Calmy A, Pinoges L, Szumilin E, Zachariah R, Ford N, Ferradini L. Generic fixed-dose combination antiretroviral treatment in resource-poor settings: multicentric observational cohort

MSF, Campaign for Access to Essential Medicines, 78 rue de Lausanne, 1205 Geneva, Switzerland.
AIDS (Impact Factor: 5.55). 06/2006; 20(8):1163-9. DOI: 10.1097/01.aids.0000226957.79847.d6
Source: PubMed


The use fixed-dose combination (FDC) is a critical tool in improving HAART. Studies on the effectiveness of combined lamivudine, stavudine and nevirapine (3TC/d4T/NVP) are scarce.
To analyse 6861 patients in a large observational cohort from 21 Médecins Sans Frontieres (MSF) HIV/AIDS programmes taking 3TC/d4T/NVP, with subcohort analyses of patients at 12 and 18 months of treatment.
Survival was analysed using Kaplan-Meier method and factors associated with progression to death with Cox proportional hazard ratio.
Median baseline CD4 cell count at initiating of FDC was 89 cells/microl [interquartile range (IQR), 33-158]. The median follow-up time was 4.1 months (IQR, 1.9-7.3). The incidence rate of death during follow-up was 14.2/100 person-years [95% confidence interval (CI), 13.8-14.5]. Estimates of survival (excluding those lost to follow-up) were 0.93 (95% CI, 92-94) at 6 months (n = 2,231) and 0.90 (95% CI, 89-91) at 12 months (n = 472). Using a Cox model, the following factors were associated with death: male gender, symptomatic infection, body mass index < 18 kg/m and CD4 cell count 15-50 cells/microl or < 15 cells/microl. Subcohort analysis of 655 patients after 1 year of follow-up (M12 FDC cohort) revealed that 77% remained on HAART, 91% of these still on the FDC regimen; 5% discontinued the FDC because of drug intolerance. At 18 months, 77% of the patients remained on HAART.
Positive outcomes for d4T/3TC/NVP are reported for up to 18 months in terms of efficacy and safety.

