Dataset Information

Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria.

ABSTRACT:

Background

Deep sequencing could improve understanding of HIV treatment failure and viral population dynamics. However, this tool is often inaccessible in low- and middle-income countries.

Objectives

To determine the genetic patterns of resistance emerging in West African HIV-1 subtypes during first-line virological failure, and the implications for future antiretroviral options.

Patients and methods

Participants were selected from a Nigerian cohort of people living with HIV who had failed first-line ART and subsequently switched to second-line therapy. Whole HIV-1 genome sequences were generated from first-line virological failure samples with Illumina MiSeq. Mutations detected at ≥2% frequency were analysed and compared by subtype.

Results

HIV-1 sequences were obtained from 101 participants (65% female, median age 30 years, median 32.9 months of nevirapine- or efavirenz-based ART). Thymidine analogue mutations (TAMs) were detected in 61%, other core NRTI mutations in 92% and NNRTI mutations in 99%. Minority variants (<20% frequency) comprised 18% of all mutations. K65R was more prevalent in CRF02_AG than G subtypes (33% versus 7%; P = 0.002), and ≥3 TAMs were more common in G than CRF02_AG (52% versus 24%; P = 0.004). Subtype G viruses also contained more RT cleavage site mutations. Cross-resistance to at least one of the newer NNRTIs, doravirine, etravirine or rilpivirine, was predicted in 81% of participants.

Conclusions

Extensive drug resistance had accumulated in people with West African HIV-1 subtypes, prior to second-line ART. Deep sequencing significantly increased the detection of resistance-associated mutations. Caution should be used if considering newer-generation NNRTI agents in this setting.

SUBMITTER: El Bouzidi K

PROVIDER: S-EPMC8809188 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria.

El Bouzidi Kate K Datir Rawlings P RP Kwaghe Vivian V Roy Sunando S Frampton Dan D Breuer Judith J Ogbanufe Obinna O Murtala-Ibrahim Fati F Charurat Man M Dakum Patrick P Sabin Caroline A CA Ndembi Nicaise N Gupta Ravindra K RK

The Journal of antimicrobial chemotherapy 20220201 2

<h4>Background</h4>Deep sequencing could improve understanding of HIV treatment failure and viral population dynamics. However, this tool is often inaccessible in low- and middle-income countries.<h4>Objectives</h4>To determine the genetic patterns of resistance emerging in West African HIV-1 subtypes during first-line virological failure, and the implications for future antiretroviral options.<h4>Patients and methods</h4>Participants were selected from a Nigerian cohort of people living with HI ...[more]

PMID: 34741609

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Project description:ObjectiveThis study described the demographics, treatment information and identified characteristics associated with virological failure and being lost to follow-up (LTFU) for patients with HIV on first-line and second-line antiretroviral therapy (ART) regimens in a large South African cohort.DesignA quantitative retrospective cohort study using secondary data analysis.SettingSeven Johannesburg inner city facilities.ParticipantsUnique records of 123 002 people with HIV receiving ART at any point in the period 1 April 2004 to 29 February 2020 were included.MeasuresDemographic characteristics, ART status, CD4 count information and retention status were collected and analysed as covariates of outcomes (viral load (VL) and LTFU).ResultsOf the total study patients, 95% (n=1 17 260) were on a first-line regimen and 5% (n=5742) were on a second-line regimen. Almost two-thirds were female (64%, n=79 226). Most patients (60%, n=72 430) were initiated on an efavirenz-based, tenofovir disoproxil fumarate-based and emtricitabine-based regimen (fixed-dose combination). 91% (n=76 737) achieved viral suppression at least once since initiating on ART and 60% (n=57 981) remained in care as at the end of February 2020. Patients from the community health centre and primary healthcare clinics were not only more likely to be virally suppressed but also more likely to be LTFU. Patients on second-line regimens were less likely to reach viral suppression (adjusted OR (aOR)=0.26, CI=0.23 to 0.28) and more likely to be LTFU (aOR=1.21, CI=1.09 to 1.35). Being older (≥25 years) and having a recent CD4 cell count≥100 cells/µL were predictors of viral suppression and retention in patients on ART.ConclusionPatients on first-line regimens had higher VL suppression rates and were more likely to remain in care than those on a second-line regimen. Being younger and having low CD4 cell counts were associated with poor outcomes, suggesting priority groups for ART adherence support.

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Dataset Information

Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria.

Background

Objectives

Patients and methods

Results

Conclusions

Publications

Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria.

Similar Datasets

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