HIV Infection In South Africa Research Articles

Longitudinal controlled attenuation parameter and liver stiffness in children with and without perinatal HIV infection in South Africa.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging cause of liver disease in HIV. Transient elastography (TE) with controlled attenuation parameter (CAP) measures liver stiffness as a marker of liver fibrosis and CAP as a measure of hepatic steatosis. Our aim was to evaluate longitudinal CAP and liver stiffness in children with perinatally acquired HIV (PHIV) on antiretroviral therapy (ART) from early life compared to children without HIV (HU). Prospective cohort study. PHIV and HU were followed annually for two years. During the study, 60% of PHIV switched from older ART regimens to tenofovir disoproxil, lamivudine and dolutegravir (TLD). Longitudinal evolution of CAP and liver stiffness were investigated in two PHIV groups - on older ART and on TLD - compared to HU children using linear mixed effects models. 263 children and adolescents (112 PHIV, 151 HU) aged 7-20 years were followed. PHIV on older ART had CAP 8.61% (95% CI 4.42-12.97, P < 0.001) greater than HU and no significant difference in CAP between PHIV on TLD and HU. No significant difference in liver stiffness was found between PHIV on older ART regimens and PHIV on TLD compared to HU. PHIV on older ART had higher CAP than HU, whereas in PHIV switched to TLD there was no difference in CAP compared to HU. There was no difference in liver stiffness between either PHIV group and HU. This suggests starting ART early in life might protect PHIV from developing hepatic fibrosis.

Effect of implementation strategies on pre-exposure prophylaxis persistence among female sex workers in South Africa: an interrupted time series study

A disproportionate number of new HIV infections in South Africa are among female sex workers; pre-exposure prophylaxis (PrEP) for HIV prevention is freely available to female sex workers in the country, but unique barriers challenge PrEP persistence. TB HIV Care, a large South African non-profit organisation that provides daily oral PrEP (tenofovir disoproxil fumarate and emtricitabine), has implemented multiple strategies to improve PrEP persistence. We aimed to evaluate the effect of different implementation strategies on PrEP persistence in a large-scale real-world setting. In this interrupted time series study, we estimated level changes in 1-month oral PrEP persistence associated with roll-out of various implementation strategies among female sex workers across nine districts in South Africa. We used routinely collected data from TB HIV Care programme files from June 7, 2016, to April 30, 2021. Poisson regression of 1-month persistence was used to assess the effect of these strategies. In secondary analyses, we tested the association between each of the strategies and 4-month persistence. The median 1-month PrEP persistence for female sex workers was 33% (IQR 27-40). SMS support and refill reminders were associated with an 11% relative increase in 1-month persistence (risk ratio [RR] 1·11, 95% CI 1·02-1·26) and clinical mentoring for PrEP providers was associated with a 127% relative increase (RR 2·27, 95% CI 1·94-2·66) among female sex workers. The loyalty rewards programme was negatively associated with 1-month persistence (RR 0·71, 95% CI 0·67-0·83). Although clinical mentoring improved 4-month persistence, SMS support text messages had no significant effect. Identification and subsequent use of clinical mentoring for PrEP providers and SMS support and refill reminders might improve the usefulness of PrEP overall to prevent new HIV infections among female sex workers. PrEP persistence remains an important issue, and strategies to build on our findings are needed. National Institute of Mental Health and National Institute of Allergy and Infectious Diseases.

The Roles of Youth in Intimate Partner Relationships and the Perceived Risk of HIV Infection in South Africa

Background: Young people in South Africa face multiple developmental challenges, including violence and HIV infection. Objective: This study examines the various roles of youth in violent intimate relationships (IPV) and its association with the perceived risk of HIV infection. Results from this study could assist in youth development programmes to increase HIV testing, as well as inform modifications to the South African Domestic Violence Act (No. 116 of 1998), which addresses all forms of intimate partner violence in the country. Methods: The study uses data from the South African National HIV Prevalence, HIV Incidence, Behaviour and Communication Survey (SABSSM) 2017. The study population is youth (15-24 years old) who responded to a question on their perceived risk of being infected with HIV. A weighted sample (N) of 1,301,550 youth is included. The main independent variable is the 'role in IPV', and the study controls for the demographic, socioeconomic, and HIV knowledge and sexual behaviours of youth. Cross-tabulations and a multivariate binary logistic regression model are used to determine the relationship between controls and the outcome. Results: About 20% of youth perceive themselves at risk of being with HIV. Their reasons for believing this are because they are sexually active, do not use condoms consistently, and do not trust their partners. Only about 4% of IPV perpetrators, compared to 23.71% of victims and 23.16% of bidirectional youth, think it is likely they will get infected with HIV. The odds of perceiving themselves at risk are higher (with p-values&lt;0.05) for victims (OR=1.21), 20-24 years old (OR=1.35), female (OR=1.25), those who responded do not think condoms reduce the risk of HIV (OR=1.49) and those who do not use condoms (OR=1.44) among others. Conclusion: IPV behaviours are associated with perceived HIV risk among young people in South Africa. For perception to change and allow youth to adopt protective behaviours against HIV, there is a need for policy to target the different roles of youth.

