Global trends in CD4 count measurement and distribution at first antiretroviral treatment initiation.

BACKGROUND: While people with HIV (PWH) start antiretroviral treatment (ART) regardless of CD4 count, CD4 measurement remains crucial for detecting advanced HIV disease and evaluating ART programmes. We explored CD4 measurement (proportion of PWH with a CD4 result available) and prevalence of CD4 <200 cells/µL at ART initiation within the International epidemiology Databases to Evaluate AIDS (IeDEA) global collaboration. METHODS: We included PWH at participating ART programmes who first initiated ART at age 15-80 years during 2005-2019. We described proportions of PWH (i) with CD4 (measured within 6 months before to 2 weeks after ART initiation); and (ii) among those with a CD4, with CD4 <200; by year of ART initiation and region. RESULTS: We included 1,355,104 PWH from 42 countries in 7 regions; 63% were female. Median (interquartile range) age at ART initiation was 37 (31-44) in men and 32 (26-39) in women. CD4 measurement initially increased, or remained stable over time until around 2013, but then declined to low levels in some regions (Southern Africa, except South Africa: from 54 to 13%; East Africa 85 to 31%; Central Africa 72 to 20%; West Africa: 91 to 53%; and Latin America: 87 to 56%). Prevalence of CD4<200 declined over time in all regions, but plateaued after 2015 at ≥30%. CONCLUSIONS: CD4 measurement has declined sharply in recent years, especially in sub-Saharan Africa. Among those with a CD4, the prevalence of CD4 <200 remains concerningly high. Scaling up CD4 testing and securing adequate funding are urgent priorities.

From conceptualising to modelling structural determinants and interventions in HIV transmission dynamics models: a scoping review and methodological framework for evidence-based analyses.

BACKGROUND: Including structural determinants (e.g. criminalisation, stigma, inequitable gender norms) in dynamic HIV transmission models is important to help quantify their population-level impacts and guide implementation of effective interventions that reduce the burden of HIV and inequalities thereof. However, evidence-based modelling of structural determinants is challenging partly due to a limited understanding of their causal pathways and few empirical estimates of their effects on HIV acquisition and transmission. METHODS: We conducted a scoping review of dynamic HIV transmission modelling studies that evaluated the impacts of structural determinants, published up to August 28, 2023, using Ovid Embase and Medline online databases. We appraised studies on how models represented exposure to structural determinants and causal pathways. Building on this, we developed a new methodological framework and recommendations to support the incorporation of structural determinants in transmission dynamics models and their analyses. We discuss the data and analyses that could strengthen the evidence used to inform these models. RESULTS: We identified 17 HIV modelling studies that represented structural determinants and/or interventions, including incarceration of people who inject drugs (number of studies [n] = 5), violence against women (n = 3), HIV stigma (n = 1), and housing instability (n = 1), among others (n = 7). Most studies (n = 10) modelled exposures dynamically. Almost half (8/17 studies) represented multiple exposure histories (e.g. current, recent, non-recent exposure). Structural determinants were often assumed to influence HIV indirectly by influencing mediators such as contact patterns, condom use, and antiretroviral therapy use. However, causal pathways' assumptions were sometimes simple, with few mediators explicitly represented in the model, and largely based on cross-sectional associations. Although most studies calibrated models using HIV epidemiological data, less than half (7/17) also fitted or cross-validated to data on the prevalence, frequency, or effects of exposure to structural determinants. CONCLUSIONS: Mathematical models can play a crucial role in elucidating the population-level impacts of structural determinants and interventions on HIV. We recommend the next generation of models reflect exposure to structural determinants dynamically and mechanistically, and reproduce the key causal pathways, based on longitudinal evidence of links between structural determinants, mediators, and HIV. This would improve the validity and usefulness of predictions of the impacts of structural determinants and interventions.

The Association of Neighborhood Socioeconomic Status with Executive Function and Processing Speed in Cognitively Normal Mexican American Elders from the Health and Aging Brains Study: Health Disparities Cohort.

