Abstract
Introduction: To assess the effectiveness of novel HIV curative strategies, “cure” trials require periods of closely monitoredantiretroviral therapy (ART) analytical treatment interruptions (ATIs). We performed a systematic review and meta-analysisto identify the impact of ATI with or without novel therapeutics in cure-related studies on the time to viral re-suppressionfollowing ART restart.
Methods: Medline, Embase and Web of Science databases were searched for human studies involving ATIs from 1 January2015 till 22 April 2024. The primary outcome was time to first viral re-suppression (plasma HIV viral load [VL] <50 copies/ml)stratified by receipt of interventional drug with ATI (IA) or ATI-only groups. Random-effects proportional meta-analysis andmultivariable Cox proportional hazards analysis were performed using R.
Results: Of 1073 studies screened, 13 were included that met the inclusion criteria with VL data available after restartingART (n = 213 participants). There was no difference between time to viral suppression in IA or ATI-only cohorts (p = 0.22).For 87% of participants, viral suppression within 12 weeks of ART restart was achieved, and all eventually had at least one VL<50 copies/ml during follow-up. After adjusting for covariables, while participants in the IA cohort were associated with lessrapid suppression (adjusted hazard ratio [aHR] 0.61, 95% CI 0.40–0.94, p = 0.026), other factors include greater log VL atART restart (aHR 0.56, 95% CI 0.46–0.68, p<0.001), duration since HIV diagnosis (aHR 0.93, 95% CI 0.89–0.96) and longerintervals between HIV VL monitoring (aHR 0.66, 95% CI 0.59–0.74, p<0.001). However, the use of integrase inhibitors wasassociated with more rapid viral suppression (aHR 1.74, 95% CI 1.16–2.59).
Discussion: When designing studies involving ATIs, information on time to viral re-suppression after restarting ART is impor-tant to share with participants, and should be regularly monitored and reported, to assess the impact and safety of specifictrial interventions in ATI studies.
Conclusions: The majority of participants achieved viral suppression after restarting ART in ATI studies. ART regimens con-taining integrase inhibitors and frequent VL monitoring should be offered for people restarting ART after ATI studies toensure rapid re-suppression
Methods: Medline, Embase and Web of Science databases were searched for human studies involving ATIs from 1 January2015 till 22 April 2024. The primary outcome was time to first viral re-suppression (plasma HIV viral load [VL] <50 copies/ml)stratified by receipt of interventional drug with ATI (IA) or ATI-only groups. Random-effects proportional meta-analysis andmultivariable Cox proportional hazards analysis were performed using R.
Results: Of 1073 studies screened, 13 were included that met the inclusion criteria with VL data available after restartingART (n = 213 participants). There was no difference between time to viral suppression in IA or ATI-only cohorts (p = 0.22).For 87% of participants, viral suppression within 12 weeks of ART restart was achieved, and all eventually had at least one VL<50 copies/ml during follow-up. After adjusting for covariables, while participants in the IA cohort were associated with lessrapid suppression (adjusted hazard ratio [aHR] 0.61, 95% CI 0.40–0.94, p = 0.026), other factors include greater log VL atART restart (aHR 0.56, 95% CI 0.46–0.68, p<0.001), duration since HIV diagnosis (aHR 0.93, 95% CI 0.89–0.96) and longerintervals between HIV VL monitoring (aHR 0.66, 95% CI 0.59–0.74, p<0.001). However, the use of integrase inhibitors wasassociated with more rapid viral suppression (aHR 1.74, 95% CI 1.16–2.59).
Discussion: When designing studies involving ATIs, information on time to viral re-suppression after restarting ART is impor-tant to share with participants, and should be regularly monitored and reported, to assess the impact and safety of specifictrial interventions in ATI studies.
Conclusions: The majority of participants achieved viral suppression after restarting ART in ATI studies. ART regimens con-taining integrase inhibitors and frequent VL monitoring should be offered for people restarting ART after ATI studies toensure rapid re-suppression
| Original language | English |
|---|---|
| Article number | e26349 |
| Journal | Journal of the International AIDS Society |
| Volume | 27 |
| Issue number | 8 |
| Number of pages | 17 |
| ISSN | 1758-2652 |
| DOIs | |
| Publication status | Published - 2024 |
Keywords
- ATI
- HIV
- HIV cure
- Antiretroviral therapy
- Treatment interruption
- Viral suppression