| Author | Avihingsanon, Anchalee | |
| Author | Hughes, Michael D. | |
| Author | Salata, Robert | |
| Author | Godfrey, Catherine | |
| Author | McCarthy, Caitlyn | |
| Author | Mugyenyi, Peter | |
| Author | Hogg, Evelyn | |
| Author | Gross, Robert | |
| Author | Cardoso, Sandra W. | |
| Author | Bukuru, Aggrey | |
| Author | Makanga, Mumbi | |
| Author | Badal-Aesen, Sharlaa | |
| Author | Mave, Vidya | |
| Author | Ndege, Beatrice Wangari | |
| Author | Fontain, Sandy Nerette | |
| Author | Samaneka, Wadzanai | |
| Author | Secours, Rode | |
| Author | Schalkwyk, Marije Van | |
| Author | Mngqibisa, Rosie | |
| Author | Mohapi, Lerato | |
| Author | Valencia, Javier | |
| Author | Sugandhavesa, Patcharaphan | |
| Author | Montalban, Esmelda | |
| Author | Munyanga, Cornelius | |
| Author | Chagomerana, Maganizo | |
| Author | Santos, Breno R. | |
| Author | Kumarasamy, Nagalingeswaran | |
| Author | Kanyama, Cecilia | |
| Author | Schooley, Robert T. | |
| Author | Mellors, John W. | |
| Author | Wallis, Carole L. | |
| Author | Collier, Ann C. | |
| Author | Grinsztejn, Beatriz | |
| Access date | 2022-11-07T19:41:35Z | |
| Available date | 2022-11-07T19:41:35Z | |
| Document date | 2022 | |
| Citation | AVIHINGSANON, Anchalee et al. Third-line antiretroviral therapy, including raltegravir (RAL), darunavir (DRV/r) and/or etravirine (ETR), is well tolerated and achieves durable virologic suppression over 144 weeks in resource-limited settings: ACTG A5288 strategy trial. Journal of the International AIDS Society, v. 25, n. 6, p. 1-6, Jun. 2022. | en_US |
| ISSN | 1758-2652 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/55522 | |
| Language | eng | en_US |
| Publisher | Wiley | en_US |
| Rights | open access | en_US |
| Title | Third-line antiretroviral therapy, including raltegravir (RAL), darunavir (DRV/r) and/or etravirine (ETR), is well tolerated and achieves durable virologic suppression over 144 weeks in resource-limited settings: ACTG A5288 strategy trial | en_US |
| Type | Article | en_US |
| DOI | 10.1002/jia2.25905 | |
| Abstract | Introduction: ACTG A5288 was a strategy trial conducted in diverse populations from multiple continents of people living with HIV (PLWH) failing second-line protease inhibitor (PI)-based antiretroviral therapy (ART) from 10 low- and middle-income countries (LMICs). Participants resistant to lopinavir (LPV) and/or multiple nucleotide reverse transcriptase inhibitors started on third-line regimens that included raltegravir (RAL), darunavir/ritonavir (DRV/r) and/or etravirine (ETR) according to their resistance profiles. At 48 weeks, 87% of these participants achieved HIV-1 RNA ≤200 copies/ml. We report here long-term outcomes over 144 weeks.
