BackgroundAmong children, early mortality following highly active antiretroviral therapy (HAART) remains high. It is important to define correlates of mortality in order to improve outcome.MethodsHIV-1-infected children aged 18 months-12 years were followed up at Kenyatta National Hospital, Nairobi after initiating NNRTI-based HAART. Cofactors for mortality were determined using multivariate Cox regression models.ResultsBetween August 2004 and November 2008, 149 children were initiated on HAART of whom 135 were followed for a total of 238 child-years (median 21 months) after HAART initiation. Baseline median CD4% was 6.8% and median HIV-1-RNA was 5.98-log10 copies/ml. Twenty children (13.4%) died at a median of 35 days post-HAART initiation. Mortality during the entire follow-up period was 8.4 deaths per 100 child-years (46 deaths/100 child-years in first 4 months and 1.0 deaths/100 child-years after 4 months post-HAART initiation). On univariate Cox regression, baseline hemoglobin (Hb) <9 g/dl, weight-for-height z-score (WHZ) < -2, and WHO clinical stage 4 were associated with increased risk of death (Hb <9 g/dl HR 3.00 [95% C.I. 1.21-7.39], p = 0.02, WHZ < -2 HR 3.41 [95% C.I. 1.28-9.08], p = 0.01, and WHO clinical stage 4, HR 3.08 [1.17-8.12], p = 0.02). On multivariate analysis Hb < 9 g/dl remained predictive of mortality after controlling for age, baseline CD4%, WHO clinical stage and weight-for-height z-score (HR 2.95 (95% C.I. 1.04-8.35) p = 0.04).ConclusionHigh early mortality was observed in this cohort of Kenyan children receiving HAART, and low baseline hemoglobin was an independent risk factor for death.

IntroductionHIV testing is the portal to serostatus knowledge that can empower linkage to care for HIV treatment and HIV prevention. However, young people's access to HIV testing is uneven worldwide. The objective of this paper is to review the context and concerns faced by youth around HIV testing in low- as well as high-income country settings.DiscussionHIV testing is a critical entry point for primary and secondary prevention as well as care and treatment for young people including key populations of vulnerable youth. We provide a framework for thinking about the role of testing in the continuum of prevention and care for young people. Brief case study examples from Kenya and the US illustrate some of the common barriers and issues involved for young people.ConclusionsYoung people worldwide need more routine access to HIV testing services that effectively address the developmental, socio-political and other issues faced by young women and men.

Objectives Few routine systems exist to test older, asymptomatic children for HIV. Testing all children in the population has high uptake but is inefficient, while testing only symptomatic children increases efficiency but misses opportunities to optimize outcomes. Testing children of HIV-infected adults in care may efficiently identify previously undiagnosed HIV-infected children before symptomatic disease. Methods HIV-infected parents in HIV care in Nairobi, Kenya were systematically asked about their children’s HIV status and testing history. Adults with untested children ≤12 years old were actively referred and offered the choice of pediatric HIV testing at home or clinic. Testing uptake and HIV prevalence were determined, as were bottlenecks in pediatric HIV testing cascade. Results Of 10,426 HIV-infected adults interviewed, 8,287 reported having children, of whom 3,477 (42%) had children of unknown HIV status, and 611 (7%) had children ≤12 years of unknown HIV status. Following implementation of active referral, the rate of pediatric HIV testing increased 3.8-fold from 3.5 to 13.6 children tested per month, (RR: 3.8, 95%CI: 2.3–6.1). Of 611 eligible adults, 279 (48%) accepted referral and were screened, and 74 (14%) adults completed testing of 1 or more children. HIV prevalence among 108 tested children was 7.4% and median age was 8 years (IQR: 2–11); one child was symptomatic at testing. Conclusions Referring HIV-infected parents in care to have their children tested revealed many untested children and significantly increased the rate of pediatric testing; prevalence of HIV was high. However, despite increases in pediatric testing, most adults did not complete testing of their children.