Protective factors for adolescent sexual risk behaviours and experiences linked to HIV infection in South Africa: a three-wave longitudinal analysis of caregiving, education, food security, and social protection

BackgroundStructural interventions are endorsed to enhance biomedical and behavioural HIV prevention programmes for adolescents. Aiming to inform future interventions, we evaluated longitudinal associations between six protective factors that link closely to existing structural HIV prevention interventions, and five sexual risk behaviours for HIV transmission in a cohort of adolescents in South Africa.MethodsWe used three rounds of data between 2014–2018 on 1046 adolescents living with HIV and 473 age-matched community peers in South Africa’s Eastern Cape (Observations = 4402). We estimated sex-specific associations between six time-varying protective factors − number of social grants, education enrolment, days with enough food, caregiver supervision, positive caregiving, and adolescent-caregiver communication; and five HIV risk behaviours − multiple sexual partners, transactional sex, age-disparate sex, condomless sex, and sex on substances. HIV risk behaviours were analysed separately in multivariable random effects within-between logistic regression models that accounted for correlation of repeated observations on the same individual. We calculated prevalence ratios (PR), contrasting adjusted probabilities of HIV risk behaviours at ‘No’ and ‘Yes’ for education enrolment, and average and maximum values for the other five protective factors.ResultsThe sample mean age was 15.29 (SD: 3.23) years and 58% were girls. Among girls, within-individuals, increases from mean to maximum scores in positive caregiving were associated with lower probability of transactional sex (PR = 0.79; 95%CI = 0.67–0.91); in caregiver supervision were associated with lower probability of transactional sex (PR = 0.75; 95%CI = 0.66–0.84), and age-disparate sex (PR = 0.84; 95%CI = 0.73–0.95); in adolescent-caregiver communication were associated with higher probability of transactional sex (PR = 1.70; 95%CI = 1.08–2.32); and in days with enough food at home were associated with lower probability of multiple sexual partners (PR = 0.89; 95%CI = 0.81–0.97), and transactional sex (PR = 0.82; 95%CI = 0.72–0.92). Change from non-enrolment in education to enrolment was associated with lower probability of age-disparate sex (PR = 0.49; 95%CI = 0.26–0.73). Between-individuals, relative to mean caregiver supervision scores, maximum scores were associated with lower probability of multiple sexual partners (PR = 0.59; 95%CI = 0.46–0.72), condomless sex (PR = 0.80; 95%CI = 0.69–0.91), and sex on substances (PR = 0.42; 95%CI = 0.26–0.59); and relative to non-enrolment, education enrolment was associated with lower probability of condomless sex (PR = 0.59; 95%CI = 0.39–0.78). Among boys, within-individuals, increases from mean to maximum scores in positive caregiving were associated with lower probability of transactional sex (PR = 0.77; 95%CI = 0.59–0.96), and higher probability of condomless sex (PR = 1.26; 95%CI = 1.08–1.43); in caregiver supervision were associated with lower probability of multiple sexual partners (PR = 0.73; 95%CI = 0.64–0.82), transactional sex (PR = 0.63; 95%CI = 0.50–0.76), age-disparate sex (PR = 0.67; 95%CI = 0.49–0.85), and sex on substances (PR = 0.61; 95%CI = 0.45–0.78), and in days with enough food at home were associated with lower probability of transactional sex (PR = 0.91; 95%CI = 0.84–0.98).ConclusionEffective structural interventions to improve food security and education enrolment among adolescent girls, and positive and supervisory caregiving among adolescent girls and boys are likely to translate into crucial reductions in sexual risk behaviours linked to HIV transmission in this population.

The Importance of the Individual in PrEP Uptake: Multilevel Correlates of PrEP Uptake Among Adolescent Girls and Young Women in Tshwane, South Africa.

