Background Previous research has reported increased risk for psychosis among individuals who use cannabis during adolescence. We conducted a systematic review and meta-analysis to investigate the interaction between adolescent cannabis use and other factors in moderating risk for psychosis later in life. Method We searched four electronic databases in June 2020 for articles that assessed adolescent cannabis use, had psychosis as an outcome and analyzed for the association between adolescent cannabis use and psychosis. Analysis was done using random-effects meta-analysis and narrative synthesis. Results A total of 63 studies were included in the narrative review and 18 studies were included in the meta-analysis. Adolescent cannabis use was found to increase risk for psychosis (RR = 1.71 (95%CI, 1.47–2.00, p < 0.00001) and predict earlier onset of psychosis. The following factors moderate the relationship between cannabis use and the risk of psychosis: age of onset of cannabis use, frequent cannabis use, exposure to childhood trauma, concurrent use of other substances and genetic factors. Conclusion Adolescent cannabis use is associated with an increased risk for psychosis later in life. In addition, there are factors that moderate this relationship; therefore there is a need for research to assess the interaction between these factors, adolescent cannabis use and psychosis risk.

Background: Early combination antiretroviral therapy (cART) reduces the size of the viral reservoir in paediatric and adult HIV infection. Very early-treated children may have higher cure/remission potential. Methods: In an observational study of 151 in utero (IU)-infected infants in KwaZulu-Natal, South Africa, whose treatment adhered strictly to national guidelines, 76 infants diagnosed via point-of-care (PoC) testing initiated cART at a median of 26 h (IQR 18À38) and 75 infants diagnosed via standard-of-care (SoC) laboratory-based testing initiated cART at 10 days (IQR 8À13). We analysed mortality, time to suppression of viraemia, and maintenance of aviraemia over the first 2 years of life. Findings: Baseline plasma viral loads were low (median 8000 copies per mL), with 12% of infants having undetectable viraemia pre-cART initiation. However, barely one-third (37%) of children achieved suppression of viraemia by 6 months that was maintained to >12 months. 24% had died or were lost to follow up by 6 months. Infant mortality was 9.3%. The high-frequency virological failure in IU-infected infants was associated not with transmitted or acquired drug-resistant mutations but with cART non-adherence (plasma cART undetectable/subtherapeutic, p<0.0001) and with concurrent maternal cART failure (OR 15.0, 95%CI 5.6À39.6; p<0.0001). High-frequency virological failure was observed in PoC-and SoC-tested groups of children. Interpretation: The success of early infant testing and cART initiation strategies is severely limited by subsequent cART non-adherence in HIV-infected children. Although there are practical challenges to administering paediatric cART formulations, these are overcome by mothers who themselves are cART-adherent. These findings point to the ongoing obligation to address the unmet needs of the mothers. Eliminating the particular barriers preventing adequate treatment for these vulnerable women and infants need to be prioritised in order to achieve durable suppression of viraemia on cART, let alone HIV cure/remission, in HIV-infected children.

Female children and adults typically generate more efficacious immune responses to vaccines and infections than age-matched males, but also suffer greater immunopathology and autoimmune disease. We here describe, in a cohort of > 170 in utero HIV-infected infants from KwaZulu-Natal, South Africa, fetal immune sex differences resulting in a 1.5-2-fold increased female susceptibility to intrauterine HIV infection. Viruses transmitted to females have lower replicative capacity (p = 0.0005) and are more type I interferon-resistant (p = 0.007) than those transmitted to males. Cord blood cells from females of HIV-uninfected sex-discordant twins are more activated (p = 0.01) and more susceptible to HIV infection in vitro (p = 0.03). Sex differences in outcome include superior maintenance of aviraemia among males (p = 0.007) that is not explained by differential antiretroviral therapy adherence. These data demonstrate sex-specific innate immune selection of HIV associated with increased female susceptibility to in utero infection and enhanced functional cure potential among infected males.

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Background Early HIV diagnosis allows combination antiretroviral therapy (cART) initiation in the first days of life following in utero (IU) infection. The impact of early cART initiation on infant viral reservoir size in the setting of high-frequency cART non-adherence is unknown. Methods Peripheral blood total HIV DNA from 164 early treated (day 0-21 of life) IU HIV-infected South African infants was measured using droplet digital PCR at birth and following suppressive cART. We evaluated the impact of cART initiation timing on HIV reservoir size and decay, and on the risk of subsequent plasma viraemia in cART-suppressed infants. Findings Baseline HIV DNA (median 2.8 log10 copies/million PBMC, range 0.7 – 4.8) did not correlate with age at cART initiation (0-21 days) but instead with maternal antenatal cART use. In 98 infants with plasma viral suppression on cART, HIV DNA half-life was 28 days. However, the probability of maintenance of plasma aviraemia was low (0.46 at 12 months) and not influenced by HIV DNA load. Unexpectedly, longer time to viral suppression was associated with protection against subsequent viral rebound. Conclusions With effective prophylaxis against mother-to-child transmission, cART initiation timing in the first 3 weeks of life is not critical to reservoir size.