INTRODUCTION: Neighborhood socioeconomic status (NSES) has been linked with overall health, and this study will evaluate whether NSES is cross-sectionally associated with cognition in non-Hispanic whites (NHWs) and Mexican Americans (MAs) from the Health and Aging Brain: Health Disparities Study (HABS-HD). METHODS: The HABS-HD is a longitudinal study conducted at the University of North Texas Health Science Center. The final sample analyzed (n = 1,312) were 50 years or older, with unimpaired cognition, and underwent an interview, neuropsychological examination, imaging, and blood draw. NSES was measured using the national area deprivation index (ADI) percentile ranking, which considered socioeconomic variables. Executive function and processing speed were assessed by the trail making tests (A and B) and the digit-symbol substitution test, respectively. Linear regression was used to assess the association of ADI and cognitive measures. RESULTS: MAs were younger, more likely to be female, less educated, had higher ADI scores, performed worse on trails B (all p < 0.05), and had lower prevalence of APOE4 + when compared to NHWs (p < 0.0001). A higher percentage of MAs lived in the most deprived neighborhoods than NHWs. For NHWs, ADI did not predict trails B or DSS scores, after adjusting for demographic variables and APOE4. For MAs, ADI predicted trails A, trails B, and DSS after adjusting for demographic covariates and APOE4 status. CONCLUSION: Our study revealed that living in an area of higher deprivation was associated with lower cognitive function in MAs but not in NHWs, which is important to consider in future interventions to slow cognitive decline.

Investigating the Associations between Drought, Poverty, High-Risk Sexual Behaviours, and HIV Incidence in Sub-Saharan Africa: A Cross-Sectional Study.

Climate change is increasing the likelihood of drought in sub-Saharan Africa, where HIV prevalence is high. Drought could increase HIV transmission through various mediating mechanisms; we investigated these associations. We used data on people aged 15-59 from Population-Based HIV Impact Assessment surveys from 2016 in Eswatini, Lesotho, Tanzania, Uganda, and Zambia. Survey data were geospatially linked to precipitation data for 2014-2016, with local droughts defined as cumulative rainfall between 2014 and 2016 being in < 15th percentile of all 2-year periods over 1981-2016. Using multivariable logistic regression, stratified by sex and rural/urban residence, we examined associations between (a) drought and poverty, (b) wealth quintiles and sexual behaviours (transactional, high-risk, and intergenerational sex), (c) sexual behaviours and recently acquiring HIV, and (d) drought and recent HIV. Among 102,081 people, 31.5% resided in areas affected by drought during 2014-2016. Experiencing drought was positively associated with poverty for women and men in rural, but not urban, areas. For each group, increasing wealth was negatively associated with transactional sex. For rural women, intergenerational sex was positively associated with wealth. Women reporting each sexual behaviour had higher odds of recent HIV, with strong associations seen for high-risk sex, and, for urban women, intergenerational sex, with weaker associations among men. Women in rural areas who had been exposed to drought had higher odds of having recently acquired HIV (2.10 [95%CI: 1.17-3.77]), but not women in urban areas, or men. Droughts could potentially increase HIV transmission through increasing poverty and then sexual risk behaviours, particularly among women in rural areas.

Secondary healthcare costs after mastectomy and immediate breast reconstruction for women with breast cancer in England: population-based cohort study.

BACKGROUND: Immediate breast reconstruction after mastectomy can improve the quality of life for women with breast cancer and rates are increasing. Long-term inpatient costs of care were estimated to understand the impact of different immediate breast reconstruction procedures on healthcare expenditure. METHODS: Hospital Episode Statistics Admitted Patient Care data were used to identify women undergoing unilateral mastectomy and immediate breast reconstruction in English National Health Service hospitals (1 April 2009 to 31 March 2015) and any subsequent procedures performed to revise, replace, or complete the breast reconstruction. Costs were assigned to Hospital Episode Statistics Admitted Patient Care data using the Healthcare Resource Group 2020/21 National Costs Grouper. Generalized linear models were used to estimate mean cumulative costs for five immediate breast reconstruction procedures over 3 and 8 years, adjusting for covariates (age/ethnicity/deprivation). RESULTS: A total of 16 890 women underwent mastectomy and immediate breast reconstruction: implant (5192; 30.7 per cent), expander (2826; 16.7 per cent), autologous latissimus dorsi flap (2372; 14.0 per cent), latissimus dorsi flap with expander/implant (3109; 18.4 per cent), and abdominal free-flap reconstruction (3391; 20.1 per cent). The mean (95 per cent c.i.) cumulative cost was lowest for latissimus dorsi flap with expander/implant reconstruction (€20 103 (€19 582 to €20 625)) over 3 years and highest for abdominal free-flap reconstruction (€27 560 (€27 037 to €28 083)). Over 8 years, expander (€29 140 (€27 659 to €30 621)) and latissimus dorsi flap with expander/implant (€29 312 (€27 622 to €31 003)) reconstructions were the least expensive, while abdominal free-flap reconstruction (€34 536 (€32 958 to €36 113)) remained the most expensive, despite having lower costs for revisions and secondary reconstructions. This was driven primarily by the cost of the index procedure (€5435 (expander reconstruction) to €15 106 (abdominal free-flap reconstruction)). CONCLUSION: Hospital Episode Statistics Admitted Patient Care Healthcare Resource Group data provided a comprehensive longitudinal cost assessment of secondary care. Although abdominal free-flap reconstruction was the most expensive option, higher costs of the index procedure need to be balanced against ongoing long-term costs of revisions/secondary reconstructions, which are higher after implant-based procedures.