Methods: Study participants were enrolled from 2013 to 2015, prior to the availability of dolutegravir in LMICs. "Extended Follow-up" of the study started after the last participant enrolled had reached 48 weeks and included participants still on antiretroviral (ARV) regimens containing RAL, DRV/r and/or ETR at that time. RAL, DRV/r and ETR were provided for an additional 96 weeks (giving total follow-up of ≥144 weeks), with HIV-1 RNA measured at 48 and 96 weeks and CD4 count at 96 weeks after entry into Extended Follow-up. Proportion of participants with HIV-1 RNA ≤200 copies/ml was estimated every 24 weeks, using imputation if necessary to handle the different measurement schedule in Extended Follow-up; mean CD4 count changes were estimated using loess regression. Results and discussion: Of 257 participants (38% females), at study entry, median CD4 count was 179 cells/mm3 , and HIV-1 RNA was 4.6 log10 copies/ml. Median follow-up was 168 weeks (IQR: 156-204); 15 (6%) participants were lost to follow-up and 9 (4%) died. 27/246 (11%), 26/246 (11%) and 13/92 (14%) of participants who started RAL, DRV/r and ETR, respectively, discontinued these drugs; only three due to adverse events. 87%, 86%, 83% and 80% of the participants had HIV-1 RNA ≤200 copies/ml at weeks 48, 96, 144 and 168 (95% CI at week 168: 74-85%), respectively. Mean increase from study entry in CD4 count at week 168 was 265 cells/mm3 (95% CI 247-283). Conclusions: Third-line regimens comprising of RAL, DRV/r and/or ETR were very well tolerated and had high rates of durable virologic suppression among PLWH in LMICs who were failing on second-line PI-based ART prior to the availability of dolutegravir. | en_US |
| Affilliation | Chulalongkorn University. Faculty of Medicine. Thai Red Cross AIDS Research Centre and Centre of Excellence in Tuberculosis. HIV-NAT. Bangkok, Thailand. | en_US |
| Affilliation | Harvard T H Chan School of Public Health. Center for Biostatistics in AIDS Research in the Department of Biostatistics. Boston, Massachusetts, USA. | en_US |
| Affilliation | Case Western Reserve University. Cleveland, Ohio, USA. | en_US |
| Affilliation | National Institutes of Health. National Institutes of Allergy and Infectious Disease. Division of AIDS. Bethesda, Maryland, USA. | en_US |
| Affilliation | Harvard T H Chan School of Public Health. Center for Biostatistics in AIDS Research in the Department of Biostatistics. Boston, Massachusetts, USA. | en_US |
| Affilliation | Joint Clinical Research Center. Kampala, Uganda. | en_US |
| Affilliation | Social & Scientific Systems, Inc., a DLH Holdings Company. Silver Spring, Maryland, USA. | en_US |
| Affilliation | University of Pennsylvania. Center for Clinical Epidemiology and Biostatistics. Philadelphia, Pennsylvania, USA. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Joint Clinical Research Center. Kampala, Uganda. | en_US |
| Affilliation | Kenya Medical Research Institute. Center of Disease Control. Kisumu, Kenya. | en_US |
| Affilliation | University of Witwatersrand. Helen Joseph Hospital. Clinical HIV Research Unit. Johannesburg, South Africa. | en_US |
| Affilliation | BJ Medical College Clinical Research Site. Pune, India. | en_US |
| Affilliation | Moi University Clinical Research Center (MUCRC) CRS. Eldoret, Kenya. | en_US |
| Affilliation | Les Centres GHESKIO Clinical Research Site. Port-au-Prince, Haiti. | en_US |
| Affilliation | University of Zimbabwe Clinical Trials Research Centre. Harare, Zimbabwe. | en_US |
| Affilliation | Les Centres GHESKIO Clinical Research Site. Port-au-Prince, Haiti. | en_US |
| Affilliation | Stellenbosch University. Family Centre for Research with Ubuntu (FAMCRU). Cape Town, South Africa. | en_US |
| Affilliation | Enhancing Care Foundation. King Edward Hospital. Durban International Clinical Research Site. Durban, South Africa. | en_US |
| Affilliation | University of the Witwatersrand. Perinatal HIV Research Unit. Clinical Research Site. Soweto AIDS Clinical Trials Group. Johannesburg, South Africa. | en_US |
| Affilliation | Barranco Clinical Research Site. Lima, Peru. | en_US |
| Affilliation | Chiang Mai University. Research Institute for Health Sciences. Chiang Mai, Thailand. | en_US |
| Affilliation | San Miguel Clinical Research Site. Lima, Peru. | en_US |
| Affilliation | University of North Carolina Project. Kamazu Central Hospital. Lilongwe, Malawi. | en_US |
| Affilliation | University of North Carolina Project. Kamazu Central Hospital. Lilongwe, Malawi. | en_US |
| Affilliation | Hospital Nossa Senhora da Conceicao CRS. Porto Alegre, RS, Brazil. | en_US |
| Affilliation | VHS Infection Disease Medical Centre. Clinical Research Site. CART. Chennai, India. | en_US |
| Affilliation | University of North Carolina Project. Kamazu Central Hospital. Lilongwe, Malawi. | en_US |
| Affilliation | University of California. Division of Infectious Diseases. San Diego, California, USA. | en_US |
| Affilliation | University of Pittsburgh School of Medicine. Department of Medicine. Division of Infectious Diseases. Pittsburgh, Pennsylvania, USA. | en_US |
| Affilliation | BARC-South Africa and Lancet Laboratories. Johannesburg, South Africa. | en_US |
| Affilliation | University of Washington. School of Medicine. Seattle, Washington, USA. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil. | en_US |
| Subject | LMIC | en_US |
| Subject | Darunavir | en_US |
| Subject | Drug resistance | en_US |
| Subject | Third-line ART | en_US |
