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      Further benefits by early start of HIV treatment in low income countries: Survival estimates of early versus deferred antiretroviral therapy

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      1 , , 1 , 1
      AIDS Research and Therapy
      BioMed Central

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          Abstract

          Background

          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.

          Methods

          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.

          Results

          Providing HAART early when CD4 is 200-350 cells/μl 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/μl 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/μl can expect to live 4.8; 2.0 and 0.7 life years respectively.

          Conclusions

          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.

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          Most cited references31

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          Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes.

          The Zambian Ministry of Health has scaled-up human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) care and treatment services at primary care clinics in Lusaka, using predominately nonphysician clinicians. To report on the feasibility and early outcomes of the program. Open cohort evaluation of antiretroviral-naive adults treated at 18 primary care facilities between April 26, 2004, and November 5, 2005. Data were entered in real time into an electronic patient tracking system. Those meeting criteria for antiretroviral therapy (ART) received drugs according to Zambian national guidelines. Survival, regimen failure rates, and CD4 cell response. We enrolled 21,755 adults into HIV care, and 16,198 (75%) started ART. Among those starting ART, 9864 (61%) were women. Of 15,866 patients with documented World Health Organization (WHO) staging, 11,573 (73%) were stage III or IV, and the mean (SD) entry CD4 cell count among the 15,336 patients with a baseline result was 143/microL (123/microL). Of 1142 patients receiving ART who died, 1120 had a reliable date of death. Of these patients, 792 (71%) died within 90 days of starting therapy (early mortality rate: 26 per 100 patient-years), and 328 (29%) died after 90 days (post-90-day mortality rate: 5.0 per 100 patient-years). In multivariable analysis, mortality was strongly associated with CD4 cell count between 50/microL and 199/microL (adjusted hazard ratio [AHR], 1.4; 95% confidence interval [CI], 1.0-2.0), CD4 cell count less than 50/microL (AHR, 2.2; 95% CI, 1.5-3.1), WHO stage III disease (AHR, 1.8; 95% CI, 1.3-2.4), WHO stage IV disease (AHR, 2.9; 95% CI, 2.0-4.3), low body mass index (<16; AHR,2.4; 95% CI, 1.8-3.2), severe anemia (<8.0 g/dL; AHR, 3.1; 95% CI, 2.3-4.0), and poor adherence to therapy (AHR, 2.9; 95% CI, 2.2-3.9). Of 11,714 patients at risk, 861 failed therapy by clinical criteria (rate, 13 per 100 patient-years). The mean (SD) CD4 cell count increase was 175/microL (174/microL) in 1361 of 1519 patients (90%) receiving treatment long enough to have a 12-month repeat. Massive scale-up of HIV and AIDS treatment services with good clinical outcomes is feasible in primary care settings in sub-Saharan Africa. Most mortality occurs early, suggesting that earlier diagnosis and treatment may improve outcomes.
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            Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies.

            Insufficient data are available from single cohort studies to allow estimation of the prognosis of HIV-1 infected, treatment-naive patients who start highly active antiretroviral therapy (HAART). The ART Cohort Collaboration, which includes 13 cohort studies from Europe and North America, was established to fill this knowledge gap. We analysed data on 12,574 adult patients starting HAART with a combination of at least three drugs. Data were analysed by intention-to-continue-treatment, ignoring treatment changes and interruptions. We considered progression to a combined endpoint of a new AIDS-defining disease or death, and to death alone. The prognostic model that generalised best was a Weibull model, stratified by baseline CD4 cell count and transmission group. FINDINGS During 24,310 person-years of follow up, 1094 patients developed AIDS or died and 344 patients died. Baseline CD4 cell count was strongly associated with the probability of progression to AIDS or death: compared with patients starting HAART with less than 50 CD4 cells/microL, adjusted hazard ratios were 0.74 (95% CI 0.62-0.89) for 50-99 cells/microL, 0.52 (0.44-0.63) for 100-199 cells/microL, 0.24 (0.20-0.30) for 200-349 cells/microL, and 0.18 (0.14-0.22) for 350 or more CD4 cells/microL. Baseline HIV-1 viral load was associated with a higher probability of progression only if 100,000 copies/microL or above. Other independent predictors of poorer outcome were advanced age, infection through injection-drug use, and a previous diagnosis of AIDS. The probability of progression to AIDS or death at 3 years ranged from 3.4% (2.8-4.1) in patients in the lowest-risk stratum for each prognostic variable, to 50% (43-58) in patients in the highest-risk strata. The CD4 cell count at initiation was the dominant prognostic factor in patients starting HAART. Our findings have important implications for clinical management and should be taken into account in future treatment guidelines.
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              Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa.

              A community-based antiretroviral therapy (ART) programme was established in 2001 in a South African township to explore the operational issues involved in providing ART in the public sector in resource-limited settings and demonstrate the feasibility of such a service. Data was analysed on a cohort of patients with symptomatic HIV disease and a CD4 lymphocyte count or =50 x 10 cells/l, and 81.8% for those with a baseline CD4 lymphocyte count < 50 x 10 cells/l. The cumulative probability of changing a single antiretroviral drug by 24 months was 15.1% due to adverse events or contraindications, and 8.4% due to adverse events alone. ART can be provided in resource-limited settings with good patient retention and clinical outcomes. With responsible implementation, ART is a key component of a comprehensive response to the epidemic in those communities most affected by HIV.
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                Author and article information

                Journal
                AIDS Res Ther
                AIDS Research and Therapy
                BioMed Central
                1742-6405
                2010
                16 January 2010
                : 7
                : 3
                Affiliations
                [1 ]University of Bergen, Department of Public Health and Centre for International Health, Research Group in Global Health: Ethics, Economics and Culture, PB 7804, 5020 Bergen, Norway
                Article
                1742-6405-7-3
                10.1186/1742-6405-7-3
                2836271
                20180966
                6b216ab7-f4d6-44a4-a2cf-21b64a0c862a
                Copyright ©2010 Johansson et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 August 2009
                : 16 January 2010
                Categories
                Research

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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