HIV-1 Drug Resistance and Third-Line Therapy Outcomes in Patients Failing Second-Line Therapy in Zimbabwe.

Chimbetete, Cleophas; Katzenstein, David; Shamu, Tinei; Spoerri, Adrian; Estill, Janne; Egger, Matthias; Keiser, Olivia (2018). HIV-1 Drug Resistance and Third-Line Therapy Outcomes in Patients Failing Second-Line Therapy in Zimbabwe. Open Forum Infectious Diseases, 5(2), ofy005. Oxford University Press 10.1093/ofid/ofy005

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Objectives To analyze the patterns and risk factors of HIV drug resistance mutations among patients failing second-line treatment and to describe early treatment responses to recommended third-line antiretroviral therapy (ART) in a national referral HIV clinic in Zimbabwe. Methods Patients on boosted protease inhibitor (PI) regimens for more than 6 months with treatment failure confirmed by 2 viral load (VL) tests >1000 copies/mL were genotyped, and susceptibility to available antiretroviral drugs was estimated by the Stanford HIVdb program. Risk factors for major PI resistance were assessed by logistic regression. Third-line treatment was provided as Darunavir/r, Raltegravir, or Dolutegravir and Zidovudine, Abacavir Lamivudine, or Tenofovir. Results Genotypes were performed on 86 patients who had good adherence to treatment. The median duration of first- and second-line ART was 3.8 years (interquartile range [IQR], 2.3-5.1) and 2.6 years (IQR, 1.6-4.9), respectively. The median HIV viral load and CD4 cell count were 65 210 copies/mL (IQR, 8728-208 920 copies/mL) and 201 cells/mm(IQR, 49-333 cells/mm). Major PI resistance-associated mutations (RAMs) were demonstrated in 44 (51%) non-nucleoside reverse transcriptase inhibitor RAMs in 72 patients (83%) and nucleoside reverse transcriptase inhibitors RAMs in 62 patients (72%). PI resistance was associated with age >24 years (= .003) and CD4 cell count <200 cells/mm(= .007). In multivariable analysis, only age >24 years was significantly associated (adjusted odds ratio, 4.75; 95% confidence interval, 1.69-13.38;= .003) with major PI mutations. Third-line DRV/r- and InSTI-based therapy achieved virologic suppression in 29/36 patients (81%) after 6 months. Conclusions The prevelance of PI mutations was high. Adolescents and young adults had a lower risk of acquiring major PI resistance mutations, possibly due to poor adherence to ART. Third-line treatment with a regimen of Darunavir/r, Raltegravir/Dolutegravir, and optimized nucleoside reverse transcriptase inhibitors was effective.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine
04 Faculty of Medicine > Faculty Institutions > Teaching Staff, Faculty of Medicine
08 Faculty of Science > Department of Mathematics and Statistics > Institute of Mathematical Statistics and Actuarial Science

UniBE Contributor:

Spörri, Adrian; Estill, Janne Anton Markus; Egger, Matthias and Keiser, Olivia

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services
500 Science > 510 Mathematics

ISSN:

2328-8957

Publisher:

Oxford University Press

Language:

English

Submitter:

Tanya Karrer

Date Deposited:

15 Feb 2018 15:57

Last Modified:

22 Oct 2019 20:17

Publisher DOI:

10.1093/ofid/ofy005

PubMed ID:

29435471

Uncontrolled Keywords:

HIV-1 drug resistance Zimbabwe second-line therapy third-line ART outcomes

BORIS DOI:

10.7892/boris.111698

URI:

https://boris.unibe.ch/id/eprint/111698

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