The evolution and interpretation of seroprevalence of SARS-CoV-2 antibodies among South African blood donors from the Beta to Omicron variant-driven waves.

BACKGROUND AND OBJECTIVES: Confirmed COVID-19 diagnoses underestimate the total number of infections. Blood donors can provide representative seroprevalence estimates, which can be leveraged into reasonable estimates of total infection counts and infection fatality rate (IFR). MATERIALS AND METHODS: Blood donors who donated after each of three epidemic waves (Beta, Delta and first Omicron waves) were tested for anti-SARS-CoV-2 nucleocapsid antibodies using the Roche Elecsys anti-SARS-CoV-2 total immunoglobulin assay. Roche Elecsys anti-spike antibody testing was done for the post-Omicron sampling. Prevalence of antibodies was estimated by age, sex, race and province and compared to official case reporting. Province and age group-specific IFRs were estimated using external excess mortality estimates. RESULTS: The nationally weighted anti-nucleocapsid seroprevalence estimates after the Beta, Delta and Omicron waves were 47% (46.2%-48.6%), 71% (68.8%-73.5%) and 87% (85.5%-88.4%), respectively. There was no variation by age and sex, but there were statistically and epidemiologically significant differences by province (except at the latest time point) and race. There was a 13-fold higher seroprevalence than confirmed case counts at the first time point. Age-dependent IFR roughly doubled for every 10 years of age increase over 6 decades from 0.014% in children to 6.793% in octogenarians. CONCLUSION: Discrepancies were found between seroprevalence and confirmed case counts. High seroprevalence rates found among Black African donors can be ascribed to historical inequities. Our IFR estimates were useful in refining previous large disagreements about the severity of the epidemic in South Africa. Blood donor-based serosurveys provided a valuable and efficient way to provide near real-time monitoring of the ongoing SARS-CoV-2 outbreak.

Coronavirus Disease 2019 Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection in the United States Before the Delta- and Omicron-Associated Surges: A Retrospective Cohort Study of Repeat Blood Donors.

BACKGROUND: To inform public health policy, it is critical to monitor coronavirus disease 2019 vaccine effectiveness (VE), including against acquiring infection. METHODS: We estimated VE using self-reported vaccination in a retrospective cohort of repeat blood donors who donated during the first half of 2021, and we demonstrated a viable approach for monitoring VE via serological surveillance. RESULTS: Using Poisson regression, we estimated an overall VE of 88.8% (95% confidence interval, 86.2-91.1), adjusted for demographic covariates and variable baseline risk. CONCLUSIONS: The time since first reporting vaccination, age, race and/or ethnicity, region, and calendar time were statistically significant predictors of incident infection.

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.

Modelling the impact of maternal HIV on uninfected children: correcting current estimates.

A mathematical model, populated primarily with data from South Africa, was developed to model the numbers of children affected by maternal HIV, and the number who will experience long-term negative developmental consequences. A micro-simulation model generated two scenarios. The first simulated a cohort of women whose HIV status mimicked that of a target population, and mother-child dyads by way of age- and disease-specific fertility rates. Factors defining risk were used to characterize the simulated environment. The second scenario simulated mother-child dyads without maternal HIV. In the first scenario an estimated 26% of children are orphaned, compared to 10% in the absence of HIV. And a further 19% of children whose mother is alive when they turn 18 are affected by maternal HIV. School drop-out among all children increased by 4 percentage points because of maternal HIV, similarly population level estimates of abuse and negative mental health outcomes are elevated. Relative to HIV unaffected children, HIV affected have elevated risk of poor outcomes, however not all will suffer long-term negative consequences. Interventions to protect children should target the proportion of children at risk, while interventions to mitigate harm should target the smaller proportion of children who experience long-term negative outcomes..

Are associations between HIV and human papillomavirus transmission due to behavioural confounding or biological effects?

