{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T11:31:40Z","timestamp":1779017500882,"version":"3.51.4"},"reference-count":16,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T00:00:00Z","timestamp":1655251200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Int AIDS Soc."],"published-print":{"date-parts":[[2022,6]]},"abstract":"Abstract<\/jats:title>Introduction<\/jats:title>ACTG A5288 was a strategy trial conducted in diverse populations from multiple continents of people living with HIV (PLWH) failing second\u2010line protease inhibitor (PI)\u2010based antiretroviral therapy (ART) from 10 low\u2010 and middle\u2010income countries (LMICs). Participants resistant to lopinavir (LPV) and\/or multiple nucleotide reverse transcriptase inhibitors started on third\u2010line 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\u20101 RNA \u2264200 copies\/ml. We report here long\u2010term outcomes over 144 weeks.<\/jats:p><\/jats:sec>Methods<\/jats:title>Study participants were enrolled from 2013 to 2015, prior to the availability of dolutegravir in LMICs. \u201cExtended Follow\u2010up\u201d 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\u2010up of \u2265144 weeks), with HIV\u20101 RNA measured at 48 and 96 weeks and CD4 count at 96 weeks after entry into Extended Follow\u2010up. Proportion of participants with HIV\u20101 RNA \u2264200 copies\/ml was estimated every 24 weeks, using imputation if necessary to handle the different measurement schedule in Extended Follow\u2010up; mean CD4 count changes were estimated using loess regression.<\/jats:p><\/jats:sec>Results and Discussion<\/jats:title>Of 257 participants (38% females), at study entry, median CD4 count was 179 cells\/mm3<\/jats:sup>, and HIV\u20101 RNA was 4.6 log10<\/jats:sub> copies\/ml. Median follow\u2010up was 168 weeks (IQR: 156\u2013204); 15 (6%) participants were lost to follow\u2010up 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\u20101 RNA \u2264200 copies\/ml at weeks 48, 96, 144 and 168 (95% CI at week 168: 74\u201385%), respectively. Mean increase from study entry in CD4 count at week 168 was 265 cells\/mm3<\/jats:sup> (95% CI 247\u2013283).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Third\u2010line 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\u2010line PI\u2010based ART prior to the availability of dolutegravir.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.25905","type":"journal-article","created":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T11:45:04Z","timestamp":1655293504000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Third\u2010line 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\u2010limited settings: ACTG A5288 strategy trial"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3222-9611","authenticated-orcid":false,"given":"Anchalee","family":"Avihingsanon","sequence":"first","affiliation":[{"name":"HIV\u2010NAT, Thai Red Cross AIDS Research Centre and Centre of Excellence in Tuberculosis Faculty of Medicine Chulalongkorn University Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Center for Biostatistics in AIDS Research in the Department of Biostatistics Harvard T H Chan School of Public Health Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Salata","sequence":"additional","affiliation":[{"name":"Case Western Reserve University Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5797-7950","authenticated-orcid":false,"given":"Catherine","family":"Godfrey","sequence":"additional","affiliation":[{"name":"Division of AIDS National Institutes of Allergy and Infectious Disease National Institutes of Health Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caitlyn","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Center for Biostatistics in AIDS Research in the Department of Biostatistics Harvard T H Chan School of Public Health Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Mugyenyi","sequence":"additional","affiliation":[{"name":"Joint Clinical Research Center Kampala Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelyn","family":"Hogg","sequence":"additional","affiliation":[{"name":"Social & Scientific Systems Inc. a DLH Holdings Company Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Gross","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology and Biostatistics University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra W.","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Infectologia Evandro Chagas Fundacao Oswaldo Cruz Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aggrey","family":"Bukuru","sequence":"additional","affiliation":[{"name":"Joint Clinical Research Center Kampala Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mumbi","family":"Makanga","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute\/Center of Disease Control Kisumu Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharlaa","family":"Badal\u2010aesen","sequence":"additional","affiliation":[{"name":"Clinical HIV Research Unit Helen Joseph Hospital University of Witwatersrand Johannesburg South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vidya","family":"Mave","sequence":"additional","affiliation":[{"name":"BJ Medical College Clinical Research Site Pune India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice Wangari","family":"Ndege","sequence":"additional","affiliation":[{"name":"Moi University Clinical Research Center (MUCRC) CRS Eldoret Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandy Nerette","family":"Fontain","sequence":"additional","affiliation":[{"name":"Les Centres GHESKIO Clinical Research Site Port\u2010au\u2010Prince Haiti"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wadzanai","family":"Samaneka","sequence":"additional","affiliation":[{"name":"University of Zimbabwe Clinical Trials Research Centre Harare Zimbabwe"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rode","family":"Secours","sequence":"additional","affiliation":[{"name":"Les Centres GHESKIO Clinical Research Site Port\u2010au\u2010Prince Haiti"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2679-901X","authenticated-orcid":false,"given":"Marije","family":"Van Schalkwyk","sequence":"additional","affiliation":[{"name":"Family Centre for Research with Ubuntu (FAMCRU) Stellenbosch University Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6540-5733","authenticated-orcid":false,"given":"Rosie","family":"Mngqibisa","sequence":"additional","affiliation":[{"name":"Durban International Clinical Research Site, King Edward Hospital, Enhancing Care Foundation Durban South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lerato","family":"Mohapi","sequence":"additional","affiliation":[{"name":"Soweto AIDS Clinical Trials Group Clinical Research Site, Perinatal HIV Research Unit University of the Witwatersrand Johannesburg South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Valencia","sequence":"additional","affiliation":[{"name":"Barranco Clinical Research Site Lima Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patcharaphan","family":"Sugandhavesa","sequence":"additional","affiliation":[{"name":"Research Institute for Health Sciences Chiang Mai University Chiang Mai Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esmelda","family":"Montalban","sequence":"additional","affiliation":[{"name":"San Miguel Clinical Research Site Lima Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelius","family":"Munyanga","sequence":"additional","affiliation":[{"name":"University of North Carolina Project, Kamazu Central Hospital Lilongwe Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4231-4553","authenticated-orcid":false,"given":"Maganizo","family":"Chagomerana","sequence":"additional","affiliation":[{"name":"University of North Carolina Project, Kamazu Central Hospital Lilongwe Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Breno R.","family":"Santos","sequence":"additional","affiliation":[{"name":"Hospital Nossa Senhora da Conceicao CRS Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nagalingeswaran","family":"Kumarasamy","sequence":"additional","affiliation":[{"name":"CART Clinical Research Site VHS Infection Disease Medical Centre Chennai India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Kanyama","sequence":"additional","affiliation":[{"name":"University of North Carolina Project, Kamazu Central Hospital Lilongwe Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert T.","family":"Schooley","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases University of California San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John W.","family":"Mellors","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Department of Medicine University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carole L.","family":"Wallis","sequence":"additional","affiliation":[{"name":"BARC\u2010South Africa and Lancet Laboratories Johannesburg South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann C.","family":"Collier","sequence":"additional","affiliation":[{"name":"University of Washington School of Medicine University of Washington Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Grinsztejn","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Infectologia Evandro Chagas Fundacao Oswaldo Cruz Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the A5288 Study 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