TY - JOUR
T1 - Suboptimal immune recovery during antiretroviral therapy with sustained HIV suppression in sub-Saharan Africa
AU - Kroeze, Stefanie
AU - Ondoa, Pascale
AU - Kityo, Cissy M.
AU - Siwale, Margaret
AU - Akanmu, Sulaimon
AU - Wellington, Maureen
AU - de Jager, Marleen
AU - Ive, Prudence
AU - Mandaliya, Kishor
AU - Stevens, Wendy
AU - Boender, T. Sonia
AU - de Pundert, Marieke E.
AU - Sigaloff, Kim C. E.
AU - Reiss, Peter
AU - Wit, Ferdinand W. N. M.
AU - Rinke de Wit, Tobias F.
AU - Hamers, Raph L.
PY - 2018/5/15
Y1 - 2018/5/15
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85046715318&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29547445
U2 - https://doi.org/10.1097/QAD.0000000000001801
DO - https://doi.org/10.1097/QAD.0000000000001801
M3 - Article
C2 - 29547445
SN - 0269-9370
VL - 32
SP - 1043
EP - 1051
JO - AIDS (London, England)
JF - AIDS (London, England)
IS - 8
ER -