OBJECTIVES: Cohort studies have shown significant increased risk of HIV acquisition following human papillomavirus (HPV) detection and increased risk of new HPV detection in individuals with HIV infection, after adjusting for behavioural risk factors. This study uses an individual-based model to assess whether confounding sexual behaviour factors and network level effects can explain these associations between HIV and HPV infection status, without biological interactions. METHODS: The model simulates infection with 13 oncogenic HPV types and HIV. It allows for different relationship types, with heterogeneity in probabilities of concurrency and rates of partner change. No effect of prevalent HPV infection on HIV acquisition is assumed and vice versa. The model is calibrated to South African HIV and type-specific HPV prevalence data using a Bayesian approach. The model is used to simulate cohorts with quarterly HIV and HPV testing from 2000 to 2002. These simulated data are analysed using proportional hazard models. RESULTS: The mean of the unadjusted HRs of HIV acquisition following detection of an oncogenic HPV type calculated for each simulated cohort is 2.6 (95% CI 2.2 to 3.1). The mean of the unadjusted HRs for the effect of HIV on newly detected HPV is 2.5 (95% CI 2.2 to 2.8). Simulated associations between HIV and HPV infection status are similar to corresponding empirical estimates. In sensitivity analyses in which HIV and HPV were assumed to increase each other's transmission risk, simulated associations were stronger but not inconsistent with empirical estimates. CONCLUSIONS: Although we cannot rule out the possibility that associations between HIV and HPV transmission may be due in part to biological interactions, these results suggest that observed associations could be explained entirely by residual confounding by behavioural factors and network-level effects that observational studies cannot account for.

Assessment of HIV transfusion transmission risk in South Africa: a 10-year analysis following implementation of individual donation nucleic acid amplification technology testing and donor demographics eligibility changes.

BACKGROUND: In 1998 we estimated that 34/million infectious window period donations were entering the blood supply at the South African National Blood Service. Selective use of donations based on donor race-ethnicity reduced this risk to 26/million donations but was deemed unethical. Consequently, in 2005 South African National Blood Service eliminated race-ethnicity-based collection policies and implemented individual-donation nucleic acid testing (ID-NAT). We describe the change in donor base demographics, human immunodeficiency virus (HIV) detection rates, and transfusion-transmissible HIV risk. STUDY DESIGN AND METHODS: In ten years 7.7 million donations were tested for anti-HIV and HIV RNA. Number of donations, HIV prevalence, ID-NAT yield rate, serology yield rate and residual transfusion-transmissible HIV risk were analyzed by donor type, race-ethnicity, age, and sex. Multiple regression analysis was performed to investigate the determinants of HIV-positive and nucleic acid testing yield donations. RESULTS: The combined strategy of increasing donations from black donors and implementing ID-NAT increased the proportion of donations from black donors from 6% in 2005 to 30% in 2015 (p < 0.00001), and reduced the transfusion-transmissible risk from 24 to 13 per million transfusions. ID-NAT interdicted 481 (1:16,100) seronegative window period donations, while one transfusion-transmissible case (0.13 per million) was documented. Race-ethnicity and donor type were highly significant predictors of HIV positivity, with adjusted odds ratio for first-time donors of 12.5 (95% confidence interval, 11.9-13.1) and for black race-ethnicity of 31.1 (95% confidence interval, 28.9-33.4). The proportion of serology yields among HIV-infected donors increased from 0.27% to 2.4%. CONCLUSION: ID-NAT enabled the South African National Blood Service to increase the number of donations from black donors fivefold while enhancing the safety of the blood supply.

Pooled PCR testing of dried blood spots for infant HIV diagnosis is cost efficient and accurate.

