The Impact of Daily Cotrimoxazole Prophylaxis and Antiretroviral Therapy on Mortality and Hospital Admissions in HIV-Infected Zambian Children

MRC Clinical Trials Unit, London, United Kingdom.
Clinical Infectious Diseases (Impact Factor: 8.89). 06/2007; 44(10):1361-7. DOI: 10.1086/515396
Source: PubMed


Data on the population effectiveness of cotrimoxazole prophylaxis and antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected African children are few.
A total of 534 Zambian children with HIV infection were randomized to receive daily cotrimoxazole prophylaxis or placebo in the Children with HIV Antibiotic Prophylaxis trial. Following trial closure, children who received the placebo initiated cotrimoxazole prophylaxis, and all children were observed in a closed cohort. Mortality and hospital admission rates were compared, over calendar time, in 9-month periods: trial recruitment (March 2001 to April 2002, May 2002 to January 2003), trial follow-up to closure (February 2003 to October 2003), initial follow-up posttrial (November 2003 to July 2004), and early and later ART availability (August 2004 to April 2005, and May 2005 to May 2006, respectively).
A total of 546 child-years of follow-up, 40 deaths, and 80 hospital admissions were observed between the time of trial closure and June 2006. A total of 117 of 283 children who were alive at trial closure received ART in the posttrial period (median child age at first use of ART, 8.8 years). Rates decreased in both groups during the trial period, suggesting a survivorship effect. Mortality and hospital admission rates before trial closure were 14 (95% confidence interval [CI], 9-21) deaths per 100 child-years and 24 (95% CI, 15-39) hospital admissions per 100 child-years, respectively, for children who were receiving cotrimoxazole, and were 23 (95% CI, 16-34) deaths per 100 child-years and 35 (95% CI, 23-53) hospital admissions per 100 child-years, respectively, for children who were receiving the placebo. After trial closure, rates remained stable in the cotrimoxazole group, but decreased to 15 (95% CI, 8-26) deaths per 100 child-years and 19 (95% CI, 10-41) hospital admissions per 100 child-years, respectively, for the group of children who received placebo and then initiated cotrimoxazole prophylaxis. In both groups combined, mortality rates decreased to 6 (95% CI, 3-11) deaths per 100 child-years and then 2 (95% CI, 0.8-6) deaths per 100 child-years during periods of ART availability; hospital admission rates decreased to 17 (95% CI, 11-27) hospital admissions per 100 child-years and 8 (95% CI, 4-15) hospital admissions per 100 child-years, respectively.
The benefits of once-daily cotrimoxazole prophylaxis continued throughout the trial and after trial closure. Mortality and hospital admissions decreased (by approximately 6-fold and approximately 3-fold, respectively) following ART availability, similar to findings observed in resource-rich countries.

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    • "This could be due to the fact that, well adherent subjects had more exposure to the co-trimoxazole drug and therefore they were more protected from malaria infection and its sequelae particularly anaemia as compared to the poor adherent one. Walker et al. [29], had previously reported the benefits of co-trimoxazole in reducing morbidities among the HIV infected population; this could similarly explain the reduction in anaemia among good adherents. "
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    ABSTRACT: HIV-infected pregnant women are particularly more susceptible to the deleterious effects of malaria infection particularly anaemia. In order to prevent opportunistic infections and malaria, a policy of daily co-trimoxazole prophylaxis without the standard Suphadoxine-Pyrimethamine intermittent preventive treatment (SP-IPT) was introduced to all HIV infected pregnant women in the year 2011. However, there is limited information about the effectiveness of this policy. This was a cross sectional study conducted among HIV-infected pregnant women receiving co-trimoxazole prophylaxis in eight public health facilities in Kinondoni Municipality from February to April 2013. Blood was tested for malaria infection and anaemia (haemoglobin <11 g/dl). Data were collected on the adherence to co-trimoxazole prophylaxis and other risk factors for malaria infection and anaemia. Pearson chi-square test, Fischer's exact test and multivariate logistic regression were used in the statistical analysis. This study enrolled 420 HIV infected pregnant women. The prevalence of malaria infection was 4.5%, while that of anaemia was 54%. The proportion of subjects with poor adherence to co-trimoxazole was 50.5%. As compared to HIV infected pregnant women with good adherence to co-trimoxazole prophylaxis, the poor adherents were more likely to have a malaria infection (Adjusted Odds Ratio, AOR = 6.81, 95%CI = 1.35-34.43, P = 0.02) or anaemia (AOR = 1.75, 95%CI = 1.03-2.98, P = 0.039). Other risk factors associated with anaemia were advanced WHO clinical stages, current malaria infection and history of episodes of malaria illness during the index pregnancy. The prevalence of malaria was low; however, a significant proportion of subjects had anaemia. Good adherence to co-trimoxazole prophylaxis was associated with reduction of both malaria infection and anaemia among HIV infected pregnant women.
    Full-text · Article · Apr 2014 · BMC pharmacology & toxicology
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    • "But a study done among Zambian children on ART reported that Daily cotrimoxazole prophylaxis has been shown to substantially reduce non–Pneumocystis jiroveci–related deaths and hospital admissions in children after infancy, and it is a recommended standard of care for all HIV-infected children. For this reason, this study recommends a further study on added impact of cotrimoxazole prophylaxis among children who are receiving ART [34]. "
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    ABSTRACT: The introduction of antiretroviral therapy in 1996 improved the longevity and wellbeing of peoples living with HIV in the industrialized world including children. This survival benefit of antiretroviral therapy (ART) in reducing HIV related deaths has been well studied in the developed world. In resource-poor settings, where such treatment was started recently, there is inadequate information about impact of ART on the survival of patients especially in children. So, this study aims to investigate predictors of mortality of children on ART. Therefore, the objective of this study was to identify predictors of mortality among children on HAART. A retrospective cohort study was conducted on 432 children who initiated antiretroviral therapy from June 2006 to June 2011 at pediatrics ART clinic in Mekelle Hospital, Northern-Ethiopia. Data were extracted from electronic and paper based medical records database and analyzed using Kaplan Meier survival and Cox proportional hazard model to identify independent predictors of children's mortality on ART. The total time contributed by the study participants were 14,235 child-months with median follow up of 36 months. The mortality rate of this cohort was 1.40 deaths per 1000 child-months or 16.85 deaths per 1000 child-years. Age less than 18 months [ Adj.HR (95% CI) = (4.39(1.15-17.41)], CD4 percentage <10 [Adj.HR (95% CI) = 2.98(1.12-7.94)], WHO clinical stage (III&IV) [Adj.HR (95% CI) = 4.457(1.01-19.66)], chronic diarrhea[Adj.HR (95% CI) = 4.637(1.50-14.31)] and hemoglobin < 8 g/dl[Adj.HR (95% CI) = 3.77(1.29-10.98)] all at baseline were significantly and independently associated with survival of children on ART. Mortality of children on ART was low and factors that affect mortality of children on ART were age less than 18 months, lower CD4 percentage, advanced WHO clinical stage (III&IV), presence of chronic diarrhea and lower hemoglobin level all at baseline. The high early mortality rate would support the value of an earlier treatment start before development of signs of immunodeficiency syndrome despite the method of HIV diagnosis and WHO stage.
    Full-text · Article · Nov 2013 · BMC Public Health
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    • "The World Health Organisation (WHO) guidelines recommend provision of co-trimoxazole prophylaxis to all HIV symptomatic adults with CD4 count lower than 350 cells per μL in resource-limited settings [51]. Co-trimoxazole prophylaxis has been found to reduce mortality and morbidity amongst PLHIV through prevention and control of opportunistic infections [52,53]. Based on their knowledge of these conventional medicines and experiences with the formal health system and social network ties, PLHIV opted to obtain antibiotics in order to manage AIDS-related ailments. "
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    ABSTRACT: Background Despite the increasingly wider availability of antiretroviral therapy (ART), some people living with HIV (PLHIV) and eligible for treatment have opted to adopt self-care practices thereby risking early AIDS-related mortality. Methods A qualitative study was conducted in urban Zambia to gain insights into PLHIV self-care practices and experiences and explore the implications for successful delivery of ART care. Between March 2010 and September 2011, in-depth interviews were conducted with PLHIV who had dropped out of treatment (n=25) and those that had opted not to initiate medication (n=37). Data was entered into and managed using Atlas ti, and analysed inductively using latent content analysis. Results PHIV used therapeutic and physical health maintenance, psychological well-being and healthy lifestyle self-care practices to maintain physical health and mitigate HIV-related symptoms. Herbal remedies, faith healing and self-prescription of antibiotics and other conventional medicines to treat HIV-related ailments were used for therapeutic and physical health maintenance purposes. Psychological well-being self-care practices used were religiosity/spirituality and positive attitudes towards HIV infection. These practices were modulated by close social network relationships with other PLHIV, family members and peers, who acted as sources of emotional, material and financial support. Cessations of sexual relationships, adoption of safe sex to avoid re-infections and uptake of nutritional supplements were the commonly used risk reduction and healthy lifestyle practices respectively. Conclusions While these self-care practices may promote physical and psychosocial well-being and mitigate AIDS-related symptoms, at least in the short term, they however undermine PLHIV access to ART care thereby putting PLHIV at risk of early AIDS-related mortality. The use of scientifically unproven herbal remedies raises health and safety concerns; faith healing may create fatalism and resignation with death while the reported self-prescription of antibiotics to treat HIV-related infections raises concerns about future development of microbial drug resistance amongst PLHIV. Collectively, these self-care practices undermine efforts to effectively abate the spread and burden of HIV and reduce AIDS-related mortality. Therefore, there is need for sensitization campaigns on the benefits of ART and the risks associated with widespread self-prescription of antibiotics and use of scientifically unproven herbal remedies.
    Full-text · Article · May 2013 · AIDS Research and Therapy
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