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Impact of antiretroviral therapy on opportunistic infections of HIV-infected children in the therapeutic research, education and AIDS training asia pediatric HIV observational database.

ABSTRACT: There are limited data on opportunistic infections (OIs) and factors associated with their occurrence after highly active antiretroviral therapy (HAART) in Asian children. The use of HAART in Asia started much later than in developed countries and therefore reported findings may not be fully applicable to the pediatric HIV epidemic in Asia.Retrospective and prospectively collected data from the Therapeutic Research, Education and AIDS Training Asia Pediatric HIV Observational Database cohort study from March 1993 to March 2009 were analyzed. OIs were defined according to World Health Organization clinical staging criteria and incidence rates calculated. Factors associated with the incidence of severe OIs were analyzed using random effects Poisson regression modeling.Of 2280 children in the cohort, 1752 were ever reported to have received antiretroviral therapy, of whom 1480 (84%) started on HAART. Before commencing any antiretroviral therapy, OIs occurred at a rate of 89.5 per 100 person-years. The incidence rate was 28.8 infections per 100 person-years during mono- or dual-therapy and 10.5 infections per 100 person-years during HAART. The most common OIs both before and after antiretroviral therapy initiation were recurrent upper respiratory tract infections, persistent oral candidiasis and pulmonary tuberculosis. The incidence rates of World Health Organization clinical stage 3 or 4 OIs after HAART were highest among children <18 months of age and those with low weight-for-age z scores, CD4 cell % <15%, and World Health Organization stage 3 at HAART initiation.Despite dramatic declines in their incidence, OIs remained important causes of morbidity after HAART initiation in this regional cohort of HIV-infected children in Asia.

SUBMITTER: Prasitsuebsai W

PROVIDER: S-EPMC4055535 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Project description:BackgroundAntiretroviral therapy (ART) has evolved rapidly since its beginnings. This analysis describes trends in first-line ART use in Asia and their impact on treatment outcomes.MethodsPatients in the TREAT Asia HIV Observational Database receiving first-line ART for ≥ 6 months were included. Predictors of treatment failure and treatment modification were assessed.ResultsData from 4662 eligible patients was analysed. Patients started ART in 2003-2006 (n = 1419), 2007-2010 (n = 2690) and 2011-2013 (n = 553). During the observation period, tenofovir, zidovudine and abacavir use largely replaced stavudine. Stavudine was prescribed to 5.8% of ART starters in 2012/13. Efavirenz use increased at the expense of nevirapine, although both continue to be used extensively (47.5% and 34.5% of patients in 2012/13, respectively). Protease inhibitor use dropped after 2004. The rate of treatment failure or modification declined over time (22.1 [95%CI 20.7-23.5] events per 100 patient/years in 2003-2006, 15.8 [14.9-16.8] in 2007-2010, and 11.6 [9.4-14.2] in 2011-2013). Adjustment for ART regimen had little impact on the temporal decline in treatment failure rates but substantially attenuated the temporal decline in rates of modification due to adverse event. In the final multivariate model, treatment modification due to adverse event was significantly predicted by earlier period of ART initiation (hazard ratio 0.52 [95%CI 0.33-0.81], p = 0.004 for 2011-2013 versus 2003-2006), older age (1.56 [1.19-2.04], p = 0.001 for ≥ 50 years versus <30 years), female sex (1.29 [1.11-1.50], p = 0.001 versus male), positive hepatitis C status (1.33 [1.06-1.66], p = 0.013 versus negative), and ART regimen (11.36 [6.28-20.54], p<0.001 for stavudine-based regimens versus tenofovir-based).ConclusionsThe observed trends in first-line ART use in Asia reflect changes in drug availability, global treatment recommendations and prescriber preferences over the past decade. These changes have contributed to a declining rate of treatment modification due to adverse event, but not to reductions in treatment failure.

Project description:IntroductionAIDS-related deaths in people living with HIV/AIDS have been decreasing in number since the introduction of combination antiretroviral treatment (cART). However, data on recent causes of death in the Asia-Pacific region are limited. Hence, we analysed and compared AIDS-related and non-AIDS-related mortality in high- and low-income settings in the region.MethodsPatients from the TREAT Asia HIV Observational Database (TAHOD) and Australian HIV Observational Database (AHOD) receiving cART between 1999 and 2017 were included. Causes of death verification were based on review of the standardized Cause of Death (CoDe) form designed by the D:A:D group. Cohorts were grouped as AHOD (all high-income sites), TAHOD-high (high/upper-middle income countries) and TAHOD-low (lower-middle income countries). TAHOD sites were split into high/upper-middle income and lower-middle income country settings based on World Bank classifications. Competing risk regression was used to analyse factors associated with AIDS and non-AIDS-related mortality.ResultsOf 10,386 patients, 522 died; 187 from AIDS-related and 335 from non-AIDS-related causes. The overall incidence rate of deaths during follow-up was 0.28 per 100 person-years (/100 PYS) for AIDS and 0.51/100 PYS for non-AIDS. Analysis indicated that the incidence rate of non-AIDS mortality decreased from 0.78/100 PYS to 0.37/100 PYS from year groups 2003 to 2007 to 2013 to 2017 (p < 0.001). Similarly, incidence rates of AIDS-related deaths decreased from 0.51/100 PYS to 0.09/100 PYS from year groups 2003 to 2007 to 2013 to 2017 (p < 0.001). More recent years of follow-up were associated with reduced hazard for non-AIDS mortality (2008 to 2012: aSHR (adjusted sub-hazard ratio) 0.72, 95% confidence interval (CI) 0.54 to 0.96, p = 0.027; 2013 to 2017: aSHR 0.64, 95% CI 0.47 to 0.87, p = 0.004) compared to years 2003 to 2007. The AHOD cohort had almost twice the hazard of non-AIDS mortality compared to TAHOD-low (lower-middle income sites) (aSHR 1.72, 95% CI, 1.20 to 2.46, p = 0.003); there were no differences between cohorts for AIDS-related mortality (p = 0.834).ConclusionAIDS and non-AIDS-related mortality rates have decreased over the past years in the Asia-Pacific region. There is a greater risk for non-AIDS-associated deaths in the AHOD cohort compared to lower-middle income settings in TAHOD.

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Impact of antiretroviral therapy on opportunistic infections of HIV-infected children in the therapeutic research, education and AIDS training asia pediatric HIV observational database.

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