Short-term risk of AIDS or death in people infected with HIV-1 before antiretroviral therapy in South Africa: A longitudinal study

Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory 7925, Cape Town, South Africa.
The Lancet (Impact Factor: 45.22). 11/2006; 368(9543):1254-9. DOI: 10.1016/S0140-6736(06)69117-4
Source: PubMed


In sub-Saharan Africa, data for short-term risk of AIDS or death, which might inform decisions about when to start antiretroviral therapy (ART), are scarce. Our aim was to investigate these risks in patients who had no access to ART or who were given zidovudine alone.
6-month risks (%) of death, AIDS, and combined risk of AIDS and death (AIDS/death) were calculated according to CD4-cell count category of less than 200 cells per microL, 200-350 cells per microL, or greater than 350 cells per microL, stratified by WHO clinical stages 1 and 2 combined, 3, or 4 in untreated patients (n=1399) seeking care in tertiary public-sector HIV clinics before widespread availability of ART in Cape Town, South Africa.
Risk of death for WHO stages 1 and 2 was 3.5% for those with less than 200 cells per microL, 2.8% for 200-350 cells per microL, and 1.2% for greater than 350 cells per microL. The corresponding rates for WHO stage 3 were 10.8%, 4.3%, and 4.9% and for stage 4, 22.2%, 10.3%, and 13.8%. 52% (90) of deaths took place in patients without AIDS. 6-month risk of AIDS for WHO stages 1 and 2 was 3.5% for those with less than 200 cells per microL, 1.6% for 200-350 cells per microL, and zero for greater than 350 cells per microL. The corresponding rates for those with WHO stage 3 disease were 17.4%, 7.0%, and 2.2%.
In this study, risk of AIDS in patients with a CD4-cell count of less than 200 cells per microL or greater than 350 cells per microL was similar to that previously reported from European cohorts, but was 1.9 times greater for those with CD4-cell counts of between 200 and 350 cells per microL. The high death rate before development of AIDS and a high risk of AIDS in those with CD4-cell counts of 200-350 cells per microL indicate that delay in initiation of ART is associated with increased morbidity and mortality. These findings might help to amend criteria for start of ART in resource-limited settings.

