Incidence of World Health Organization Stage 3 and 4 Events, Tuberculosis and Mortality in Untreated, HIV-infected Children Enrolling in Care Before 1 Year of Age

Abstract

Background Few studies have reported CD4%- and age-stratified rates of WHO Stage 3 (WHO3) events, WHO Stage 4 (WHO4) events, tuberculosis (TB), and mortality in HIV-infected infants before initiation of antiretroviral therapy (ART). Methods HIV-infected children enrolled before 1 year of age in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) East Africa region (10/01/2002-11/30/2008) were included. We estimated incidence rates of earliest clinical event (WHO3, WHO4, and TB), prior to ART initiation per local guidelines, stratified by current age (< or ≥6 months) and current CD4% (<15%, 15–24%, ≥25%). CD4%-stratified mortality rates were estimated separately for children who did not experience a clinical event (“background” mortality) and for children who experienced an event, including “acute” mortality (≤30 days post-event) and “later” mortality (>30 days post-event). Results Among 847 children (median enrollment age: 4.8 months; median pre-ART follow-up: 10.8 months; 603 (71%) with ≥1 CD4% recorded), event rates were comparable for those aged <6 and ≥6 months. Current CD4% was associated with risk of WHO4 events for children <6 months old, and with all evaluated events for children ≥6 months old (p<0.05). “Background” mortality was 3.7–8.4/100py. “Acute” mortality (≤30 days post-event) was 33.8/100py (after TB) and 41.1/100py (after WHO3 or WHO4). “Later” mortality (>30 days post-event) ranged by CD4% from 4.7–29.1/100py. Conclusions In treatment-naïve, HIV-infected infants, WHO3, WHO4, and TB events were common before and after 6 months of age and led to substantial increases in mortality. Early infant HIV diagnosis and treatment are critically important, regardless of CD4%.

Trends in AIDS Deaths, New Infections and ART Coverage in the Top 30 Countries with the Highest AIDS Mortality Burden; 1990–2013

“…Our work is incomplete in that it does not report on ART and mortality burdens among marginalized and vulnerable populations such as the urban and rural poor, [ 38 ] sex workers, [ 39 ] men who have sex with men, [ 40 ] drug users, [ 41 ] pregnant women and children. [ 42 ] Improving data collection regarding ART coverage for these important key populations would improve the feasibility of estimating progress towards reducing the impact of HIV on incidence, prevalence and mortality.…”

Incidence of tuberculosis in children on antiretroviral therapy: a retrospective cohort study

“…Notably, 0.28 per 100 person-years reported in Latin America [16], 0.83 in China [20], 4.0 in South Africa [21], and 17.4 in East Africa [22]. …”

Clinical Impact and Cost-effectiveness of Diagnosing HIV Infection During Early Infancy in South Africa: Test Timing and Frequency

“…Cohort characteristics, MTCT risks, disease progression, and ART outcomes were from African trials and cohort studies (Table 1 and Supplementary Table A) [23,26,27,38,39]. NAAT sensitivity (base case, 100% >1 month after infection), specificity (98.8%), and costs ($25) were from WHO systematic reviews, published data, and expert opinion, and their values were varied widely in sensitivity analyses [9,25].…”