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Background: Adverse childhood experiences (ACEs), substance use, depressive symptoms, and HIV outcomes in people living with HIV (PLWHIV) have not been comprehensively investigated within a single study., Aim: The aim of this study was to investigate the prevalence and association of ACEs, substance use, depressive symptoms and human immunodeficiency virus (HIV) outcomes in PLWHIV accessing HIV care during the coronavirus disease 2019 (COVID-19) pandemic., Setting: District hospital HIV clinic in South Africa., Methods: A total of 196 PLWHIV completed a socio-demographic and clinical questionnaire; an adapted World Health Organization (WHO) Alcohol, Smoking and Substance Involvement Screening Test; WHO ACEs International Questionnaire, and Patient Health Questionnaire., Results: The most common ACEs were having one or no parent, parental separation or divorce ( n = 131, 66.8%), exposure to collective ( n = 57, 29.1%) and community violence ( n = 55, 28.1%), with 40.3% ( n = 79) experiencing ≥ 3 ACEs. The most commonly used substances were alcohol ( n = 34, 17.3%), tobacco ( n = 33, 16.8%), and cannabis ( n =13, 6.6%). The prevalence of depressive symptoms was 19.4% ( n = 38). Linear regression analyses indicated greater alcohol (adj β = 2.84, p < 0.01), tobacco (adj β = 3.64, p < 0.01) and cannabis use risk scores (adj β = 2.39, p < 0.01) were associated with ≥ 3 ACEs. Logistic regression indicated depressive risk (adjusted odds ratio [OR] = 9.39, 95% confidence interval [CI] 4.78-23.51) was associated with ≥ 3 ACEs., Conclusion: A high prevalence of ACEs, substance use and depressive symptoms exists among PLWHIV, along with an association between cumulative ACEs and both substance use and depressive symptoms., Contribution: Enhanced screening and management services are recommended to address this triple burden in PLWHIV., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2024. The Authors.)

Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article.