Download full-text


Available from: Robin Wood, Jul 10, 2014
4 Reads
  • Source
    • "HIV progression rates prior to and while receiving ART were based on published studies from South Africa [32,33]. ART was assumed to reduce mortality and lower infectivity. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Antiretroviral therapy (ART) and oral pre-exposure prophylaxis (PrEP) are effective in reducing HIV transmission in heterosexual adults. The epidemiologic impact and cost-effectiveness of combined prevention approaches in resource-limited settings remain unclear. We develop a dynamic mathematical model of the HIV epidemic in South Africa's adult population. We assume ART reduces HIV transmission by 95% and PrEP by 60%. We model two ART strategies: scaling up access for those with CD4 counts ≤ 350 cells/μL (Guidelines) and for all identified HIV-infected individuals (Universal). PrEP strategies include use in the general population (General) and in high-risk individuals (Focused). We consider strategies where ART, PrEP, or both are scaled up to 100% of remaining eligible individuals yearly. We measure infections averted, quality-adjusted life-years (QALYs) gained and incremental cost-effectiveness ratios over 20 years. Scaling up ART to 50% of eligible individuals averts 1,513,000 infections over 20 years (Guidelines) and 3,591,000 infections (Universal). Universal ART is the most cost-effective strategy at any scale ($160-$220/QALY versus comparable scale Guidelines ART expansion). General PrEP is costly and provides limited benefits beyond ART scale-up ($7,680/QALY to add 100% PrEP to 50% Universal ART). Cost-effectiveness of General PrEP becomes less favorable when ART is widely given ($12,640/QALY gained when added to 100% Universal ART). If feasible, Focused PrEP is cost saving or highly cost effective versus status quo and when added to ART strategies. Expanded ART coverage to individuals in early disease stages may be more cost-effective than current guidelines. PrEP can be cost-saving if delivered to individuals at increased risk of infection.
    BMC Medicine 03/2014; 12(1):46. DOI:10.1186/1741-7015-12-46 · 7.25 Impact Factor
  • Source
    • "Effect size in terms of life expectancy can therefore only be evaluated through modelling. We identified six observational studies showing survival before initiation of HAART in low-income settings with accurate information on stratified survival according to baseline CD4 count (table 1); two from South Africa [27,28] and Thailand [29,30] and one from Uganda [31] and Gambia [32]. We found 13 observational studies showing survival after HAART in low-income settings with accurate information on stratified survival according to baseline CD4 count at start of HAART (table 2); two from Senegal [13,33], South Africa [27,34] and Botswana [35,36] and one from Cambodia [37], Côte d'Ivoire [38], Zambia [12], West-Africa [15] Haiti [39] and Malawi [14] and one multicentre study from several low income countries (ART LINC) [9]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: International HIV guidelines have recently shifted from a medium-late to an early-start treatment strategy. As a consequence, more people will be eligible to Highly Active Antiretroviral Therapy (HAART). We estimate mean life years gained using different treatment indications in low income countries. We carried out a systematic search to identify relevant studies on the treatment effect of HAART. Outcome from identified observational studies were combined in a pooled-analyses and we apply these data in a Markov life cycle model based on a hypothetical Tanzanian HIV population. Survival for three different HIV populations with and without any treatment is estimated. The number of patients included in our pooled-analysis is 35,047. Providing HAART early when CD4 is 200-350 cells/microl is likely to be the best outcome strategy with an expected net benefit of 14.5 life years per patient. The model predicts diminishing treatment benefits for patients starting treatment when CD4 counts are lower. Patients starting treatment at CD4 50-199 and <50 cells/microl have expected net health benefits of 7.6 and 7.3 life years. Without treatment, HIV patients with CD4 counts 200-350; 50-199 and < 50 cells/microl can expect to live 4.8; 2.0 and 0.7 life years respectively. This study demonstrates that HIV patients live longer with early start strategies in low income countries. Since low income countries have many constraints to full coverage of HAART, this study provides input to a more transparent debate regarding where to draw explicit eligibility criteria during further scale up of HAART.
    AIDS Research and Therapy 01/2010; 7(1):3. DOI:10.1186/1742-6405-7-3 · 1.46 Impact Factor
  • Source
    • "Moreover pre-ART loss to follow-up (LTFU) is high in resource-limited settings (RLSs) and underreported (Bassett et al. 2009). A significant amount of HIV-associated morbidity and mortality occurs even prior to eligibility (Badri et al. 2006; Lawn & Wood 2007). In this paper we want to highlight the importance of a comprehensive approach to programme monitoring, including as well patients who are not yet on ART. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate a 5-year HIV care programme (2003-2007) in the Sihanouk Hospital Center of HOPE, Phnom Penh, Cambodia. Analysis of routine programme indicators per year: number of new patients, active patients, antiretroviral therapy (ART) coverage in the cohort, mortality and loss to follow-up. Comparison of mortality before and after the start of ART using Kaplan-Meier survival curves. Analysis of risk factors using Cox regression for the combined endpoint of mortality and loss to follow-up in patients on ART. 3844 patients were registered in the hospital between March 2003 and December 2007. The mortality and loss to follow-up rate fell and paralleled the rise of ART coverage from 23% in 2003 to 90% in 2007. The mortality and the loss to follow-up rate was significantly higher in patients not on ART but eligible (Log rank P < 0.001). The combined endpoint of mortality and loss to follow-up was 48.7% after one year in patients who were waiting for ART. 1667 patients were started on ART. The combined endpoint (mortality and loss to follow-up) in this group was 11.5% at 12 months and 14.2% at 24 months. Risk factors for mortality in the ART group were male sex, CD4 count <50 cells/microl, BMI <18 and haemoglobin levels <10 g/dl. Better access to ART is associated with lower mortality and fewer losses to follow-up. Pre-ART attrition remains significant. Strategies are needed to enable an earlier start of ART and to promote retention in care.
    Tropical Medicine & International Health 08/2009; 14(9):1048-58. DOI:10.1111/j.1365-3156.2009.02334.x · 2.33 Impact Factor
Show more