Impact of procedure type on revisional surgery and secondary reconstruction after immediate breast reconstruction in a population-based cohort.

BACKGROUND: Women considering immediate breast reconstruction require high-quality information about the likely need for secondary reconstruction and the long-term risk of revisional surgery to make fully informed decisions about different reconstructive options. Such data are currently lacking. This study aimed to explore the impact of reconstruction type on the number of revisions and secondary reconstructions performed 3, 5, and 8 years after immediate breast reconstruction in a large population-based cohort. METHODS: Women undergoing unilateral mastectomy and immediate breast reconstruction for breast cancer or ductal carcinoma in situ in England between 1 April 2009 and 31 March 2015 were identified from National Health Service Hospital Episode Statistics. Numbers of revisions and secondary reconstructions in women undergoing primary definitive immediate breast reconstruction were compared by procedure type at 3, 5, and 8 years after index surgery. RESULTS: Some 16 897 women underwent immediate breast reconstruction with at least 3 years' follow-up. Of these, 14 069 had a definitive reconstruction with an implant only (5193), latissimus dorsi flap with (3110) or without (2373) an implant, or abdominal free flap (3393). Women undergoing implant-only reconstruction were more likely to require revision, with 69.5 per cent (747 of 1075) undergoing at least one revision by 8 years compared with 49.3 per cent (1568 of 3180) in other reconstruction groups. They were also more likely to undergo secondary reconstruction, with the proportion of women having further reconstructive procedures increasing over time: 12.8 per cent (663 of 5193) at 3 years, 14.3 per cent (535 of 3752) at 5 years, and 17.6 per cent (189 of 1075) at 8 years. CONCLUSION: Long-term rates of revisions and secondary reconstructions were considerably higher after primary implant-based reconstruction than autologous procedures. These results should be shared with patients to support informed decision-making.

BACKGROUND: Breast reconstruction is performed to improve well-being for women who need mastectomy (removal of the breast) as part of breast cancer treatment. There are many different types of breast reconstruction operation, and it can be difficult for women to decide which operation, if any, is right for them. Information about the number of extra operations that a woman is likely to need after breast reconstruction surgery is an important factor in helping them make this decision. This study aimed to investigate the number of extra operations that women who had breast reconstruction needed by 3, 5, and 8 years after surgery, and how this differed by the type of breast reconstruction surgery they had. Routinely collected hospital record data were used to identify women having breast reconstruction at the time of mastectomy for breast cancer, and identify any extra operations performed for problems related to the reconstruction in the 8 years after the first operation. The number of extra operations performed after different types of breast reconstructions was compared at 3, 5, and 8 years after the mastectomy. Women who had implant-based reconstruction required more extra operations than those having reconstruction using their own tissue. They were also more likely to have the implant replaced with another type of breast reconstruction than women undergoing tissue-based reconstruction at 3, 5, and 8 years after the first surgery. This information should be discussed with women thinking about breast reconstruction to help them decide what type of operation would be best for them.

Long-term patient-reported outcomes of immediate breast reconstruction after mastectomy for breast cancer: population-based cohort study.

BACKGROUND: Breast reconstruction is offered to improve quality of life for women after mastectomy for breast cancer, but information regarding the long-term patient-reported outcomes of different reconstruction procedures is currently lacking. The Brighter study aimed to evaluate long-term patient-reported outcomes after immediate breast reconstruction (IBR) in a population-based cohort. METHODS: Women who underwent mastectomy with IBR for breast cancer in England between 1 January 2008 and 31 March 2009 were identified from National Health Service Hospital Episode Statistics. Surviving women were invited to complete the BREAST-Q, EQ-5D-5L™, and ICECAP-A at least 12 years after the index procedure. Questionnaires were scored according to developers' instructions and compared by IBR type. RESULTS: Some 1236 women underwent IBR; 343 (27.8 per cent) had 2-stage expander/implant, 630 (51.0 per cent) latissimus dorsi, and 263 (21.3 per cent) abdominal flap reconstructions, with a mean(s.d.) follow-up of 13.3(0.5) years. Women who underwent abdominal flap reconstruction reported higher scores in all BREAST-Q domains than those who had other procedures. These differences remained statistically significant and clinically meaningful after adjusting for age, ethnicity, geographical region, socioeconomic status, smoking, BMI, and complications. The greatest difference was seen in scores for satisfaction with breasts; women who had abdominal flap reconstructions reported scores that were 13.17 (95 per cent c.i. 9.48 to 16.87) points; P < 0.001) higher than those among women who had two-stage expander/implant procedures. Women who underwent latissimus dorsi reconstruction reported significantly more pain/discomfort on the EQ-5D-5L™, but no other differences between procedures were seen. CONCLUSION: Long-term patient-reported outcomes are significantly better following abdominal flap reconstruction than other traditional procedure types. These findings should be shared with women considering IBR to help them make informed decisions about their surgical options.