Purpose: Informing adolescents of their own HIV infection is critical as the number of adolescents living with HIV increases. We assessed the association between HIV disclosure and retention in care and mortality among adolescents aged 10-14 years in Kenya's national program. Methods: We abstracted routinely collected patient-level data for adolescents enrolled into HIV care in 50 health facilities from November 1, 2004, through March 31, 2010. We defined disclosure as any documentation that the adolescent had been fully or partially made aware of his or her HIV status. We compared weighted proportions for categorical variables using χ2 and weighted logistic regression to identify predictors of HIV disclosure; we estimated the probability of LTFU using Kaplan-Meier methods and dying using Cox regression-based test for equality of survival curves.

BackgroundDespite expanded programs for prevention of mother-to-child HIV transmission (PMTCT), HIV-infected infants may not be diagnosed until they are ill. Comparing HIV prevalence and outcomes in infants diagnosed in PMTCT programs to those in hospital settings may improve pediatric HIV diagnosis strategies.MethodsHIV-exposed infants <12 months old were recruited from 9 PMTCT sites in public maternal child health (MCH) clinics or from an inpatient setting in Nairobi, Kenya and tested for HIV using HIV DNA assays. A subset of HIV-infected infants <4.5 months of age was enrolled in a research study and followed for 2 years. HIV prevalence, number needed to test, infant age at testing, and turnaround time for tests were compared between PMTCT programs and hospital sites. Among the enrolled cohort, baseline characteristics, survival, and timing of antiretroviral therapy (ART) initiation were compared between infants diagnosed in PMTCT programs versus hospital.ResultsAmong 1,923 HIV-exposed infants, HIV prevalence was higher among infants tested in hospital than PMTCT early infant diagnosis (EID) sites (41% vs. 11%, p < 0.001); the number of HIV-exposed infants needed to test to diagnose one infection was 2.4 in the hospital vs. 9.1 in PMTCT. Receipt of HIV test results was faster among hospitalized infants (7 vs. 25 days, p < 0.001). Infants diagnosed in hospital were older at the time of testing than PMTCT diagnosed infants (5.0 vs. 1.6 months, respectively, p < 0.001).In the subset of 99 HIV-infected infants <4.5 months old followed longitudinally, hospital-diagnosed infants did not differ from PMTCT-diagnosed infants in time to ART initiation; however, hospital-diagnosed infants were >3 times as likely to die (HR = 3.1, 95% CI = 1.3-7.6).ConclusionsAmong HIV-exposed infants, hospital-based testing was more likely to detect an HIV-infected infant than PMTCT testing. Because young symptomatic infants diagnosed with HIV during hospitalization have very high mortality, every effort should be made to diagnose HIV infections before symptom onset. Systems to expedite turnaround time at PMTCT EID sites and to routinize inpatient pediatric HIV testing are necessary to improve pediatric HIV outcomes.

Objective Treatment interruption (TI) has been safe and durable in some pediatric studies but none have compared TI to continued antiretroviral treatment (ART) following ART initiation in early HIV. The objective of this study was to compare outcomes in TI versus continued ART among early-treated infants. Design Randomized trial (OPH-03; NCT00428116) Methods The trial included HIV-infected infants who initiated ART at <13 months of age, received ART for 24 months, and, if eligible (CD4>25%, normal growth), were randomized to TI vs. continued ART. Children in the TI group re-started ART if they met WHO ART-eligibility criteria. During 18-months post-randomization, primary outcomes were incidence of serious adverse events (SAEs) and growth. CD4, viral load, morbidity, and growth were compared. Results Of 140 infants enrolled, 121 started ART, of whom 75 completed ≥24 months ART and 42 were randomized (21 per arm). ART was initiated at median age 5 months and randomization at 30 months. Among 21 TI children, 14 met ART re-start criteria within 3 months. Randomization was discontinued by DSMB due to low TI durability. At 18 months post-randomization, growth and SAEs were comparable between arms; hypercholesteremia incidence was higher in the continued arm (p=0.03). CD4% and VL did not differ between arms (CD4% 35% and median VL undetectable (<150 c/ml) in both arms, p=0.9 for each comparison). No infants had post-treatment viral control. Conclusion Short TI did not compromise 18-month CD4%, viral control, growth, or morbidity compared to continued ART among infants who started ART in early HIV infection.