BACKGROUND: Access to qualitative HIV PCRs for early infant diagnosis (EID) is restricted in resource-limited settings due to cost. We hypothesised that pooling of dried blood spots (DBS), defined as combining multiple patient samples in a single test with subsequent individual testing of positive pools, would be cost saving while retaining clinical accuracy compared to individual patient testing. METHODS: Cost savings: A model was developed to simulate reagent and consumable cost saving of pooled compared to individual sample testing. Daily sample/result data of a public health laboratory in South Africa were used to illustrate outputs from the model. Samples were randomly allocated to pools and the process was repeated 1000 times to measure variation in estimates due to this stochasticity. Clinical accuracy: 1170 patient samples were tested using the Roche CAP/CTM Qual assay in pools of five 50 µl DBS. Negative pools comprised DBS previously tested in single reactions; positive pools included 1 positive sample. RESULTS: Pooling would have saved 64% of laboratory costs in 2015. The model is published as an R-based web tool, into which the user enters sample/positivity estimates and workflow management parameters to obtain cost saving estimates at an optimal pool size. Sensitivity of pooled testing was 98.8% overall; 100% for strongly reactive pools. One pool tested false positive which would not impact clinical specificity as individual patient testing is performed prior to reporting. CONCLUSIONS: Pooled PCR testing for EID remains accurate and dramatically reduces costs in settings with moderate to low prevalence rates and sufficient sample numbers.

Interpreting HIV diagnostic histories into infection time estimates: analytical framework and online tool.

BACKGROUND: It is frequently of epidemiological and/or clinical interest to estimate the date of HIV infection or time-since-infection of individuals. Yet, for over 15 years, the only widely-referenced infection dating algorithm that utilises diagnostic testing data to estimate time-since-infection has been the 'Fiebig staging' system. This defines a number of stages of early HIV infection through various standard combinations of contemporaneous discordant diagnostic results using tests of different sensitivity. To develop a new, more nuanced infection dating algorithm, we generalised the Fiebig approach to accommodate positive and negative diagnostic results generated on the same or different dates, and arbitrary current or future tests - as long as the test sensitivity is known. For this purpose, test sensitivity is the probability of a positive result as a function of time since infection. METHODS: The present work outlines the analytical framework for infection date estimation using subject-level diagnostic testing histories, and data on test sensitivity. We introduce a publicly-available online HIV infection dating tool that implements this estimation method, bringing together 1) curatorship of HIV test performance data, and 2) infection date estimation functionality, to calculate plausible intervals within which infection likely became detectable for each individual. The midpoints of these intervals are interpreted as infection time 'point estimates' and referred to as Estimated Dates of Detectable Infection (EDDIs). The tool is designed for easy bulk processing of information (as may be appropriate for research studies) but can also be used for individual patients (such as in clinical practice). RESULTS: In many settings, including most research studies, detailed diagnostic testing data are routinely recorded, and can provide reasonably precise estimates of the timing of HIV infection. We present a simple logic to the interpretation of diagnostic testing histories into infection time estimates, either as a point estimate (EDDI) or an interval (earliest plausible to latest plausible dates of detectable infection), along with a publicly-accessible online tool that supports wide application of this logic. CONCLUSIONS: This tool, available at https://tools.incidence-estimation.org/idt/ , is readily updatable as test technology evolves, given the simple architecture of the system and its nature as an open source project.

HIV Antibody Level as a Marker of HIV Persistence and Low-Level Viral Replication.

Background: Human immunodeficiency virus (HIV) antibodies are generated and maintained by ongoing systemic expression of HIV antigen. We investigated whether HIV antibody responses as measured by high-throughput quantitative and qualitative assays could be used to indirectly measure persistent HIV replication in individuals receiving antiretroviral therapy (ART). Methods: HIV antibody responses were measured over time in the presence or absence of suppressive ART and were compared to the HIV reservoir size and expression of antiviral restriction factors. Results: Among untreated individuals, including both elite controllers (ie, persons with a viral load of ≤40 copies/mL) and noncontrollers, antibody parameters were stable over time and correlated with the individual viral load. Viral suppression with ART led to a progressive decline in antibody responses after treatment induction that persisted for 5-7 years. Higher levels of HIV antibodies during suppressive therapy were associated with later initiation of ART after infection, with higher DNA and cell-associated RNA levels, and with lower expression of multiple anti-HIV host restriction factors. Discussion: These findings suggest that declining antibody levels during ART reflect lower levels of antigen production and/or viral replication in the persistent HIV reservoir. Results of relatively inexpensive and quantitative HIV antibody assays may be useful indirect markers that enable efficient monitoring of the viral reservoir and suppression during functional-cure interventions.

