Emerging integrase strand transfer inhibitor drug resistance mutations among children and adults on ART in Tanzania: findings from a national representative HIV drug resistance survey.


Journal

The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617

Informations de publication

Date de publication:
02 03 2023
Historique:
received: 13 07 2022
accepted: 03 01 2023
pubmed: 22 1 2023
medline: 4 3 2023
entrez: 21 1 2023
Statut: ppublish

Résumé

Despite the scale-up of ART and the rollout in Tanzania of dolutegravir, an integrase strand transfer inhibitor (INSTI), treatment success has not been fully realized. HIV drug resistance (HIVDR), including dolutegravir resistance, could be implicated in the notable suboptimal viral load (VL) suppression among HIV patients. To determine the prevalence and patterns of acquired drug resistance mutations (DRMs) among children and adults in Tanzania. A national cross-sectional HIVDR survey was conducted among 866 children and 1173 adults. Genotyping was done on dried blood spot and/or plasma of participants with high HIV VL (≥1000 copies/mL). HIV genes (reverse transcriptase, protease and integrase) were amplified by PCR and directly sequenced. The Stanford HIVDR Database was used for HIVDR interpretation. HIVDR genotyping was performed on blood samples from 137 participants (92 children and 45 adults) with VL ≥ 1000 copies/mL. The overall prevalence of HIV DRMs was 71.5%, with DRMs present in 78.3% of children and 57.8% of adults. Importantly, 5.8% of participants had INSTI DRMs including major DRMs: Q148K, E138K, G118R, G140A, T66A and R263K. NNRTI, NRTI and PI DRMs were also detected in 62.8%, 44.5% and 8% of participants, respectively. All the participants with major INSTI DRMs harboured DRMs targeting NRTI backbone drugs. More than 7 in 10 patients with high HIV viraemia in Tanzania have DRMs. The early emergence of dolutegravir resistance is of concern for the efficacy of the Tanzanian ART programme.

Sections du résumé

BACKGROUND
Despite the scale-up of ART and the rollout in Tanzania of dolutegravir, an integrase strand transfer inhibitor (INSTI), treatment success has not been fully realized. HIV drug resistance (HIVDR), including dolutegravir resistance, could be implicated in the notable suboptimal viral load (VL) suppression among HIV patients.
OBJECTIVES
To determine the prevalence and patterns of acquired drug resistance mutations (DRMs) among children and adults in Tanzania.
METHODS
A national cross-sectional HIVDR survey was conducted among 866 children and 1173 adults. Genotyping was done on dried blood spot and/or plasma of participants with high HIV VL (≥1000 copies/mL). HIV genes (reverse transcriptase, protease and integrase) were amplified by PCR and directly sequenced. The Stanford HIVDR Database was used for HIVDR interpretation.
RESULTS
HIVDR genotyping was performed on blood samples from 137 participants (92 children and 45 adults) with VL ≥ 1000 copies/mL. The overall prevalence of HIV DRMs was 71.5%, with DRMs present in 78.3% of children and 57.8% of adults. Importantly, 5.8% of participants had INSTI DRMs including major DRMs: Q148K, E138K, G118R, G140A, T66A and R263K. NNRTI, NRTI and PI DRMs were also detected in 62.8%, 44.5% and 8% of participants, respectively. All the participants with major INSTI DRMs harboured DRMs targeting NRTI backbone drugs.
CONCLUSIONS
More than 7 in 10 patients with high HIV viraemia in Tanzania have DRMs. The early emergence of dolutegravir resistance is of concern for the efficacy of the Tanzanian ART programme.

Identifiants

pubmed: 36680436
pii: 6995278
doi: 10.1093/jac/dkad010
doi:

Substances chimiques

Anti-HIV Agents 0
Integrases EC 2.7.7.-
HIV Integrase EC 2.7.7.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

779-787

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Auteurs

Doreen Kamori (D)

Muhimbili University of Health and Allied Sciences, P.O. Box 650001, Dar es Salaam, Tanzania.

Godfrey Barabona (G)

Muhimbili University of Health and Allied Sciences, P.O. Box 650001, Dar es Salaam, Tanzania.
Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.

Joan Rugemalila (J)

Internal Medicine Department, Muhimbili National Hospital, Dar es Salaam, Tanzania.

Werner Maokola (W)

National AIDS Control Programme, Directorate of Preventive Services, Ministry of Health, Dodoma, Tanzania.

Salim S Masoud (SS)

Muhimbili University of Health and Allied Sciences, P.O. Box 650001, Dar es Salaam, Tanzania.

Mucho Mizinduko (M)

Muhimbili University of Health and Allied Sciences, P.O. Box 650001, Dar es Salaam, Tanzania.

Amon Sabasaba (A)

Muhimbili University of Health and Allied Sciences, P.O. Box 650001, Dar es Salaam, Tanzania.

George Ruhago (G)

Muhimbili University of Health and Allied Sciences, P.O. Box 650001, Dar es Salaam, Tanzania.

Veryeh Sambu (V)

National AIDS Control Programme, Directorate of Preventive Services, Ministry of Health, Dodoma, Tanzania.

Jeremiah Mushi (J)

National AIDS Control Programme, Directorate of Preventive Services, Ministry of Health, Dodoma, Tanzania.

George S Mgomella (GS)

Division of Global HIV & Tuberculosis, US Centers for Disease Control and Prevention, Dar es Salaam, Tanzania.

James J Mcollogi (JJ)

National AIDS Control Programme, Directorate of Preventive Services, Ministry of Health, Dodoma, Tanzania.

Frank Msafiri (F)

Muhimbili University of Health and Allied Sciences, P.O. Box 650001, Dar es Salaam, Tanzania.

Sabina Mugusi (S)

Muhimbili University of Health and Allied Sciences, P.O. Box 650001, Dar es Salaam, Tanzania.

Jullu Boniface (J)

Management and Development for Health, Dar es Salaam, Tanzania.

Ritah Mutagonda (R)

Muhimbili University of Health and Allied Sciences, P.O. Box 650001, Dar es Salaam, Tanzania.

Linda Mlunde (L)

Muhimbili University of Health and Allied Sciences, P.O. Box 650001, Dar es Salaam, Tanzania.

Davis Amani (D)

Muhimbili University of Health and Allied Sciences, P.O. Box 650001, Dar es Salaam, Tanzania.

Erick Mboya (E)

Muhimbili University of Health and Allied Sciences, P.O. Box 650001, Dar es Salaam, Tanzania.

Macdonald Mahiti (M)

Muhimbili University of Health and Allied Sciences, P.O. Box 650001, Dar es Salaam, Tanzania.

Anath Rwebembera (A)

National AIDS Control Programme, Directorate of Preventive Services, Ministry of Health, Dodoma, Tanzania.

Takamasa Ueno (T)

Muhimbili University of Health and Allied Sciences, P.O. Box 650001, Dar es Salaam, Tanzania.
Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.

Andrea Pembe (A)

Muhimbili University of Health and Allied Sciences, P.O. Box 650001, Dar es Salaam, Tanzania.

Prosper Njau (P)

National AIDS Control Programme, Directorate of Preventive Services, Ministry of Health, Dodoma, Tanzania.

Beatrice Mutayoba (B)

National AIDS Control Programme, Directorate of Preventive Services, Ministry of Health, Dodoma, Tanzania.

Bruno Sunguya (B)

Muhimbili University of Health and Allied Sciences, P.O. Box 650001, Dar es Salaam, Tanzania.
Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH