Low rates of nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor drug resistance in Botswana.
Adolescent
Adult
Anti-HIV Agents
/ pharmacology
Botswana
Drug Resistance, Viral
Female
Gene Frequency
Genotype
Genotyping Techniques
HIV Infections
/ virology
HIV Reverse Transcriptase
/ genetics
HIV-1
/ genetics
Humans
Male
Middle Aged
Mutation
Nucleosides
/ pharmacology
Prevalence
Reverse Transcriptase Inhibitors
/ pharmacology
Young Adult
Journal
AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219
Informations de publication
Date de publication:
01 05 2019
01 05 2019
Historique:
entrez:
5
4
2019
pubmed:
5
4
2019
medline:
5
6
2020
Statut:
ppublish
Résumé
Scale-up of antiretroviral therapy (ART) and introduction of treat-all strategy necessitates population-level monitoring of acquired HIV drug resistance (ADR) and pretreatment drug resistance (PDR) mutations. Blood samples were collected from 4973 HIV-positive individuals residing in 30 communities across Botswana who participated in the Botswana Combination Prevention Project (BCPP) in 2013-2018. HIV sequences were obtained by long-range HIV genotyping. Major drug-resistance mutations (DRMs) and surveillance drug resistance mutations (SDRMs) associated with nucleoside reverse transcriptase inhibitors (NRTI) and nonnucleoside reverse transcriptase inhibitors (NNRTI) were analyzed according to the Stanford University HIV Drug Resistance Database. Viral sequences were screened for G-to-A hypermutations. A threshold of 2% was used for hypermutation adjustment. Viral suppression was considered at HIV-1 RNA load ≤400 copies/ml. Among 4973 participants with HIV-1C sequences, ART data were available for 4927 (99%) including 3858 (78%) on ART. Among those on ART, 3435 had viral load data and 3297 (96%) were virologically suppressed. Among 1069 (22%) HIV-infected individuals not on ART, we found NRTI-associated and NNRTI-associated SDRMs were found in 1.5% (95% confidence interval [CI] 1.0-2.5%) and 2.9% (95% CI 2.0-4.2%), respectively. Of the 138 (4%) of individuals who had detectable HIV-1 RNA, we found NRTI-associated and NNRTI-associated drug resistance mutations in 16% (95% CI 10-25%) and 33% (95% CI 25-42%), respectively. We found a low prevalence of NRTI-associated and NNRTI-associated PDR-resistance mutations among residents of rural and peri-urban communities across Botswana. However, individuals on ART with detectable virus had ADR NRTI and NNRTI mutations above 15%.
Sections du résumé
BACKGROUND
Scale-up of antiretroviral therapy (ART) and introduction of treat-all strategy necessitates population-level monitoring of acquired HIV drug resistance (ADR) and pretreatment drug resistance (PDR) mutations.
METHODS
Blood samples were collected from 4973 HIV-positive individuals residing in 30 communities across Botswana who participated in the Botswana Combination Prevention Project (BCPP) in 2013-2018. HIV sequences were obtained by long-range HIV genotyping. Major drug-resistance mutations (DRMs) and surveillance drug resistance mutations (SDRMs) associated with nucleoside reverse transcriptase inhibitors (NRTI) and nonnucleoside reverse transcriptase inhibitors (NNRTI) were analyzed according to the Stanford University HIV Drug Resistance Database. Viral sequences were screened for G-to-A hypermutations. A threshold of 2% was used for hypermutation adjustment. Viral suppression was considered at HIV-1 RNA load ≤400 copies/ml.
RESULTS
Among 4973 participants with HIV-1C sequences, ART data were available for 4927 (99%) including 3858 (78%) on ART. Among those on ART, 3435 had viral load data and 3297 (96%) were virologically suppressed. Among 1069 (22%) HIV-infected individuals not on ART, we found NRTI-associated and NNRTI-associated SDRMs were found in 1.5% (95% confidence interval [CI] 1.0-2.5%) and 2.9% (95% CI 2.0-4.2%), respectively. Of the 138 (4%) of individuals who had detectable HIV-1 RNA, we found NRTI-associated and NNRTI-associated drug resistance mutations in 16% (95% CI 10-25%) and 33% (95% CI 25-42%), respectively.
CONCLUSION
We found a low prevalence of NRTI-associated and NNRTI-associated PDR-resistance mutations among residents of rural and peri-urban communities across Botswana. However, individuals on ART with detectable virus had ADR NRTI and NNRTI mutations above 15%.
Identifiants
pubmed: 30946161
doi: 10.1097/QAD.0000000000002166
pii: 00002030-201905010-00015
pmc: PMC6467559
doi:
Substances chimiques
Anti-HIV Agents
0
Nucleosides
0
Reverse Transcriptase Inhibitors
0
reverse transcriptase, Human immunodeficiency virus 1
EC 2.7.7.-
HIV Reverse Transcriptase
EC 2.7.7.49
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1073-1082Subventions
Organisme : CGH CDC HHS
ID : U01 GH000447
Pays : United States
Organisme : NIAID NIH HHS
ID : K24 AI131928
Pays : United States
Organisme : FIC NIH HHS
ID : D43 TW010543
Pays : United States
Organisme : FIC NIH HHS
ID : D43 TW009610
Pays : United States
Organisme : Wellcome Trus
ID : 107752/Z/15/Z
Pays : International
Organisme : PEPFAR
Pays : United States
Organisme : CGH CDC HHS
ID : U2G GH001911
Pays : United States
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