BackgroundPrior research suggests that a high prevalence of depression, with a detrimental impact on treatment outcomes exists among HIV-infected youth. Data on potential risk factors of depression among HIV-infected youth in sub-Saharan Africa are scarce. This cross-sectional study aimed to identify contributory/protective factors associated with depression in Malawian adolescents 12–18 years old living with HIV.MethodsDepression was measured by a validated Chichewa version of the Beck Depression Inventory version-II (BDI-II) and the Children’s Depression Rating Scale-Revised (CDRS-R). Data on variables thought to potentially be contributory/protective were collected and included: socio-demographics, past traumatic events/stressors, behavioural factors/social support, and bio-clinical parameters. Chi-square test or two-sample t-test was used to explore associations between factors and depression. Additional testing via linear/logistic regression, adjusting for age and sex, identified candidate variables (p < 0.1). Final regression models included variables with significant main effects and interactions.ResultsOf the 562 participants enrolled (mean age, 14.5 years [SD 2.0]; 56.1 % female), the prevalence of depression was 18.9 %. In multivariate linear regression, the variables significantly associated with higher BDI-II score were female gender, fewer years of schooling, death in the family/household, failing a school term/class, having a boyfriend/girlfriend, not disclosed or not having shared one’s HIV status with someone else, more severe immunosuppression, and bullied for taking medications. Bullying victimization was reported by 11.6 % of respondents. We found significant interactions: older participants with lower height-for-age z-scores and dissatisfied with their physical appearance had higher BDI-II scores. In multivariate logistic regression, factors significantly associated with depression were: older age, OR 1.23 (95 % CI 1.07-1.42); fewer years of schooling, OR 3.30 (95 % CI 1.54-7.05); and bullied for taking medications, (OR 4.20 (95 % CI 2.29-7.69).ConclusionHaving fewer years of schooling and being bullied for taking medications were most clearly associated with depression. Programmes to support the mental health needs of HIV-infected adolescents that address issues such as disclosure, educational support, and, most notably, bullying may improve treatment outcomes and are recommended.

Objective To determine whether adipose tissue functions as a reservoir for HIV-1. Design We examined memory CD4 T cells and HIV DNA in adipose tissue-stromal-vascular-fraction (AT-SVF) of 5 patients (4 ART-treated and 1 untreated). To determine if adipocytes stimulate CD4 T cells and regulate HIV production, primary human adipose cells were co-cultured with HIV-infected CD4 T cells. Methods AT-SVF T cells were studied by flow cytometry, and AT-SVF HIV DNA (Gag and Env) was examined by nested PCR and sequence analyses. CD4 T cell activation and HIV production were measured by flow cytometry and ELISA. Results AT-SVF CD3 T cells were activated (>60% CD69+) memory CD4 and CD8 T cells in uninfected and HIV-infected persons, but the AT-SVF CD4/CD8 ratio was lower in HIV patients. HIV DNA (Gag and Env) was detected in AT-SVF of all 5 patients examined by nested PCR, comparably to other tissues (PBMC, lymph node, or thymus). In co-culture experiments, adipocytes increased CD4 T cell activation and HIV production ∼2-3 fold in synergy with gamma-chain cytokines IL2, IL7, or IL15. These effects were mitigated by neutralizing antibodies against IL6 and integrin-α1β1. Adipocytes also enhanced T cell viability. Conclusions Adipose tissues of ART-treated patients harbor activated memory CD4 T cells and HIV DNA. Adipocytes promote CD4 T cell activation and HIV production in concert with intrinsic adipose factors. Adipose tissue may be an important reservoir for HIV.

