Pre-treatment and acquired HIV drug resistance in Dar es Salaam, Tanzania in the era of tenofovir and routine viral load monitoring

Author:

Barabona Godfrey1,Mahiti Macdonald234,Masoud Salim4,Mbelele Peter5,Mgunya Amina Shaban6,Minja Lilian6,Sunguya Bruno14,Shigemi Urara7,Matsuda Masakazu7,Hachiya Atsuko7,Iwatani Yasumasa78,Lyamuya Eligius14,Ueno Takamasa12ORCID

Affiliation:

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

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.

Funder

Japan Agency for Medical Research and Development

AMED

Japan Society for the Promotion of Science

JSPS

KAKENHI

JSPS Core-to-Core Program

JSPS KAKENHI

Terumo Foundation for Life Sciences and Arts

Ministry of Education, Culture, Sports, Science and Technology, Japan

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)

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