Aim: Mental disorders and HIV are the main contributors to the increase in years lived with disability rates per person in sub-Saharan Africa. A complex inter-relationship exists between HIV and mental illness, especially in a region with a high HIV prevalence. We examined the duration of untreated psychosis (DUP), and the nature of psychotic and cognitive symptoms in people with first episode psychosis (FEP) living with and without HIV., Methods: Adults aged between 18 and 45 years were assessed using a clinical interview, physical examination and several psychiatric tools. These included the Mini International Neuro-psychiatric Interview to confirm psychosis, Positive and Negative Syndrome Scale, International HIV Dementia Scale and other scales to measure symptom variables. HIV ELISA was used for HIV serology testing, with measures being carried out within 6 weeks of the first presentation., Results: Of the 172 people presenting with FEP, 36 (21%) had comorbid HIV, those with both being older and more likely to be female (p < .001). Clinically, participants with FEP and HIV scored lower on the positive subscale (p = .008). There were no statistically significant differences for DUP or cognitive screening. Of those living with HIV and FEP (n = 36) comorbidity, nine were newly diagnosed with HIV at the time of the study., Conclusion: Individuals presenting with FEP and comorbid HIV were older, female and reported more mood symptoms. The identification of nine new HIV infections also reflects the ongoing need to test for HIV in people presenting with severe mental illness., (© 2024 The Author(s). Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Background: The COVID-19 pandemic and the lockdown experience may have not only precipitated or exacerbated mental illness but also influenced access to care and the nature and content of the psychotic symptomatology of people with psychosis., Aim: This study aimed to evaluate the association of the COVID-19 pandemic and lockdown experience on clinical presentation and quality of life of people (QOL) with first episode psychosis (FEP)., Method: Two first episode psychosis cohorts from the same epidemiological area collected prior to, and during the COVID-19 pandemic and lockdown were compared in terms of clinical symptomatology, substance use and QOL. All adult in- and outpatients with FEP at five clinical units in KwaZulu-Natal, South Africa, aged between 18 and 45 years, were assessed with the MINI interview for psychosis, Positive and Negative Symptoms Scale, WHO Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) and the WHO QOL scales., Results: Eighty-eight FEP participants were recruited between 2019 and 2020 (cohort 1) before the pandemic. Study recruitment was suspended in March 2020 due to the pandemic. On study resumption from November 2020 to November 2022, 95 new participants (cohort 2) were recruited. There were no sociodemographic differences between the two cohorts, except unemployment status (57% vs. 65%) and household income. The cohort presenting post-COVID-19 pandemic onset had significantly more positive psychotic symptoms (21.9 vs. 23.7), lower PANSS domain depressive score, more lifetime use of tobacco, cannabis and alcohol. However, they reported improved QOL (196 vs. 239)., Conclusion: Following the pandemic and lockdown experience participants presented with more severe psychotic symptoms and concomitant substance use but improved perceived QOL. This suggests the need to explore individual and social factors that may influence the clinical presentation., (© 2023 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Background: Four out of five adolescents worldwide are physically inactive based on recommended standards., Aim: We determined whether physical activity is associated with lower behavioural challenges in adolescents to promote buy-in from stakeholders., Setting: KwaZulu-Natal province, South Africa, from January 2020 to March 2020., Methods: A cross-sectional study was conducted among 187 adolescent learners (12-18 years) from three government schools in KwaZulu-Natal Province, South Africa, from January to March 2020. We fitted linear regression models between the Strengths and Difficulties Questionnaire scores (total, internalising, externalising, and prosocial) and hours of physical activity exposure, adjusting for demographic covariates, and depression history., Results: The median age was 14.4 years (interquartile range = 1.36) and 75.9% of the participants were females. Overall average and weekday physical activity were each associated with lower total and externalising but higher pro-social scores. Depression was associated with higher inactivity scores (total, internalising and externalising)., Conclusions: The article shows that physical activity can reduce the behavioural and emotional problems in adolescents., Contribution: Physical activity is critical for a healthy adolescent hood and needs to be actively included in childhood development., Competing Interests: The authors declare that they have no financial or personal relationship(s) that may have inappropriately influenced them in writing this article., (© 2023. The Authors.)

Adverse childhood experiences (ACEs) and interpersonal violence (IPV) in mentally ill women are often neglected and need to be reviewed in light of the suggested increase in IPV during the COVID-19 pandemic.We investigated the prevalence of ACEs and IPV in women living with severe mental illness (SMI) attending an outpatient psychiatry service at a public hospital in KwaZulu-Natal, South Africa, during the COVID-19 pandemic. We also described the association of ACEs with later IPV.A written survey comprising socio-demographic and clinical questionnaire, WHO Adverse Childhood Experiences International Questionnaire (ACE-IQ) for ACEs and the Women abuse screening tool (WAST) for IPV, was completed by the 154 women with SMI.141 (91.6%) participants scored positive for ACEs and 104 (67.5%) had experienced three or more ACEs. The most prevalent forms of ACEs were emotional neglect 72 (46.8%), one or no parents, parental separation, or divorce 104 (67.5%), contact sexual abuse 67 (43.5%) and witnessing a household member treated violently 67 (43.5%). Sixty-one (46.6%) participants reported IPV with scores  13 (indicative of abuse). On logistic regression, experience of three or more ACEs was significantly associated with IPV in adulthood (aOR 3.3, 95% CI: 1.2-9.6).The high prevalence of IPV and association of IPV with cumulative ACEs reflect firstly the hidden epidemic of domestic violence and secondly the vulnerability of those with ACEs to become victims of abuse later which is often  missed in the care of women with SMI.

