Dolutegravir vs Lopinavir/Ritonavir for Second-Line HIV Treatment in South Africa
Introduction
Dolutegravir (DTG) is recommended for second-line antiretroviral therapy (ART) after virological failure on first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens in people living with HIV in low-income and middle-income countries.
Aim
To assess the effectiveness of DTG plus either emtricitabine or lamivudine [XTC] in combination with zidovudine (AZT) or tenofovir disoproxil fumarate (TDF) versus the previously recommended AZT/XTC/ritonavir-boosted lopinavir (LPV/r) regimen for second-line treatment in people who experienced virological failure while taking an NNRTI based first-line ART in routine health-care clinics in South Africa.
Patient Profile
HIV-positive individuals aged 15 or older who experienced virological failure (two consecutive viral loads ≥1000 copies/mL at least 56 days apart) on their initial NNRTI-based ART containing TDF and subsequently transitioned to second-line ART.
Methods
- Retrospective observational cohort study
- 1214 participants included in this analysis,
- 689 (57%) were switched to AZT/XTC/LPV/r
- 217 (18%) to AZT/XTC/DTG
- 308 (25%) to TDF/XTC/DTG second-line regimens
Study Outcomes
Primary outcomes were retention in care and viral suppression (<50 copies per mL) at 12 months after starting second-line treatment.
Result
Retention in Care
- DTG regimens (AZT/XTC/DTG and TDF/XTC/DTG) had higher retention than LPV/r after 12 months
- While TDF/XTC/DTG had lower observed retention than AZT/XTC/DTG, the difference was not statistically significant in adjusted analysis
Figure 1: Retention-in care at 12 months
Table 1: Follow-up outcomes in people living with HIV who were switched to second-line ART after virological failure while receiving EFV-based* or NVP-based* first-line treatment
|
|
Overall (n=1214) |
Second-line ART regimen combination |
||
|
|
|
AZT/XTC/LPV/r (n=689) |
AZT/XTC/DTG (n=217) |
TDF/XTC/DTG (n=308) |
|
Median time to second-line regimen change within 12 months, days |
158 |
146 |
182 |
160 |
|
Second-line regimen (of participants who changed regimen within 12 months) |
||||
|
AZT/XTC/LPV/r |
14% |
0 |
19% |
32% |
|
AZT/XTC/DTG |
29% |
27% |
0 |
46% |
|
TDF/XTC/DTG |
21% |
20% |
67% |
0 |
|
Other |
36% |
53% |
14% |
22% |
|
Follow-up outcome at 12 months |
||||
|
Lost to follow-up |
15% |
16% |
9% |
15% |
|
Died |
1% |
1% |
2% |
1% |
|
Transferred out to another clinic |
7% |
7% |
3% |
7% |
|
Retained in care |
78% |
75% |
86% |
77% |
|
Viral load test done at 12 months (of participants retained in care at 12 months) |
85% |
86% |
81% |
85% |
|
Median time to viral load test at 12 months (of participants retained in care at 12 months), days |
357 |
362 |
342 |
357 |
|
Viral load at 12 months (of participants retained in care at 12 months with a viral load test done) |
||||
|
<50 copies per mL |
53% |
47% |
59% |
61% |
|
50–199 copies per mL |
13% |
14% |
13% |
10% |
|
200–999 copies per mL |
9% |
9% |
13% |
7% |
|
≥1000 copies per mL |
25% |
31% |
14% |
22% |
Viral Suppression
- Both AZT/XTC/DTG and TDF/XTC/DTG achieved higher viral suppression (undetectable HIV) compared to AZT/XTC/LPV/r
Figure 1: Viral load at 12 months <50 copies per mL
Conclusion
- Second-line DTG-based regimens (AZT/XTC/DTG and TDF/XTC/ DTG) demonstrated similar or better retention in care and better viral suppression than the previously recommended second-line AZT/XTC/LPV/r regimen.
- The study supports WHO’s recommendation of DTG use replacing LPV/r for second-line treatment in resource-limited settings.
- Findings also suggest that recycling first-line TDF instead of replacing it with AZT for a DTG-based second-line regimen can be an effective alternative for viral suppression.
Reference
Lancet Glob Health 2024; 12: e282–91.