An agent-based model of binge drinking, inequitable gender norms and their contribution to HIV transmission, with application to South Africa.

BACKGROUND: Binge drinking, inequitable gender norms and sexual risk behaviour are closely interlinked. This study aims to model the potential effect of alcohol counselling interventions (in men and women) and gender-transformative interventions (in men) as strategies to reduce HIV transmission. METHODS: We developed an agent-based model of HIV and other sexually transmitted infections, allowing for effects of binge drinking on sexual risk behaviour, and effects of inequitable gender norms (in men) on sexual risk behaviour and binge drinking. The model was applied to South Africa and was calibrated using data from randomized controlled trials of alcohol counselling interventions (n = 9) and gender-transformative interventions (n = 4) in sub-Saharan Africa. The model was also calibrated to South African data on alcohol consumption and acceptance of inequitable gender norms. Binge drinking was defined as five or more drinks on a single day, in the last month. RESULTS: Binge drinking is estimated to be highly prevalent in South Africa (54% in men and 35% in women, in 2021), and over the 2000-2021 period 54% (95% CI: 34-74%) of new HIV infections occurred in binge drinkers. Binge drinking accounted for 6.8% of new HIV infections (0.0-32.1%) over the same period, which was mediated mainly by an effect of binge drinking in women on engaging in casual sex. Inequitable gender norms accounted for 17.5% of incident HIV infections (0.0-68.3%), which was mediated mainly by an effect of inequitable gender norms on male partner concurrency. A multi-session alcohol counselling intervention that reaches all binge drinkers would reduce HIV incidence by 1.2% (0.0-2.5%) over a 5-year period, while a community-based gender-transformative intervention would reduce incidence by 3.2% (0.8-7.2%) or by 7.3% (0.6-21.2%) if there was no waning of intervention impact. CONCLUSIONS: Although binge drinking and inequitable gender norms contribute substantially to HIV transmission in South Africa, recently-trialled alcohol counselling and gender-transformative interventions are likely to have only modest effects on HIV incidence. Further innovation in developing locally-relevant interventions to address binge drinking and inequitable gender norms is needed.

Associations of inter-annual rainfall decreases with subsequent HIV outcomes for persons with HIV on antiretroviral therapy in Southern Africa: a collaborative analysis of cohort studies.

BACKGROUND: Periods of droughts can lead to decreased food security, and altered behaviours, potentially affecting outcomes on antiretroviral therapy (ART) among persons with HIV (PWH). We investigated whether decreased rainfall is associated with adverse outcomes among PWH on ART in Southern Africa. METHODS: Data were combined from 11 clinical cohorts of PWH in Lesotho, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe, participating in the International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration. Adult PWH who had started ART prior to 01/06/2016 and were in follow-up in the year prior to 01/06/2016 were included. Two-year rainfall from June 2014 to May 2016 at the location of each HIV centre was summed and ranked against historical 2-year rainfall amounts (1981-2016) to give an empirical relative percentile rainfall estimate. The IeDEA-SA and rainfall data were combined using each HIV centre's latitude/longitude. In individual-level analyses, multivariable Cox or generalized estimating equation regression models (GEEs) assessed associations between decreased rainfall versus historical levels and four separate outcomes (mortality, CD4 counts < 200 cells/mm3, viral loads > 400 copies/mL, and > 12-month gaps in follow-up) in the two years following the rainfall period. GEEs were used to investigate the association between relative rainfall and monthly numbers of unique visitors per HIV centre. RESULTS: Among 270,708 PWH across 386 HIV centres (67% female, median age 39 [IQR: 32-46]), lower rainfall than usual was associated with higher mortality (adjusted Hazard Ratio: 1.18 [95%CI: 1.07-1.32] per 10 percentile rainfall rank decrease) and unsuppressed viral loads (adjusted Odds Ratio: 1.05 [1.01-1.09]). Levels of rainfall were not strongly associated with CD4 counts < 200 cell/mm3 or > 12-month gaps in care. HIV centres in areas with less rainfall than usual had lower numbers of PWH visiting them (adjusted Rate Ratio: 0.80 [0.66-0.98] per 10 percentile rainfall rank decrease). CONCLUSIONS: Decreased rainfall could negatively impact on HIV treatment behaviours and outcomes. Further research is needed to explore the reasons for these effects. Interventions to mitigate the health impact of severe weather events are required.