Background: There is an increased prevalence of depression, anxiety, and burnout among medical students worldwide with no information from Namibia., Aim: This study aimed to determine the prevalence and factors associated with depression, anxiety, and burnout among medical students at the University of Namibia (UNAM)., Methods: A quantitative descriptive cross-sectional survey was conducted utilising a specially designed questionnaire for the study and standardised instruments to evaluate depression, anxiety, and burnout., Results: Of the 229 students in this study, 71.6% were female and 28.4% were male. The prevalence of depression, anxiety, and burnout was 43.6%, 30.6%, and 36.2%, respectively. The prevalence of emotional exhaustion (EX), cynicism (CY), and professional efficacy (EF) was 68.1% ( n = 156), 77.3% ( n = 177) and 53.3% ( n = 122), respectively. In the final regression model, participants with a current psychiatric illness were more likely to screen positive for depression (adjusted odds ratio [aOR] 4.06, confidence interval [CI] 1.28-12.91; p = 0.02) and anxiety (aOR: 3.63, CI: 1.17-11.23; p = 0.03). Emotional exhaustion and cynicism were significantly associated with female gender (EX: aOR, 0.40, CI: 0.20-0.79; p = 0.01) (CY: aOR, 0.42, CI: 0.20-0.91; p = 0.03)., Conclusion: More than one in three medical students at the UNAM were either depressed or burnt out., Contribution: This is the first study to highlight the mental health needs of medical students at the University of Namibia., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2023. The Authors.)

Background: Human immunodeficiency virus (HIV) and psychosis share a complex bidirectional relationship, with people living with HIV being at increased risk of psychosis and those with psychosis at increased risk of HIV. However, people living with severe mental illness often have limited or reduced access to HIV testing and care., Aim: This study aimed to determine the prevalence of HIV and describe the access to HIV testing and care among adult patients with recent-onset psychosis who were admitted to a psychiatric hospital in KwaZulu-Natal (KZN) province, South Africa., Setting: A psychiatric hospital in Pietermaritzburg, KZN province, South Africa., Method: A retrospective chart review of 294 patients with recent-onset psychosis admitted between May 2018 and November 2020., Results: A total of 291 (99%) patients had access to HIV testing during the study period, with the HIV seroprevalence rate being 21.5% among the 294 patients; HIV seropositivity was associated with the 25-49 age category (adjusted odds ratio [aOR] = 3.09, 95% confidence interval [CI] 1.27-7.50), female gender (aOR = 9.55, 95% CI 4.40-20.74), current alcohol and cannabis use (aOR = 3.43, 95% CI 1.01-11.62), family history of psychosis (aOR = 3.22, 95% CI 1.03-10.02) and no tertiary education (aOR = 3.7, 95% CI 0.14-0.99). All those living with HIV were on antiretroviral treatment., Conclusion: This study showed that HIV testing and care was accessible at a psychiatric hospital but the prevalence of HIV in people living with recent onset psychosis remains high., Contribution: The study findings suggest the importance of integrating mental health and HIV management., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2023. The Authors.)