Adolescent girls and young women (AGYW) account for 25% of new HIV infections in South Africa. Pre-exposure prophylaxis (PrEP) is approved by the South African Government, but the factors that promote PrEP uptake among AGYW are not well understood. This study examines multilevel factors associated with PrEP uptake among AGYW in six clinic catchment areas in Tshwane (Pretoria), South Africa. After consent/assent, PrEP-eligible AGYW (n = 448) completed a questionnaire assessing factors at the individual, network/interpersonal, and community levels and were prescribed PrEP in study clinics, if interested. A multivariable model, adjusting for clustering, assessed factors associated with PrEP uptake over a 9-month period. At the individual level, multiple partners in the past 3 months (OR = 0.47), perceived risk of HIV (OR = 0.71), and PrEP-related shame (OR = 0.63) were correlated with lower odds of PrEP uptake (ps ≤ 0.05). The findings highlight modifiable factors that should be addressed to support PrEP uptake efforts.

Maternal ART throughout gestation prevents caudate volume reductions in neonates who are HIV exposed but uninfected.

Successful programmes for prevention of vertical HIV transmission have reduced the risk of infant HIV infection in South Africa from 8% in 2008 to below 1% in 2018/2019, resulting in an increasing population of children exposed to HIV perinatally but who are uninfected (HEU). However, the long-term effects of HIV and antiretroviral treatment (ART) exposure on the developing brain are not well understood. Whereas children who are HEU perform better than their HIV-infected counterparts, they demonstrate greater neurodevelopmental delay than children who are HIV unexposed and uninfected (HUU), especially in resource-poor settings. Here we investigate subcortical volumetric differences related to HIV and ART exposure in neonates. We included 120 infants (59 girls; 79 HEU) born to healthy women with and without HIV infection in Cape Town, South Africa, where HIV sero-prevalence approaches 30%. Of the 79 HEU infants, 40 were exposed to ART throughout gestation (i.e., mothers initiated ART pre conception; HEU-pre), and 39 were exposed to ART for part of gestation (i.e., mothers initiated ART post conception; HEU-post). Post-conception mothers had a mean (± SD) gestational age (GA) of 15.4 (± 5.7) weeks at ART initiation. Mothers with HIV received standard care fixed drug combination ART (Tenofovir/Efavirenz/Emtricitabine). Infants were imaged unsedated on a 3T Skyra (Siemens, Erlangen, Germany) at mean GA equivalent of 41.5 (± 1.0) weeks. Selected regions (caudate, putamen, pallidum, thalamus, cerebellar hemispheres and vermis, and corpus callosum) were manually traced on T1-weighted images using Freeview. HEU neonates had smaller left putamen volumes than HUU [β (SE) = -90.3 (45.3), p = 0.05] and caudate volume reductions that depended on ART exposure duration in utero. While the HEU-pre group demonstrated no caudate volume reductions compared to HUU, the HEU-post group had smaller caudate volumes bilaterally [β (SE) = -145.5 (45.1), p = 0.002, and -135.7 (49.7), p = 0.008 for left and right caudate, respectively]. These findings from the first postnatal month suggest that maternal ART throughout gestation is protective to the caudate nuclei. In contrast, left putamens were smaller across all HEU newborns, despite maternal ART.

‘We don’t openly discuss these things’: Cultural complexities in teaching about sexuality and HIV in South Africa

It is well documented that rates of HIV infection in South Africa are alarmingly high, with approximately 7.5 million people living with HIV in 2021. This study aimed to explore how culture in the form of the values, practices, norms and beliefs prevalent in society influences teaching about sexuality and HIV in South Africa. The study adopted a qualitative, narrative approach and drew on findings from a purposive sample of six further education and training life orientation teachers from six schools in the province of KwaZulu-Natal, South Africa. Data were analysed using thematic analysis and cultural diamond principles. Socio-cultural complexities were found to shape discussion of sexuality and HIV. Five key themes were developed from an analysis of participants’ responses: school guidelines, culture of silence, personal experiences, cultural taboos, and language as a barrier. Findings signal the value of an integrated whole-school approach to the design and delivery of the curriculum involving key stakeholders and the perspectives of parents and religious leaders about the teaching of sexuality and HIV. The national departments of education and health in South Africa should also provide resources and guidelines detailing best practices to assist life orientation teachers.

Strengthening health system's capacity for linkage to HIV care for adolescent girls and young women and adolescent boys and young men in South Africa (SheS'Cap-Linkage): Protocol for a mixed methods study in KwaZulu-Natal, South Africa.

