Brady MT, Oleske JM, Williams PL, et al. Declines in mortality rates and changes in causes of death in HIV-1-infected children during the HAART era

Nationwide Children's Hospital, Columbus, OH, USA. michael.Brady@nationalwidechildren'
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 01/2010; 53(1):86-94. DOI: 10.1097/QAI.0b013e3181b9869f
Source: PubMed


Introduction of highly active antiretroviral therapy has significantly decreased mortality in HIV-1-infected adults and children. Although an increase in non-HIV-related mortality has been noted in adults, data in children are limited.
To evaluate changes in causes and risk factors for death among HIV-1-infected children in Pediatric AIDS Clinical Trials Group 219/219C.
Multicenter, prospective cohort study designed to evaluate long-term outcomes in HIV-1-exposed and infected US children. There were 3553 HIV-1-infected children enrolled and followed up between April 1993 and December 2006, with primary cause of mortality identified in the 298 observed deaths.
Mortality rates per 100 child-years overall and by demographic factors; survival estimates by birth cohort; and hazard ratios for mortality by various demographic, health, and antiretroviral treatment factors were determined.
Among 3553 HIV-1-infected children followed up for a median of 5.3 years, 298 deaths occurred. Death rates significantly decreased between 1994 and 2000, from 7.2 to 0.8 per 100 person-years, and remained relatively stable through 2006. After adjustment for other covariates, increased risk of death was identified for those with low CD4 and AIDS-defining illness at entry. Decreased risks of mortality were identified for later birth cohorts, and for time-dependent initiation of highly active antiretroviral therapy (hazard ratio 0.54, P < 0.001). The most common causes of death were "End-stage AIDS" (N = 48, 16%) and pneumonia (N = 41, 14%). The proportion of deaths due to opportunistic infections (OIs) declined from 37% in 1994-1996 to 24% after 2000. All OI mortality declined during the study period. However, a greater decline was noted for deaths due to Mycobacterium avium complex and cryptosporidium. Deaths from "End-stage AIDS," sepsis and renal failure increased.
Overall death rates declined from 1993 to 2000 but have since stabilized at rates about 30 times higher than for the general US pediatric population. Deaths due to OIs have declined, but non-AIDS-defining infections and multiorgan failure remain major causes of mortality in HIV-1-infected children.

