SEXUAL BEHAVIOR AND SEXUAL NETWORKS IN SOUTH AFRICA: IMPLICATIONS FOR HIV TRANSMISSION

HIV is largely spread through sexual transmission in sub-Saharan Africa. Despite major biomedical innovations in HIV prevention, South Africa continues to bear a disproportionate burden of HIV. This dissertation aims to assess sexual behavior among people living with HIV comparing those on antiretroviral therapy (ART) to those not, describe sexual mixing patterns and number of sexual partners, and characterize sexual networks consistent with limited network data and assess the impact of network structure on disease potential. Throughout this dissertation, we present analyses of the Human Sciences Research Council’s 2012 South African National HIV Prevalence, Incidence and Behaviour Survey (SABSSM IV), a nationally representative household based cross- sectional survey. We first use logistic regression to assess the relationship between ART and sexual behavior among those living with HIV. We find that ART is associated with increased odds of condom use among those living with HIV (aOR>2), but not associated with reporting multiple sexual partners. This aim suggests that people living with HIV not yet on ART in South Africa likely contribute the greatest number of transmissions (both due to sexual behavior and ART reducing infectivity), and reinforces the importance of engaging individuals living with HIV in care. Next, we use mixing matrices and Newman’s assortativity coefficients to describe sexual mixing patterns, and fit a number of count distributions to degree distribution (number of sexual partners in the past year) data. Sexual mixing patterns are strongly assortative in South Africa, with assortativity coefficients for age, race, education, HIV- status, number of sexual partners and ARV status indicating strong assortativity in household partnerships (>0.6). Number of sexual partners was low (mean in past year = 1.34) but men were 5 times more likely to report 2+ partners in the past year. Our findings suggest that the strongly assortative nature of sexual networks in South Africa could have implications for HIV combination prevention intervention efficacy. Finally, we use a nonparametric Markov chain Monte Carlo approach to simulate complete sexual networks consistent with mixing patterns and degree distribution data. We assess network characteristics on these consistent networks, and assess the impact of assumptions to balance male and female degree on these networks. We then estimate the impact of network structure on disease transmission. Simulated sexual networks consistent with our limited sexual network data varied little, but were highly dependent on assumptions made to balance male and female degree distributions. Networks with FSW populations had the greatest potential for HIV spread. Network characteristics were associated with potential HIV spread. Our results suggest the importance of capturing highly connected individuals in survey data, as these individuals will play a major role in disease transmission. Sexual networks have the potential to dramatically influence the impact of HIV combination prevention interventions. This dissertation builds upon a body of work to provide an improved understanding of sexual behavior, sexual mixing and sexual networks within South Africa. These results can be utilized in the development of interventions to predict the potential effect an intervention could have in order to efficiently target interventions to have the greatest impact on HIV burden in South Africa

HIV acquisition in pregnancy: implications for mother-to-child transmission at the population level in sub-Saharan Africa.

INTRODUCTION: A recent sero-discordant couple study showed an elevated risk of HIV-acquisition during the pregnancy/postpartum period per-condomless-coital-act. This, along with previous studies, has led to concern over possible increased risk of mother-to-child (vertical) transmission, due to the initial high viral load in the first months after seroconversion, in a time when the woman and health services may be unaware of her status. This study looks at whether behavioural differences during the pregnant/postpartum period could reduce the impact of elevated risk of HIV acquisition per-condomless-coital-act at the population level. METHODS: We used data from 60 demographic and health surveys from 32 sub-Saharan African countries. Using the HIV status of couples, we estimated differences in serodiscordancy between HIV-negative women who were pregnant/postpartum compared to those who were not pregnant/postpartum. We compare the risk of sexual activity over the pregnant/postpartum period to those not pregnant/postpartum. Using these risks of serodiscordancy and sexual activity along with estimates of increased HIV risk in the pregnancy/postpartum period per-condomless-coital-act, we estimated a population-level risk of HIV acquisition and acute infection, during pregnancy/postpartum compared to those not pregnant/postpartum. RESULTS: Sexual activity during pregnancy/postpartum varies considerably. In general, sexual activity is high in the first trimester of pregnancy, then declines to levels lower than among women not pregnant/postpartum, and is at its lowest in the first months postpartum. Adjusted for age and survey, pooled results show HIV-negative pregnant women are less likely to have an HIV-positive partner compared to those not pregnant/postpartum (risk ratio (RR) = 0.78, 95% CI = 0.68-0.89) and comparing the postpartum period (RR = 0.85, 95% CI = 0.73-0.99). Estimated population-level risk for HIV acquisition and acute infection in pregnancy/postpartum was lower than would be inferred directly from per-condomless-coital-act estimates in most countries, over the time of most risk of mother-to-child transmission, though there was variation by country and month of pregnancy/postpartum. CONCLUSIONS: Estimates of population-level HIV acquisition risk in sub-Saharan Africa should not be taken directly from per-condomless-coital-act studies to estimate vertical transmission. Changes in sexual behaviour and differences in HIV-serodiscordancy during pregnancy/postpartum reduce the impact of increased risk of HIV acquisition per-condomless-coital-act, this will vary by region

