A Comparison of Biomarker Based Incidence Estimators

BACKGROUND: Cross-sectional surveys utilizing biomarkers that test for recent infection provide a convenient and cost effective way to estimate HIV incidence. In particular, the BED assay has been developed for this purpose. Controversy surrounding the way in which false positive results from the biomarker should be handled has lead to a number of different estimators that account for imperfect specificity. We compare the estimators proposed by McDougal et al., Hargrove et al. and McWalter & Welte. METHODOLOGY/PRINCIPAL FINDINGS: The three estimators are analyzed and compared. An identity showing a relationship between the calibration parameters in the McDougal methodology is shown. When the three estimators are tested under a steady state epidemic, which includes individuals who fail to progress on the biomarker, only the McWalter/Welte method recovers an unbiased result. CONCLUSIONS/SIGNIFICANCE: Our analysis shows that the McDougal estimator can be reduced to a formula that only requires calibration of a mean window period and a long-term specificity. This allows simpler calibration techniques to be used and shows that all three estimators can be expressed using the same set of parameters. The McWalter/Welte method is applicable under the least restrictive assumptions and is the least prone to bias of the methods reviewed

Biology as population dynamics : heuristics for transmission risk

Population-type models, accounting for phenomena such as population lifetimes, mixing patterns, recruitment patterns, genetic evolution and environmental conditions, can be usefully applied to the biology of HIV infection and viral replication. A simple dynamic model can explore the effect of a vaccine-like stimulus on the mortality and infectiousness, which formally looks like fertility, of invading virions; the mortality of freshly infected cells; and the availability of target cells, all of which impact on the probability of infection. Variations on this model could capture the importance of the timing and duration of different key events in viral transmission, and hence be applied to questions of mucosal immunology. The dynamical insights and assumptions of such models are compatible with the continuum of between- and within-individual risks in sexual violence and may be helpful in making sense of the sparse data available on the association between HIV transmission and sexual violence.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1600-0897hb2013ay201

Coital frequency and condom use in monogamous and concurrent sexual relationships in Cape Town, South Africa

Introduction: A decreased frequency of unprotected sex during episodes of concurrent relationships may dramatically reduce the role of concurrency in accelerating the spread of HIV. Such a decrease could be the result of coital dilution - the reduction in per-partner coital frequency from additional partners - and/or increased condom use during concurrency. To study the effect of concurrency on the frequency of unprotected sex, we examined sexual behaviour data from three communities with high HIV prevalence around Cape Town, South Africa. Methods: We conducted a cross-sectional survey from June 2011 to February 2012 using audio computer-assisted self-interviewing to reconstruct one-year sexual histories, with a focus on coital frequency and condom use. Participants were randomly sampled from a previous TB and HIV prevalence survey. Mixed effects logistic and Poisson regression models were fitted to data from 527 sexually active adults reporting on 1210 relationship episodes to evaluate the effect of concurrency status on consistent condom use and coital frequency. Results: The median of the per-partner weekly average coital frequency was 2 (IQR: 1-3), and consistent condom use was reported for 36% of the relationship episodes. Neither per-partner coital frequency nor consistent condom use changed significantly during episodes of concurrency (aIRR=1.05; 95% confidence interval (CI): 0.99-1.24 and aOR=1.01; 95% CI: 0.38-2.68, respectively). Being male, coloured, having a tertiary education, and having a relationship between 2 weeks and 9 months were associated with higher coital frequencies. Being coloured, and having a relationship lasting for more than 9 months, was associated with inconsistent condom use. Conclusions: We found no evidence for coital dilution or for increased condom use during concurrent relationship episodes in three communities around Cape Town with high HIV prevalence. Given the low levels of self-reported consistent condom use, our findings suggest that if the frequency of unprotected sex with each of the sexual partners is sustained during concurrent relationships, HIV-positive individuals with concurrent partners may disproportionately contribute to onward HIV transmission

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 \u3e2 sexual partners in the past year, a concurrent relationship in the past year, and \u3e 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

Tuberculosis in a South African prison - a transmission modelling analysis

Background. Prisons are recognised internationally as institutions with very high tuberculosis (TB) burdens where transmission is predominantly determined by contact between infectious and susceptible prisoners. A recent South African court case described the conditions under which prisoners awaiting trial were kept. With the use of these data, a mathematical model was developed to explore the interactions between incarceration conditions and TB control measures. Methods. Cell dimensions, cell occupancy, lock-up time, TB incidence and treatment delays were derived from court evidence and judicial reports. Using the Wells-Riley equation and probability analyses of contact between prisoners, we estimated the current TB transmission probability within prison cells, and estimated transmission probabilities of improved levels of case finding in combination with implementation of national and international minimum standards for incarceration. Results. Levels of overcrowding (230%) in communal cells and poor TB case finding result in annual TB transmission risks of 90% per annum. Implementing current national or international cell occupancy recommendations would reduce TB transmission probabilities by 30% and 50%, respectively. Improved passive case finding, modest ventilation increase or decreased lock-up time would minimally impact on transmission if introduced individually. However, active case finding together with implementation of minimum national and international standards of incarceration could reduce transmission by 50% and 94%, respectively. Conclusions. Current conditions of detention for awaiting-trial prisoners are highly conducive for spread of drug-sensitive and drug-resistant TB. Combinations of simple well-established scientific control measures should be implemented urgently

Cross-Sectional HIV Incidence Surveillance: A Benchmarking of Approaches for Estimating the 'Mean Duration of Recent Infection'.

The application of biomarkers for 'recent' infection in cross-sectional HIV incidence surveillance requires the estimation of critical biomarker characteristics. Various approaches have been employed for using longitudinal data to estimate the Mean Duration of Recent Infection (MDRI) - the average time in the 'recent' state. In this systematic benchmarking of MDRI estimation approaches, a simulation platform was used to measure accuracy and precision of over twenty approaches, in thirty scenarios capturing various study designs, subject behaviors and test dynamics that may be encountered in practice. Results highlight that assuming a single continuous sojourn in the 'recent' state can produce substantial bias. Simple interpolation provides useful MDRI estimates provided subjects are tested at regular intervals. Regression performs the best - while 'random effects' describe the subject-clustering in the data, regression models without random effects proved easy to implement, stable, and of similar accuracy in scenarios considered; robustness to parametric assumptions was improved by regressing 'recent'/'non-recent' classifications rather than continuous biomarker readings. All approaches were vulnerable to incorrect assumptions about subjects' (unobserved) infection times. Results provided show the relationships between MDRI estimation performance and the number of subjects, inter-visit intervals, missed visits, loss to follow-up, and aspects of biomarker signal and noise.MRC Funding: MC_UP_1302/3’ and U10526056

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