Dataset Information

Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya.

ABSTRACT:

Introduction

in Kenya, about 1.5 million people are living with the Human Immunodeficiency Virus (HIV). Antiretroviral therapy aids in viral suppression. However, drug-resistance threaten the gains of the HIV infection control program. To determine the prevalence of HIV-1 drug-resistant mutations among adults on ARV therapy attending Khunyangu sub-county hospital in Busia County, Kenya, 50 blood samples were analyzed.

Methods

the samples were collected from November 2019 to January 2020 and tested for HIV-1 viral load. HIV-1 drug-resistance was analyzed through the sequencing of the HIV-1 pol gene. Generated sequences were aligned using RECall (beta v3.05) software. HIV-1 drug-resistance was determined using the Stanford University HIV database.

Results

females were 34 and males 16. The general prevalence of HIV-1 drug-resistance was 68%. Out of 34 participants on first-line drugs, 59.9% had mutations against these drugs and 5.9% against the second-line drugs. Out of 16 participants on second-line drugs, 43.8% had mutations against these drugs and 50% against the first-line drugs. The prevalence of mutations encoding resistance to Nucleotide reverse transcriptase inhibitors (NRTIs) were 23(46%); Non-nucleotide Reverse transcriptase inhibitors (NNRTIs), 29(58%) and protease inhibitors (PIs), 7(14%). Dual and multi-class HIV-1 drug-resistance prevalence was as follows: NRTIs + NNRTIs 16(32%); NRTIs + NNRTs + PIs 4(8%); NRTIs + PIs 1(2%). A total of 126 mutations were identified. Predominant NNRTIs mutations were K103N (15), Y181C (9), G190A (7), and H221Y (6) NRTIs, M184V (17), Y115F (5) and PIs, I54V (4).

Conclusion

the study demonstrates a high prevalence of HIV-1 drug-resistance which calls for intervention for the strengthening of health programs.

SUBMITTER: Makwaga O

PROVIDER: S-EPMC7896523 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya.

Makwaga Olipher O Adhiambo Maureen M Mulama David Hughes DH Muoma John J Adungo Ferdinard F Wanjiku Humphrey H Ongaya Asiko A Maitha Geoffrey Mutisya GM Mwau Matilu M

The Pan African medical journal 20201203

<h4>Introduction</h4>in Kenya, about 1.5 million people are living with the Human Immunodeficiency Virus (HIV). Antiretroviral therapy aids in viral suppression. However, drug-resistance threaten the gains of the HIV infection control program. To determine the prevalence of HIV-1 drug-resistant mutations among adults on ARV therapy attending Khunyangu sub-county hospital in Busia County, Kenya, 50 blood samples were analyzed.<h4>Methods</h4>the samples were collected from November 2019 to Januar ...[more]

PMID: 33654530

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Project description:BACKGROUND:For second-line antiretroviral therapy, WHO recommends a boosted protease inhibitor plus nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs). However, concerns about toxicity and cross-resistance motivated a search for regimens that do not contain NRTIs. We aimed to assess whether boosted lopinavir plus raltegravir would be non-inferior to boosted lopinavir plus NRTIs for virological suppression in resource-limited settings. METHODS:A5273 was a randomised, open-label, phase 3, non-inferiority study at 15 AIDS Clinical Trials Group (ACTG) research sites in nine resource-limited countries (three sites each in India and South Africa, two each in Malawi and Peru, and one each in Brazil, Kenya, Tanzania, Thailand, and Zimbabwe). Adults with plasma HIV-1 RNA concentrations of at least 1000 copies per mL after at least 24 weeks on a regimen based on a non-NRTI inhibitor were randomly assigned (1:1) to receive oral ritonavir-boosted lopinavir (100 mg ritonavir, 400 mg lopinavir) plus 400 mg raltegravir twice a day (raltegravir group) or to ritonavir-boosted lopinavir plus two or three NRTIs selected from an algorithm (eg, zidovudine after failure with tenofovir and vice versa; NRTI group). Randomised group assignment was done with a computer algorithm concealed to site personnel, and stratified by HIV-1 RNA viral load, CD4 cell count, and intention to use zidovudine, with the groups balanced by each site. The primary endpoint was time to confirmed virological failure (two measurements of HIV-1 RNA viral load >400 copies per mL) at or after week 24 in the intention-to-treat population. Non-inferiority (10% margin) was assessed by comparing the cumulative probability of virological failure by 48 weeks. This trial was registered with ClinicalTrials.gov, NCT01352715. FINDINGS:Between March 13, 2012, and Oct 2, 2013, we randomly assigned 515 participants: 260 to the raltegravir group and 255 to the NRTI group; two participants in the raltegravir group and one in the NRTI group were excluded from analyses because of ineligibility. By the end of follow-up (October, 2014), 96 participants had virological failure (46 in the raltegravir group and 50 in the NRTI group). By 48 weeks, the cumulative probability of virological failure was 10·3% (95% CI 6·5-14·0) in the raltegravir group and 12·4% (8·3-16·5) in the NRTI group, with a weighted difference of -3·4% (-8·4 to 1·5), indicating that raltegravir was non-inferior, but not superior, to NRTIs. 62 (24%) participants in the raltegravir group and 81 (32%) in the NRTI group had grade 3 or higher adverse events; 19 (7%) and 29 (11%), respectively, had serious adverse events. Three participants in each group died, all from HIV-related causes. INTERPRETATION:In settings with extensive NRTI resistance but no available resistance testing, our data support WHO's recommendation for ritonavir-boosted lopinavir plus NRTI for second-line antiretroviral therapy. Ritonavir-boosted lopinavir plus raltegravir is an appropriate alternative, especially if NRTI use is limited by toxicity. FUNDING:National Institutes of Health.

