Godfrey Barabona1, Macdonald Mahiti2,3,4, Salim Masoud4, Peter Mbelele5, Amina Shaban Mgunya6, Lilian Minja6, Bruno Sunguya1,4, Urara Shigemi7, Masakazu Matsuda7, Atsuko Hachiya7, Yasumasa Iwatani7,8, Eligius Lyamuya1,4, Takamasa Ueno1,2. 1. Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan. 2. International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan. 3. St Francis University College of Health and Allied Sciences, Ifakara, Tanzania. 4. Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. 5. Kibong'oto Infectious Diseases Hospital, Moshi, Tanzania. 6. Muhimbili National Hospital, Dar es Salaam, Tanzania. 7. Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan. 8. Nagoya University Graduate School of Medicine, Nagoya, Japan.
Abstract
OBJECTIVES: We investigated the prevalence and patterns of pre-treatment and acquired HIV drug resistance mutations (DRMs) in Tanzania as a 'treat all' strategy, virological monitoring and the progressive increase in usage of tenofovir are being implemented in HIV treatment programmes. METHODS: Viral RNA was isolated from plasma of 60 ART-naive and 166 treated-but-viraemic (>400 copies/mL) HIV-1-infected adults attending a care and treatment clinic at Muhimbili National Hospital, Dar es Salaam, Tanzania, between June and October 2017. Viral genes encoding protease and reverse transcriptase were amplified by PCR and directly sequenced. RESULTS: Viral genotyping of successfully amplified samples revealed pre-treatment DRMs in 14/47 (29.8%) ART-naive subjects. Of these, 7/47 (14.9%) harboured mutations that confer high-level resistance to at least one drug of the default first-line regimen. In treated-but-viraemic subjects, DRMs were found in 100/111 (90%), where DRMs against NNRTI, NRTI and PI were observed in 95/100 (95%), 92/100 (92%) and 13/100 (13%), respectively. Tenofovir-resistance mutations K65R and K70G/E or ≥3 thymidine analogue resistance mutations including M41L and L210W were found in 18/36 (50%) subjects on a tenofovir-containing regimen at failure. Four patients harboured multiple DRMs, which can confer resistance to all available ART regimens in Tanzania. CONCLUSIONS: Taken together, pre-treatment and acquired DRMs were highly prevalent, which represents a major risk for the efficacy of ART programmes in Tanzania. Availability of a newer generation of antiretroviral drugs with a higher genetic barrier to resistance and robust treatment monitoring is warranted for effective and sustainable HIV treatment.
OBJECTIVES: We investigated the prevalence and patterns of pre-treatment and acquired HIV drug resistance mutations (DRMs) in Tanzania as a 'treat all' strategy, virological monitoring and the progressive increase in usage of tenofovir are being implemented in HIV treatment programmes. METHODS: Viral RNA was isolated from plasma of 60 ART-naive and 166 treated-but-viraemic (>400 copies/mL) HIV-1-infected adults attending a care and treatment clinic at Muhimbili National Hospital, Dar es Salaam, Tanzania, between June and October 2017. Viral genes encoding protease and reverse transcriptase were amplified by PCR and directly sequenced. RESULTS: Viral genotyping of successfully amplified samples revealed pre-treatment DRMs in 14/47 (29.8%) ART-naive subjects. Of these, 7/47 (14.9%) harboured mutations that confer high-level resistance to at least one drug of the default first-line regimen. In treated-but-viraemic subjects, DRMs were found in 100/111 (90%), where DRMs against NNRTI, NRTI and PI were observed in 95/100 (95%), 92/100 (92%) and 13/100 (13%), respectively. Tenofovir-resistance mutations K65R and K70G/E or ≥3 thymidine analogue resistance mutations including M41L and L210W were found in 18/36 (50%) subjects on a tenofovir-containing regimen at failure. Four patients harboured multiple DRMs, which can confer resistance to all available ART regimens in Tanzania. CONCLUSIONS: Taken together, pre-treatment and acquired DRMs were highly prevalent, which represents a major risk for the efficacy of ART programmes in Tanzania. Availability of a newer generation of antiretroviral drugs with a higher genetic barrier to resistance and robust treatment monitoring is warranted for effective and sustainable HIV treatment.
Authors: Shimba Henerico; Sello Given Mikasi; Samuel Elias Kalluvya; Jan M Brauner; Seif Abdul; Eric Lyimo; Bernard Desderius; Klaus Korn; Gert van Zyl; Graeme Brendon Jacobs; Wolfgang Preiser; Christa Kasang Journal: J Antimicrob Chemother Date: 2022-02-02 Impact factor: 5.790