A quantitative assessment of the consistency of projections from five mathematical models of the HIV epidemic in South Africa: a model comparison study.

BACKGROUND: Mathematical models are increasingly used to inform HIV policy and planning. Comparing estimates obtained using different mathematical models can test the robustness of estimates and highlight research gaps. As part of a larger project aiming to determine the optimal allocation of funding for HIV services, in this study we compare projections from five mathematical models of the HIV epidemic in South Africa: EMOD-HIV, Goals, HIV-Synthesis, Optima, and Thembisa. METHODS: The five modelling groups produced estimates of the total population, HIV incidence, HIV prevalence, proportion of people living with HIV who are diagnosed, ART coverage, proportion of those on ART who are virally suppressed, AIDS-related deaths, total deaths, and the proportion of adult males who are circumcised. Estimates were made under a "status quo" scenario for the period 1990 to 2040. For each output variable we assessed the consistency of model estimates by calculating the coefficient of variation and examining the trend over time. RESULTS: For most outputs there was significant inter-model variability between 1990 and 2005, when limited data was available for calibration, good consistency from 2005 to 2025, and increasing variability towards the end of the projection period. Estimates of HIV incidence, deaths in people living with HIV, and total deaths displayed the largest long-term variability, with standard deviations between 35 and 65% of the cross-model means. Despite this variability, all models predicted a gradual decline in HIV incidence in the long-term. Projections related to the UNAIDS 95-95-95 targets were more consistent, with the coefficients of variation below 0.1 for all groups except children. CONCLUSIONS: While models produced consistent estimates for several outputs, there are areas of variability that should be investigated. This is important if projections are to be used in subsequent cost-effectiveness studies.

Medical comorbidities and ethnicity impact plasma Alzheimer's disease biomarkers: Important considerations for clinical trials and practice.

INTRODUCTION: Despite the clinical implementation, there remain significant gaps in our knowledge regarding the impact of race/ethnicity or common medical comorbidity on plasma Alzheimer's disease (AD) biomarkers. METHODS: Plasma biomarkers of amyloid beta (Aß)40, Aß42 , total tau, and neurofilament light chain (NfL) were measured across cognitively normal Mexican Americans (n = 445) and non-Hispanic Whites (n = 520). RESULTS: Dyslipidemia was associated with elevated Aß40 (P = .01) and Aß42 (P = .001) while hypertension was associated with elevated Aß40 (P = .003), Aß42 (P < .001), and total tau (P = .002) levels. Diabetes was associated with higher Aß40 (P < .001), Aß42 (P < .001), total tau (P < .001), and NfL (P < .001) levels. Chronic kidney disease (CKD) was associated with elevations in Aß40 (P < .001), Aß42 (P < .001), total tau (P < .001), and NfL (P < .001) levels. Mexican Americans had significantly lower Aß40 (P < .001) and higher total tau (P = .005) levels. DISCUSSION: Plasma AD biomarkers vary significantly in association with common medical comorbidities as well as ethnicity. These findings are important for those using these biomarkers in clinical practice and clinical trials.

Prevalence of curable STIs and bacterial vaginosis during pregnancy in sub-Saharan Africa: a systematic review and meta-analysis.

OBJECTIVE: STIs remain a global public health problem with a high burden among pregnant women. STIs in pregnant women may lead to various adverse pregnancy outcomes. In most sub-Saharan African countries, syndromic management is used for screening and treatment of STIs. We aimed to update and summarise pooled prevalence of curable STIs and bacterial vaginosis (BV) among pregnant women in sub-Saharan Africa. METHODS: Electronic databases and reference lists of relevant published and unpublished studies were searched from March 2015 to October 2020. Studies were included if they estimated prevalence of Chlamydia trachomatis (CT), Trichomonas vaginalis (TV), Neisseria gonorrhoeae (NG), Treponema pallidum (syphilis), Mycoplasma genitalium (MG) and BV among pregnant women in sub-Saharan Africa. Meta-analyses were performed with observed prevalences corrected for diagnostic errors to estimate the pooled prevalence of diagnosed infections by region. RESULTS: A total of 48 studies met the inclusion criteria, providing 85-point prevalence estimates for curable STIs and BV. Pooled prevalence estimates (with 95% CI and number of women tested) were as follows: MG: 13.5% (4.0-27.2, n=1076); CT: 10.8% (6.9-15.5, n=6700); TV: 13.8% (10.0-18.0, n=9264); NG: 3.3% (2.1-4.7, n=6019); syphilis: 2.9% (2.0-4.0, n=95 308) and BV: 36.6% (27.1-46.6, n=5042). By region, BV was the most prevalent and ranged from 28.5% (24.5-32.8, n=1030) in Eastern Africa to 52.4% (33.5-70.9, n=2305) in Southern Africa; NG had the lowest prevalence, ranging from 1.4% (95% CI 0.1 to 3.1, n=367) in Central Africa to 4.4% (95% CI 2.6 to 6.4, n=4042) in Southern Africa. CONCLUSION: The prevalence of curable STIs and BV in sub-Saharan Africa is substantial in pregnant women but most prevalent in Southern Africa where HIV prevalence is highest. It is crucial to integrate screening of curable STIs into antenatal care programmes that have previously focused on diagnosis and treatment of syphilis and HIV.