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Available from: Laurent Ferradini
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    • "Retention proportions are also greatly affected by the choice of LTFU definition (Shepherd et al. 2013). Many of the baseline clinical characteristics predictive of attrition reinforce findings from other studies in sub- Saharan Africa, including younger age (<30 years), being male, having a higher WHO clinical stage, weight loss of >10% of body mass, a lower CD4 cell count and a poorer functional status (Coetzee et al. 2004; Ferradini et al. 2006; Calmy et al. 2006). These findings reaffirm the need for early identification of HIV-infected individuals and early initiation of ART. "
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    ABSTRACT: Objectives We assessed retention and predictors of attrition (recorded death or loss to follow-up) in antiretroviral treatment (ART) clinics in Tanzania, Uganda and Zambia.Methods We conducted a retrospective cohort study among adults (≥18 years) starting ART during 2003–2010. We purposefully selected six health facilities per country and randomly selected 250 patients from each facility. Patients who visited clinics at least once during the 90 days before data abstraction were defined as retained. Data on individual and programme level risk factors for attrition were obtained through chart review and clinic manager interviews. Kaplan–Meier curves for retention across sites were created. Predictors of attrition were assessed using a multivariable Cox-proportional hazards model, adjusted for site-level clustering.ResultsFrom 17 facilities, 4147 patients were included. Retention ranged from 52.0% to 96.2% at 1 year to 25.8%–90.4% at 4 years. Multivariable analysis of ART initiation characteristics found the following independent risk factors for attrition: younger age [adjusted hazard ratio (aHR) and 95% confidence interval (95%CI) = 1.30 (1.14–1.47)], WHO stage 4 ([aHR (95% CI): 1.56 (1.29–1.88)], >10% bodyweight loss [aHR (95%CI) = 1.17 (1.00–1.38)], poor functional status [ambulatory aHR (95%CI) = 1.29 (1.09–1.54); bedridden aHR1.54 (1.15–2.07)], and increasing years of clinic operation prior to ART initiation in government facilities [aHR (95%CI) = 1.17 (1.10–1.23)]. Patients with higher CD4 cell count were less likely to experience attrition [aHR (95%CI) = 0.88 (0.78–1.00)] for every log (tenfold) increase. Sites offering community ART dispensing [aHR (95%CI) = 0.55 (0.30–1.01) for women; 0.40 (0.21–0.75) for men] had significantly less attrition.Conclusions Patient retention to an individual programme worsened over time especially among males, younger persons and those with poor clinical indicators. Community ART drug dispensing programmes could improve retention.
    Full-text · Article · Sep 2014 · Tropical Medicine & International Health
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    • "Hepatotoxicity studies in these settings reveal a heterogeneous picture. Reported rates of early hepatotoxicity in people initiating HAART in African studies are generally low at 1-2% [25-33] but occasionally much higher at 3.4-18.4% [34-37]. "
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    ABSTRACT: Background The development of jaundice after initiation of HAART in HIV-TB co-infected patients is a challenging presentation in resource constrained settings, and is often attributed to drug induced liver injury (DILI).Some investigators have described hepatic tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) as a cause of liver disease in patients initiating HAART, which could also cause jaundice. Case presentations We report the clinical and histopathological features of five HIV-TB co-infected patients presenting with a syndrome of jaundice, tender hepatomegaly, bile canalicular enzyme rise and return of constitutional symptoms within 8 weeks of initiation of highly active antiretroviral therapy (HAART) for advanced HIV infection at a rural clinic in KwaZulu Natal, South Africa. All five patients had been diagnosed with tuberculosis infection prior to HAART initiation and were on antituberculous medication at time of developing jaundice. There was evidence of multiple aetiologies of liver injury in all patients. However, based on clinical course and pathological findings, predominant hepatic injury was thought to be drug induced in one case and hepatic tuberculosis associated immune reconstitution inflammatory syndrome (TB-IRIS) in the other four. In these later 4 patients, liver biopsy findings included necrotising and non-necrotising granulomatous inflammation in the lobules and portal tracts. The granulomas demonstrated – in addition to epithelioid histiocytes and Langhans giant cells – neutrophils, plasma cells and large numbers of lymphocytes, which are not features of a conventional untreated tuberculous response. Conclusion In this high TB prevalent, low resource setting, TB-IRIS may be an important cause of jaundice post-HAART initiation. Clinicopathological correlation is essential for optimal diagnosis. Further multi-organ based histopathological studies in the context of immune reconstitution would be useful to clinicians in low resource settings dealing with this challenging presentation.
    Full-text · Article · Oct 2012 · BMC Infectious Diseases
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    • "National government initiatives sometimes supported by UNAIDS, and programmes implemented by non-governmental organizations clearly demonstrated in the late 1990s and early 2000s that programmes addressing access to antiretroviral treatment (ART) in low- and middle-income countries (LMIC) were feasible [1–5]. "
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    ABSTRACT: Many successes have been achieved in HIV care in low- and middle-income countries (LMIC): increased number of HIV-infected individuals receiving antiretroviral treatment (ART), wide decentralization, reduction in morbidity and mortality and accessibility to cheapest drugs. However, these successes should not hide existing failures and difficulties. In this paper, we underline several key challenges. First, ensure long-term financing, increase available resources, in order to meet the increasing needs, and redistribute the overall budget in a concerted way amongst donors. Second, increase ART coverage and treat the many eligible patients who have not yet started ART. Competition amongst countries is expected to become a strong driving force in encouraging the least efficient to join better performing countries. Third, decrease early mortality on ART, by improving access to prevention, case-finding and treatment of tuberculosis and invasive bacterial diseases and by getting people to start ART much earlier. Fourth, move on from WHO 2006 to WHO 2010 guidelines. Raising the cut-off point for starting ART to 350 CD4/mm(3) needs changing paradigm, adopting opt-out approach, facilitating pro-active testing, facilitating task shifting and increasing staff recruitments. Phasing out stavudine needs acting for a drastic reduction in the costs of other drugs. Scaling up routine viral load needs a mobilization for lower prices of reagents and equipments, as well as efforts in relation to point-of-care automation and to maintenance. The latter is a key step to boost the utilization of second-line regimens, which are currently dramatically under prescribed. Finally, other challenges are to reduce lost-to-follow-up rates; manage lifelong treatment and care for long-term morbidity, including drug toxicity, residual AIDS and HIV-non-AIDS morbidity and aging-related morbidity; and be able to face unforeseen events such as socio-political and military crisis. An old African proverb states that the growth of a deep-rooted tree cannot be stopped. Our tree is well rooted in existing field experience and is, therefore, expected to grow. In order for us to let it grow, long-term cost-effectiveness approach and life-saving evidence-based programming should replace short-term budgeting approach.
    Full-text · Article · Aug 2012 · Journal of the International AIDS Society
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