Adolescent girls and young women (AGYW) aged 15-24 years and adolescent boys and young men (ABYM) aged 15-34 years represent one of the populations at highest risk for HIV-infection in South Africa. The National Department of Health adopted the universal test and treat (UTT) strategy in 2016, resulting in increases in same-day antiretroviral therapy initiations and linkage to care. Monitoring progress towards attainment of South Africa's 95-95-95 targets amongst AGYW and ABYM relies on high quality data to identify and address gaps in linkage to care. The aim of this study is to describe the current approaches for engaging AGYW and ABYM in the treatment continuum to generate knowledge that can guide efforts to improve linkage to, and retention in, HIV care among these populations in KwaZulu-Natal, South Africa. This is a mixed methods study, which will be conducted in uMgungundlovu district of KwaZulu-Natal, over a 24-month period, in 22 purposively selected HIV testing and treatment service delivery points (SDPs). For the quantitative component, a sample of 1100 AGYW aged 15-24 years and ABYM aged 15-35 years old will be recruited into the study, in addition to 231 healthcare providers (HCPs) involved in the implementation of the UTT program. The qualitative component will include 30 participating patients who were successfully linked to care, 30 who were not, and 30 who have never tested for HIV. Key informant interviews will also be conducted with 24 HCPs. Logistic regression will be used to model the primary outcomes on SDP types, while a time to event analysis will be conducted using a Cox regression model and adjusting the standard errors of the hazard ratio for the clustering of participants within SDPs. For qualitative data, a general inductive approach of analysis will be used. Findings from the study will be communicated to the study population and results will be presented to stakeholders and at appropriate local and international conferences. Outputs will also include a policy brief, peer reviewed journal articles and research capacity building through research degrees.

Longitudinal comparison of insulin resistance and dyslipidemia in children with and without perinatal HIV infection in South Africa.

HIV infection is associated with insulin resistance and dyslipidaemia driven by HIV-associated immune dysregulation and antiretroviral therapy (ART). Children living with perinatally acquired HIV (CHIV) face many decades of exposure to these factors. We evaluated the longitudinal trajectory of insulin resistance and dyslipidaemia in CHIV and HIV-exposed uninfected children (CHEU), compared with children HIV-unexposed (CHU). Four hundred and eighty-five children (141 CHIV, 169 CHEU, 175 CHU) aged 5-16 years, previously part of CHER and P1060 trials, were followed annually at Tygerberg Children's Hospital, South Africa. The primary outcome was Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Secondary outcomes included low-density lipoprotein (LDL) cholesterol, triglyceride-to-HDL ratio, android fat mass and SBP. Outcomes were evaluated using linear mixed effects models, adjusting for potential confounders. CHIV had 73% greater HOMA-IR than CHU in ages 6-8 years (95% CI 15.9-158.2%, P < 0.001), and 24.7% greater HOMA-IR than CHU in ages 9-10 years (0.3-55.1%, P = 0.04). By 10-11 years, the difference was not significant (P = 0.161). Longitudinally, triglyceride-to-HDL was 47.94% (34.50-62.73%, P < 0.001) higher in CHIV vs. CHU; LDL was 0.25 mmol/l (0.10-0.39, P = 0.001) higher in CHIV vs. CHU; android fat mass was 11.57% (-21.11 to -0.87%, P = 0.035) lower in CHIV than CHU. No significant difference in SBP was found. CHEU and CHU had similar outcomes. Early-treated CHIV have elevated insulin resistance, which resolves with time. Triglyceride-to-HDL ratio and LDL cholesterol were elevated into puberty. CHIV should be monitored for insulin resistance, dyslipidaemia and subclinical cardiovascular disease.

Seroprevalence and characterisation of herpes simplex virus from human immunodeficiency virus in samples collected from two provinces in South Africa: a retrospective study.

Background:Herpes simplex virus (HSV) is a widely distributed human pathogen that is known for its ulcerative lesions at the infection site. HSV can cause persistent infection in the host that is often followed by a period of latency within the neurons. Considering the high rate of HIV infection in South Africa, it is important to assess the seroprevalence of HSV with a focus to determine the epidemiological association between HSV-DNA and HIV-1 in the population. Methods:A total of 44 sera samples were screened for HSV and HIV-1 using the highly sensitive enzyme-linked immunosorbent assay (ELISA). The ELISA positive samples were characterized using polymerase chain reaction (PCR) to confirm the positivity of both viruses and to further differentiate HSV into HSV-1 and -2. Thereafter, the samples were analysed for relatedness using phylogenetic analysis. Results:Of the 44 samples, 36 (81.8%) were positive for HIV-1, while 35 (79.5%) were positive for HSV when screened with ELISA kits. The PCR results, with the use of type specific primers, showed that 4/35 (11.4%) samples were specific for HSV-1 while 30/35 (85.7%) were specific for HSV-2. Statistical analysis performed using the chi-squared goodness-of-fit test showed that there is a significant relationship between HSV-2 and HIV-1 transmission. Conclusions:There is a significant positive association between HSV-2 and HIV-1 in the study population. Our study shows that some of the HSV-2 isolates are not related to the clinical isolate SD90e from South Africa, suggesting diversity in HSV-2 viral transmission.

