An HIV Vaccine Protective Allele in FCGR2C Associates With Increased Odds of Perinatal HIV Acquisition

In the Thai RV144 HIV-1 vaccine trial, a three-variant haplotype within the Fc gamma receptor 2C gene (FCGR2C) reduced the risk of HIV-1 acquisition. A follow-on trial, HVTN702, of a similar vaccine candidate found no efficacy in South Africa, where the predominant population is polymorphic for only a single variant in the haplotype, c.134-96C>T (rs114945036). To investigate a role for this variant in HIV-1 acquisition in South Africans, we used the model of maternal-infant HIV-1 transmission. A nested case-control study was conducted of infants born to mothers living with HIV-1, comparing children with perinatally-acquired HIV-1 (cases, n = 176) to HIV-1-exposed uninfected children (controls, n = 349). All had received nevirapine for prevention of mother-to-child transmission. The FCGR2C copy number and expression variants (c.−386G>C, c.−120A>T c.169T>C, and c.798+1A>G) were determined using a multiplex ligation-dependent probe amplification assay and the c.134-96C>T genotype with Sanger sequencing. The copy number, genotype and allele carriage were compared between groups using univariate and multivariate logistic regression. The FCGR2C c.134-96C>T genotype distribution and copy number differed significantly between HIV-1 cases and exposed-uninfected controls (P = 0.002, PBonf = 0.032 and P = 0.010, PBonf = > 0.05, respectively). The FCGR2C c.134-96T allele was overrepresented in the cases compared to the controls (58% vs 42%; P = 0.001, PBonf = 0.016). Adjusting for birthweight and FCGR2C copy number, perinatal HIV-1 acquisition was associated with the c.134-96C>T (AOR = 1.89; 95% CI 1.25-2.87; P = 0.003, PBonf = 0.048) and c.169C>T (AOR = 2.39; 95% CI 1.45-3.95; P = 0.001, PBonf = 0.016) minor alleles but not the promoter variant at position c.−386G>C. The c.134-96C>T variant was in strong linkage disequilibrium with the c.169C>T variant, but remained significantly associated with perinatal acquisition when adjusted for c.169C>T in multivariate analysis. In contrast to the protective effect observed in the Thai RV144 trial, we found the FCGR2C variant c.134-96T-allele associated with increased odds of perinatal HIV-1 acquisition in South African children. These findings, taken together with a similar deleterious association found with HIV-1 disease progression in South African adults, highlight the importance of elucidating the functional relevance of this variant in different populations and vaccination/disease contexts.

Cytomegalovirus pneumonia of infants in Africa: a narrative literature review

Cytomegalovirus pneumonia has repeatedly been described in the context of HIV-exposed uninfected and HIV-infected infants. Despite its significant role in the etiology of childhood pneumonia, there is still a paucity of literature generally, and specifically in Africa, suggesting that it might be a neglected disease. Emerging evidence highlights the importance of postnatal transmission through breastmilk. The pathogenetic significance of the multiplicity of strains acquired through repeated re-infections in early infancy is unknown. The development of cheap, accurate diagnostic tools and safe, effective antivirals and the maintenance of effective prevention and treatment of pediatric HIV are needed to manage cytomegalovirus pneumonia in low-resource settings.

Correlates of Health-related Quality of Life in Primary Caregivers of HIV Infected and HIV Exposed Uninfected Adolescents at the Kenyan Coast

Background: Mothers and other primary caregivers play a crucial role in looking after HIV infected, and HIV exposed uninfected adolescents in sub-Saharan Africa. Daily caring may expose these caregivers to adverse states of health. Unfortunately, very few studies have examined their health-related quality of life (HRQoL) despite the additional risk of poor health outcomes. Our study documents the HRQoL profile, and associated factors in primary caregivers of perinatally HIV infected, perinatally HIV exposed but uninfected and HIV unexposed/uninfected adolescents aged 12 – 17 years at the Kenyan Coast. Methods: This was a cross-sectional analysis of 485 primary caregivers: 195 of perinatally HIV infected adolescents, 128 of perinatally HIV exposed but uninfected adolescents and 162 of HIV unexposed/uninfected adolescents. All caregivers completed a self-report measure of HRQoL, depressive symptoms, and parenting stress. They also provided their sociodemographic information and that of the participating adolescents. We used one-way analysis of variance (and its non-parametric version) to assess statistical differences among the groups. Linear regression analyses were used to identify correlates of HRQoL among caregivers. Results: Linear regression analyses indicated that depressive symptoms, increasing age of caregiver, and caring for an HIV exposed adolescent were significantly associated with reduced HRQoL at both the RAND SF-36 overall and sub-scale level. Having a professional job relative to subsistence farming was the only factor associated with improved overall HRQoL. At subscale level, higher socioeconomic status correlated positively with HRQoL (within the limitations due to emotional problems domain) while being a grandparent, and level of education (physical functioning domain), and parenting stress (vitality domain) were negatively associated with HRQoL. Moreover, caring for a male adolescent (vitality domain) and increasing adolescent age (pain domain) was associated with declining HRQoL. Conclusions: Caregivers in this sample, especially those who are ageing, at risk of mental ill-health, and taking care of HIV exposed adolescents, appear to be vulnerable. Inclusive and multi-component interventions tailored to the caregivers' psychosocial and mental needs will potentially enhance their quality of life. Longitudinal studies are also needed to understand the underlying mechanisms and longer-term implications of the correlates of caregivers HRQoL identified in the present study.

Longitudinal Follow-Up of Blood Telomere Length in HIV-Exposed Uninfected Children Having Received One Year of Lopinavir/Ritonavir or Lamivudine as Prophylaxis

Telomere shortening can be enhanced upon human immunodeficiency virus (HIV) infection and by antiretroviral (ARV) exposures. The aim of this study was to evaluate the acute and long-term effect on telomere shortening of two ARV prophylaxes, lopinavir/ritonavir (LPV/r) and lamivudine (3TC), administered to children who are HIV-exposed uninfected (CHEU) to prevent HIV acquisition through breastfeeding during the first year of life, and to investigate the relationship between telomere shortening and health outcomes at six years of age. We included 198 CHEU and measured telomere length at seven days of life, at week-50 and at six years (year-6) using quantitative polymerase chain reaction. At week-50, telomere shortening was observed among 44.3% of CHEU, irrespective of the prophylactic treatment. Furthermore, this telomere shortening was neither associated with poor growth indicators nor neuropsychological outcomes at year-6, except for motor abilities (MABC test n = 127, β = −3.61, 95%CI: −7.08, −0.14; p = 0.04). Safety data on telomere shortening for infant HIV prophylaxis are scarce. Its association with reduced motor abilities deserves further attention among CHEU but also HIV-infected children receiving ARV treatment.