Frequency and impact of suboptimal immune recovery on first-line antiretroviral therapy (ART) within the IeDEA-East Africa cohort

Damalie Nakanjako, Agnes N. Kiragga, Beverly Musick, Constantin Yiannoutsos, Kara Wools-Kaloustian, Lameck Diero, Patrick Oyaro, Emanuel Lugina, John C. Ssali, Andrew Kambugu, Philippa Easterbrook

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

BACKGROUND:: A proportion of HIV-infected patients who initiate antiretroviral therapy (ART) fail to achieve an optimal CD4 recovery (OP-IR), and remain at risk of HIV-related opportunistic infections and associated morbidity and mortality. Our objective was to describe patterns of suboptimal immune response (SO-IR) and associated AIDS-related illnesses during the first five years following first-line ART initiation across seven ART sites in East Africa. METHODS:: Seven ART clinical sites (3 Uganda, 2 Kenya and 2 Tanzania) in the IeDEA East African region participated in this analysis. Routine viral load monitoring was not available. SO-IR was defined as failure to attain a CD4 count threshold of: i) 200?cells/μl (SO-IR200), ii) 350?cells/μl (SO-IR350), and iii) 500?cells/μl (SO-IR500), during the first five years of first-line ART. Kaplan Meier survival analysis techniques were used to assess the cumulative probability and predictors of SO-IR. RESULTS:: Overall 80,843 adults initiated NNRTI-based first-line ART; 65% were female and median CD4 count was 126 [Interquartile range (IQR), 52–202] cells/μl. After five years, the cumulative probability of SO-IR200, SO-IR350, SO-IR500 was 40%, 50% and 55% respectively. For all CD4 count thresholds, the incidence rates of AIDS-related illnesses were higher among SO-IR than those with OP-IR. The most common events were pulmonary tuberculosis [Incident rate (IR) 19.6 (19.2–20.1) /100 person-years at risk (PYAR), oral candidiasis [IR 13.8 (13.4–14.2) and Herpes zoster [IR 7.9 (7.6–8.2) events/100 PYAR. With attainment of a CD4 >200?cells/μl, there was a substantial reduction in OI events by 93% to IR 1.30 (1.23 - 1.37) events/100 PYAR for TB, by 94% to IR 0.85 (0.79–0.91) events/100 PYAR for oral candidiasis, by 90% to IR 0.79 (0.74 - 0.85) events/100 PYAR for Herpes Zoster and by 87% to IR 0.77 (0.72 - 0.83) events/100 PYAR for chronic diarrhea. Nadir CD4 count350?cells/μl after five years of first-line ART, and remain at increased risk of AIDS-related illnesses. This has important programmatic implications, as these patients require closer monitoring for the development of AIDS-defining and non-AIDS defining clinical events, as well as more prolonged prophylaxis.

Original languageEnglish (US)
JournalAIDS
DOIs
StateAccepted/In press - Mar 8 2016

Fingerprint

Eastern Africa
Acquired Immunodeficiency Syndrome
CD4 Lymphocyte Count
Oral Candidiasis
Herpes Zoster
Therapeutics
AIDS-Related Opportunistic Infections
Uganda
Tanzania
Kenya
Kaplan-Meier Estimate
Survival Analysis
Viral Load
Pulmonary Tuberculosis
Diarrhea
HIV
Morbidity
Mortality
Incidence

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Frequency and impact of suboptimal immune recovery on first-line antiretroviral therapy (ART) within the IeDEA-East Africa cohort. / Nakanjako, Damalie; Kiragga, Agnes N.; Musick, Beverly; Yiannoutsos, Constantin; Wools-Kaloustian, Kara; Diero, Lameck; Oyaro, Patrick; Lugina, Emanuel; Ssali, John C.; Kambugu, Andrew; Easterbrook, Philippa.

In: AIDS, 08.03.2016.