Background Ninety percent of HIV-1-infected children live in sub-Saharan Africa. In the absence of diagnosis and antiretroviral therapy (ART), approximately 50% die before 2 years. Methods We evaluated sensitivity and specificity of clinical algorithms for diagnosis of HIV-1 infection and ART initiation among HIV-1-exposed children aged less than 18 months. Children were identified with routine HIV-1 testing and assessed using 3 sets of criteria: 1) Integrated Management of Childhood Illnesses (IMCI), 2) World Health Organization Presumptive Diagnosis (WHO-PD) for HIV-1 infection, and 3) CD4 T-lymphocyte cell subsets. HIV-1 infection status was determined using DNA PCR testing. Findings A total of 1,418 children (median age 5.4 months) were screened for HIV-1 antibodies, of whom 144 (10.2%) were seropositive. Of these, 134 (93%) underwent HIV-1 DNA testing and 80 (60%) were found to be HIV-1-infected. Compared to HIV-1 DNA testing, sensitivity and specificity of the IMCI were 19% and 96% and for WHO-PD criteria 43% and 88%, respectively. Inclusion of severe immune deficiency determined by CD4 percent improved sensitivity of IMCI and WHO-PD to 74% and 84% respectively, however, specificity declined to 43% and 41%, respectively. Interpretation Diagnosis of HIV-1 infection among exposed children less than 18 months in a high prevalence, resource-limited setting remains a challenge and current recommended algorithms have low sensitivity. This underscores the need for rapid scale-up of viral assays for early infant diagnosis.

ObjectiveWe compared the impact and costs of HIV prevention strategies focusing on youth (15–24 year-old persons) versus on adults (15+ year-old persons), in a high-HIV burden context of a large generalized epidemic.DesignCompartmental age-structured mathematical model of HIV transmission in Nyanza, Kenya.InterventionsThe interventions focused on youth were high coverage HIV testing (80% of youth), treatment at diagnosis (TasP, i.e., immediate start of antiretroviral therapy [ART]) and 10% increased condom usage for HIV-positive diagnosed youth, male circumcision for HIV-negative young men, pre-exposure prophylaxis (PrEP) for high-risk HIV-negative females (ages 20–24 years), and cash transfer for in-school HIV-negative girls (ages 15–19 years). Permutations of these were compared to adult-focused HIV testing coverage with condoms and TasP.ResultsThe youth-focused strategy with ART treatment at diagnosis and condom use without adding interventions for HIV-negative youth performed better than the adult-focused strategy with adult testing reaching 50–60% coverage and TasP/condoms. Over the long term, the youth-focused strategy approached the performance of 70% adult testing and TasP/condoms. When high coverage male circumcision also is added to the youth-focused strategy, the combined intervention outperformed the adult-focused strategy with 70% testing, for at least 35 years by averting 94,000 more infections, averting 5.0 million more disability-adjusted life years (DALYs), and saving US$46.0 million over this period. The addition of prevention interventions beyond circumcision to the youth-focused strategy would be more beneficial if HIV care costs are high, or when program delivery costs are relatively high for programs encompassing HIV testing coverage exceeding 70%, TasP and condoms to HIV-infected adults compared to combination prevention programs among youth.ConclusionFor at least the next three decades, focusing in high burden settings on high coverage HIV testing, ART treatment upon diagnosis, condoms and male circumcision among youth may outperform adult-focused ART treatment upon diagnosis programs, unless the adult testing coverage in these programs reaches very high levels (>70% of all adults reached) at similar program costs. Our results indicate the potential importance of age-targeting for HIV prevention in the current era of ‘test and start, ending AIDS’ goals to ameliorate the HIV epidemic globally.