Growth, morbidity, and mortality in a cohort of institutionalized HIV-1-infected African children

OBJECTIVE: As a result of the HIV epidemic in Africa, much debate exists on whether institutionalized compared with community-based care provides optimum management of infected children. Previous reports calculated 89% mortality by age 3 years among outpatients in Malawi. No similar data are available for infected children in institutionalized care. We characterized patterns of morbidity and mortality among HIV-1-infected children residing at an orphanage in Nairobi. METHODS: Medical records for 174 children followed over 5 years were reviewed. Mortality was analyzed by Kaplan-Meier methods with adjustment to account for survival in the community before admission. Anthropometric indices were calculated to include mean z scores for weight for length and length for age. Low indices reflected wasting and stunting. Opportunistic infections were documented. RESULTS: Of 174 children, 64 had died. Survival was 70% at age 3 years. Morbidity included recurrent respiratory tract infections, gastroenteritis, parotitis, and lymphoid interstitial pneumonitis. No new cases of tuberculosis disease were noted after admission. Mean z scores for length for age suggested overall stunting (z = -1.65). Wasting was not observed (z = -0.39). CONCLUSION: The optimal form of care for HIV-infected children in resource-poor settings may be the development of similar homes. Absence of tuberculosis disease in long-standing residents may have contributed to improved survival. Stunting in the absence of wasting implied that growth was compromised by opportunistic infections and other cofactors.     

Distinct patterns of emergence and fading of K103N and Y181C in women with subtype A vs. D after single-dose nevirapine: HIVNET 012

BACKGROUND: The HIVNET 012 trial in Uganda demonstrated that single-dose nevirapine (NVP) can prevent HIV-1 mother-to-child transmission. NVP resistance (NVPR) mutations were detected in 25% of women 6 to 8 weeks after NVP, with a higher rate of NVPR in women with subtype D than A. This study examined emergence and fading of specific NVPR mutations in women with these subtypes. METHODS: Plasma HIV-1 was analyzed with the ViroSeq genotyping system (Celera Diagnostics, Alameda, CA). Genotypes were obtained from paired samples collected 7 days and 6 to 8 weeks after NVP from 140 women, 83 with subtype A and 57 with subtype D. RESULTS: The rate of NVPR was similar in women with subtype A vs. D at 7 days but was higher in subtype D than A at 6 to 8 weeks. The higher rate of NVPR in subtype D was explained by at least 2 factors: Y181C faded from detection at a greater rate in women with subtype A (odds ratio = 3.06; 95% CI, 1.04, 8.90) and K103N accumulated at a greater rate in women with subtype D (odds ratio = 1.74; 95% CI, 0.62, 4.87). CONCLUSIONS: HIV-1 subtype influences selection and fading of HIV-1 variants with specific drug resistance mutations after antiretroviral drug exposure.     

Intersecting stigma and HIV testing practices among urban refugee adolescents and youth in Kampala,Uganda: qualitative findings

IntroductionHIV‐related risks may be exacerbated in humanitarian contexts. Uganda hosts 1.3 million refugees, of which 60% are aged under 18. There are knowledge gaps regarding HIV testing facilitators and barriers, including HIV and intersecting stigmas, among urban refugee youth. In response, we explored experiences and perspectives towards HIV testing strategies, including HIV self‐testing, with urban refugee youth in Kampala, Uganda.MethodsWe implemented a qualitative study with refugee cisgender youth aged 16 to 24 living in Kampala''s informal settlements from February‐April 2019. We conducted five focus groups with refugee youth, including two with adolescent boys and young men, two with adolescent girls and young women and one with female sex workers. We also conducted five key informant (KI) interviews with government, non‐government and community refugee agencies and HIV service providers. We conducted thematic analyses to understand HIV testing experiences, perspectives and recommendations.ResultsParticipants (n = 49) included young men (n = 17) and young women (n = 27) originally from the Democratic Republic of Congo [DRC] (n = 29), Rwanda (n = 11), Burundi (n = 3) and Sudan (n = 1), in addition to five KI (gender: n = 3 women, n = 2 men; country of origin: n = 2 Rwanda, n = 2 Uganda, n = 1 DRC). Participant narratives revealed stigma drivers included fear of HIV infection; misinformation that HIV is a “Ugandan disease”; and blame and shame for sexual activity. Stigma facilitators included legal precarity regarding sex work, same‐sex practices and immigration status, alongside healthcare mistreatment and confidentiality concerns. Stigma experiences were attributed to the social devaluation of intersecting identities (sex work, youth, refugees, sexual minorities, people living with HIV, women). Participants expressed high interest in HIV self‐testing. They recommended HIV self‐testing implementation strategies to be peer supported and expressed concerns regarding sexual‐ and gender‐based violence with partner testing.ConclusionsIntersecting stigma rooted in fear, misinformation, blame and shame, legal precarity and healthcare mistreatment constrain current HIV testing strategies with urban refugee youth. Findings align with the Health Stigma and Discrimination Framework that conceptualizes stigma drivers and facilitators that devalue intersecting health conditions and social identities. Findings can inform multi‐level strategies to foster enabling HIV testing environments with urban refugee youth, including tackling intersecting stigma and leveraging refugee youth peer support.     

