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.

Population-level adult mortality following the expansion of antiretroviral therapy in Rakai, Uganda.

There are limited data on the impact of antiretroviral therapy (ART) on population-level adult mortality in sub-Saharan Africa. We analysed data for 2000-14 from the Rakai Community Cohort Study (RCCS) in Uganda, where free ART was scaled up after 2004. Using non-parametric and parametric (Weibull) survival analysis, we estimated trends in average person-years lived between exact ages 15 and 50, per capita life-years lost to HIV, and the mortality hazards of people living with HIV (PLHIV). Between 2000 and 2014, average adult life-years lived before age 50 increased significantly, from 26.4 to 33.5 years for all women and from 28.6 to 33.8 years for all men. As of 2014, life-years lost to HIV had declined significantly, to 1.3 years among women and 0.4 years among men. Following the roll-out of ART, mortality reductions among PLHIV were initially larger in women than men, but this is no longer the case.

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.

OBJECTIF: Le statut vital des patients perdus au suivi reste souvent inconnu dans les programmes de traitement antirétroviral (ART) en Afrique subsaharienne parce que les dossiers médicaux ne sont plus mis à jour une fois que le patient se désengage des soins. Notre objectif était d'évaluer les résultats des patients dans le nord-est de l'Afrique du Sud. MÉTHODES: A l'aide de données provenant d'une zone rurale du nord-est de l'Afrique du Sud, nous avons estimé l'incidence cumulée des résultats pour les patients (i) après le début du traitement à l'aide des dossiers cliniques et (ii) après la perte au suivi (PS) à l'aide des données des patients qui ont été reliées individuellement à la base de données du système de surveillance démographique et de santé (AHDSS) d'Agincourt. Outre les PS, nous avons pris en compte la mortalité, le réengagement et la migration hors du site de l'étude. La régression des risques proportionnels de Cox a été utilisée pour identifier les covariables de ces résultats pour le patient. RÉSULTATS: Entre avril 2014 et juillet 2017, 3.700 patients ont commencé l'ART constituant un suivi total de 6.818 années-personnes. Trois ans après le début de l'ART, les estimations des PS, de la mortalité et des transferts documentés selon les registres cliniques étaient de 41,0% (IC95%: 38,5% à 43,4%), 1,9% (IC95%: 1,0% à 3,2%) et 0,1% (IC95%: 0,0% -0,9%), respectivement. Parmi ceux qui étaient PS, l'incidence cumulative de réengagement, d'émigration et de mortalité à trois ans était de 38,1% (IC95%: 33,1% à 43,0%), 49,4% (IC95%: 43,1% à 55,3%) et 4,7% (IC95%: 3,5% -6,2%), respectivement. Les femmes enceintes ou allaitantes, les étrangers et les personnes qui ont commencé l'ART le plus récemment couraient un risque accru de PS. CONCLUSION: La PS chez les patients commençant une ART dans le nord-est de l'Afrique du Sud est relativement élevée et a augmenté ces dernières années à mesure que davantage de patients asymptomatiques ont commencé le traitement. Même si cette tendance est préoccupante à la lumière de la prévention de la transmission, nous avons également constaté que le réengagement dans les soins était courant et que la mortalité parmi les PS était relativement faible.

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.

The Epidemiologic and Economic Impact of Improving HIV Testing, Linkage, and Retention in Care in the United States.

BACKGROUND: Recent guidelines advocate early antiretroviral therapy (ART) to decrease human immunodeficiency virus (HIV) morbidity and prevent transmission, but suboptimal engagement in care may compromise impact. We sought to determine the economic and epidemiologic impact of incomplete engagement in HIV care in the United States. METHODS: We constructed a dynamic transmission model of HIV among US adults (aged 15-65 years) and conducted a cost-effectiveness analysis of improvements along the HIV care continuum : We evaluated enhanced HIV testing (annual for high-risk groups), increased 3-month linkage to care (to 90%), and improved retention (50% relative reduction in yearly disengagement and 50% increase in reengagement). Our primary outcomes were HIV incidence, mortality, costs and quality-adjusted life-years (QALYs). RESULTS: Despite early ART initiation, a projected 1.39 million (95% uncertainty range [UR], 0.91-2.2 million) new HIV infections will occur at a (discounted) cost of $256 billion ($199-298 billion) over 2 decades at existing levels of HIV care engagement. Enhanced testing with increased linkage has modest epidemiologic benefits and could reduce incident HIV infections by 21% (95% UR, 13%-26%) at a cost of $65 700 per QALY gained ($44 500-111 000). By contrast, comprehensive improvements that couples enhanced testing and linkage with improved retention would reduce HIV incidence by 54% (95% UR, 37%-68%) and mortality rate by 64% (46%-78%), at a cost-effectiveness ratio of $45 300 per QALY gained ($27 800-72 300). CONCLUSIONS: Failure to improve engagement in HIV care in the United States leads to excess infections, treatment costs, and deaths. Interventions that improve not just HIV screening but also retention in care are needed to optimize epidemiologic impact and cost-effectiveness.

Antiretroviral Treatment and Sexual Risk Behavior in South Africa.

