Suboptimal immune recovery during antiretroviral therapy with sustained HIV suppression in sub-Saharan Africa

Stefanie Kroeze, Pascale Ondoa, Cissy M Kityo, Margaret Siwale, Sulaimon Akanmu, Maureen Wellington, Marleen de Jager, Prudence Ive, Kishor Mandaliya, Wendy Stevens, T Sonia Boender, Marieke E de Pundert, Kim C E Sigaloff, Peter Reiss, Ferdinand W N M Wit, Tobias F Rinke de Wit, Raph L Hamers

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)1043-1051
Number of pages9
JournalAIDS
Volume32
Issue number8
DOIs
Publication statusPublished - 15 May 2018

Cite this

Kroeze, S., Ondoa, P., Kityo, C. M., Siwale, M., Akanmu, S., Wellington, M., ... Hamers, R. L. (2018). Suboptimal immune recovery during antiretroviral therapy with sustained HIV suppression in sub-Saharan Africa. AIDS, 32(8), 1043-1051. https://doi.org/10.1097/QAD.0000000000001801
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. / Suboptimal immune recovery during antiretroviral therapy with sustained HIV suppression in sub-Saharan Africa. In: AIDS. 2018 ; Vol. 32, No. 8. pp. 1043-1051.
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title = "Suboptimal immune recovery during antiretroviral therapy with sustained HIV suppression in sub-Saharan Africa",
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.",
author = "Stefanie Kroeze and Pascale Ondoa and Kityo, {Cissy M} and Margaret Siwale and Sulaimon Akanmu and Maureen Wellington and {de Jager}, Marleen and Prudence Ive and Kishor Mandaliya and Wendy Stevens and Boender, {T Sonia} and {de Pundert}, {Marieke E} and Sigaloff, {Kim C E} and Peter Reiss and Wit, {Ferdinand W N M} and {Rinke de Wit}, {Tobias F} and Hamers, {Raph L}",
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Kroeze, S, Ondoa, P, Kityo, CM, Siwale, M, Akanmu, S, Wellington, M, de Jager, M, Ive, P, Mandaliya, K, Stevens, W, Boender, TS, de Pundert, ME, Sigaloff, KCE, Reiss, P, Wit, FWNM, Rinke de Wit, TF & Hamers, RL 2018, 'Suboptimal immune recovery during antiretroviral therapy with sustained HIV suppression in sub-Saharan Africa' AIDS, vol. 32, no. 8, pp. 1043-1051. https://doi.org/10.1097/QAD.0000000000001801

Suboptimal immune recovery during antiretroviral therapy with sustained HIV suppression in sub-Saharan Africa. / 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.

In: AIDS, Vol. 32, No. 8, 15.05.2018, p. 1043-1051.

Research output: Contribution to journalArticleAcademicpeer-review

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.

U2 - 10.1097/QAD.0000000000001801

DO - 10.1097/QAD.0000000000001801

M3 - Article

VL - 32

SP - 1043

EP - 1051

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 8

ER -