Persistence of nevirapine exposure during the postpartum period after intrapartum single-dose nevirapine in addition to zidovudine prophylaxis for the prevention of mother-to-child transmission of HIV-1

OBJECTIVE: To determine nevirapine (NVP) plasma levels during the postpartum period after a single intrapartum NVP dose for the prevention of mother-to-child transmission. METHODS: Plasma samples at delivery and during days 8 to 45 postpartum were obtained from HIV-infected Thai women who received an intrapartum NVP dose in the Perinatal HIV Prevention Clinical Trial-2 (PHPT-2) for the prevention of perinatal HIV transmission. These data were combined with NVP concentration data from 2 phase 1 studies of NVP for a population analysis. RESULTS: The median NVP level fell to 68 ng/mL (range: <50-228, n = 43) 8 to 14 days after dosing and to 51 ng/mL (range: <50-166, n = 25) between 15 and 21 days. During the second and third weeks postpartum, NVP levels were below the limit of quantitation in 23% and 44% of samples, respectively. Between 21 and 45 days, no sample had a quantifiable NVP concentration. A simulation derived from the population analysis predicts that NVP concentration falls to less than 10 ng/mL in 5% of women by 11 days, in 50% of women by 17.5 days, and in 95% of women by 28 days. CONCLUSIONS: Significant NVP concentrations remained for up to 20 days in these Thai women. To ensure that coverage is maintained until NVP concentrations fall to nonsuppressive levels, 1 month of additional antiretroviral treatment after delivery should be considered to prevent the emergence of resistant viruses.     

Human immunodeficiency virus infection and cerebral malaria in children in Uganda: a case-control study

Background  

Human immunodeficiency virus (HIV)-1 infection increases the burden of malaria by increasing susceptibility to infection and decreasing the response to malarial treatment. HIV-1 has also been found to suppress the immune system and predispose to severe forms of malaria in adults. There is still a paucity of data on the association between HIV-1 infection and cerebral malaria in children. The aim of this study was to determine whether HIV-1 infection is a risk factor for cerebral malaria in children.     

Evaluation of tuberculosis diagnostics in children: 1. Proposed clinical case definitions for classification of intrathoracic tuberculosis disease. Consensus from an expert panel

There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis.     

Pediatric HIV-1 disease in a Kampala Hospital

Data of pediatric patients screened for HIV-1 infection between 1985 and 1989 were studied retrospectively in one of the major mission hospitals of Kampala (Uganda). Symptomatic HIV-1 infection was mainly acquired perinatally and was diagnosed in 87 per cent in children under 2 years of age. The mortality rate was 40 per cent in pediatric in-patients with symptomatic HIV-1 infection as compared to 12 per cent in overall pediatric inpatients. Symptoms included in the WHO clinical case definition for pediatric AIDS were mainly insensitive, unspecific and demonstrated a low positive predictive value. There was no difference in the prevalence of malaria and measles between HIV-1 positive and HIV-1 negative children.