IntroductionThere is a remarkable dearth of evidence on mental illness in adolescents living with HIV/AIDS, particularly in the African setting. Furthermore, there are few studies in sub-Saharan Africa validating the psychometric properties of diagnostic and screening tools for depression amongst adolescents. The primary aim of this cross-sectional study was to estimate the prevalence of depression amongst a sample of HIV-positive adolescents in Malawi. The secondary aim was to develop culturally adapted Chichewa versions of the Beck Depression Inventory-II (BDI-II) and Children's Depression Inventory-II-Short (CDI-II-S) and conduct a psychometric evaluation of these measures by evaluating their performance against a structured depression assessment using the Children's Rating Scale, Revised (CDRS-R).Study designCross-sectional study.MethodsWe enrolled 562 adolescents, 12–18 years of age from two large public HIV clinics in central and southern Malawi. Participants completed two self-reports, the BDI-II and CDI-II-S, followed by administration of the CDRS-R by trained clinicians. Sensitivity, specificity and positive and negative predictive values for various BDI-II and CDI-II-S cut-off scores were calculated with receiver operating characteristics analysis. The area under the curve (AUC) was also calculated. Internal consistency was measured by standardized Cronbach's alpha coefficient, and correlation between self-reports and CDRS-R by Spearman's correlation.ResultsPrevalence of depression as measured by the CDRS-R was 18.9%. Suicidal ideation was expressed by 7.1% (40) using the BDI-II. The AUC for the BDI-II was 0.82 (95% CI 0.78–0.89) and for the CDI-II-S was 0.75 (95% CI 0.70–0.80). A score of ≥13 in BDI-II achieved sensitivity of >80%, and a score of ≥17 had a specificity of >80%. The Cronbach's alpha was 0.80 (BDI-II) and 0.66 (CDI-II-S). The correlation between the BDI-II and CDRS-R was 0.42 (p<0.001) and between the CDI-II-S and CDRS-R was 0.37 (p<0.001).ConclusionsThis study demonstrates that the BDI-II has sound psychometric properties in an outpatient setting among HIV-positive adolescents in Malawi. The high prevalence of depression amongst HIV-positive Malawian adolescents noted in this study underscores the need for the development of comprehensive services for HIV-positive adolescents.

This study aimed to investigate prospectively the contribution of maternal physical health and/or breastfeeding problems to maternal mood (depression, anxiety, fatigue, irritability, confusion, vigor) at 8-weeks postpartum. A prospective study was conducted. Participants were recruited antenatally from a public and a private maternity hospital in Melbourne, Australia. Nulliparous pregnant women (N = 229), ≥ 18 years of age, ≥ 36-week gestation, singleton pregnancy and with sufficient English were eligible. Data were collected by self-report questionnaire (pregnancy, weeks 1-4 postpartum) and telephone interview (week 8 postpartum). A high burden of physical problems was classified as ≥ 3 problems (caesarean/perineal pain; back pain; constipation; haemorrhoids; urinary and bowel incontinence) for ≥ 2 time points. A high burden of breastfeeding problems was having ≥ 2 problems (mastitis; nipple pain; frequent expressing; over- or under-supply of milk) for ≥ 2 time points. Multivariate linear regression was used to investigate the relationship between maternal mood, assessed using Profile of Mood States (8-week postpartum), and a high burden of breastfeeding and/or physical health problems. Forty-six women (20.1%) had a high burden of physical symptoms, 44 (19.2%) a high burden of breastfeeding problems only and 25 women (11.0%) had both. A high burden of breastfeeding problems alone (β = 10.6, p = 0.01) or with co-morbid physical problems (β = 15.35, p = 0.002) was significantly associated with poorer maternal mood at 8 weeks. Early, effective postnatal treatment of maternal health and breastfeeding problems could reduce women's risk for poor mental health.

Stress response pathways are critical for cellular homeostasis, promoting survival through adaptive changes in gene expression and metabolism. They play key roles in numerous diseases and are implicated in cancer progression and chemoresistance. However, the underlying mechanisms are only poorly understood. We have employed a multi-omics approach to monitor changes to gene expression after induction of a stress response pathway, the unfolded protein response (UPR), probing in parallel the transcriptome, the proteome, and changes to translation. Stringent filtering reveals the induction of 267 genes, many of which have not previously been implicated in stress response pathways. We experimentally demonstrate that UPR‐mediated translational control induces the expression of enzymes involved in a pathway that diverts intermediate metabolites from glycolysis to fuel mitochondrial one‐carbon metabolism. Concomitantly, the cells become resistant to the folate-based antimetabolites Methotrexate and Pemetrexed, establishing a direct link between UPR‐driven changes to gene expression and resistance to pharmacological treatment.

