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Uptake and 24-month outcomes of dolutegravir- versus lopinavir-based second-line antiretroviral therapy for people with HIV in South Africa: a retrospective cohort study and emulated target trial

Abstract:
Background

Aligning with the WHO, South Africa has replaced LPV/r with DTG in second-line ART after treatment failure with TDF/XTC/EFV. Initial guidance included special considerations for DTG use among women.

Methods

We analysed routine de-identified data of adults switched from TDF/XTC/EFV to second-line AZT/XTC/LPV/r, AZT/XTC/DTG, or TDF/XTC/DTG between December 2019 and December 2023 at 108 healthcare facilities in KwaZulu-Natal, South Africa. Among people switched before July 2021, we emulated a target trial comparing 24-month death or loss to follow-up (LTFU), and viraemia (>50 copies/mL). We conducted intention-to-treat and per-protocol analyses using weighted logistic regression with bootstrapped CIs.

Results

Overall, women were less likely than men to switch to DTG (RR: 0.92 [95% CI: 0.88, 0.96]; N=3649). Of 2321 people switched before July 2021, 915 (39%) switched to AZT/XTC/LPV/r, 415 (18%) to AZT/XTC/DTG, and 991 (43%) to TDF/XTC/DTG. Median age was 36 years (IQR: 30, 43) and 1364 (59%) were women. In intention-to-treat analyses, the standardised 24-month risk of death or LTFU was similar with AZT/XTC/LPV/r (31%), AZT/XTC/DTG (30%), and TDF/XTC/DTG (34%). The standardised risk of 24-month viraemia among those retained in care with a viral load result (N=1270) was higher with AZT/XTC/LPV/r (49%) than with AZT/XTC/DTG (39%; aRD: -11% [95% CI -17%, -4%]) or TDF/XTC/DTG (38%; aRD: -11% [95% CI -17%, -4%]). Per-protocol analyses gave similar results.

Conclusions

While retention was similar across regimens, viraemia was less common on DTG-based ART, supporting current guidelines.

Publication status:
Published
Peer review status:
Not peer reviewed

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Preprint server copy:
10.12688/verixiv.686.1

Authors

More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Primary Care Health Sciences
Role:
Author
ORCID:
0000-0003-1874-6153


More from this funder
Funder identifier:
https://ror.org/0456r8d26
Grant:
INV-051067
More from this funder
Funder identifier:
https://ror.org/00yjd3n13
Grant:
221966
More from this funder
Funder identifier:
https://ror.org/0187kwz08
Grant:
CL-2022–13–005


Preprint server:
VeriXiv
Publication date:
2025-03-09
DOI:
EISSN:
3029-0988
Server owner:
F1000 Research


Language:
English
Keywords:
Pubs id:
2094272
Local pid:
pubs:2094272
Deposit date:
2026-05-29
ARK identifier:

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