Stefanie Kroeze1, Pascale Ondoa1,2, Cissy M Kityo3, Margaret Siwale4, Sulaimon Akanmu5, Maureen Wellington6, Marleen de Jager7, Prudence Ive8, Kishor Mandaliya9, Wendy Stevens10, T Sonia Boender1,11, Marieke E de Pundert1, Kim C E Sigaloff1, Peter Reiss1,11,12, Ferdinand W N M Wit1,11, Tobias F Rinke de Wit1, Raph L Hamers1,12. 1. Amsterdam Institute for Global Health and Development, and Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands. 2. African Society of Laboratory Medicine, Addis Ababa, Ethiopia. 3. Joint Clinical Research Centre, Kampala, Uganda. 4. Lusaka Trust Hospital, Lusaka, Zambia. 5. Department of Haematology and Blood Transfusion, Lagos University Teaching Hospital, Lagos, Nigeria. 6. Newlands Clinics, Harare, Zimbabwe. 7. Muelmed Hospital, Pretoria. 8. Clinical HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa. 9. Coast Province General Hospital, Mombasa, Kenya. 10. Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg and the National Health Laboratory Service, Johannesburg, South Africa. 11. Stichting HIV Monitoring, Amsterdam. 12. Division of Infectious Diseases, Department of Internal Medicine, Academic Medical Center of the University of Amsterdam, and Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands.
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.
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-ARTCD4+ 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-ARTCD4+ 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.
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