Long-term immunologic response to antiretroviral therapy in low-income countries: Collaborative analysis of prospective studies

Abstract

Abstract Background—Few data are available on the long-term immunologic response to ART in resourcelimited settings, where antiretroviral therapy (ART) is being scaled up using a public health approach, with a limited repertoire of drugs. Objectives—To describe immunologic response to ART in a network of cohorts from sub-Saharan Africa, Latin America, and Asia. Study population/methods—Treatment-naïve patients aged 15 and older from 27 treatment programs were eligible. Multi-level, linear mixed models were used to assess associations between predictor variables and CD4 count trajectories following ART initiation. Correspondence to: Denis Nash, PhD, MPH, Columbia University, Mailman School of Public Health, International Center for AIDS Care and Treatment Programs (ICAP), 722 W. 168th St., Room 706, New York, NY 10032 USA, dn2145@columbia.edu, Phone: +1-718-530-0684, Fax: +1-360-851-7175. Writing Committee Denis Nash, Monica Katyal, Martin W.G. Brinkhof, Olivia Keiser, Margaret May, Rachael Hughes, Francois Dabis, Robin Wood, Eduardo Sprinz, Mauro Schechter, Matthias Egger for the ART-LINC Collaboration of IeDEA Central Coordinating Team Martin Brinkhof, Eric Balestre, Claire Graber (project manager), Catherine Seyler, Hapsatou Touré, François Dabis (principal investigator), Matthias Egger (principal investigator), Mauro Schechter (principal investigator). Steering committee Kathryn Anastos (Kigali); David Bangsberg (Mbarara/Kampala); Andrew Boulle (Cape Town); Jennipher Chisanga (Lusaka); Eric Delaporte (Dakar); Diana Dickinson (Gaborone); Ernest Ekong (Lagos); Kamal Marhoum El Filali (Casablanca); Mina Hosseinipour (Lilongwe); Charles Kabugo (Kampala); Silvester Kimaiyo (Eldoret); Mana Khongphatthanayothin (Bangkok); N Kumarasamy (Chennai); Christian Laurent (Yaounde); Ruedi Luthy (Harare); James McIntyre (Johannesburg); Timothy Meade (Lusaka); Eugene Messou (Abidjan); Denis Nash (New York); Winstone Nyandiko Mokaya (Eldoret); Margaret Pascooe (Harare); Larry Pepper (Mbarara); Papa Salif Sow (Dakar); Sam Phiri (Lilongwe); Mauro Schechter (Rio de Janeiro); John Sidle (Eldoret); Eduardo Sprinz (Porto Alegre); Besigin Tonwe-Gold (Abidjan); Siaka Touré (Abidjan); Stefaan Van der Borght (Amsterdam); Ralf Weigel (Lilongwe); Robin Wood (Cape Town). Participating centers Service des Maladies Infectieuses, Casablanca, Maroc; Moi Teaching and Referral Hospital, Eldoret, Kenya; Immune Suppression Syndrome clinic, Mbarara, Uganda; Generic Antiretroviral Treatment Project, Kampala, Uganda; Centre de Prise en Charge, de Recherche et de Formation sur le VIH/SIDA (CEPREF), Abidjan, Côte d'Ivoire; ANRS 1215/1290 Study Group, Dakar, Senegal; Independent Surgery, Gaborone, Botswana; Lighthouse Trust Clinic, Lilongwe, Malawi; Gugulethu ART Programme, Gugulethu, South Africa; Perinatal HIV Research Unit (PHRU), Soweto, South Africa; Khayelitsha ART Programme, Khayelitsha, South Africa; Helen Joseph Hospital Themba Lethu Clinic, Johannesburg, South Africa; CorpMed Medical Centre, Lusaka, Zambia; Connaught Clinic, Harare, Zimbabwe; Prospective Evaluation in the Use and Monitoring of Antiretrovirals in Argentina (PUMA), Buenos Aires, Argentina; Rio HIV Cohort, Rio de Janeiro, Brazil; South Brazil HIV Cohort (SOBRHIV), Hospital de Clinicas, Porto Alegre, Brazil; YRG Care, Chennai, India; Thai Red Cross AIDS Research Centre, Bangkok, Thailand; International Center for AIDS Care and Treatment Programs, MTCT-Plus Initiative, Mailman School of Public Health, Columbia University, New York, USA; Heineken ART Programme, Amsterdam, The Netherlands. NIH Public Access Author Manuscript AIDS. Author manuscript; available in PMC 2009 December 15. Published in final edited form as: AIDS. 2008 November 12; 22(17): 2291–2302. doi:10.1097/QAD.0b013e3283121ca9. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript Results—Of 29,175 patients initiating ART, 8,933 patients (31%) were excluded due to insufficient follow-up time and early lost to follow-up or death. The remaining 19,967 patients contributed 39,200 person-years on ART and 71,067 CD4 measurements. The median baseline CD4 count was 114 cells/ μL, with 35%<100 cells μL and substantial inter-site variation (range: 61-181 cells/μL). Females had higher median baseline CD4 counts than males (121 vs. 104 cells/μL). The median CD4 count increased from 114 cells/μL at ART initiation to 230 (IQR:144-338) at 6 months, 263 (IQR:175-376) at 1 year, 336 (IQR:224-472) at 2 years, 372 (IQR:242-537) at 3 years, 377 (IQR:221-561) at 4 years, and 395 (IQR:240-592) at 5 years. In multivariable models, baseline CD4 count was the most important determinant of subsequent CD4 count trajectories. Conclusions—These data demonstrate robust and sustained CD4 response to ART among patients remaining on therapy. Public health and programmatic interventions leading to earlier HIV diagnosis and initiation of ART could substantially improve patient outcomes in resource-limited settings