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
. 2021 Oct 5;73(7):e2217-e2225.
doi: 10.1093/cid/ciaa1068.

Drug Resistance Mutations Among South African Children Living With HIV on WHO-recommended ART Regimens

Stephanie Hackett  1 , Chloe A Teasdale  2   3   4 , Sherri Pals  1 , Anthony Muttiti  3 , Mary Mogashoa  5 , Joy Chang  1 , Clement Zeh  1 , Artur Ramos  6 , Emilia D Rivadeneira  1 , Joshua DeVos  1 , Katrina Sleeman  1 , Elaine J Abrams  3   4   7
Affiliations

Drug Resistance Mutations Among South African Children Living With HIV on WHO-recommended ART Regimens

Stephanie Hackett et al. Clin Infect Dis. .

Abstract

Background: Children living with human immunodeficiency virus (HIV) (CLHIV) receiving antiretroviral therapy (ART) in resource-limited settings are susceptible to high rates of acquired HIV drug resistance (HIVDR), but few studies include children initiating age-appropriate World Health Organization (WHO)-recommended first-line regimens. We report data from a cohort of ART-naive South African children who initiated first-line ART.

Methods: ART-eligible CLHIV aged 0-12 years were enrolled from 2012 to 2014 at 5 public South African facilities and were followed for up to 24 months. Enrolled CLHIV received standard-of-care WHO-recommended first-line ART. At the final study visit, a dried blood spot sample was obtained for viral load and genotypic resistance testing.

Results: Among 72 successfully genotyped CLHIV, 49 (68.1%) received ABC/3TC/LPV/r, and 23 (31.9%) received ABC/3TC/EFV. All but 2 children on ABC/3TC/LPV/r were <3 years, and all CLHIV on ABC/3TC/EFV were ≥3 years. Overall, 80.6% (58/72) had at least one drug resistance mutation (DRM). DRMs to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) were found among 65% and 51% of all CLHIV, respectively, with no statistical difference by ART regimen. More CLHIV on ABC/3TC/EFV, 47.8% (11/23), were found to have 0 or only 1 effective antiretroviral drug remaining in their current regimen compared to 8.2% (4/49) on ABC/3TC/LPV/r.

Conclusions: High levels of NNRTI and NRTI DRMs among CLHIV receiving ABC/3TC/LPV/r suggests a lasting impact of failed mother-to-child transmission interventions on DRMs. However, drug susceptibility analysis reveals that CLHIV with detectable viremia on ABC/3TC/LPV/r are more likely to have maintained at least 2 effective agents on their current HIV regimen than those on ABC/3TC/EFV.

Keywords: HIV drug resistance; children; pediatric HIV; resource-limited settings.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest. J. D. reports patent US10053741B2 with royalties paid to Life Technologies. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Heat map of HIV drug resistance and drug susceptibility among South African children 0–12 years with detectable viremia (viral load >832 copies/mL) and successful amplification of dried blood spot samples by ART regimen (n = 72). Abbreviations: 3TC, lamivudine; ABC, abacavir; ART, antiretroviral therapy; AZT, zidovudine; EFV, efavirenz; HIV, human immunodeficiency virus; LPV/r, lopinavir/ritonavir.
Figure 2.
Figure 2.
Major drug resistance mutations by ART regimen type among South African children on LPV/r- and EFV-based therapy in South Africa from 2012–2015. Abbreviations: 3TC, lamivudine; ABC, abacavir; ART, antiretroviral therapy; AZT, zidovudine; EFV, efavirenz; LPV/r, lopinavir/ritonavir; NNRTIs, nonnucleoside reverse transcriptase inhibitors; NRTIs, nucleoside reverse transcriptase inhibitors..
Figure 3.
Figure 3.
Effectiveness of current ART regimen among South African children 0–12 years living with HIV with detectable viremia (viral load >832 copies/mL) and successful amplification of dried blood spot samples (n = 72). Abbreviations: 3TC, lamivudine; ABC, abacavir; ART, antiretroviral therapy; ARVs, antiretrovirals; EFV, efavirenz; HIV, human immunodeficiency virus; LPV/r, lopinavir/ritonavir.
See this image and copyright information in PMC

References

    1. UNAIDS. Fact sheet—global AIDS update 2019. Geneva: UNAIDS, 2019.
    1. UNAIDS. Miles to go: closing gaps, breaking barriers, righting injustices. Geneva: UNAIDS, 2018.
    1. Boerma RS, Boender TS, Bussink AP, et al. Suboptimal viral suppression rates among HIV-infected children in low- and middle-income countries: a meta-analysis. Clin Infect Dis 2016; 63:1645–54. - PubMed
    1. Saito S Population HIV impact assessments: what we can learn about pediatric HIV?. In: International Workshop on HIV Pediatrics. Mexico City, Mexico, 2019.
    1. Eswatini GotKo. Swaziland HIV Incidence Measurement Survey 2 (SHIMS2) 2016–2017. Mbabane: Government of the Kingdom of Eswatini, 2019.

Publication types

Substances