Low rates of nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor drug resistance in Botswana

Abstract Background Increased access to antiretroviral therapy (ART) has resulted in rising levels of pretreatment human immunodeficiency virus drug resistance (PDR). This is the first systematic review and meta-analysis to assess the impact of PDR on treatment outcomes among people initiating nonnucleoside reverse transcriptase inhibitor (NNRTI)–based ART, including the combination of efavirenz (EFV), tenofovir (TDF), and lamivudine or emtricitabine (XTC). Methods We systematically reviewed studies and conference proceedings comparing treatment outcomes in populations initiating NNRTI-based ART with and without PDR. We conducted subgroup analyses by regimen: (1) NNRTIs + 2 nucleoside reverse transcriptase inhibitors (NRTIs), (2) EFV + 2 NRTIs, or (3) EFV/TDF/XTC; by population (children vs adults); and by definition of resistance (PDR vs NNRTI PDR). Results Among 6197 studies screened, 32 were analyzed (31 441 patients). We found that individuals with PDR initiating NNRTIs across all the subgroups had increased risk of virological failure compared to those without PDR. Risk of acquisition of new resistance mutations and ART switch was also higher in people with PDR. Conclusions This review shows poorer treatment outcomes in the presence of PDR, supporting the World Health Organization’s recommendation to avoid using NNRTIs in countries where levels of PDR are high.

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Moderate Levels of Pretreatment HIV Drug Resistance — Zimbabwe, April–July 2015

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.1069 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S424-S424

Author(s):

Juliana Da Silva ◽

Janet Dzangare ◽

Elizabeth Gonese ◽

Mutsa Mhangara ◽

Owen Mugurungi ◽

...

Keyword(s):

Drug Resistance ◽

Antiretroviral Therapy ◽

Reverse Transcriptase ◽

Nucleoside Reverse Transcriptase Inhibitor ◽

Transcriptase Inhibitor ◽

World Health ◽

First Line ◽

Cross Sectional ◽

Hiv Drug Resistance ◽

Reverse Transcriptase Inhibitor

Abstract Background The World Health Organization (WHO) HIV Drug Resistance (HIVDR) report 2012 demonstrated that the levels of HIVDR to first-line antiretroviral therapy (ART) are increasing. This finding threatens to reverse a decade of gains in HIV/AIDS epidemic control. The WHO Global Action Plan for HIVDR emphasizes strengthening surveillance of drug resistance through the implementation of national cross-sectional surveys. We conducted such survey to determine the prevalence of HIVDR among ART-naive patients in Zimbabwe and to describe the profile of the surveillance drug resistance mutations (SDRM) encountered in the country. Methods A prospective, nationally representative, cross-sectional survey was conducted in 35 clinical sites selected using two stage probability proportional to size sampling. Patients were enrolled during April–July 2015. Specimens were sent for genotyping to CDC Atlanta. SDRM were interpreted using Stanford HIV Drug Resistance Database classification. Results A total of 361 subjects were surveyed. Most participants were female (60.3%) and the median age was 35.8 years. Thirty-four out of 361subjects presented with ≥1 SDRM (9.4%, 95% confidence interval: 6.8–12.8%) prior to initiation antiretroviral therapy (ART). Non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations were the most commonly detected mutation (n = 30). Only two patients presented with a nucleoside reverse transcriptase inhibitor mutation and one patient presented with a protease inhibitor mutation. In two patients, ≥3 SDRMs were detected, which may suggest they were not truly ART-naïve. Conclusion This study provides national estimates of HIVDR in a high burden country with broad access to ART and provides valuable inisight on the state of HIVDR in such setting. Zimbabwe has reached moderate levels of HIVDR in ART-naive patients, as specified by the WHO classification. These levels may impact the ability to achieve viral suppression in a significant number of patients initiating standard ART regimens in Zimbabwe, where NNRTI-based regimens are used as the first line. The use of drugs with high resistance barrier, such as dolutegravir, may improve the care of patients in the developing world, where individualized pretreatment genotype is not feasible. Disclosures All authors: No reported disclosures.

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Molecular Epidemiology of HIV-1 Infected Migrants Followed Up in Portugal: Trends between 2001–2017

Viruses ◽

10.3390/v12030268 ◽

2020 ◽

Vol 12 (3) ◽

pp. 268 ◽

Cited By ~ 2

Author(s):

Victor Pimentel ◽

Marta Pingarilho ◽

Daniela Alves ◽

Isabel Diogo ◽

Sandra Fernandes ◽

...