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Available from: Lynne M Mofenson, Aug 29, 2014
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    • "Due to the scale up of antiretroviral therapy over the last decade, survival of perinatally-infected children has improved dramatically, enabling them to live into adolescence and beyond [5]. As they do so, the issue of informing adolescents about their HIV status arises, a process termed “status disclosure” [6]–[8]. "
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    ABSTRACT: Due to the scale up of antiretroviral therapy, increasing numbers of HIV-infected children are living into adolescence. As these children grow and surpass the immediate threat of death, the issue of informing them of their HIV status arises. This study aimed to understand how perinatally-infected adolescents learn about their HIV-status as well as to examine their preferences for the disclosure process. In-depth interviews were conducted with 31 (14 male, 17 female) perinatally-infected adolescents aged 16-20 at an HIV clinic in Harare, Zimbabwe, and focused on adolescents' experiences of disclosure. In addition, 15 (1 male, 14 female) healthcare workers participated in two focus groups that were centred on healthcare workers' practices surrounding disclosure in the clinic. Purposive sampling was used to recruit participants. A coding frame was developed and major themes were extracted using grounded theory methods. Healthcare workers encouraged caregivers to initiate disclosure in the home environment. However, many adolescents preferred disclosure to take place in the presence of healthcare workers at the clinic because it gave them access to accurate information as well as an environment that made test results seem more credible. Adolescents learned more specific information about living with an HIV-positive status and the meaning of that status from shared experiences among peers at the clinic. HIV-status disclosure to adolescents is distinct from disclosure to younger children and requires tailored, age-appropriate guidelines. Disclosure to this age group in a healthcare setting may help overcome some of the barriers associated with caregivers disclosing in the home environment and make the HIV status seem more credible to an adolescent. The study also highlights the value of peer support among adolescents, which could help reduce the burden of psychosocial care on caregivers and healthcare workers.
    PLoS ONE 01/2014; 9(1):e87322. DOI:10.1371/journal.pone.0087322 · 3.23 Impact Factor
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    • "By 2007, according to the CDC, 49% of PHIVA in the United States were over 15 years of age [59]. UNAIDS reports less than 100 deaths among HIV-infected children less than 15 years of age, but again, given the age distribution of the perinatally infected population, this likely represents less than half the number of deaths among the perinatally infected in the United States, especially since older individuals are at increased risk of death [1]. Nevertheless, given the low mortality and very low number of newly infected babies (<100 per year), the perinatally infected population in the United States is at a relatively stable number of over 10,000 individuals, most of whom are now young adults and with the oldest members now entering the fourth decade of life. "
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    ABSTRACT: The global paediatric HIV epidemic is shifting into a new phase as children on antiretroviral therapy (ART) move into adolescence and adulthood, and face new challenges of living with HIV. UNAIDS reports that 3.4 million children aged below 15 years and 2 million adolescents aged between 10 and 19 years have HIV. Although the vast majority of children were perinatally infected, older children are combined with behaviourally infected adolescents and youth in global reporting, making it difficult to keep track of their outcomes. Perinatally HIV-infected adolescents (PHIVA) are a highly unique patient sub-population, having been infected before development of their immune systems, been subject to suboptimal ART options and formulations, and now face transition from complete dependence on adult caregivers to becoming their own caregivers. As we are unable to track long-term complications and survival of PHIVA through national and global reporting systems, local and regional cohorts are the main sources for surveillance and research among PHIVA. This global review will utilize those data to highlight the epidemiology of PHIVA infection, treatment challenges and chronic disease risks. Unless mechanisms are created to count and separate out PHIVA outcomes, we will have few opportunities to characterize the negative consequences of life-long HIV infection in order to find ways to prevent them.
    Journal of the International AIDS Society 06/2013; 16(1):18555. DOI:10.7448/IAS.16.1.18555 · 5.09 Impact Factor
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    • "Over this time period, the management of PHIV+ infants, children and adolescents changed dramatically. Before the introduction of ART in 1995, 50% of PHIV+ children died before the age of two [4], with a few slow progressors surviving to adolescence [5]. Prior to 1997, children in Europe and the United States may have received multiple antiretroviral regimens, including those that would now be considered suboptimal therapy. "
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    ABSTRACT: Globally, an estimated 3.4 million children are living with HIV, yet little is known about the effects of HIV and antiretroviral treatment (ART) on the developing brain, and the neurodevelopmental and behavioural outcomes of perinatally HIV-infected (PHIV+) adolescents. We reviewed the literature on neurodevelopmental outcomes in PHIV+ children and adolescents, and summarized the current evidence on behaviour, general cognition, specific domains, hearing and language, school performance and physical disabilities due to neurological problems. Evidence suggests that PHIV+ children do not perform as well as controls on general cognitive tests, processing speed and visual–spatial tasks, and are at much higher risk for psychiatric and mental health problems. Children with AIDS-defining diagnoses are particularly at risk for poorer outcomes. A striking finding is the lack of published data specific to the adolescent age group (10–25 years), particularly from resource-constrained countries, which have the highest HIV prevalence. In addition, extreme heterogeneity in terms of timing and source of infection, and antiretroviral experience limits our ability to summarize findings of studies and generalize results to other settings. Due to the complex nature of the developing adolescent brain, environmental influences and variation in access to ART, there is an urgent need for research on the longitudinal trajectory of neurodevelopment among children and adolescents perinatally infected with HIV, especially in high burden resource-constrained settings.
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