The sexual behavior of individuals living with HIV determines the onward transmission of HIV. With the understanding that antiretroviral therapy (ART) prevents transmission of HIV, the sexual behaviors of the individuals not on ART with unsuppressed viral loads becomes of the greatest importance in elucidating transmission. We assessed the association between being on ART and sexual risk behavior among those living with HIV in a nationally representative population-based cross-sectional survey of households in South Africa that was conducted in 2012. Of 2237 adults (aged 15-49) who tested HIV-seropositive, 667 (29.8 %) had detectable antiretroviral drugs in their blood specimens. Among males, 77.7 % of those on ART reported having had sex in the past year contrasted with 88.4 % of those not on ART (p = 0.001); among females, 72.2 % of those on ART reported having had sex in the past year while 80.3 % of those not on ART did (p < 0.001). For males and females, the odds of reporting consistent condom use and condom use at last sex were statistically significantly higher for individuals on ART compared to those not on ART (males: consistent condom use aOR 2.8, 95 % CI 1.6-4.9, condom use at last sex aOR 2.6, 95 % CI 1.5-4.6; females: consistent condom use aOR 2.3, 95 % CI 1.7-3.1, condom use at last sex aOR 2.3, 95 % CI 1.7-3.1), while there were no statistically significant differences in odds of reporting multiple sexual partners in the past year. In this nationally representative population-based survey of South African adults, we found evidence of less risky sexual risk behavior among people living with HIV on ART compared to those not on ART.

Does marital status matter in an HIV hyperendemic country? Findings from the 2012 South African National HIV Prevalence, Incidence and Behaviour Survey.

South Africa has experienced declining marriage rates and the increasing practice of cohabitation without marriage. This study aims to improve the understanding of the relationship between marital status and HIV in South Africa, an HIV hyperendemic country, through an analysis of findings from the 2012 South African National HIV Prevalence, Incidence and Behaviour Survey. The nationally representative population-based cross-sectional survey collected data on HIV and socio-demographic and behavioural determinants in South Africa. This analysis considered respondents aged 16 years and older who consented to participate in the survey and provided dried blood spot specimens for HIV testing (N = 17,356). After controlling for age, race, having multiple sexual partners, condom use at last sex, urban/rural dwelling and level of household income, those who were married living with their spouse had significantly reduced odds of being HIV-positive compared to all other marital spouses groups. HIV incidence was 0.27% among respondents who were married living with their spouses; the highest HIV incidence was found in the cohabiting group (2.91%). Later marriage (after age 24) was associated with increased odds of HIV prevalence. Our analysis suggests an association between marital status and HIV prevalence and incidence in contemporary South Africa, where odds of being HIV-positive were found to be lower among married individuals who lived with their spouses compared to all other marital status groups. HIV prevention messages therefore need to be targeted to unmarried populations, especially cohabitating populations. As low socio-economic status, low social cohesion and the resulting destabilization of sexual relationships may explain the increased risk of HIV among unmarried populations, it is necessary to address structural issues including poverty that create an environment unfavourable to stable sexual relationships.

Individual, partner, and community variables associated with method-specific contraceptive beliefs in urban and rural Kenya.

OBJECTIVES: Global unmet need for contraception remains high. Contraceptive health-related beliefs are a barrier to contraceptive use but are poorly understood. This study examined quantitative differences in two health-related beliefs between pills, injectables, and implants. STUDY DESIGN: We used cross-sectional baseline data collected between August and December 2016 from Nairobi (urban) and Homa Bay (rural) Kenya among women aged 15 to 39 years (N = 5081). Dichotomous outcome variables were constructed for two health-related beliefs (infertility and serious health problems) for the three methods. Using a socioecological framework, possible risk factors at individual, relationship, and community levels were identified a priori. We used logistic regression to identify factors associated with method-specific beliefs. RESULTS: Roughly a quarter of participants believed the methods caused serious health problems, while a smaller overall proportion believed the methods caused infertility. Risk factors patterned similarly across methods but differed between beliefs. In adjusted models, perceived partner approval of a method was associated with lower odds of believing it caused infertility or serious health problems. Unsatisfactory or mixed social network experiences predicted serious health problems but not infertility beliefs. Current use was associated with lower odds of believing all three methods caused serious health problems, but only implant users were more likely to believe they caused infertility. Past use was associated with higher odds of serious health problems but not infertility beliefs. CONCLUSIONS: Across three methods, negative community and perceived partner attitudes toward specific contraceptive methods were associated with higher individual-level odds of contraceptive health beliefs in Kenya. IMPLICATIONS: Efforts to support women who want to use contraception should focus on providing information on contraceptive health and fertility concerns, ideally targeting partners and women of all ages in addition to potential contraceptive users. It is reasonable to address these concerns broadly across commonly used contraceptive methods.

Effects of ACE inhibitor/ARB therapy and long COVID on kidney disease: a retrospective cohort study using real-world data.