Introduction: Access to mental health services is a challenge, especially for young people who are over-represented in the unemployment and poverty index in South Africa. Therefore, continuing care is a problem after hospital discharge for young people with first-episode psychosis (FEP) due to a lack of clinical engagement and follow-up, for which they need support, including financial, to improve their outcomes. This pilot randomised control trial (RCT) aims to assess the feasibility and acceptability of financial support, in the form of an unconditional cash transfer (UCT), among young patients with FEP to prevent relapse., Methods and Analysis: This study will use a 1:1 ratio two-arm open-label pilot RCT of 60 young participants (18-29 years) with FEP in remission, who will be recruited from specialised psychiatric facilities in KwaZulu-Natal Province, South Africa. This study will implement an UCT and assess its feasibility, acceptability and preliminary clinical outcomes (ie, medication adherence, relapse, quality of life, personal and social function). The follow-up time will be 3 months, the outcomes being measured at baseline, months 1 and 3. Descriptive and conventional content analysis will be done for quantitative and qualitative data, respectively., Ethics and Dissemination: The study obtained provisional approval from the Biomedical Research Ethics Committee at the University of KwaZulu-Natal(#BREC/00004117/2022). Also is registered on the South African National clinical trial registry (#DOH-27-092022-5894) and approved by the KwaZulu-Natal department of health (#NHRD Ref: KZ&#95;2002209&#95;033). The results from this investigation will be actively disseminated through peer-reviewed journal publications, conference presentations and stakeholder engagement., Trial Registration Number: DOH-27-092022-5894., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is a high prevalence of cannabis use in patients with schizophrenia spectrum and other psychotic disorders, with comorbid cannabis use in this population being associated with poorer long-term outcomes., Aim: To determine the prevalence of cannabis use in patients with a schizophrenia spectrum and other psychotic disorders., Setting: The study was conducted at a psychiatric hospital in Durban, KwaZulu-Natal Province, South Africa., Methods: A review of clinical records of patients admitted to the hospital for the period, June 2018 to June 2020, was conducted., Results: A total of 370 clinical records were reviewed, of which 48.9% reported current and 51.1% lifetime cannabis use. Being male was significantly associated with current and lifetime cannabis use (OR = 4.90, 95% CI 2.49-9.62 and OR = 6.27, 95% CI 3.28-11.95, respectively). Current alcohol use was also associated with current cannabis use (CCU) (OR = 3.06, 95% CI 1.78-5.28), and age 45 years and older was associated with a lower odds of cannabis use (OR = 0.30, 95% CI 0.09-0.96). Forty-eight per cent of participants were admitted three or more times, and readmission was associated with cannabis use ( p = 0.01). There was a lack of association between cannabis use, readmission and human immunodeficiency virus (HIV) status, after controlling for variables such as alcohol use and gender., Conclusion: Almost 50% of people admitted with schizophrenia spectrum and other psychotic disorders have comorbid current and lifetime cannabis use. There is a need for dual diagnosis units to address comorbid substance use in people with psychotic disorders, as it leads to poorer outcomes., Contribution: The study found that there is a high prevalence of cannabis use in people with psychosis. Therefore, it is imperative that we revise treatment programs in our psychiatric units and there is an urgent need for dual diagnosis programs that address substance use in this group of patients., Competing Interests: The authors have declared that no competing interest exists., (© 2022. The Authors.)