Strengthening HIV surveillance in the antiretroviral therapy era: rationale and design of a longitudinal study to monitor HIV prevalence and incidence in the uMgungundlovu District, KwaZulu-Natal, South Africa.

BACKGROUND: South Africa has over 6,000,000 HIV infected individuals and the province of KwaZulu-Natal (KZN) is the most severely affected. As public health initiatives to better control the HIV epidemic are implemented, timely, detailed and robust surveillance data are needed to monitor, evaluate and inform the programmatic interventions and policies over time. We describe the rationale and design of the HIV Incidence Provincial Surveillance System (HIPSS) to monitor HIV prevalence and incidence. METHODS/DESIGN: The household-based survey will include a sample of men and women from two sub-districts of the uMgungundlovu municipality (Vulindlela and the Greater Edendale) of KZN, South Africa. The study is designed as two sequential cross-sectional surveys of 10,000 randomly selected individuals aged 15-49 years to be conducted one year apart. From the cross sectional surveys, two sequential cohorts of HIV negative individuals aged 15-35 years will be followed-up one year later to measure the primary outcome of HIV incidence. Secondary outcomes include the laboratory measurements for pulmonary tuberculosis, sexually transmitted infections and evaluating tests for estimating population-level HIV incidence. Antiretroviral therapy (ART) access, HIV-1 RNA viral load, and CD4 cell counts in HIV positive individuals will assess the effectiveness of the HIV treatment cascade. Household and individual-level socio-demographic characteristics, exposure to HIV programmatic interventions and risk behaviours will be assessed as predictors of HIV incidence. The incidence rate ratio of the two cohorts will be calculated to quantify the change in HIV incidence between consecutive samples. In anticipation of better availability of population-level HIV prevention and treatment programmes leading to decreases in HIV incidence, the sample size provides 84% power to detect a reduction of 30% in the HIV incidence rate between surveys. DISCUSSION: The results from HIPSS will provide critical data regarding HIV prevalence and incidence in this community and will establish whether HIV prevention and treatment efforts in a "real world", non-trial setting have an impact on HIV incidence at a population level. Importantly, the study design and methods will inform future methods for HIV surveillance.

Potential for high dynamic range Sedia Limiting Antigen antibody assay to support viral load monitoring during antiretroviral therapy.

INTRODUCTION: Viral Load (VL) monitoring is a crucial component of patient care during antiretroviral therapy (ART) but is not routinely available in many resource-constrained settings, where millions of patients will require care for decades to come. We hypothesise a serologic 'recent infection' test (Sedia LAg assay) which has a high dynamic range for detecting antigen-driven antibody response can provide informative proxies for VL trajectories. METHODS: A retrospective study where we analysed data linked via specimens in a well-described repository for recent infection test benchmarking (CEPHIA collaboration). Patient panels were comprised of 1) observations straddling ART start; 2) observations from a period of stable viral suppression; 3) observations straddling rebound after a period of viral suppression. We analysed an individual's Sedia LAg ELISA normalised optical density (ODn) trends within these categories. Using groups 2) and 3) we evaluated the specificity and sensitivity of a proposed proxy for "the latest observation is at a time of VL rebound"; proxy was defined as follows: we estimated patient-specific mean-previous-ODn for all observations with at least two preceding virally suppressed observations. We considered various thresholds to define both "VL suppression" and "ODn uptick". RESULTS: In regression analysis by category: 1) ODn gradients are statistically significantly negative just after ART-start (p = 0.010); 2) During periods of stable viral suppression, ODn tended to decline, but not statistically significantly, for a range of clinically meaningful "VL suppression" thresholds; 3) comparing ODn values just before, versus at, "VL rebound", ODn changes were statistically significantly increasing at rebound (p = 0.001). In the analysis comparing groups 2) and 3), at a Z score threshold of 0.8, the proposed proxy for a first viral rebound had an observed specificity and sensitivity both close to 90%. CONCLUSION: The high dynamic range of serological tests previously investigated for defining 'recent infection' has potential, as demonstrated using the Sedia LAg ELISA, to provide meaningful information about the success of ART, during treatment initiation, at times of stable suppression, and to flag possible viral rebound. It should be investigated how this can be combined with patient management workflows and (clinical and) other data, to provide efficiencies in long-term monitoring viral control in resource-limited settings.