Seroprevalence and characterisation of herpes simplex virus from human immunodeficiency virus in samples collected from two provinces in South Africa: a retrospective study

Background: Herpes simplex virus (HSV) is a widely distributed human pathogen that is known for its ulcerative lesions at the infection site. HSV can cause persistent infection in the host that is often followed by a period of latency within the neurons. Considering the high rate of HIV infection in South Africa, it is important to assess the seroprevalence of HSV with a focus to determine the epidemiological association between HSV-DNA and HIV-1 in the population. Methods: A total of 44 sera samples were screened for HSV and HIV-1 using the highly sensitive enzyme-linked immunosorbent assay (ELISA). The ELISA positive samples were characterized using polymerase chain reaction (PCR) to confirm the positivity of both viruses and to further differentiate HSV into HSV-1 and -2. Thereafter, the samples were analysed for relatedness using phylogenetic analysis. Results: Of the 44 samples, 36 (81.8%) were positive for HIV-1, while 35 (79.5%) were positive for HSV when screened with ELISA kits. The PCR results, with the use of type specific primers, showed that 4/35 (11.4%) samples were specific for HSV-1 while 30/35 (85.7%) were specific for HSV-2. Statistical analysis performed using the chi-squared goodness-of-fit test showed that there is a significant relationship between HSV-2 and HIV-1 transmission. Conclusions:There is a significant relationship between HSV-2 and HIV-1 in the study population. Our study shows that some of the HSV-2 isolates are not related to the clinical isolate SD90e from South Africa, suggesting diversity in HSV-2 viral transmission.

Impact of Disclosure over Time on the Emotional Well-Being of Children with Perinatally Acquired HIV Infection in South Africa.

The aim of this study was to describe the disclosure process in children with perinatally acquired HIV infection (PHIV+) and its impact on their emotional well-being and adherence to antiretroviral therapy (ART) in South Africa. This prospective cohort study followed PHIV+ children aged 7 to 13 years attending counseling over 18 months. Standardized disclosure tools were used by a counselor with both child and caregiver present. Assessments included the Child Behavior Checklist (CBCL), Vineland Adaptive Behavior Scale (VABS), Child Depression Inventory (CDI), and Revised Children's Manifest Anxiety Scale (RCMAS). Adherence to ART was recorded through pharmacy pill returns. Changes over time and their differences from baseline were assessed by linear mixed models. Thirty children with median age 10 years (interquartile range [IQR]: 9.0-11.0) were enrolled. The median time to disclosure was 48 weeks (IQR: 48.0-54.6). There was a significant decrease from baseline (p < 0.0001) and over time (p = 0.0037) in the total CDI score. A positive trend in the changes from baseline and over time was observed for internalizing (p values < 0.0001) and externalizing (p values < 0.0001) CBCL scales and Total Anxiety score of the RCMAS (p < 0.0001 and p < 0.0002, respectively). Only the Defensiveness median T-score increased during the follow-up (p = 0.004) and in the change from baseline (p = 0.0005). The adaptive (p = 0.0092) and maladaptive (p < 0.0001) scores of the VABS showed a decrease from baseline. ART adherence remained high throughout this study. Disclosure does not worsen the child's emotional well-being and adherence to ART over time. This study adds to research from low- and middle-income countries to alleviate fears that disclosure may have an adverse outcome on children with PHIV+.

