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 language | English (US) |
|---|---|
| Journal | AIDS |
| DOIs | |
| State | Accepted/In press - Mar 8 2016 |
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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 journal › Article
}
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 -