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High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment.

ABSTRACT: OBJECTIVES:HIV-1 integrase inhibitors are recommended as first-line therapy by WHO, though efficacy and resistance data for non-B subtypes are limited. Two recent trials have identified the integrase L74I mutation to be associated with integrase inhibitor treatment failure in HIV-1 non-B subtypes. We sought to define the prevalence of integrase resistance mutations, including L74I, in West Africa. METHODS:We studied a Nigerian cohort of recipients prior to and during receipt of second-line PI-based therapy, who were integrase inhibitor-naive. Illumina next-generation sequencing with target enrichment was used on stored plasma samples. Drug resistance was interpreted using the Stanford Resistance Database and the IAS-USA 2019 mutation lists. RESULTS:Of 115 individuals, 59.1% harboured CRF02_AG HIV-1 and 40.9% harboured subtype G HIV-1. Four participants had major IAS-USA integrase resistance-associated mutations detected at low levels (2%-5% frequency). Two had Q148K minority variants and two had R263K (one of whom also had L74I). L74I was detected in plasma samples at over 2% frequency in 40% (46/115). Twelve (26.1%) had low-level minority variants of between 2% and 20% of the viral population sampled. The remaining 34 (73.9%) had L74I present at >20% frequency. L74I was more common among those with subtype G infection (55.3%, 26/47) than those with CRF02_AG infection (29.4%, 20/68) (P?=?0.005). CONCLUSIONS:HIV-1 subtypes circulating in West Africa appear to have very low prevalence of major integrase mutations, but significant prevalence of L74I. A combination of in vitro and clinical studies is warranted to understand the potential implications.

SUBMITTER: El Bouzidi K

PROVIDER: S-EPMC7225870 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment.

El Bouzidi Kate K Kemp Steven A SA Datir Rawlings P RP Murtala-Ibrahim Fati F Aliyu Ahmad A Kwaghe Vivian V Frampton Dan D Roy Sunando S Breuer Judith J Sabin Caroline A CA Ogbanufe Obinna O Charurat Man E ME Bonsall David D Golubchik Tanya T Fraser Christophe C Dakum Patrick P Ndembi Nicaise N Gupta Ravindra K RK

The Journal of antimicrobial chemotherapy 20200601 6

<h4>Objectives</h4>HIV-1 integrase inhibitors are recommended as first-line therapy by WHO, though efficacy and resistance data for non-B subtypes are limited. Two recent trials have identified the integrase L74I mutation to be associated with integrase inhibitor treatment failure in HIV-1 non-B subtypes. We sought to define the prevalence of integrase resistance mutations, including L74I, in West Africa.<h4>Methods</h4>We studied a Nigerian cohort of recipients prior to and during receipt of se ...[more]

PMID: 32105319

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Project description:Although physical function decline is common with aging, the burden of this impairment remains underestimated in patients living with HIV (PLHIV), particularly in the older people receiving antiretroviral treatment (ART) and living in sub-Saharan Africa (SSA). PLHIV aged ≥50 years old and on ART since ≥6 months were included (N = 333) from three clinics (two in Côte d'Ivoire, one in Senegal) participating in the International epidemiological Databases to Evaluate AIDS (IeDEA) West Africa collaboration. Physical function was measured using the Short Physical Performance Battery (SPPB), the unipodal balance test and self-reported questionnaires. Grip strength was also assessed. Logistic regression was used to identify the factors associated with SPPB performance specifically. Median age was 57 (54-61) years, 57.7% were female and 82.7% had an undetectable viral load. The mean SPPB score was 10.2 ±1.8. Almost 30% had low SPPB performance with the 5-sit-to-stand test being the most altered subtest (64%). PLHIV with low SPPB performance also had significantly low performance on the unipodal balance test (54.2%, p = 0.001) and low mean grip strength (but only in men (p = 0.005)). They also showed some difficulties in daily life activities (climbing stairs, walking one block, both p<0.0001). Age ≥60 years (adjusted OR (aOR) = 3.4; CI95% = 1.9-5.9,), being a female (aOR = 2.1; CI95% = 1.1-4.1), having an abdominal obesity (aOR = 2.1; CI95% = 1.2-4.0), a longer duration of HIV infection (aOR = 2.9; CI95% = 1.5-5.7), old Nucleoside reverse transcriptase inhibitors (NRTIs) (i.e., AZT: zidovudine, ddI: didanosine, DDC: zalcitabine, D4T: stavudine) in current ART (aOR = 2.0 CI95% = 1.1-3.7) were associated with low SPPB performance. As in western countries, physical function limitation is now part of the burden of HIV disease complications of older PLHIV living in West Africa, putting this population at risk for disability. How to screen those impairments and integrate their management in the standards of care should be investigated, and specific research on developing adapted daily physical activity program might be conducted.

Dataset Information

High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment.

Publications

High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment.

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