BACKGROUND: Little is known about duration of protection after the infant primary series of hepatitis B (HB) vaccine in settings of low HB endemicity. This study sought to determine the proportion of adolescents immunized as infants who had protective titers of antibody to hepatitis B surface antigen (anti-HBs) before and after a challenge dose of vaccine. METHODS: US-born 16- through 19-year-olds who received a recombinant HB vaccine 3-dose series initiated within 7 days of birth (group 1) or at ≥4 weeks of age (group 2) and completed by 12 months of age were enrolled. Participants had serologic testing before and 2 weeks after randomization to receive a challenge dose of 10 µg or 20 µg of Engerix-B. Baseline and postchallenge levels of anti-HBs were compared by group, challenge dosage, and demographic and behavioral characteristics. RESULTS: At baseline, 24% had protective anti-HBs levels of ≥10 IU/mL; 92% achieved protective levels after challenge dose. Although group 1 had a lower proportion of seroprotection at baseline, group and challenge dosage were not associated with postchallenge proportion of seroprotection. Being in group 2, higher test dosage, higher baseline geometric mean titer, and nonwhite race were associated with significantly higher geometric mean titer after challenge dose. CONCLUSIONS: More than 90% of study participants immunized against HB as infants exhibited a seroprotective response to a challenge dose of vaccine. Duration of protection from the primary infant HB vaccine series extended through the adolescent years in the setting of low HB endemicity.

Objective In 2011, Malawi implemented Option B+ (B+), lifelong antiretroviral therapy (ART) for pregnant and breast-feeding women. We aimed to describe changes in service uptake and outcomes along the antenatal PMTCT cascade post B+ implementation. Design Pre/post study using routinely collected program data from two large Lilongwe-based health centers. Methods We compared testing of HIV-infected pregnant women at antenatal care, enrollment into PMTCT services, receipt of ART and six-month ART outcomes pre- (Oct 2009–Mar 2011) and post- (Oct 2011–Mar 2013) B+. Results A total of 13,926 (pre) and 14,532 (post) women presented to antenatal care. Post-B+ a smaller proportion were HIV tested (99.3% vs. 87.7% post-; p<0.0001). There were 1654 (pre) and 1535 (post) HIV-infected women identified, with a larger proportion already known to be HIV-infected (18.1% vs. 41.2% post-; p<0.001) and on ART post-B+ (18.7% vs. 30.2% post-; p<0.001). A significantly greater proportion enrolled into the PMTCT program (68.3% vs. 92.6% post-; p<0.001) and was retained through delivery post-B+ (51.1% vs. 65% post-; p<0.0001). Amongst those not on ART at enrollment there was no change in the proportion newly initiating ART/ARVs (79% vs. 81.9% post-; p=0.11); although median days to initiation of ART decreased (48d [19,130] vs. 0d [0,15.5] post-; p<0.001). Amongst those newly initiating ART, a smaller proportion was alive on ART six-months post-initiation (89.3% vs. 78.8% post-; p=0.0004). Conclusion While several improvements in PMTCT program performance were noted with implementation of B+, challenges remain at several critical steps along the cascade requiring innovative solutions to ensure an AIDS-free generation.

BackgroundTreatment of hepatitis C (HCV) is very effective, achieving a cure in 50–90% of patients. Besides its own good for individuals, this most likely translates in reduced transmission, but this phenomenon has yet to be fully explored.Methods and FindingsIn this mathematical modeling study done in the context of Vietnam, we estimated the public health benefit that HCV therapy for injecting drug users (IDUs) may achieve. Treatment coverage of 25, 50 and 75% of chronically HCV-infected IDUs (4 years into infection) is predicted to reduce the chronic HCV viremia prevalence respectively by 21, 37 and 50%, 11 years after full scale up to the intended coverage. At a constant 50% coverage level, earlier treatment, 3, 2, and 1 year into infection is predicted to reduce the chronic HCV viremia prevalence by 46, 60 and 85%. In these later 3 scenarios, for every 100 treatment courses provided, a total of respectively 50, 61 and 94 new infections could be averted. These benefits were projected in the context of current low coverage of methadone maintenance therapy and needles/syringes exchange programs, and these services expansion showed complementary preventive benefits to HCV therapy. The program treatment commitment associated with the various scenarios is deemed reasonable. Our model projections are robust under adjustment for uncertainty in the model parameter values.ConclusionsIn this case study in Vietnam, we project that treatment of HCV for injecting drug users will have a preventative herd effect in addition to curing patients in need for therapy, achieving a substantial reduction in HCV transmission and prevalence.