Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Dec 12;11(6):e0125123.
doi: 10.1128/spectrum.01251-23. Epub 2023 Oct 12.

Fostemsavir resistance-associated polymorphisms in HIV-1 subtype C in a large cohort of treatment-naïve and treatment-experienced individuals in Botswana

Boitumelo J L Zuze #  1 , Botshelo T Radibe #  1 , Wonderful T Choga  1   2 , Ontlametse T Bareng  1   2 , Natasha O Moraka  1   2 , Dorcas Maruapula  1   3 , Kedumetse Seru  1 , Patrick Mokgethi  1   3 , Baitshepi Mokaleng  1   2 , Nokuthula Ndlovu  1 , Nametso Kelentse  1   2 , Molly Pretorius-Holme  4 , Roger Shapiro  1   4 , Shahin Lockman  1   4   5 , Joseph Makhema  1   4 , Vlad Novitsky  1   4 , Kaelo K Seatla  1 , Sikhulile Moyo  1   4 , Simani Gaseitsiwe  1   4
Affiliations

Fostemsavir resistance-associated polymorphisms in HIV-1 subtype C in a large cohort of treatment-naïve and treatment-experienced individuals in Botswana

Boitumelo J L Zuze et al. Microbiol Spectr. .

Abstract

Fostemsavir (FTR) is a newly licensed antiretroviral drug that has been shown to have activity against HIV-1. The mechanism of action of FTR is different from all currently available antiretrovirals (ARVs), and as such, it offers hope for HIV-1 suppression in those people with HIV (PWH) who harbor HIV-1 variants with drug resistance mutations to currently used ARVs. Using 6,030 HIV-1 sequences covering the HIV-1 envelope from PWH in Botswana who are antiretroviral therapy (ART) naïve as well as those who are failing ART, we explored the sequences for FTR resistance-associated polymorphisms. We found the prevalence of FTR polymorphisms to be similar in both ART-naïve and ART-experienced individuals with VF in this setting, with no prior FTR exposure. Further studies on the phenotypic impact of these polymorphisms are warranted to guide how to monitor for FTR resistance.

Keywords: Botswana; HIV-1 C; drug-resistant mutations (DRMs); entry inhibitors; fostemsavir (FTR); polymorphisms.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig 1
Fig 1
Study schema for specimen selection. n, population size.
Fig 2
Fig 2
Overall prevalence of individuals with FTR resistanceassociated polymorphisms among ART naïve and individuals experiencing VF on ART. The analysis focused on ART naïve (n = 1,282) and on ART with VF (n = 213) individuals, total 1,495 individuals, only 199 had FTR polymorphisms.
Fig 3
Fig 3
Overall prevalence of specific FTR resistance-associated polymorphisms (≥ 1.0%). Of the 32 detected amino acid substitutions, only 3 had a prevalence (greater than or equal to) 1.0%, these were M475I, M434I, and M426L.
Fig 4
Fig 4
Prevalence of specific FTR resistance-associated polymorphisms among ART naïve and ART experienced with VF individuals. Of the 32 detected amino acid substitutions, 7 were found in both ART naïve and on ART with VF, these were A204del, S375T, M475I, M434del, M434V, M423I, and M426L, having only M434V being statistically significant between these groups (P-value <0.05%).
Fig 5
Fig 5
HIV-1 envelope group C amino acid profile. HIV-1 envelope group C amino acid profile. The consensus sequence is indicated in black. Non-consensus amino acids with prevalence (greater than or equal to) 5.0%, 1.1%–4.9%, and 0.1%–1.0% are indicated in red, blue, and green, respectively.
See this image and copyright information in PMC

References

    1. Parker E, Judge MA, Macete E, Nhampossa T, Dorward J, Langa DC, Schacht CD, Couto A, Vaz P, Vitoria M, Molfino L, Idowu RT, Bhatt N, Naniche D, Le Souëf PN. 2021. HIV infection in Eastern and Southern Africa: highest burden, largest challenges, greatest potential. South Afr J HIV Med 22:1237. doi:10.4102/sajhivmed.v22i1.1237 - DOI - PMC - PubMed
    1. World Health Organisation . 2021. HIV/AIDS
    1. Mine M. 2022. Botswana achieved the joint united nations programme on HIV/AIDS (UNAIDS) 95 ‐ 95 ‐ 95 targets: results from the fifth botswana HIV/AIDS impact survey (BAIS V). J Int AIDS Soc 25:231–232.
    1. Gaolathe T, Wirth KE, Holme MP, Makhema J, Moyo S, Chakalisa U, Yankinda EK, Lei Q, Mmalane M, Novitsky V, Okui L, van Widenfelt E, Powis KM, Khan N, Bennett K, Bussmann H, Dryden-Peterson S, Lebelonyane R, El-Halabi S, Mills LA, Marukutira T, Wang R, Tchetgen EJT, DeGruttola V, Essex M, Lockman S, Botswana Combination Prevention Project study team . 2016. Botswana's progress toward achieving the 2020 UNAIDS 90-90-90 antiretroviral therapy and virological suppression goals: a population-based survey. Lancet HIV 3:e221–e230. doi:10.1016/S2352-3018(16)00037-0 - DOI - PMC - PubMed
    1. Barak T, Neo DT, Tapela N, Mophuthegi P, Zash R, Kalenga K, Perry ME, Malane M, Makhema J, Lockman S, Shapiro R. 2019. HIV-associated morbidity and mortality in a setting of high ART coverage: prospective surveillance results from a district hospital in Botswana. J Int AIDS Soc 22:e25428. doi:10.1002/jia2.25428 - DOI - PMC - PubMed