Outcomes of laboratory-confirmed SARS-CoV-2 infection in the Omicron-driven fourth wave compared with previous waves in the Western Cape Province, South Africa.

OBJECTIVES: The objective was to compare COVID-19 outcomes in the Omicron-driven fourth wave with prior waves in the Western Cape, assess the contribution of undiagnosed prior infection to differences in outcomes in a context of high seroprevalence due to prior infection and determine whether protection against severe disease conferred by prior infection and/or vaccination was maintained. METHODS: In this cohort study, we included public sector patients aged ≥20 years with a laboratory-confirmed COVID-19 diagnosis between 14 November and 11 December 2021 (wave four) and equivalent prior wave periods. We compared the risk between waves of the following outcomes using Cox regression: death, severe hospitalisation or death and any hospitalisation or death (all ≤14 days after diagnosis) adjusted for age, sex, comorbidities, geography, vaccination and prior infection. RESULTS: We included 5144 patients from wave four and 11,609 from prior waves. The risk of all outcomes was lower in wave four compared to the Delta-driven wave three (adjusted hazard ratio (aHR) [95% confidence interval (CI)] for death 0.27 [0.19; 0.38]. Risk reduction was lower when adjusting for vaccination and prior diagnosed infection (aHR: 0.41, 95% CI: 0.29; 0.59) and reduced further when accounting for unascertained prior infections (aHR: 0.72). Vaccine protection was maintained in wave four (aHR for outcome of death: 0.24; 95% CI: 0.10; 0.58). CONCLUSIONS: In the Omicron-driven wave, severe COVID-19 outcomes were reduced mostly due to protection conferred by prior infection and/or vaccination, but intrinsically reduced virulence may account for a modest reduction in risk of severe hospitalisation or death compared to the Delta-driven wave.

The Link between APOE4 Presence and Neuropsychological Test Performance among Mexican Americans and Non-Hispanic Whites of the Multiethnic Health & Aging Brain Study - Health Disparities Cohort.

INTRODUCTION: The APOEε4 allele is the single strongest genetic risk for late-onset Alzheimer's disease (AD). Prior work demonstrates that not only the APOEε4 allele varies by race/ethnicity but also the risk for AD and cognitive impairment conveyed by the APOEε4 allele varies by the racial/ethnic group as well as genetic ancestry. Here, we sought to examine the link between the APOEε4 and neuropsychological functioning among Mexican Americans (MAs). METHODS: Data were examined from 1,633 (852 MAs and 781 non-Hispanic Whites [NHWs]) participants of the Health & Aging Brain Study - Health Disparities (HABS-HD) and were enrolled with all requisite data to be included into the current analyses. RESULTS: The frequency of both ε4 and ε2 alleles was significantly lower among MAs as compared to NHWs. Among MAs, APOEε4 allele presence was associated specifically with poorer immediate and delayed memory (Wechsler Memory Scale - Third Edition [WMS-III] Logical Memory and Spanish-English Verbal Learning Test [SEVLT]). Among NHWs, APOEε4 allele presence was associated with poorer immediate and delayed memory as well as worse executive functioning (Trials B) and verbal fluency (Animal naming). DISCUSSION/CONCLUSION: The APOEε4 allele was associated with poorer cognition across multiple domains among NHWs; however, allele presence was specifically associated with poorer memory performance among MAs. When combined with prior work, the current findings demonstrate that the risk factors associated with cognitive dysfunction differ among MAs as compared to NHWs and require additional investigation.

Impact of aetiological screening of sexually transmitted infections during pregnancy on pregnancy outcomes in South Africa.

