its preventive efficacy. This study investigated rilpivirine cross-resistance among recombinant subtype C HIV-1 derived from 100 individuals failing on first-line non-nucleoside reverse transcriptase inhibitor-containing antiretroviral therapy in South Africa whose samples were sent for routine HIV-1 drug resistance testing to Lancet Laboratories (Johannesburg, South Africa). Methods Plasma samples were selected from individuals with HIV-1 RNA > 10,000 copies/ml and ≥1 non-nucleoside reverse transcriptase inhibitor-resistance mutation in reverse transcriptase. Recombinant HIV-1LAI-containing bulk-cloned full-length reverse transcriptase sequences from plasma were assayed for susceptibility to nevirapine (NVP), efavirenz (EFV) and rilpivirine in TZM-bl cells. Fold-change (FC) decreases in drug susceptibility were calculated against a mean IC50 from 12 subtype C HIV-1 samples from treatment-naïve individuals in South Africa. Cross-resistance was evaluated based on biological cutoffs established for rilpivirine (2.5-FC) and the effect of mutation combinations on rilpivirine phenotype. Results Of the 100 samples from individuals on failing antiretroviral therapy, 69 had 2.5- to 75-fold decreased susceptibility to rilpivirine and 11 had >75-fold resistance. Rilpivirine resistance was strongly associated with K103N especially in combination with other rilpivirine-associated mutations. Conclusion The frequently observed cross-resistance of HIV-1 suggests that the preventive efficacy of TMC278LA pre-exposure prophylaxis could be compromised by transmission of HIV-1 from individuals with failure of first-line non-nucleoside reverse transcriptase inhibitor-containing antiretroviral therapy.

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Prevalence of minority Human Immunodeficiency virus multi-drug resistant mutations among patients failing a Nucleoside Reverse Transcriptase Inhibitor based regimen in Uganda

10.21203/rs.3.rs-666492/v1 ◽

2021 ◽

Author(s):

Immaculate Lillian Nankya ◽

Eva Nabulime ◽

Fred Kyeyune ◽

Cissy Mutuluza Kityo ◽

Miguel Mateu Quinones

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Nucleoside Reverse Transcriptase Inhibitor ◽

Transcriptase Inhibitor ◽

Cross Resistance ◽

Drug Resistant ◽

Susceptible Genotype ◽

Subtype C ◽

Subtype A ◽

Reverse Transcriptase Inhibitor

Abstract Objective To determine the prevalence of multi-drug resistant variants among patients failing on a nucleoside reverse transcriptase inhibitor (NRTI) based regimen with a detectable viral load ≥ 1000 copies/ml among patients harboring HIV subtype A, C and D. Methods Samples were obtained from patients who were failing on an NRTI based regimen. Sanger based sequencing was performed as part of the standard of care. Mutation analysis was performed using the Stanford HIV drug Resistance database. A subset of these patient samples was further analyzed using the Next Generation Sequencing (NGS) technology and analysis of the drug resistance mutations was performed at the 20% and 1% cut off Results Analysis of the Non-nucleoside reverse transcriptase inhibitor (NNRTI) coding region revealed that the K101 and the Y181 mutations were more predominant among subtype C than subtype A and D. Although Thymidine analog mutations (TAMs) were prevalent in all subtypes, our analyses showed that these mutations occurred in significantly less proportions among subtype C infections when compared with the subtype A and D counterparts. Furthermore, the Q151M mutation complex which involves mutations in multiple domains was significantly more prominent among patients harboring subtype C variants. Analysis using NGS revealed that minority drug resistant mutations that confer multi-drug resistance (MDR) were present even in patients who exhibited a susceptible genotype based on the Sanger sequencing technique. Conclusion Although HIV-1 MDR variants occur in all subtypes, their predominance is subtype specific with TAMs being significantly more predominant among subtype A and D while the Q151M complex being significantly more predominant among patients harboring subtype C viruses. Even in patients with a susceptible genotype based on Sanger technology, minority variants are present and their evolution to full blown MDR occurs over time such that by the time they are detectable, cross resistance to other drugs has occurred in some cases.

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