A Role for Health Communication in the Continuum of HIV Care, Treatment, and Prevention

Health communication has played a pivotal role in HIV prevention efforts since the beginning of the epidemic. The recent paradigm of combination prevention, which integrates behavioral, biomedical, and structural interventions, offers new opportunities for employing health communication approaches across the entire continuum of care. We describe key areas where health communication can significantly enhance HIV treatment, care, and prevention, presenting evidence from interventions that include health communication components. These interventions rely primarily on interpersonal communication, especially individual and group counseling, both within and beyond clinical settings to enhance the uptake of and continued engagement in care. Many successful interventions mobilize a network of trained community supporters or accompagnateurs, who provide education, counseling, psychosocial support, treatment supervision, and other pragmatic assistance across the care continuum. Community treatment supporters reduce the burden on overworked medical providers, engage a wider segment of the community, and offer a more sustainable model for supporting people living with HIV. Additionally, mobile technologies are increasingly seen as promising avenues for ongoing cost-effective communication throughout the treatment cascade. A broader range of communication approaches, traditionally employed in HIV prevention efforts, that address community and sociopolitical levels through mass media, school- or workplace-based education, and entertainment modalities may be useful to interventions seeking to address the full care continuum. Future interventions would benefit from development of a framework that maps appropriate communication theories and approaches onto each step of the care continuum to evaluate the efficacy of communication components on treatment outcomes

The case for expanding the definition of ‘key populations’ to include high-risk groups in the general population to improve targeted HIV prevention efforts

Background. Two additional key populations within the general population in South Africa (SA) that are at risk of HIV infection are black African women aged 20 - 34 years and black African men aged 25 - 49 years.Objective. To investigate the social determinants of HIV serostatus for these two high-risk populations.Methods. Data from the 2012 South African National HIV Prevalence, Incidence, and Behaviour Survey were analysed for black African women aged 20 - 34 years and black African men aged 25 - 49 years.Results. Of the 6.4 million people living with HIV in SA in 2012, 1.8 million (28%) were black women aged 20 - 34 years and 1.9 million (30%) black men aged 25 - 49 years. In 2012, they constituted 58% of the total HIV-positive population and 48% of the newly infected population. Low socioeconomic status (SES) was strongly associated (p<0.001) with being HIV-positive among black women aged 20 - 34 years, and was marginally significant among black men aged 25 - 49 years (p<0.1).Conclusion. Low SES is a critical social determinant for HIV infection among the high-risk groups of black African women aged 20 - 34 years and black African men aged 25 - 49 years. Targeted interventions for these key populations should prioritise socioeconomic empowerment, access to formal housing and services, access to higher education, and broad economic transformation

Outcomes of patients lost to follow-up after antiretroviral therapy initiation in rural north-eastern South Africa.

OBJECTIVE: The vital status of patients lost to follow-up often remains unknown in antiretroviral therapy (ART) programmes in sub-Saharan Africa because medical records are no longer updated once the patient disengages from care. Thus, we aimed to assess the outcomes of patients lost to follow-up after ART initiation in north-eastern South Africa. METHODS: Using data from a rural area in north-eastern South Africa, we estimated the cumulative incidence of patient outcomes (i) after treatment initiation using clinical records, and (ii) after loss to follow-up (LTFU) using data from clients that have been individually linked to Agincourt Health and Demographic Surveillance System (AHDSS) database. Aside from LTFU, we considered mortality, re-engagement and migration out of the study site. Cox proportional hazards regression was used to identify covariates of these patient outcomes. RESULTS: Between April 2014 and July 2017, 3700 patients initiated ART and contributed a total of 6818 person-years of follow-up time. Three years after ART initiation, clinical record-based estimates of LTFU, mortality and documented transfers were 41.0% (95% CI: 38.5-43.4%), 1.9% (95% CI 1.0-3.2%) and 0.1% (95% CI 0.0-0.9%), respectively. Among those who were LTFU, the cumulative incidence of re-engagement, out-migration and mortality at 3 years were 38.1% (95% CI 33.1-43.0%), 49.4% (95% CI 43.1-55.3%) and 4.7% (95% CI 3.5-6.2%), respectively. Pregnant or breastfeeding women, foreigners and those who initiated ART most recently were at an increased risk of LTFU. CONCLUSION: LTFU among patients starting ART in north-eastern South Africa is relatively high and has increased in recent years as more asymptomatic patients have initiated treatment. Even though this tendency is of concern in light of the prevention of onwards transmission, we also found that re-engagement in care is common and mortality among persons LTFU relatively low