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Molecular Epidemiology ◽

Nucleoside Reverse Transcriptase Inhibitor ◽

Country Of Origin ◽

Transcriptase Inhibitor ◽

Subtype B ◽

Reverse Transcriptase Inhibitor ◽

Hiv 1 ◽

Over Time

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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Drugs in traditional drug classes (nucleoside reverse transcriptase inhibitor/nonnucleoside reverse transcriptase inhibitor/protease inhibitors) with activity against drug-resistant virus (tipranavir, darunavir, etravirine)

Current Opinion in HIV and AIDS ◽

10.1097/coh.0b013e328331b911 ◽

2009 ◽

Vol 4 (6) ◽

pp. 507-512 ◽

Cited By ~ 8

Author(s):

Jose R Arribas

Keyword(s):

Reverse Transcriptase ◽

Nucleoside Reverse Transcriptase Inhibitor ◽

Transcriptase Inhibitor ◽

Drug Resistant ◽

Resistant Virus ◽

Nonnucleoside Reverse Transcriptase Inhibitor ◽

Drug Classes ◽

Traditional Drug ◽

Reverse Transcriptase Inhibitor ◽

Drug Resistant Virus

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HIV-1 drug resistance mutations in children after failure of first-line nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy

HIV Medicine ◽

10.1111/j.1468-1293.2010.00828.x ◽

2010 ◽

Vol 11 (9) ◽

pp. 565-572 ◽

Cited By ~ 19

Author(s):

T Puthanakit ◽

G Jourdain ◽

S Hongsiriwon ◽

P Suntarattiwong ◽

K Chokephaibulkit ◽

...

Keyword(s):

Drug Resistance ◽

Antiretroviral Therapy ◽

Reverse Transcriptase ◽

Transcriptase Inhibitor ◽

Resistance Mutations ◽

First Line ◽

Drug Resistance Mutations ◽

Nonnucleoside Reverse Transcriptase Inhibitor ◽

Reverse Transcriptase Inhibitor ◽

Hiv 1

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Triple nucleoside reverse transcriptase inhibitor- vs. nonnucleoside reverse transcriptase inhibitor-containing regimens as first-line therapy: efficacy and durability in a prospective cohort of French HIV-infected patients

HIV Medicine ◽

10.1111/j.1468-1293.2005.00315.x ◽

2005 ◽

Vol 6 (6) ◽

pp. 388-395 ◽

Cited By ~ 3

Author(s):

L Cuzin ◽

P Pugliese ◽

F Bugnon ◽

C Delpierre ◽

E Cua ◽

...

Keyword(s):

Reverse Transcriptase ◽

Prospective Cohort ◽

Nucleoside Reverse Transcriptase Inhibitor ◽

Transcriptase Inhibitor ◽

First Line ◽

Therapy Efficacy ◽

First Line Therapy ◽

Nonnucleoside Reverse Transcriptase Inhibitor ◽

Line Therapy ◽

Reverse Transcriptase Inhibitor

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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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Development of HIV drug resistance in a cohort of adults on first-line antiretroviral therapy in Tanzania during the stavudine era

10.21203/rs.3.rs-110477/v1 ◽

2020 ◽

Author(s):

Raphael Z Sangeda ◽

Perpétua Gómes ◽

Soo-Yon Rhee ◽

Fausta Mosha ◽

Ricardo J. Camacho ◽

...

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Nucleoside Reverse Transcriptase Inhibitor ◽

Transcriptase Inhibitor ◽

Resistance Mutations ◽

First Line ◽

Nnrti Resistance ◽

One Year ◽

Reverse Transcriptase Inhibitor

Abstract As more HIV patients start combination antiretroviral therapy (cART), the emergence of HIV drug resistance (HIVDR) is inevitable. This will have consequences for the transmission of HIVDR, the success of ART, and the nature and trend of the epidemic. We recruited a cohort of 223 patients starting or continuing their first-line cART in Tanzania during the stavudine era in 2010. Patients were then followed up for one year. From those with a viral load test at baseline and follow-up time, 34% were failing virologically at the one-year endpoint. From 41 patients, protease and reverse transcriptase genotyping were successful. Eighteen samples were from therapy-naïve patients and 23 samples were taken under therapy either baseline for patients already under cART at study entry, or follow-up sample. The isolates were mostly subtype A, followed by C and D at 41.5%, 22% and 12.2% of the patients, respectively. No transmitted HIVDR was detected, as scored using the surveillance drug resistance mutations (DRMs) list. However, in 3 of the 18 samples from therapy-naïve patients, the clinical Rega interpretation algorithm scored 44D or 138A as non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated polymorphisms. The most observed nucleoside reverse transcriptase inhibitor (NRTI) mutation was 184V. The mutation was found in 16 patients causing resistance to lamivudine and emtricitabine. Nineteen patients had NNRTI resistance mutations, the most common of which was 103N observed in 8 patients. These high levels of resistance calls for regular drug resistance surveillance in Tanzania to control the emergence and transmission of HIVDR.

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