Seroprevalence and characterisation of herpes simplex virus from human immunodeficiency virus in samples collected from two provinces in South Africa: a retrospective study

Background: Herpes simplex virus (HSV) is a widely distributed human pathogen that is known for its ulcerative lesions at the infection site. HSV can cause persistent infection in the host that is often followed by a period of latency within the neurons. Considering the high rate of HIV infection in South Africa, it is important to assess the seroprevalence of HSV with a focus to determine the epidemiological association between HSV-DNA and HIV-1 in the population. Methods: A total of 44 sera samples were screened for HSV and HIV-1 using the highly sensitive enzyme-linked immunosorbent assay (ELISA). The ELISA positive samples were characterized using polymerase chain reaction (PCR) to confirm the positivity of both viruses and to further differentiate HSV into HSV-1 and -2. Thereafter, the samples were analysed for relatedness using phylogenetic analysis. Results: Of the 44 samples, 36 (81.8%) were positive for HIV-1, while 35 (79.5%) were positive for HSV when screened with ELISA kits. The PCR results, with the use of type specific primers, showed that 4/35 (11.4%) samples were specific for HSV-1 while 30/35 (85.7%) were specific for HSV-2. Statistical analysis performed using the chi-squared goodness-of-fit test showed that there is a significant relationship between HSV-2 and HIV-1 transmission. Conclusions: The prevalence of HSV in the population is high with an increased HSV-2 infection in women. Our study shows that some of the HSV-2 isolates are not related to the clinical isolate SD90e from South Africa, suggesting diversity in HSV-2 viral transmission.

Seroprevalence and characterisation of herpes simplex virus from human immunodeficiency virus in samples collected from two provinces in South Africa: a retrospective study

Background: Herpes simplex virus (HSV) is a widely distributed human pathogen that is known for its ulcerative lesions at the infection site. HSV can cause persistent infection in the host that is often followed by a period of latency within the neurons. Considering the high rate of HIV infection in South Africa, it is important to assess the seroprevalence of HSV with a focus to determine the epidemiological association between HSV-DNA and HIV-1 in the population. Methods: A total of 44 sera samples were screened for HSV and HIV-1 using the highly sensitive enzyme-linked immunosorbent assay (ELISA). The ELISA positive samples were characterized using polymerase chain reaction (PCR) to confirm the positivity of both viruses and to further differentiate HSV into HSV-1 and -2. Thereafter, the samples were analysed for relatedness using phylogenetic analysis. Results: Of the 44 samples, 36 (81.8%) were positive for HIV-1, while 35 (79.5%) were positive for HSV when screened with ELISA kits. The PCR results, with the use of type specific primers, showed that 4/35 (11.4%) samples were specific for HSV-1 while 30/35 (85.7%) were specific for HSV-2. Statistical analysis performed using the chi-squared goodness-of-fit test showed that there is a significant relationship between HSV-2 and HIV-1 transmission. Conclusions: There is a significant positive association between HSV-2 and HIV-1 in the study population. Our study shows that some of the HSV-2 isolates are not related to the clinical isolate SD90e from South Africa, suggesting diversity in HSV-2 viral transmission.

Associations of gamma-glutamyl transferase with cardio-metabolic diseases in people living with HIV infection in South Africa.

Gamma-glutamyl transferase (GGT) has recently been reported as a biomarker for cardiovascular (CVD) risk in general populations. We investigated the associations of GGT with cardio-metabolic diseases and CVD risk in South Africans living with HIV. In this cross-sectional study, HIV-infected adults were randomly recruited across 17 HIV clinics in the Western Cape Province. Homeostatic model assessment for insulin resistance (HOMA-IR), hypertension, diabetes, metabolic syndrome by Joint Interim Statement criteria (JIS-MS), a ≥5% and ≥10% predicted risk for a CVD event within 10 years by the Framingham risk score (10-years-CVD risk) were computed. Associations between GGT and cardio-metabolic trait were explored using linear and binomial logistic regressions adjusted for age, gender, lifestyle behaviours and HIV-related characteristics. Among 709 participants (561 women, mean age 38.6 years), log-GGT was positively associated with waist circumference (β=2.75; p<0.001), diastolic blood pressure (β=1.65; p=0.006), total cholesterol (β=0.21; p<0.001), low-density lipoprotein-cholesterol (β=0.16; p<0.001), high-density lipoprotein-cholesterol and log-triglycerides (both β=0.12; p<0.001), fasting plasma glucose (β=0.19; p=0.031), 2-hour-post-glucose-load plasma glucose (β=0.26; p=0.007), HOMA-IR (β=0.13; p=0.001), log-high-sensitivity C-reactive-protein (β=0.3; p<0.001) in linear regression analyses; with hypertension [OR=1.41 (95%CI, 1.13-1.75); p=0.001], JIS-MS [OR=1.33 (1.05-1.68); p=0.016], ≥5% 10-year-CVD risk [OR=1.55 (1.24-1.9400); p<0.001] and ≥10% 10-year-CVD risk [OR=1.56 (1.08-2.23); p=0.016] but not with diabetes [OR=1.24 (0.88-1.71), p=0.205] in logistic regression analyses. In this study, GGT levels were associated with cardio-metabolic variables independent of HIV specific attributes. If confirmed in longitudinal studies, GGT evaluation maybe included in CVD risk monitoring strategies in people living with HIV.