SMN Protein Can Be Reliably Measured in Whole Blood with an Electrochemiluminescence (ECL) Immunoassay: Implications for Clinical Trials

Spinal muscular atrophy (SMA) is caused by defects in the survival motor neuron 1 (SMN1) gene that encodes survival motor neuron (SMN) protein. The majority of therapeutic approaches currently in clinical development for SMA aim to increase SMN protein expression and there is a need for sensitive methods able to quantify increases in SMN protein levels in accessible tissues. We have developed a sensitive electrochemiluminescence (ECL)-based immunoassay for measuring SMN protein in whole blood with a minimum volume requirement of 5μL. The SMN-ECL immunoassay enables accurate measurement of SMN in whole blood and other tissues. Using the assay, we measured SMN protein in whole blood from SMA patients and healthy controls and found that SMN protein levels were associated with SMN2 copy number and were greater in SMA patients with 4 copies, relative to those with 2 and 3 copies. SMN protein levels did not vary significantly in healthy individuals over a four-week period and were not affected by circadian rhythms. Almost half of the SMN protein was found in platelets. We show that SMN protein levels in C/C-allele mice, which model a mild form of SMA, were high in neonatal stage, decreased in the first few weeks after birth, and then remained stable throughout the adult stage. Importantly, SMN protein levels in the CNS correlated with SMN levels measured in whole blood of the C/C-allele mice. These findings have implications for the measurement of SMN protein induction in whole blood in response to SMN-upregulating therapy

Challenges in the Evaluation of Interventions to Improve Engagement Along the HIV Care Continuum in the United States: A Systematic Review.

In the United States (US), there are high levels of disengagement along the HIV care continuum. We sought to characterize the heterogeneity in research studies and interventions to improve care engagement among people living with diagnosed HIV infection. We performed a systematic literature search for interventions to improve HIV linkage to care, retention in care, reengagement in care and adherence to antiretroviral therapy (ART) in the US published from 2007-mid 2015. Study designs and outcomes were allowed to vary in included studies. We grouped interventions into categories, target populations, and whether results were significantly improved. We identified 152 studies, 7 (5%) linkage studies, 33 (22%) retention studies, 4 (3%) reengagement studies, and 117 (77%) adherence studies. 'Linkage' studies utilized 11 different outcome definitions, while 'retention' studies utilized 39, with very little consistency in effect measurements. The majority (59%) of studies reported significantly improved outcomes, but this proportion and corresponding effect sizes varied substantially across study categories. This review highlights a paucity of assessments of linkage and reengagement interventions; limited generalizability of results; and substantial heterogeneity in intervention types, outcome definitions, and effect measures. In order to make strides against the HIV epidemic in the US, care continuum research must be improved and benchmarked against an integrated, comprehensive framework

Experiences and lessons learned from the real-world implementation of an HIV recent infection testing algorithm in three routine service-delivery settings in Kenya and Zimbabwe.

INTRODUCTION: Testing for recent HIV infection can distinguish recently acquired infection from long-standing infections. Given current interest in the implementation of recent infection testing algorithms (RITA), we report our experiences in implementing a RITA in three pilot studies and highlight important issues to consider when conducting recency testing in routine settings. METHODS: We applied a RITA, incorporating a limited antigen (LAg) avidity assay, in different routine HIV service-delivery settings in 2018: antenatal care clinics in Siaya County, Kenya, HIV testing and counselling facilities in Nairobi, Kenya, and female sex workers clinics in Zimbabwe. Discussions were conducted with study coordinators, laboratory leads, and facility-based stakeholders to evaluate experiences and lessons learned in relation to implementing recency testing. RESULTS: In Siaya County 10/426 (2.3%) of women testing HIV positive were classified as recent, compared to 46/530 (8.7%) of women and men in Nairobi and 33/313 (10.5%) of female sex workers in Zimbabwe. Across the study setting, we observed differences in acceptance, transport and storage of dried blood spot (DBS) or venous blood samples. For example, the acceptance rate when testing venous blood was 11% lower than when using DBS. Integrating our study into existing services ensured a quick start of the study and kept the amount of additional resources required low. From a laboratory perspective, the LAg avidity assay was initially difficult to operationalise, but developing a network of laboratories and experts to work together helped to improve this. A challenge that was not overcome was the returning of RITA test results to clients. This was due to delays in laboratory testing, the need for multiple test results to satisfy the RITA, difficulties in aligning clinic visits, and participants opting not to return for test results. CONCLUSION: We completed three pilot studies using HIV recency testing based on a RITA in Kenya and Zimbabwe. The main lessons we learned were related to sample collection and handling, LAg avidity assay performance, integration into existing services and returning of test results to participants. Our real-world experience could provide helpful guidance to people currently working on the implementation of HIV recency testing in sub-Saharan Africa