Research output: Contribution to journalArticle

Nakanjako, Damalie ; Kiragga, Agnes N. ; Musick, Beverly ; Yiannoutsos, Constantin ; Wools-Kaloustian, Kara ; Diero, Lameck ; Oyaro, Patrick ; Lugina, Emanuel ; Ssali, John C. ; Kambugu, Andrew ; Easterbrook, Philippa. / Frequency and impact of suboptimal immune recovery on first-line antiretroviral therapy (ART) within the IeDEA-East Africa cohort. In: AIDS. 2016.
@article{9427147933a34bbe8a9878cb8fbbbe2a,
title = "Frequency and impact of suboptimal immune recovery on first-line antiretroviral therapy (ART) within the IeDEA-East Africa cohort",
abstract = "BACKGROUND:: A proportion of HIV-infected patients who initiate antiretroviral therapy (ART) fail to achieve an optimal CD4 recovery (OP-IR), and remain at risk of HIV-related opportunistic infections and associated morbidity and mortality. Our objective was to describe patterns of suboptimal immune response (SO-IR) and associated AIDS-related illnesses during the first five years following first-line ART initiation across seven ART sites in East Africa. METHODS:: Seven ART clinical sites (3 Uganda, 2 Kenya and 2 Tanzania) in the IeDEA East African region participated in this analysis. Routine viral load monitoring was not available. SO-IR was defined as failure to attain a CD4 count threshold of: i) 200?cells/μl (SO-IR200), ii) 350?cells/μl (SO-IR350), and iii) 500?cells/μl (SO-IR500), during the first five years of first-line ART. Kaplan Meier survival analysis techniques were used to assess the cumulative probability and predictors of SO-IR. RESULTS:: Overall 80,843 adults initiated NNRTI-based first-line ART; 65{\%} were female and median CD4 count was 126 [Interquartile range (IQR), 52–202] cells/μl. After five years, the cumulative probability of SO-IR200, SO-IR350, SO-IR500 was 40{\%}, 50{\%} and 55{\%} respectively. For all CD4 count thresholds, the incidence rates of AIDS-related illnesses were higher among SO-IR than those with OP-IR. The most common events were pulmonary tuberculosis [Incident rate (IR) 19.6 (19.2–20.1) /100 person-years at risk (PYAR), oral candidiasis [IR 13.8 (13.4–14.2) and Herpes zoster [IR 7.9 (7.6–8.2) events/100 PYAR. With attainment of a CD4 >200?cells/μl, there was a substantial reduction in OI events by 93{\%} to IR 1.30 (1.23 - 1.37) events/100 PYAR for TB, by 94{\%} to IR 0.85 (0.79–0.91) events/100 PYAR for oral candidiasis, by 90{\%} to IR 0.79 (0.74 - 0.85) events/100 PYAR for Herpes Zoster and by 87{\%} to IR 0.77 (0.72 - 0.83) events/100 PYAR for chronic diarrhea. Nadir CD4 count350?cells/μl after five years of first-line ART, and remain at increased risk of AIDS-related illnesses. This has important programmatic implications, as these patients require closer monitoring for the development of AIDS-defining and non-AIDS defining clinical events, as well as more prolonged prophylaxis.",
author = "Damalie Nakanjako and Kiragga, {Agnes N.} and Beverly Musick and Constantin Yiannoutsos and Kara Wools-Kaloustian and Lameck Diero and Patrick Oyaro and Emanuel Lugina and Ssali, {John C.} and Andrew Kambugu and Philippa Easterbrook",
year = "2016",
month = "3",
day = "8",
doi = "10.1097/QAD.0000000000001085",
language = "English (US)",
journal = "AIDS",
issn = "0269-9370",
publisher = "Lippincott Williams and Wilkins",

}

TY - JOUR

T1 - Frequency and impact of suboptimal immune recovery on first-line antiretroviral therapy (ART) within the IeDEA-East Africa cohort

AU - Nakanjako, Damalie

AU - Kiragga, Agnes N.

AU - Musick, Beverly

AU - Yiannoutsos, Constantin

AU - Wools-Kaloustian, Kara

AU - Diero, Lameck

AU - Oyaro, Patrick

AU - Lugina, Emanuel

AU - Ssali, John C.