The COVID-19 pandemic brought in its wake an unforeseen mental health crisis. The World Health Organization published a guideline as a way of supporting mental health and psychosocial well-being of different groups during this pandemic. The impact of the pandemic has pushed governments to put measures in place to curb not only the physical health of individuals but their mental health and psychosocial well-being as well. The aim of our paper was to review mental health guidelines of some Sub Saharan African (SSA) countries: (i) to assess their appropriateness for the immediate mental health needs at this time, (ii) to form as a basis for ongoing reflection as the current pandemic evolves. Guidelines were retrieved openly from internet search and some were requested from mental health practitioners in various SSA countries. The authors designed a semi structured questionnaire, as a self-interview guide to gain insight on the experience of COVID-19 from experts in the mental health sector in the various countries. While we used a document analysis approach to analyze the data, we made use of the Mental Health Preparedness and Action Framework to discuss our findings. We received health or mental health guidelines from 10 SSA countries. Cameroon, Kenya, South Africa, Tanzania, and Uganda all had mental health guidelines or mental health component in their health guidelines. Our experts highlight that the mental health needs of the people are of concern during this pandemic but have not been given priority. They go further to suggest that the mental health needs are slightly different during this time and requiring a different approach especially considering the measures taken to curb the spread of disease. We conclude that despite the provision of Mental Health and Psychosocial Support guidelines, gaps still exist making them inadequate to meet the mental health needs of their communities.

Background: Preconception antiretroviral therapy (PCART) followed by sustained viral suppression is effective in preventing mother-to-child transmission of HIV. The rates of persistent and transient viraemia in such patients have not been prospectively assessed in South Africa.Objectives: We determined the prevalence of transient and persistent viraemia in HIV-positive women entering antenatal care on PCART and studied variables associated with viraemia.Methods: We performed a prospective cross-sectional observational study of HIV-positive pregnant women presenting to a primary healthcare facility in KwaZulu-Natal. All had received at least 6 months of first-line PCART. Viral load (VL) was measured, patients were interviewed, adherence estimated using a visual analogue scale and adherence counselling provided. Viral load was repeated after 4 weeks where baseline VL exceeded 50 copies/mL.Results: We enrolled 82 participants. Of them, 59 (72%) pregnancies were unplanned. Fifteen participants (18.3%) were viraemic at presentation with VL > 50 copies/mL. Of these, seven (8.5%) had viral suppression (VL < 50 copies/mL), and eight remained viraemic at the second visit. Adherence correlated significantly with viraemia at baseline. Level of knowledge correlated with adherence but not with lack of viral suppression at baseline. Socio-economic indicators did not correlate with viraemia. No instances of vertical transmission were observed at birth.Conclusions: Approximately 20% of women receiving PCART may demonstrate viraemia. Half of these may be transient. Poor adherence is associated with viraemia, and efforts to encourage and monitor adherence are essential. The rate of unplanned pregnancies is high, and antiretroviral therapy programmes should focus on family planning needs of women in the reproductive age group to prevent viral non-suppression prior to pregnancy.Keywords: Preconception Antiretroviral Therapy; HIV; Viraemia; Antenatal Care; Adherence.

A systematic review and meta-analysis was conducted to synthesize data on HIV prevalence in individuals with first-episode psychosis (FEP) and to provide an overview of the association of HIV with clinical variables of FEP. Electronic databases were searched for quantitative studies published from January 1986 to November 2019. Meta-analyses were undertaken to calculate the pooled HIV/FEP proportion based on random effects modeling with inverse variance method. Seven HIV/FEP studies from sub-Sahara Africa (SSA) met inclusion criteria. The prevalence of HIV in FEP ranged from 24% to 40%, and FEP in people living with HIV (PLWHIV) ranged from 17% to 29%. The pooled proportion of HIV in FEP was 26% (95% confidence interval [CI], 10%-43%), with significant heterogeneity (n = 3, I 2 = 89%, p < 0.01), and of FEP in PLWHIV was 23% (95% CI, 15%-32%), without significant heterogeneity (n = 3, I 2 = 0%, p = 0.43). There are concerning levels of HIV and FEP comorbidity in SSA, necessitating an integrated health care service.