BACKGROUND: Sexually transmitted infections (STIs) during pregnancy may increase the risk of adverse pregnancy outcomes. STI syndromic management is standard of care in South Africa but has its limitations. We evaluated the impact of diagnosing and treating curable STIs during pregnancy on adverse pregnancy and birth outcomes. METHODS: We combined data from two prospective studies of pregnant women attending public sector antenatal care (ANC) clinics in Tshwane District and Cape Town, South Africa. Pregnant women were enrolled, tested and treated for STIs. We evaluated the association between any STI at the first ANC visit and a composite adverse pregnancy outcome (miscarriage, stillbirth, preterm birth, early neonatal death, or low birthweight) using modified Poisson regression models, stratifying by HIV infection and adjusting for maternal characteristics. RESULTS: Among 619 women, 61% (n = 380) were from Tshwane District and 39% (n = 239) from Cape Town; 79% (n = 486) were women living with HIV. The prevalence of any STI was 37% (n = 228); C. trachomatis, 26% (n = 158), T. vaginalis, 18% (n = 120) and N. gonorrhoeae, 6% (n = 40). There were 93% (n = 574) singleton live births, 5% (n = 29) miscarriages and 2% (n = 16) stillbirths. Among the live births, there were 1% (n = 3) neonatal deaths, 7% (n = 35) low birthweight in full-term babies and 10% (n = 62) preterm delivery. There were 24% (n = 146) for the composite adverse pregnancy outcome. Overall, any STI diagnosis and treatment at first ANC visit was not associated with adverse outcomes in women living with HIV (adjusted relative risk (aRR); 1.43, 95% CI: 0.95-2.16) or women without HIV (aRR; 2.11, 95% CI: 0.89-5.01). However, C. trachomatis (aRR; 1.57, 95% CI: 1.04-2.39) and N. gonorrhoeae (aRR; 1.69, 95% CI: 1.09-3.08), were each independently associated with the composite adverse outcome in women living with HIV. CONCLUSION: Treated STIs at the first ANC visit were not associated with adverse pregnancy outcome overall. In women living with HIV, C. trachomatis or N. gonorrhoeae at first ANC were each independently associated with adverse pregnancy outcome. Our results highlights complex interactions between the timing of STI detection and treatment, HIV infection and pregnancy outcomes, which warrants further investigation.

Characterizing plasma NfL in a community-dwelling multi-ethnic cohort: Results from the HABLE study.

INTRODUCTION: No large-scale characterizations of neurofilament light chain (NfL) have been conducted in diverse populations. METHODS: Baseline data were analyzed among n = 890 Mexican Americans and n = 813 non-Hispanic Whites from the multi-ethnic Health & Aging Brain among Latino Elders (HABLE) study. Plasma NfL was measured on the Simoa platform. RESULTS: In unadjusted models, NfL was significantly associated with age (P < .001), hypertension (P  < .001), dyslipidemia (P = .02), and diabetes (P  < .001). Covarying for age and sex, NfL was associated with neurodegeneration (P  < .001) and global amyloid burden levels (P = .02) in a subset with available data. NfL levels were significantly associated with diagnostic groups (Normal Cognition [NC], mild cognitive impairment [MCI], Dementia; P  < .001); however, there was no cut-score that yielded acceptable diagnostic accuracy. NfL levels produced a sensitivity of 0.60 and specificity of 0.78 with negative predictive value of 89% for detecting amyloid positivity. DISCUSSION: Plasma NfL levels are significantly impacted by age and medical co-morbidities that are common among older adults, which complicate its utility as a diagnostic biomarker.

A blood screening tool for detecting mild cognitive impairment and Alzheimer's disease among community-dwelling Mexican Americans and non-Hispanic Whites: A method for increasing representation of diverse populations in clinical research.

INTRODUCTION: Representation of Mexican Americans in Alzheimer's disease (AD) clinical research has been extremely poor. METHODS: Data were examined from the ongoing community-based, multi-ethnic Health & Aging Brain among Latino Elders (HABLE) study. Participants underwent functional exams, clinical labs, neuropsychological testing, and 3T magnetic resonance imaging of the brain. Fasting proteomic markers were examined for predicting mild cognitive impairment (MCI) and AD using support vector machine models. RESULTS: Data were examined from n = 1649 participants (Mexican American n = 866; non-Hispanic White n = 783). Proteomic profiles were highly accurate in detecting MCI (area under the curve [AUC] = 0.91) and dementia (AUC = 0.95). The proteomic profiles varied significantly between ethnic groups and disease state. Negative predictive value was excellent for ruling out MCI and dementia across ethnic groups. DISCUSSION: A blood-based screening tool can serve as a method for increasing access to state-of-the-art AD clinical research by bridging between community-based and clinic-based settings.

Potential Impact and Cost-Effectiveness of Condomless-Sex-Concentrated PrEP in KwaZulu-Natal Accounting for Drug Resistance.