AU - Kambugu, Andrew

AU - Easterbrook, Philippa

PY - 2016/3/8

Y1 - 2016/3/8

N2 - BACKGROUND:: A proportion of HIV-infected patients who initiate antiretroviral therapy (ART) fail to achieve an optimal CD4 recovery (OP-IR), and remain at risk of HIV-related opportunistic infections and associated morbidity and mortality. Our objective was to describe patterns of suboptimal immune response (SO-IR) and associated AIDS-related illnesses during the first five years following first-line ART initiation across seven ART sites in East Africa. METHODS:: Seven ART clinical sites (3 Uganda, 2 Kenya and 2 Tanzania) in the IeDEA East African region participated in this analysis. Routine viral load monitoring was not available. SO-IR was defined as failure to attain a CD4 count threshold of: i) 200?cells/μl (SO-IR200), ii) 350?cells/μl (SO-IR350), and iii) 500?cells/μl (SO-IR500), during the first five years of first-line ART. Kaplan Meier survival analysis techniques were used to assess the cumulative probability and predictors of SO-IR. RESULTS:: Overall 80,843 adults initiated NNRTI-based first-line ART; 65% were female and median CD4 count was 126 [Interquartile range (IQR), 52–202] cells/μl. After five years, the cumulative probability of SO-IR200, SO-IR350, SO-IR500 was 40%, 50% and 55% respectively. For all CD4 count thresholds, the incidence rates of AIDS-related illnesses were higher among SO-IR than those with OP-IR. The most common events were pulmonary tuberculosis [Incident rate (IR) 19.6 (19.2–20.1) /100 person-years at risk (PYAR), oral candidiasis [IR 13.8 (13.4–14.2) and Herpes zoster [IR 7.9 (7.6–8.2) events/100 PYAR. With attainment of a CD4 >200?cells/μl, there was a substantial reduction in OI events by 93% to IR 1.30 (1.23 - 1.37) events/100 PYAR for TB, by 94% to IR 0.85 (0.79–0.91) events/100 PYAR for oral candidiasis, by 90% to IR 0.79 (0.74 - 0.85) events/100 PYAR for Herpes Zoster and by 87% to IR 0.77 (0.72 - 0.83) events/100 PYAR for chronic diarrhea. Nadir CD4 count350?cells/μl after five years of first-line ART, and remain at increased risk of AIDS-related illnesses. This has important programmatic implications, as these patients require closer monitoring for the development of AIDS-defining and non-AIDS defining clinical events, as well as more prolonged prophylaxis.

AB - BACKGROUND:: A proportion of HIV-infected patients who initiate antiretroviral therapy (ART) fail to achieve an optimal CD4 recovery (OP-IR), and remain at risk of HIV-related opportunistic infections and associated morbidity and mortality. Our objective was to describe patterns of suboptimal immune response (SO-IR) and associated AIDS-related illnesses during the first five years following first-line ART initiation across seven ART sites in East Africa. METHODS:: Seven ART clinical sites (3 Uganda, 2 Kenya and 2 Tanzania) in the IeDEA East African region participated in this analysis. Routine viral load monitoring was not available. SO-IR was defined as failure to attain a CD4 count threshold of: i) 200?cells/μl (SO-IR200), ii) 350?cells/μl (SO-IR350), and iii) 500?cells/μl (SO-IR500), during the first five years of first-line ART. Kaplan Meier survival analysis techniques were used to assess the cumulative probability and predictors of SO-IR. RESULTS:: Overall 80,843 adults initiated NNRTI-based first-line ART; 65% were female and median CD4 count was 126 [Interquartile range (IQR), 52–202] cells/μl. After five years, the cumulative probability of SO-IR200, SO-IR350, SO-IR500 was 40%, 50% and 55% respectively. For all CD4 count thresholds, the incidence rates of AIDS-related illnesses were higher among SO-IR than those with OP-IR. The most common events were pulmonary tuberculosis [Incident rate (IR) 19.6 (19.2–20.1) /100 person-years at risk (PYAR), oral candidiasis [IR 13.8 (13.4–14.2) and Herpes zoster [IR 7.9 (7.6–8.2) events/100 PYAR. With attainment of a CD4 >200?cells/μl, there was a substantial reduction in OI events by 93% to IR 1.30 (1.23 - 1.37) events/100 PYAR for TB, by 94% to IR 0.85 (0.79–0.91) events/100 PYAR for oral candidiasis, by 90% to IR 0.79 (0.74 - 0.85) events/100 PYAR for Herpes Zoster and by 87% to IR 0.77 (0.72 - 0.83) events/100 PYAR for chronic diarrhea. Nadir CD4 count350?cells/μl after five years of first-line ART, and remain at increased risk of AIDS-related illnesses. This has important programmatic implications, as these patients require closer monitoring for the development of AIDS-defining and non-AIDS defining clinical events, as well as more prolonged prophylaxis.

UR - http://www.scopus.com/inward/record.url?scp=84960193579&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84960193579&partnerID=8YFLogxK

U2 - 10.1097/QAD.0000000000001085

DO - 10.1097/QAD.0000000000001085

M3 - Article

C2 - 26959510

AN - SCOPUS:84960193579

JO - AIDS

JF - AIDS

SN - 0269-9370

ER -