Estimating the contribution of key populations towards HIV transmission in South Africa.

IntroductionIn generalized epidemic settings, there is insufficient understanding of how the unmet HIV prevention and treatment needs of key populations (KPs), such as female sex workers (FSWs) and men who have sex with men (MSM), contribute to HIV transmission. In such settings, it is typically assumed that HIV transmission is driven by the general population. We estimated the contribution of commercial sex, sex between men, and other heterosexual partnerships to HIV transmission in South Africa (SA).MethodsWe developed the “Key‐Pop Model”; a dynamic transmission model of HIV among FSWs, their clients, MSM, and the broader population in SA. The model was parameterized and calibrated using demographic, behavioural and epidemiological data from national household surveys and KP surveys. We estimated the contribution of commercial sex, sex between men and sex among heterosexual partnerships of different sub‐groups to HIV transmission over 2010 to 2019. We also estimated the efficiency (HIV infections averted per person‐year of intervention) and prevented fraction (% IA) over 10‐years from scaling‐up ART (to 81% coverage) in different sub‐populations from 2020.ResultsSex between FSWs and their paying clients, and between clients with their non‐paying partners contributed 6.9% (95% credibility interval 4.5% to 9.3%) and 41.9% (35.1% to 53.2%) of new HIV infections in SA over 2010 to 2019 respectively. Sex between low‐risk groups contributed 59.7% (47.6% to 68.5%), sex between men contributed 5.3% (2.3% to 14.1%) and sex between MSM and their female partners contributed 3.7% (1.6% to 9.8%). Going forward, the largest population‐level impact on HIV transmission can be achieved from scaling up ART to clients of FSWs (% IA = 18.2% (14.0% to 24.4%) or low‐risk individuals (% IA = 20.6% (14.7 to 27.5) over 2020 to 2030), with ART scale‐up among KPs being most efficient.ConclusionsClients of FSWs play a fundamental role in HIV transmission in SA. Addressing the HIV prevention and treatment needs of KPs in generalized HIV epidemics is central to a comprehensive HIV response.

Determinants of intergenerational sexual relationships and HIV risk among South African women outpatients in Gauteng

ABSTRACT Age-discrepant sexual relationships may place women at risk for HIV infection in South Africa. Results are based on medical records and case–control interview data of 889 sexually experienced women outpatients aged 15–29 in a Gauteng township. Women with partners at least ten years older (intergenerational) show an elevated chance of having an early sexual debut, concurrent and transactional partners, and intimate partner violence. Hardship during childhood including parental loss, food insecurity and abuse are related to age asymmetric relationships. HIV is two times more likely (aOR=1.96) with an intergenerational partner. Transactional sex increases the odds of HIV independently (aOR=1.76) as does intimate partner violence (aOR=1.6). To the extent that transactional and intergenerational sex overlap the chance of contracting HIV increases more than two-fold (uOR=4.57). Girls (15–19) with intergenerational partners face the highest chance of HIV (uOR=8.55) compared to other age groups. They are also five times more likely than controls to have lived with a cross-age partner. Our findings indicate there are multiple pathways emanating from childhood leading to women’s choice of intergenerational partners, and the link to HIV is strongest among the youngest women.

Establishing the significance of a pre-operative day absolute CD4 count in patients booked for elective brain tumor surgery – A prospective cohort study from a single neurosurgical center in South Africa

IntroductionUnlike the situation in many 1st World-countries, new HIV infections in South Africa continue to rise. While mandatory HIV testing is unethical, a pre-operative absolute CD4 count can be performed in patient’s pre-elective brain tumour surgery. Materials and methodsThis was a prospective cohort study performed by consecutively enrolling 78 patients admitted to the adult neurosurgical wards at our hospital, from the 01 July 2018–30 March 2020, with neoplastic brain tumours that were taken for elective resection. Data collected and analysed in this study included subject age, gender, HIV status, admission absolute CD4 count, admission Glasgow Coma Score, pre-operative corticosteroid therapy, length in in-hospital stay prior to surgery, pre-operative day absolute CD4 count, operative day Glasgow Coma Score, intra-operative blood loss, duration of surgery, extent of resection, histological diagnosis, day-7 nosocomial infection incidence, and Glasgow Outcome Score. ResultsHigh significance was demonstrated between admission absolute CD4 count and the pre-operative day absolute CD4 count (p < 0.0001). With regards elective brain tumour surgery the relationship between the use of pre-operative steroids and the pre-operative absolute CD4 count is insignificant (p = 0.73). While no significance was demonstrated (p = 0.93), a clinical trend was suggested that the lower the pre-operative day absolute CD4 count, the longer the duration of surgery. No significance was demonstrated between pre-operative CD4 count and histology result (p = 0.45), although our results suggested a trend for cancers, of known and suspecting links to infective aetiology, to cluster in subjects with a pre-operative CD4 count < 500 cells/mm. No significance was demonstrated between pre-operative CD4 count and day 7 nosocomial infection incidence (p = 0.59). ConclusionHIV infection, and its complications, remain very real to HIV positive patients presenting with brain tumours in South Africa. Through the trends demonstrated we recommend the use of a pre-operative absolute CD4 count in the work-up of these patients.