Project description:ObjectiveTo evaluate associations between hair antiretroviral hair concentrations as an objective, cumulative adherence metric, with self-reported adherence and virologic outcomes.DesignAnalysis of cohort A of the ACTG-A5288 study. These patients in resource-limited settings were failing second-line protease inhibitor-based antiretroviral therapy (ART) but were susceptible to at least one nucleoside reverse transcriptase inhibitor (NRTI) and their protease inhibitor, and continued taking their protease inhibitor-based regimen.MethodsAntiretroviral hair concentrations in participants taking two NRTIs with boosted atazanavir (n = 69) or lopinavir (n = 112) were analyzed at weeks 12, 24, 36 and 48 using liquid-chromatography--tandem-mass-spectrometry assays. Participants' self-reported percentage of doses taken in the previous month; virologic failure was confirmed HIV-1 RNA at least 1000 copies/ml at week 24 or 48.ResultsFrom 181 participants with hair samples (61% women, median age: 39 years; CD4+ cell count: 167 cells/μl; HIV-1 RNA: 18 648 copies/ml), 91 (50%) experienced virologic failure at either visit. At 24 weeks, median hair concentrations were 2.95 [interquartile range (IQR) 0.49-4.60] ng/mg for atazanavir, 2.64 (IQR 0.73--7.16) for lopinavir, and 0.44 (IQR 0.11--0.76) for ritonavir. Plasma HIV-1 RNA demonstrated inverse correlations with hair levels (rs -0.46 to -0.74) at weeks 24 and 48. Weaker associations were seen with self-reported adherence (rs -0.03 to -0.24). Decreasing hair concentrations were significantly associated with virologic failure, the hazard ratio (95% CI) for ATV, LPV, and RTV were 0.69 (0.56-0.86), 0.77 (0.68-0.87), and 0.12 (0.06-0.27), respectively.ConclusionProtease inhibitor hair concentrations showed stronger associations with subsequent virologic outcomes than self-reported adherence in this cohort. Hair adherence measures could identify individuals at risk of second-line treatment failure in need of interventions.

Project description:BackgroundThe results of international clinical trials that are assessing when to initiate antiretroviral therapy (ART) will not be available for several years.ObjectiveTo inform HIV treatment decisions about the optimal CD4 threshold at which to initiate ART in South Africa while awaiting the results of these trials.DesignCost-effectiveness analysis by using a computer simulation model of HIV disease.Data sourcesPublished data from randomized trials and observational cohorts in South Africa.Target populationHIV-infected patients in South Africa.Time horizon5-year and lifetime.PerspectiveModified societal.InterventionNo treatment, ART initiated at a CD4 count less than 0.250 x 10(9) cells/L, and ART initiated at a CD4 count less than 0.350 x 10(9) cells/L.Outcome measuresMorbidity, mortality, life expectancy, medical costs, and cost-effectiveness.Results of base-case analysisIf 10% to 100% of HIV-infected patients are identified and linked to care, a CD4 count threshold for ART initiation of 0.350 x 10(9) cells/L would reduce severe opportunistic diseases by 22,000 to 221,000 and deaths by 25,000 to 253,000 during the next 5 years compared with ART initiation at 0.250 x 10(9) cells/L; cost increases would range from $142 million (10%) to $1.4 billion (100%). Either ART initiation strategy would increase long-term survival by at least 7.9 years, with a mean per-person life expectancy of 3.8 years with no ART and 12.5 years with an initiation threshold of 0.350 x 10(9) cells/L. Compared with an initiation threshold of 0.250 x 10(9) cells/L, a threshold of 0.350 x 10(9) cells/L has an incremental cost-effectiveness ratio of $1200 per year of life saved.Results of sensitivity analysisInitiating ART at a CD4 count less than 0.350 x 10(9) cells/L would remain cost-effective over the next 5 years even if the probability that the trial would demonstrate the superiority of earlier therapy is as low as 17%.LimitationThis model does not consider the possible benefits of initiating ART at a CD4 count greater than 0.350 x 10(9) cells/L or of reduced HIV transmission.ConclusionEarlier initiation of ART in South Africa will probably reduce morbidity and mortality, improve long-term survival, and be cost-effective. While awaiting trial results, treatment guidelines should be liberalized to allow initiation at CD4 counts less than 0.350 x 10(9) cells/L, earlier than is currently recommended.Primary funding sourceNational Institute of Allergy and Infectious Diseases and the Doris Duke Charitable Foundation.

Dataset Information

Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya.

Introduction

Methods

Results

Conclusion

Publications

Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya.

Similar Datasets

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