Suboptimal immune recovery during antiretroviral therapy with sustained HIV suppression in sub-Saharan Africa. (15th May 2018)

• Record Type: Journal Article
• Authors: Kroeze, Stefanie; Ondoa, Pascale; Kityo, Cissy M.; Siwale, Margaret; Akanmu, Sulaimon; Wellington, Maureen; de Jager, Marleen; Ive, Prudence; Mandaliya, Kishor; Stevens, Wendy; Boender, T. Sonia; de Pundert, Marieke E.; Sigaloff, Kim C.E.; Reiss, Peter; Wit, Ferdinand W.N.M.; Rinke de Wit, Tobias F.; Hamers, Raph L.
• Is Part Of: AIDS. Volume 32:Number 8(2018)
• Publication Date: 2018-05-15
• Subjects: CD4+ cell count -- first-line antiretroviral therapy -- HIV-related illnesses -- immune recovery -- Kenya -- Nigeria -- South Africa -- sub-Saharan Africa -- Uganda -- Zambia -- Zimbabwe; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000001801
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : Objective: To assess incidence, determinants and clinical consequences of suboptimal immune recovery in HIV-1 infected adults in sub-Saharan Africa with sustained viral suppression on antiretroviral therapy (ART). Design: Multicountry prospective cohort. Methods: Suboptimal immune recovery was defined as proportions of participants who failed to attain clinically relevant CD4 + cell count thresholds (>200, >350 and >500 cells/μl) despite sustained viral suppression on continuous first-line ART. Participants were censored at the earliest of death, loss to follow-up, last viral load less than 50 copies/ml, or database closure. Determinants of immune recovery were assessed using multivariable Cox regression. We estimated incidence rates of AIDS, pulmonary tuberculosis and all-cause mortality for CD4 + strata. Results: One thousand, five hundred and ninety-two participants were included; 60% were women, median age was 37 years (IQR 31–43) and median pre-ART CD4 + cell count was 147 cells/μl (IQR 76–215). After 6 years of ART, suboptimal immune recovery at CD4 + cell counts less than 200 cells/μl, less than 350 cells/μl, and less than 500 cells/μl occurred in 7, 27, and 57% of participants, respectively. Compared with participants with CD4 + cell count greater than 500 cells/μl, on-ART incidence rates were 12.5, 4.1, 0.9 times higher for AIDS and 16.9, 3.5, and 2.3 times higher for pulmonary tuberculosis in participants with CD4 + cell count less than 200, 200–349, and 350–499 cells/μl, respectively. All-cause mortality was highest in participants with CD4 + cell count less than 200 cells/μl, and comparable across the higher CD4 + strata. Older age, male sex, and lower pre-ART CD4 + cell count were strongly associated with suboptimal immune recovery. Conclusion: These findings warrant close clinical and laboratory monitoring until adequate immune reconstitution is achieved and support early ART initiation before decline of CD4 + cell count. Abstract : Supplemental Digital Content is available in the text