AIDS and Non-AIDS Morbidity and Mortality Across the Spectrum of CD4 Cell Counts in HIV-Infected Adults Before Starting Antiretroviral Therapy in Côte d’Ivoire

Anglaret, Xavier; Minga, Albert; Gabillard, Delphine; Ouassa, Timothée; Messou, Eugène; Morris, Brandon; Traoré, Moussa; Coulibaly, Adama; Freedberg, Kenneth A.; Lewden, Charlotte; Menan, Hervé; Abo, Yao; Dakoury-Dogbo, Nicole; Touré, Siaka; Seyler, Catherine

doi:10.1093/cid/cir898

Cited by 90 publications

(88 citation statements)

References 27 publications

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“…The burden of AIDS and mortality seen in our study, and in other cohorts in Africa, 16 is higher than in European populations with similar CD4 counts. 17 Time-to-first AIDS event was significantly longer in patients allocated to the early treatment group than in those assigned to delayed antiretroviral treatment.…”

Section: Discussioncontrasting

confidence: 53%

Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial

Grinsztejn

Hosseinipour

Ribaudo

et al. 2014

The Lancet Infectious Diseases

471

396

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Summary Background Use of antiretroviral treatment for HIV-1 infection has decreased AIDS-related morbidity and mortality and prevents sexual transmission of HIV-1. However, the best time to initiate antiretroviral treatment to reduce progression of HIV-1 infection or non-AIDS clinical events is unknown. We reported previously that early antiretroviral treatment reduced HIV-1 transmission by 96%. We aimed to compare the effects of early and delayed initiation of antiretroviral treatment on clinical outcomes. Methods The HPTN 052 trial is a randomised controlled trial done at 13 sites in nine countries. We enrolled HIV-1-serodiscordant couples to the study and randomly allocated them to either early or delayed antiretroviral treatment by use of permuted block randomisation, stratified by site. Random assignment was unblinded. The HIV-1-infected member of every couple initiated antiretroviral treatment either on entry into the study (early treatment group) or after a decline in CD4 count or with onset of an AIDS-related illness (delayed treatment group). Primary events were AIDS clinical events (WHO stage 4 HIV-1 disease, tuberculosis, and severe bacterial infections) and the following serious medical conditions unrelated to AIDS: serious cardiovascular or vascular disease, serious liver disease, end-stage renal disease, new-onset diabetes mellitus, and non-AIDS malignant disease. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00074581. Findings 1763 people with HIV-1 infection and a serodiscordant partner were enrolled in the study; 886 were assigned early antiretroviral treatment and 877 to the delayed treatment group (two individuals were excluded from this group after randomisation). Median CD4 counts at randomisation were 442 (IQR 373–522) cells per μL in patients assigned to the early treatment group and 428 (357–522) cells per μL in those allocated delayed antiretroviral treatment. In the delayed group, antiretroviral treatment was initiated at a median CD4 count of 230 (IQR 197–249) cells per μL. Primary clinical events were reported in 57 individuals assigned to early treatment initiation versus 77 people allocated to delayed antiretroviral treatment (hazard ratio 0·73, 95% CI 0·52–1·03; p=0·074). New-onset AIDS events were recorded in 40 participants assigned to early antiretroviral treatment versus 61 allocated delayed initiation (0·64, 0·43–0·96; p=0·031), tuberculosis developed in 17 versus 34 patients, respectively (0·49, 0·28–0·89, p=0·018), and primary non-AIDS events were rare (12 in the early group vs nine with delayed treatment). In total, 498 primary and secondary outcomes occurred in the early treatment group (incidence 24·9 per 100 person-years, 95% CI 22·5–27·5) versus 585 in the delayed treatment group (29·2 per 100 person-years, 26·5–32·1; p=0·025). 26 people died, 11 who were allocated to early antiretroviral treatment and 15 who were assigned to the delayed treatment group. Interpretation Early initiation of antiretroviral treatment...

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Section: Discussioncontrasting

confidence: 53%

Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial

Grinsztejn

Hosseinipour

Ribaudo

et al. 2014

The Lancet Infectious Diseases

471

396

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“…These infectious diseases are both common and opportunistic, meaning that their incidence is high in the general population, higher among HIV-infected patients with high CD4+ cell counts, and extremely high among patients with low CD4+ cell counts. 8, 9 They have consistently been shown to be major causes of death among HIV-infected patients in settings where access to diagnosis and treatment is low. [10][11][12][13][14][15][16] These diseases triggered the question "Should we start ART earlier?"…”

mentioning

confidence: 99%

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

2015

N Engl J Med

1,034

447

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BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.)

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“…Infections, such as tuberculosis (TB), malaria, bacteraemia, and fungal infections, along with malnutrition are main causes of morbidity and mortality among drug-naïve individuals living with HIV in Africa (Brindle et al, 1993;Lucas et al, 1993;Grant et al, 1997;Anglaret et al, 1999;Freedberg, 2003;Ole-Nguyaine et al, 2004;Holmes, Losina, Walensky, Yazdanpanah, & Iwuji et al, 2011;Anglaret et al, 2012). Gastroenteritis and chronic diarrhoea have been reported frequently in drug-naïve patients living with HIV (Clerinx et al, 1995;Grant et al, 1997;Ole-Nguyaine et al, 2004;Anglaret et al, 2012).…”

mentioning

confidence: 99%

“…Gastroenteritis and chronic diarrhoea have been reported frequently in drug-naïve patients living with HIV (Clerinx et al, 1995;Grant et al, 1997;Ole-Nguyaine et al, 2004;Anglaret et al, 2012). Bacterial pneumonia was the most common illness observed in a Ugandan cohort study both before and after ART became available (Iwuji et al, 2011).…”

mentioning

confidence: 99%

“…Other serious infections documented in HIV-infected drug-naïve individuals include parasitic infections, cerebral toxoplasmosis, isosporiasis (a protozoal gastrointestinal infection), and fungal infections such as candidiasis, cryptococcosis and cryptococcal meningitis (Lucas et al, 1993;Grant et al, 1997;Anglaret et al, 1999;McCarthy et al, 2006;Iwuji et al, 2011;Anglaret et al, 2012). After controlling for the use of antivirals and antifungals, CD4 counts < 200 cells/µL have been associated with oral candidiasis in women (Greenspan et al, 2000).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Morbidity and nutrition status of rural drug-naïve Kenyan women living with HIV

Neumann

Nyandiko

Siika

et al. 2016

African Journal of AIDS Research

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AIDS and Non-AIDS Morbidity and Mortality Across the Spectrum of CD4 Cell Counts in HIV-Infected Adults Before Starting Antiretroviral Therapy in Côte d’Ivoire

Abstract: Rates of AIDS or death, tuberculosis, and invasive bacterial diseases are substantial in patients with CD4 cell counts ≥200 cells/μL. Tuberculosis and bacterial diseases should be the most important outcomes in future trials of early ART in sub-Saharan Africa.

Cited by 90 publications

References 27 publications

Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial

Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

Morbidity and nutrition status of rural drug-naïve Kenyan women living with HIV

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