Correction: Early mortality in tuberculosis patients initially lost to follow up following diagnosis in provincial hospitals and primary health care facilities in Western Cape, South Africa.

[This corrects the article DOI: 10.1371/journal.pone.0252084.].

Evaluating audio computer assisted self-interviews in urban South African communities: evidence for good suitability and reduced social desirability bias of a cross-sectional survey on sexual behaviour.

BACKGROUND: Efficient HIV prevention requires accurate identification of individuals with risky sexual behaviour. However, self-reported data from sexual behaviour surveys are prone to social desirability bias (SDB). Audio Computer-Assisted Self-Interviewing (ACASI) has been suggested as an alternative to face-to-face interviewing (FTFI), because it may promote interview privacy and reduce SDB. However, little is known about the suitability and accuracy of ACASI in urban communities with high HIV prevalence in South Africa. To test this, we conducted a sexual behaviour survey in Cape Town, South Africa, using ACASI methods. METHODS: Participants (n = 878) answered questions about their sexual relationships on a touch screen computer in a private mobile office. We included questions at the end of the ACASI survey that were used to assess participants' perceived ease of use, privacy, and truthfulness. Univariate logistic regression models, supported by multivariate models, were applied to identify groups of people who had adverse interviewing experiences. Further, we constructed male-female ratios of self-reported sexual behaviours as indicators of SDB. We used these indicators to compare SDB in our survey and in recent FTFI-based Demographic and Health Surveys (DHSs) from Lesotho, Swaziland, and Zimbabwe. RESULTS: Most participants found our methods easy to use (85.9%), perceived privacy (96.3%) and preferred ACASI to other modes of inquiry (82.5%) when reporting on sexual behaviours. Unemployed participants and those in the 40-70 year old age group were the least likely to find our methods easy to use (OR 0.69; 95% CI: 0.47-1.01 and OR 0.37; 95% CI: 0.23-0.58, respectively). In our survey, the male-female ratio for reporting >2 sexual partners in the past year, a concurrent relationship in the past year, and > 2 sexual partners in a lifetime was 3.4, 2.6, and 1.2, respectively- far lower than the ratios observed in the Demographic and Health Surveys. CONCLUSIONS: Our analysis suggests that most participants in our survey found the ACASI modality to be acceptable, private, and user-friendly. Moreover, our results indicate lower SDB than in FTFI techniques. Targeting older and unemployed participants for ACASI training prior to taking the survey may help to improve their perception of ease and privacy.

Evidence of HIV incidence reduction in young women, but not in adolescent girls, in KwaZulu-Natal, South Africa.

Objectives: We estimated changes in the HIV incidence from 2013-2018 in Eshowe/Mbongolwane, KwaZulu-Natal, South Africa where Médecins Sans Frontières is engaged in providing HIV testing and care since 2011. Methods: Using data from two cross-sectional household-based surveys conducted in 2013 and 2018, with consenting participants aged 15-59 years, we applied the incidence estimation frameworks of Mahiane et al and Kassanjee et al. Results: In total, 5599 (62.4% women) and 3276 (65.9% women) individuals were included in 2013 and 2018, respectively. We found a mean incidence in women aged 20-29 years of 2.71 cases per 100 person-years (95% confidence interval [CI]: 1.23;4.19) in 2013 and 0.4 cases per 100 person-years (95% CI: 0.0;1.5) in 2018. The incidence in men aged 20-29 years was 1.91 cases per 100 person-years (95% CI: 0.87; 2.93) in 2013 and 0.53 cases per 100 person-years (95% CI: 0.0; 1.4) in 2018. The incidence decline among women aged 15-19 was -0.34 cases per 100 person-years (95% CI: -1.31;0.64). Conclusions: The lack of evidence of incidence decline among adolescent girls is noteworthy and disconcerting. Our findings suggest that large-scale surveys should seriously consider focusing their resources on the core group of women aged 15-19 years.

