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. 2022 Aug:148:135-145.
doi: 10.1016/j.jclinepi.2022.02.005. Epub 2022 Feb 19.

Acquired HIV drug resistance mutations on first-line antiretroviral therapy in Southern Africa: Systematic review and Bayesian evidence synthesis

Anthony Hauser  1 , Fardo Goldstein  1 , Martina L Reichmuth  1 , Roger D Kouyos  2 , Gilles Wandeler  3 , Matthias Egger  4 , Julien Riou  5
Affiliations

Acquired HIV drug resistance mutations on first-line antiretroviral therapy in Southern Africa: Systematic review and Bayesian evidence synthesis

Anthony Hauser et al. J Clin Epidemiol. 2022 Aug.

Abstract

Objective: To estimate the prevalence of NRTI and NNRTI drug resistance mutations in patients failing NNRTI-based ART in Southern Africa.

Study design: We conducted a systematic review to identify studies reporting drug resistance mutations among adult people living with HIV (PLWH) who experienced virological failure on first-line NNRTI-based ART in Southern Africa. We used a Bayesian hierarchical meta-regression model to synthesize the evidence on the frequency of eight NRTI- and seven NNRTI-DRMs across different ART regimens, accounting for ART duration and study characteristics.

Results: We included 19 study populations, including 2,690 PLWH. Patients failing first-line ART including emtricitabine or lamivudine showed high levels of the M184V/I mutation after 2 years: 75.7% (95% Credibility Interval [CrI] 61.9%-88.9%) if combined with tenofovir, and 72.1% (95% CrI 56.8%-85.9%) with zidovudine. With tenofovir disoproxil fumarate, the prevalence of the K65R mutation was 52.0% (95% CrI 32.5%-76.8%) at 2 years. On efavirenz, K103 was the most prevalent NNRTI resistance mutation (57.2%, 95% CrI 40.9%-80.1%), followed by V106 (46.8%, 95% CrI 31.3%-70.4%).

Conclusions: NRTI/NNRTI drug resistance mutations are common in patients failing first-line ART in Southern Africa. These patients might switch to dolutegravir-based regimen with compromised NRTIs, which could impair the long-term efficacy of ART.

Keywords: ART; HIV; HIV drug resistance; Meta-analysis; Southern Africa; Systematic review.

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Conflict of interest statement

Potential conflicts of interest.

The authors have no conflict of interest to declare.

Figures

Figure 1.
Figure 1.
Bayesian hierarchical model adjusting for the different levels of heterogeneity.
Figure 2.
Figure 2.
PRISMA flow-chart of inclusion of studies and populations in the systematic review.
Figure 3.
Figure 3.. Prevalence of nine NRTI drug resistance mutations by first-line regimen.
Panel A: baseline prevalence and prevalence after 2 years of treatment according to NRTI use. Panel B: Prevalence of the K65 mutation over time. Panel C: Prevalence of the M184 mutation over time. Points and vertical lines: median and 95% credibility intervals of baseline prevalence (black), prevalence after 2 years on FTC/3TC + TDF (red) or FTC/3TC + ZDV (blue). Shaded area: 95% credibility interval over time.
Figure 4.
Figure 4.. Prevalence of seven NNRTI drug resistance mutations.
Panel A: Prevalences after 2 years on either EFV- or NVP-based regimen. Panel B: Prevalence of the K103 mutation over time. Panel C: Prevalence of the Y181 mutation over time. Points and vertical lines: median and 95% credibility intervals of baseline prevalence (black), prevalence after 2 years on EFV (orange) or NVP (green). Shaded area: 95% credibility interval over time. In contrast to Figure 3, the Panel A do not report baseline prevalence because EFV and NVP select for the same NNRTI DRMs, which prevents the model from providing reliable estimates.
See this image and copyright information in PMC

References

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