Can HIV recent infection surveillance help us better understand where primary prevention efforts should be targeted? Results of three pilots integrating a recent infection testing algorithm into routine programme activities in Kenya and Zimbabwe.

INTRODUCTION: Surveillance of recent HIV infections in national testing services has the potential to inform primary prevention programming activities. Focusing on procedures required to accurately determine recent infection, and the potential for recent infection surveillance to inform prevention efforts, we present the results of three independent but linked pilots of recency testing. METHODS: To distinguish recently acquired HIV infection from long-standing infection, in 2018 we applied a Recent Infection Testing Algorithm that combined a laboratory-based Limiting Antigen Avidity Enzyme Immunoassay with clinical information (viral-load; history of prior HIV diagnosis; antiretroviral therapy-exposure). We explored potential misclassification of test results and analysed the characteristics of participants with recent infection. We applied the algorithm in antenatal clinics providing prevention of mother-to-child transmission services in Siaya County, Kenya, outreach sites serving female sex workers in Zimbabwe, and routine HIV testing and counselling facilities in Nairobi, Kenya. In Nairobi, we also conducted recency testing among partners of HIV-positive participants. RESULTS: In Siaya County, 2.3% (10/426) of HIV-positive pregnant women were classified as recent. A risk factor analysis comparing women testing recent with those testing HIV-negative found women in their first trimester were significantly more likely to test recent than those in their second or third trimester. In Zimbabwe, 10.5% (33/313) of female sex workers testing HIV-positive through the outreach programme were classified recent. A risk factor analysis of women testing recent versus those testing HIV-negative, found no strong evidence of an association with recent infection. In Nairobi, among 532 HIV-positive women and men, 8.6% (46) were classified recent. Among partners of participants, almost a quarter of those who tested HIV-positive were classified as recent (23.8%; 5/21). In all three settings, the inclusion of clinical information helped improve the positive predictive value of recent infection testing by removing cases that were likely misclassified. CONCLUSIONS: We successfully identified recently acquired infections among persons testing HIV-positive in routine testing settings and highlight the importance of incorporating additional information to accurately classify recent infection. We identified a number of groups with a significantly higher proportion of recent infection, suggesting recent infection surveillance, when rolled-out nationally, may help in further targeting primary prevention efforts

Comparison of programmatic data from antenatal clinics with population-based HIV prevalence estimates in the era of universal test and treat in western Kenya.

OBJECTIVE: To compare HIV prevalence estimates from routine programme data in antenatal care (ANC) clinics in western Kenya with HIV prevalence estimates in a general population sample in the era of universal test and treat (UTT). METHODS: The study was conducted in the area covered by the Siaya Health Demographic Surveillance System (Siaya HDSS) in western Kenya and used data from ANC clinics and the general population. ANC data (n = 1,724) were collected in 2018 from 13 clinics located within the HDSS. The general population was a random sample of women of reproductive age (15-49) who reside in the Siaya HDSS and participated in an HIV sero-prevalence survey in 2018 (n = 2,019). Total and age-specific HIV prevalence estimates were produced from both datasets and demographic decomposition methods were used to quantify the contribution of the differences in age distributions and age-specific HIV prevalence to the total HIV prevalence estimates. RESULTS: Total HIV prevalence was 18.0% (95% CI 16.3-19.9%) in the ANC population compared with 18.4% (95% CI 16.8-20.2%) in the general population sample. At most ages, HIV prevalence was higher in the ANC population than in the general population. The age distribution of the ANC population was younger than that of the general population, and because HIV prevalence increases with age, this reduced the total HIV prevalence among ANC attendees relative to prevalence standardised to the general population age distribution. CONCLUSION: In the era of UTT, total HIV prevalence among ANC attendees and the general population were comparable, but age-specific HIV prevalence was higher in the ANC population in most age groups. The expansion of treatment may have led to changes in both the fertility of women living with HIV and their use of ANC services, and our results lend support to the assertion that the relationship between ANC and general population HIV prevalence estimates are highly dynamic