Pediatric HIV therapy in armed conflict

Abstract

Worldwide, an estimated 2.5 million children were living with HIV/AIDS at the end of 2006 [1]. Combination antiretroviral therapy (cART) access among children remains limited, with only 115 500 (15%) of clinically eligible individuals receiving treatment in 2006 [2]. Childhood mortality is particularly high in sub-Saharan African countries affected by recent armed conflict [3], and accelerated among young children with HIV [2]. A recent study from the Democratic Republic of Congo demonstrated that adult cART patients in conflict settings have immunological and clinical outcomes equal those of patients in politically stable settings [4]. No studies have examined patient outcomes of children receiving cART in armed conflicts. Northern Uganda has been in a state of humanitarian emergency for over 20 years, in what has been called one of Africa's longest standing armed conflicts with the least international attention. Of the estimated 1.6 million internally displaced people in northern Uganda between 2002 and 2008, the majority reside in protected camps [5]. The AIDS Support Organization (TASO) began providing cART to adults and children in northern Uganda in 2005, and remains the largest free treatment programme in the area. We evaluated the demographic and clinical outcomes of TASO's pediatric cART patients in Gulu district. We extracted outcomes regarding change in CD4 cell count, CD4%, mortality, pharmacy and counsellor-monitored adherence, and opportunistic infections. We present descriptive statistics and multivariate regression assessing demographic and clinical status on major outcomes. This study was approved by the ethical review board of the Mbale Regional Referral Hospital. As of February 2008, 57 HIV-positive children were receiving cART, median age 8 [interquartile range (IQR) 5–11] years, with an average follow-up 227 (IQR 87-403) days since initiation, contributing 43.8 person-years. All patients were receiving cART regimens of two nucleosides (NRTI) and one nonnucleoside. Thirty-four were girls (60%), and 25 (44%) were either single or double orphans. No patients died after cART initiation. We found no differences between orphans and nonorphans in terms of CD4% [odds ratio (OR) = 1.05, 95% confidence interval (CI) = 0.98–1.12, P = 0.12] and CD4 cell counts (OR = 0.99, 95% CI = 0.99–1.00, P = 0.28), weight (P = 0.32), presence of tuberculosis (P = 0.47), or World Health Organization (WHO) staging (P = 0.22) at initiation. Tuberculosis was present in three patients at initiation and one postcART. Adherence was consistently excellent (>95%) in 92% of patients. We found no major opportunistic infections. Our study represents the first attempt to examine pediatric cART patient outcomes in a conflict setting. Our results are consistent with cART outcomes from other small pediatric cohorts in politically stable sub-Saharan African countries. Studies in neighbouring Kenya, for example, have also found high adherence, low mortality and improved immunological outcomes among pediatric cART patients [6,7]. Notably, one of these studies also found that short-term clinical outcomes among pediatric patients were not affected by orphan status [6]. In Zambia, a cohort analysis of 4975 children on cART reported equally positive immunological and clinical outcome during the first 3 months of therapy, but identified the age of cART onset as a statistically significant predictor of mortality [8]. Although earlier policy guidelines for humanitarian responses suggested that the provision of cART is not feasible in complex emergencies [9], there is now emerging evidence that treating HIV-positive individuals in these settings is imperative from public health and human rights perspectives [10]. Contrary to previously held assumptions, displaced populations are not highly mobile and have social support structure, which contribute to good cART adherence [11]. The United Nations High Commissioner for Refugees (UNHCR) has recently developed clinical and operational guidelines for the management of cART in displaced populations [11]. These policy developments will undoubtedly contribute to improved pediatric cART access and outcomes in conflict-affected countries. In northern Uganda, maintaining positive clinical outcomes among children on cART may be challenging in the face of anticipated population movements. In 2008, international organizations expect that 35% of internally displaced people in northern Uganda will relocate ‘home’, 45% will be in transit and 20% will remain in camps [12]. Community-based and clinical measures should be put in place to ensure that families and children travelling long distances continue receive cART without interruption [11].