Abstract: The rise in use of digital technology among adolescents is unquestionable, with few studies having explored the effect of screen time on mental or behavior challenges in sub-Saharan Africa. We investigated the extent of screen time and its associations with mental/behavior challenges in South Africa. A multisite study was conducted among adolescents aged 15 to 17 years from three government schools in KwaZulu-Natal Province, South Africa. Measures included depressive symptoms (using Patient Health Questionnaire-9), behavioral problems (using Strengths and Difficulties Questionnaire), and screen time (using Children's Leisure Activities Study Survey). The prevalence of severe depressive symptoms, conduct features, and negative prosocial behavior was 11.2% (n = 20), 13.6% (n = 25), and 4.9% (n = 9), respectively. The mean screen time was 2.1 h/d (SD = 2.4) during weekday and 4.7 h/d (SD = 5.5) during weekend. Weekend screen time was significantly associated with a greater likelihood of severe depression and conduct challenges, based on multivariable regression. We also found that greater weekend cell phone use was significantly associated with lower prosocial behavior. No role of weekday screen time was detected in this study. Parents or legal guardians need to be aware of their children's weekend screen time, including cell phones, as access to digital devices becomes more ubiquitous in resource-limited settings., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Untreated post-traumatic stress disorder (PTSD) results in considerable morbidity and higher risk of mortality. However, little is being done to treat PTSD in sub-Saharan Africa (SSA) settings where rates of PTSD are likely to be elevated due to mass exposure of the population to traumatic events. This systematic review aims to summarise available evidence on the efficacy of psychological therapies for PTSD in SSA., Methods and Analysis: A systematic search of the literature will be conducted in four electronic databases: PubMed, PsychInfo, EMBASE and Cochrane Register of Controlled Trials using keywords and synonyms related to 'PTSD', 'psychological therapies' and 'SSA'. Studies will be included if they were conducted in SSA and used a randomised controlled trial design. Two researchers will screen the studies for eligibility to be included, and data on intervention types, population, comorbidities, comparison group intervention and PTSD outcomes will be extracted from those included. Risk of bias will be assessed using Cochrane risk-of-bias tool for randomised trials (version 2). Narrative synthesis of data will be conducted and pooled effect estimates calculated., Ethics and Dissemination: Ethical approval is not required as this is a protocol of a systematic review of available data. Findings will be disseminated to the scientific community through peer-reviewed publications and presentation at conferences., Prospero Registration: CRD42020181638., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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 nonadherence 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 viremia in cART-suppressed infants., Results: Baseline HIV DNA (median 2.8 log10 copies/million peripheral blood mononuclear cells, 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 aviremia 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 Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Abstract: 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, I2 = 89%, p < 0.01), and of FEP in PLWHIV was 23% (95% CI, 15%-32%), without significant heterogeneity (n = 3, I2 = 0%, p = 0.43). There are concerning levels of HIV and FEP comorbidity in SSA, necessitating an integrated health care service., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: South Africa (SA) has a high HIV prevalence and limited mental healthcare resources. Neuropsychiatric complications such as psychosis onset in people living with HIV (PLWHIV) remains poorly understood. The study aims to compare the socio-demographic, clinical, substance use, cognitive and trauma profile of PLWHIV presenting with first episode psychosis (FEP) to those with the condition but without HIV., Methods and Analysis: This study will compare presentation, course, and outcome of a cohort of PLWHIV and FEP with a control group recruited over a 3-year period. We will prospectively test the hypothesis that the 2 groups are socio-demographically, clinically and cognitively distinct at illness presentation, with higher trauma burden and poorer outcomes in those with the dual burden of HIV and FEP. FEP participants, confirmed by a structured neuropsychiatric interview, will have their socio-demographic, psychosis, mood, motor, trauma and substance use variables assessed. A neuropsychological battery will be completed to assess cognition, while quality of life, psychotic symptoms and HIV markers will be measured at 3, 6 and 12 months., Ethics and Dissemination: The study protocol has been reviewed and ethics approval obtained from the Biomedical Research Ethics Committee (BC 571/18) of the University of KwaZulu-Natal. The results from this investigation will be actively disseminated through peer-reviewed journal publications and conference presentations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Molebatsi, Musindo, Ntlantsana and Wambua.)

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.

The exploration of resilience in schizophrenia is recent and poorly understood. Literature suggests that exploration of the construct will help with the understanding of not only risk but also protective factors in individuals living with psychosis. We performed a systematic review and meta-analysis with the primary aim of synthesizing the evidence of an existing relationship between resilience and schizophrenia-spectrum disorders (SSD). We searched electronic databases for relevant articles that evaluated resilience and psychosocial functioning in participants with schizophrenia-spectrum disorders. Sixteen studies were deemed eligible for review. We also conducted a random-effects meta-analysis to explore resilience levels of study participants. Our findings highlight lower levels of resilience in SSD cohorts and poorer psychosocial functioning among those with low levels of resilience. Evidence also suggests that the presence of resilience in individuals with schizophrenia-spectrum disorders is associated with improved psychosocial functioning., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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 18-38) and 75 infants diagnosed via standard-of-care (SoC) laboratory-based testing initiated cART at 10 days (IQR 8-13). 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 5.6-39.6; 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., Funding: Wellcome Trust, National Institutes of Health., Competing Interests: Dr. Martinez-Picado reports institutional grants and educational/consultancy fees outside the submitted work from AbiVax, Astra-Zeneca, Gilead Sciences, Grifols, Janssen, Merck and ViiV Healthcare. Dr. Millar reports personal fees from Cepheid, outside the submitted work., (© 2020 The Author(s).)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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.

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., Competing Interests: The authors declare that they have no financial or personal relationship(s) that may have inappropriately influenced them in writing this article.