INTRODUCTION: Oral preexposure prophylaxis (PrEP) in the form of tenofovir-disoproxil-fumarate/emtricitabine is being implemented in selected sites in South Africa. Addressing outstanding questions on PrEP cost-effectiveness can inform further implementation. METHODS: We calibrated an individual-based model to KwaZulu-Natal to predict the impact and cost-effectiveness of PrEP, with use concentrated in periods of condomless sex, accounting for effects on drug resistance. We consider (1) PrEP availability for adolescent girls and young women aged 15-24 years and female sex workers, and (2) availability for everyone aged 15-64 years. Our primary analysis represents a level of PrEP use hypothesized to be attainable by future PrEP programs. RESULTS: In the context of PrEP use in adults aged 15-64 years, there was a predicted 33% reduction in incidence and 36% reduction in women aged 15-24 years. PrEP was cost-effective, including in a range of sensitivity analyses, although with substantially reduced (cost) effectiveness under a policy of ART initiation with efavirenz- rather than dolutegravir-based regimens due to PrEP undermining ART effectiveness by increasing HIV drug resistance. CONCLUSIONS: PrEP use concentrated during time periods of condomless sex has the potential to substantively impact HIV incidence and be cost-effective.

Modelling the impact of prevention strategies on cervical cancer incidence in South Africa.

In 2020, the World Health Organisation (WHO) published a strategy to eliminate cervical cancer as a public health concern. In South Africa, despite having a national screening policy in place since 2000, diagnosed cervical cancer incidence has shown no signs of decline. We extend a previously developed individual-based model for human immunodeficiency virus (HIV) and human papillomavirus (HPV) infection to include progression to cervical cancer. The model accounts for future reductions in HIV incidence and prevalence and includes a detailed cervical cancer screening algorithm, based on individual-level data from the public health sector. We estimate the impact of the current prevention programme and alternative screening scenarios on cervical cancer incidence. The South African screening programme prevented 8600 (95%CI 4700-12 300) cervical cancer cases between 2000 and 2019. At current levels of prevention (status quo vaccination, screening, and treatment), age-standardised cervical cancer incidence will reduce from 49.4 per 100 000 women (95%CI 36.6-67.2) in 2020, to 12.0 per 100 000 women (95%CI 8.0-17.2) in 2120. Reaching WHO's prevention targets by 2030 could help South Africa reach elimination (at the 10/100 000 threshold) by 2077 (94% probability of elimination by 2120). Using new screening technologies could reduce incidence to 4.7 per 100 000 women (95%CI 2.8-6.7) in 2120 (44% probability of elimination at the 4/100 000 threshold). HPV vaccination and decreasing HIV prevalence will substantially reduce cervical cancer incidence in the long term, but improvements to South Africa's current screening strategy will be required to prevent cases in the short term. Switching to new screening technologies will have the greatest impact.

Prevalence, incidence and associated risk factors of STIs during pregnancy in South Africa.

OBJECTIVE: STIs during pregnancy increase adverse pregnancy and birth outcomes and may increase HIV risk. STI syndromic management is standard of care in South Africa. Our study evaluated the prevalence and incidence of STIs in pregnant women and the associated risk factors. METHODS: We combined data from two prospective observational studies of pregnant women enrolled while attending their first antenatal clinic (ANC) visit in Tshwane District and Cape Town. Women ≥18 years were tested at first ANC visit and at their first postpartum visit for Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis using Xpert assays (Cepheid, USA). We evaluated the prevalence and incidence of STI and the associated risk factors using multivariable regression models. RESULTS: We enrolled 669 pregnant women, 64% (n=427) from Tshwane District and 36% (n=242) from Cape Town; 80% (n=534) were women living with HIV (WLHIV) and 20% (n=135) without HIV. At enrolment, 37% (n=250) were diagnosed with at least one STI, of which 76% (n=190) were asymptomatic. STI prevalence was 40% (n=213) in WLHIV and 27% (n=37) in women without HIV (p=0.01). Baseline STI infection was associated with younger age (OR=0.95 per year, 95% CI 0.92 to 0.98), higher gestational age (adjusted OR (aOR)=1.03 per week, 95% CI 1.00 to 1.05), single relationship status (aOR=1.53, 95% CI 1.09 to 2.15) and HIV status (aOR=1.86, 95% CI 1.17 to 2.95). Of 419 participants with no STI at baseline, 21 had an incident STI during follow-up, with a mean follow-up time of 140 days. The incidence rate of STI during pregnancy and early post partum was 15 infections per 100 women-years (95% CI 9 to 23). Younger age was associated with STI incidence. CONCLUSION: Our study shows high prevalence and incidence of STIs in pregnancy, especially in WLHIV, demonstrating the need for STI screening in ANC to prevent adverse pregnancy and birth outcomes. Most STI cases were asymptomatic and would have gone untreated with syndromic management. Aetiological STI screening is urgently needed to reduce the burden of STIs in pregnancy.