Drug resistance from preferred antiretroviral regimens for HIV infection in South Africa: A modeling study.

BackgroundTenofovir-containing regimens comprise the preferred first-line antiretroviral therapy (ART) in many countries including South Africa, where utilization of second-line regimens is limited. Considerable HIV drug resistance has occurred among persons failing tenofovir-containing first-line ART. We evaluated drug resistance at the population level using mathematical modeling.SettingHeterosexual HIV epidemic in KwaZulu-Natal, South Africa.MethodsWe constructed a stochastic individual-based model and simulated scenarios of ART implementation, either CD4-based (threshold < 500 cells/mL) or Fast-track (81% coverage by 2020), with consideration of major drug-associated mutations (M184V, K65R and non-nucleoside reverse transcriptase inhibitor (NNRTI)). Using base case and uncertainty analyses, we assessed (majority) drug resistance levels.ResultsBy 2030, the median total resistance (proportion of HIV-infected persons with drug resistance) is predicted to reach 31.4% (interquartile range (IQR): 16.5%-50.2%) with CD4-based ART, decreasing to 14.5% (IQR: 7.7%-25.8%) with Fast-track implementation. In both scenarios, we find comparably high prevalence (~80%) of acquired NNRTI-associated, M184V and K65R mutations. Over 48% of individuals with acquired resistance harbor dual, 44% triple and 7% just single drug mutations. Drug-resistant HIV is predicted to comprise 40% (IQR: 27%-50%) of incident infections, while 70% of prevalent transmitted resistance is NNRTI-associated. At 2018, the projected total resistance is 15% (IQR: 7.5%-25%), with 18% (IQR: 13%-24%) of incident infections from transmitted drug-resistant HIV.ConclusionsWHO-recommended preferred first-line ART could lead to substantial drug resistance. Effective surveillance of HIV drug resistance and utilization of second-line as well as alternative first-line regimens is crucial.

The potential impact of a \u201ccurative intervention\u201d for HIV: a modelling study

BackgroundEfforts to develop an HIV “cure” (i.e., an intervention leading to durable ART-free remission or eradication of HIV infection) have become better resourced and coordinated in recent years. Given, however, the availability of other interventions for prevention and treatment of HIV disease, it is unclear whether, to what extent, and under which circumstances a curative intervention would have an impact in ending the AIDS epidemic and which characteristics of its implementation would be most important. We designed a range of analyses to investigate these unknowns.MethodsWe used a deterministic, compartmental model of HIV infection in South Africa to estimate the impact of a curative intervention. We first examined how its impact would be affected by the state of the epidemic at the time that it is introduced, by the timing and pace of scale-up, and by various targeting strategies. We then investigated the impact of a curative intervention relative to its ability to maintain viral suppression.FindingsTo the extent that other interventions have failed to control the epidemic, i.e., if incidence and AIDS deaths remain high, a curative intervention would result in a larger reduction in incidence. Earlier and faster scale-up allows for greater impact. We also found that a curative intervention would more efficiently reduce transmission if it is prioritised to those not able to obtain or remain on ART and to those aged 15–25 rather than older persons. On the other hand, an intervention that does not maintain viral suppression if the individual is exposed to re-infection could lead to an increase in HIV incidence.ConclusionsOur findings suggest that a curative intervention for HIV would have the greatest impact if the epidemic is not under control by 2030, particularly if the intervention is targeted to those who are more likely to transmit virus, and if it maintained durable viral suppression, even upon exposure to re-infection. These considerations underscore the need to carefully consider the “target product profiles” for an HIV cure in the context of how and where it would be used, and suggest that such profiles may require revision as the epidemic evolves in the coming years.