HIV treatment as prevention: principles of good HIV epidemiology modelling for public health decision-making in all modes of prevention and evaluation.

Public health responses to HIV epidemics have long relied on epidemiological modelling analyses to help prospectively project and retrospectively estimate the impact, cost-effectiveness, affordability, and investment returns of interventions, and to help plan the design of evaluations. But translating model output into policy decisions and implementation on the ground is challenged by the differences in background and expectations of modellers and decision-makers. As part of the PLoS Medicine Collection "Investigating the Impact of Treatment on New HIV Infections"--which focuses on the contribution of modelling to current issues in HIV prevention--we present here principles of "best practice" for the construction, reporting, and interpretation of HIV epidemiological models for public health decision-making on all aspects of HIV. Aimed at both those who conduct modelling research and those who use modelling results, we hope that the principles described here will become a shared resource that facilitates constructive discussions about the policy implications that emerge from HIV epidemiology modelling results, and that promotes joint understanding between modellers and decision-makers about when modelling is useful as a tool in quantifying HIV epidemiological outcomes and improving prevention programming.

A new general biomarker-based incidence estimator.

BACKGROUND: Estimating disease incidence from cross-sectional surveys, using biomarkers for "recent" infection, has attracted much interest. Despite widespread applications to HIV, there is currently no consensus on the correct handling of biomarker results classifying persons as "recently" infected long after the infections occurred. METHODS: We derive a general expression for a weighted average of recent incidence that-unlike previous estimators-requires no particular assumption about recent infection biomarker dynamics or about the demographic and epidemiologic context. This is possible through the introduction of an explicit timescale T that truncates the period of averaging implied by the estimator. RESULTS: The recent infection test dynamics can be summarized into 2 parameters, similar to those appearing in previous estimators: a mean duration of recent infection and a false-recent rate. We identify a number of dimensionless parameters that capture the bias that arises from working with tractable forms of the resulting estimator and elucidate the utility of the incidence estimator in terms of the performance of the recency test and the population state. Estimation of test characteristics and incidence is demonstrated using simulated data. The observed confidence interval coverage of the test characteristics and incidence is within 1% of intended coverage. CONCLUSIONS: Biomarker-based incidence estimation can be consistently adapted to a general context without the strong assumptions of previous work about biomarker dynamics and epidemiologic and demographic history.

Sexual risk behaviors among HIV-infected South African men and women with their partners in a primary care program: implications for couples-based prevention.

We studied 1163 sexually-active HIV-infected South African men and women in an urban primary care program to understand patterns of sexual behaviors and whether these behaviors differed by partner HIV status. Overall, 40% reported a HIV-positive partner and 60% a HIV-negative or status unknown partner; and 17.5% reported >2 sex acts in the last 2 weeks, 16.4% unprotected sex in the last 6 months, and 3.7% >1 sex partner in the last 6 months. Antiretroviral therapy (ART) was consistently associated with decreased sexual risk behaviors, as well as with reporting a HIV-negative or status unknown partner. The odds of sexual risk behaviors differed by sex; and were generally higher among participants reporting a HIV-positive partner, but continued among those with a HIV-negative or status unknown partner. These data support ART as a means of HIV prevention. Engaging in sexual risk behaviors primarily with HIV-positive partners was not widely practiced in this setting, emphasizing the need for couples-based prevention.

Age-disparate relationships and implications for STI transmission among young adults in Cape Town, South Africa.

OBJECTIVES: To estimate the prevalence of age-disparate (AD) relationships among young black and coloured adults in Cape Town (South Africa) and determine socio-demographic predictors and individual and relationship characteristics of women in these relationships. METHODS: A secondary analysis of the Cape Area Panel Study (N = 1960) data was conducted. Descriptive statistics were used to quantify the age-mixing pattern and logistic regression was used to identify significant socio-demographic and behavioural correlates of AD relationships. RESULTS: Prevalence of AD relationships was high in both black (36%) and coloured (28%) women. The average age difference between male respondents and their partners increased with age. Young, black women who spent fewer nights under the same roof in one week, had a deceased parent, and were not currently attending classes were more likely to be in an AD relationship. Reports of sexually-transmitted infection (STI) symptoms in the last month and unprotected sex were more common among women in AD relationships. CONCLUSIONS: AD relationships are common among young women in Cape Town. Home and family stability is preventative of young women engaging in AD relationships. Therefore, holistic, societal interventions may reduce AD relationships, which are a risk factor for STIs.

Quantitative interpretation of Sedia LAg Assay test results after HIV diagnosis.

BACKGROUND: Testing for 'recent HIV infection' is common in surveillance, where only population-level estimates (of incidence) are reported. Typically, 'recent infection' is a category, obtained by applying a threshold on an underlying continuous biomarker from some laboratory assay(s). Interpreting the biomarker values obtained for individual subjects, as estimates of the date of infection, has obvious potential applications in the context of studies of early infection, and has also for some years attracted significant interest as an extra component of post-test counselling and treatment initiation. The applicable analyses have typically run aground on the complexity of the full biomarker growth model, which is in principle a non-linear mixed-effects model of unknown structure, the fitting of which seems infeasible from realistically obtainable data. METHODS: It is known that to estimate Mean Duration of Recent Infection (MDRI) at a given value of the recent/non-recent -infection discrimination threshold, one may compress the full biomarker growth model into a relation capturing the probability of a recent test result as a function of time t since infection, given a value of assay threshold h which defines the recent/non-recent discrimination. We demonstrate that the derivative (gradient), with respect to h. of the probability of recent infection, seen as a function of both t and h, is identical to the formal likelihood relevant to Bayesian inference of the time since seroconversion, for a subject yielding an assay result h, at or close to the date of their first positive HIV test. This observation bypasses the need for fitting a complex detailed biomarker growth model. Using publicly available data from the CEPHIA collaboration, we calibrated this likelihood function for the Sedia Lag assay, and performed Bayesian inference on hypothetical infection data. RESULTS: We demonstrate the generation of posteriors for infection date, for patients with various delays between their last negative and first positive HIV test, and a range of LAg assay results (ODn) hypothetically obtained on the date of the first positive result. CONCLUSION: Depending on the last-negative / first-positive interval, there is a range of ODn values that yields posteriors significantly different from the uniform prior one would be left with based merely on interval censoring. Hence, a LAg ODn obtained on the date of, or soon after, diagnosis contains potentially significant information about infection dating. It seems worth analysing other assays with meaningful dynamic range, especially tests already routinely used in primary HIV diagnosis (for example chemiluminescent assays and reader/cartridge lateral flow tests which admit objective variable line intensity readings) which have a sufficient dynamic range that corresponds to a clinically meaningful range of times-since-infection that are worth distinguishing from each other.

Estimates of prevalence of anti-SARS-CoV-2 antibodies among blood donors in South Africa in March 2022.

In line with previous instalments of analysis from this ongoing study to monitor 'Covid Seroprevalence' among blood donors in South Africa, we report on an analysis of 3395 samples obtained in mid-March 2022 from all provinces of South Africa - a timepoint just after the fourth (primarily omicron) wave of infections. As in our previous analyses, we see no evidence of age and sex dependence of prevalence, but significant variation by race. Differences between provinces have largely disappeared, as prevalence appears to have saturated. In contrast to previous estimates from this study, which reported only prevalence of anti-nucleocapsid antibodies, this present work also reports results from testing for anti-spike antibodies. This addition allows us to categorise those donors whose only antibodies are from vaccination. Our race-weighted national extrapolation is that 98% of South Africans have some antibodies, noting that 10% have anti-spike antibodies but not anti-nucleocapsid antibodies - a reasonable proxy for having both 1) been vaccinated and 2) avoided infection.