Background: The association between angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and severe acute respiratory syndrome coronavirus 2 susceptibility, particularly via ACE-2 receptor upregulation in the kidneys, raises concerns about potential kidney disease risks in long coronavirus disease (COVID) patients. This study explores the association of ACEI/ARB therapy on acute kidney injury (AKI), chronic kidney disease (CKD) and all-cause mortality in patients with and without long COVID. Methods: A retrospective cohort study using TriNetX datasets was conducted, with diagnoses of long COVID via International Classification of Diseases, Tenth Revision (ICD-10) codes and prescription for ACEI/ARB as the classification of four cohorts: long COVID ACEI/ARB users (LCAUs), long COVID ACEI/ARB non-users (LCANs), non-long COVID ACEI/ARB users (NLCAUs) and non-long COVID ACEI/ARB non-users (NLCANs). Multivariable stratified Cox proportional hazards regression models assessed the adjusted hazard ratios (aHRs) across groups. Additional analyses were conducted, including time-dependent exposure analysis and comparison with an active comparator, calcium channel blockers. Results: Our study included 18 168 long COVID and 181 680 propensity score-matched non-long COVID patients from October 2021 to October 2023. ACEI/ARB use did not significantly affect the risk of AKI or CKD when comparing LCAUs with LCANs and NLCAUs with NLCANs. However, a protective effect against all-cause mortality was observed {aHR 0.79 [95% confidence interval (CI) 0.65-0.93]} in the NLCAU group compared with the NLCAN group. Conversely, long COVID was associated with increased risks of CKD [aHR 1.49 (95% CI 1.03-2.14)] and all-cause mortality [aHR 1.49 (95% CI 1.00-2.23)] when comparing LCANs with NLCANs. The additional analyses support the primary findings. Conclusions: ACEI/ARB treatment does not increase the incidence of CKD or AKI, regardless of long COVID status. However, long COVID itself is associated with increasing risks of kidney diseases and all-cause mortality.

Substance use and variation in sexual partnership rates among young MSM and young transgender women: Disaggregating between and within-person associations.

BACKGROUND: Substance use has been extensively linked to sexual behavior and HIV/STI risk among men who have sex with men (MSM) and transgender women (TW). However, the impact of specific substances and on specific partnership types is not well characterized. The current study seeks to estimate the association between specific substances and partnership rates while carefully disaggregating between and within-person associations to characterize the nature of these associations and inform prevention interventions. METHODS: Using data from a longitudinal cohort (n = 1159) of young MSM (YMSM) and young TW (YTW), we utilized a series of hybrid mixed effect models to estimate the associations between substance use (i.e., heavy episodic drinking [HED], marijuana, cocaine, ecstasy, methamphetamine, poppers, prescription stimulant, prescription painkiller, and prescription depressants) and partnerships (i.e., one-time, casual, and main). RESULTS: Results from multivariable models indicated people using substances had higher one-time (HED, poppers) and casual (HED, methamphetamine, poppers) partnership rates. In addition, participants reported higher rates of one-time (HED, ecstasy, methamphetamine, poppers) and casual partners (HED, marijuana, cocaine, methamphetamines, poppers) during periods of substance use. CONCLUSION: These findings confirm that the highest rates of sexual activity occur among YMSM-YTW using substances during periods of substance use. Yet, these findings should caution researchers against simplistic generalizations as these associations differ across substance and partnership types. Efforts to promote the health of MSM-YTW who use substances should carefully consider this complexity as interventions accounting for the unique cultural context of substance use in these populations are most likely to be successful.

Partnership types and coital frequency as predictors of gonorrhea and chlamydia among young MSM and young transgender women.

BACKGROUND: Sexually transmitted infections pose a major public health challenge in the United States and this burden is especially acute in subpopulations like young men who have sex with men (YMSM) and young transgender women (YTW). Yet, the direct behavioral antecedents of these infections are not well understood making it difficult to identify the cause of recent increases in incidence. This study examines how variations in partnership rates and the number of condomless sex acts are associated with STI infections among YMSM-YTW. METHOD: This study leveraged 3 years of data from a large longitudinal cohort of YMSM-YTW. A series of generalized linear mixed models examined the association between the number of condomless anal sex acts, number of one-time partners, number of casual partners, and number of main partners and chlamydia, gonorrhea, or any STI. RESULTS: Results indicated the number of casual partners was associated with gonorrhea [aOR = 1.17 (95% CI: 1.08, 1.26)], chlamydia [aOR = 1.12 (95% CI: 1.05, 1.20)], and any STI [aOR = 1.14 (95% CI: 1.08, 1.21)] while the number of one-time partners was only associated with gonorrhea [aOR = 1.13 (95% CI: 1.02, 1.26)]. The number of condomless anal sex acts was not associated with any outcome. CONCLUSION: These findings suggest the number of casual partners is a consistent predictor of STI infection among YMSM-YTW. This may reflect the quick saturation of risk within partnerships making the number of partners, rather than the number of acts, the more relevant factor for STI risk.

Spatio-temporal estimates of HIV risk group proportions for adolescent girls and young women across 13 priority countries in sub-Saharan Africa.

The Global AIDS Strategy 2021-2026 identifies adolescent girls and young women (AGYW) as a priority population for HIV prevention, and recommends differentiating intervention portfolios geographically based on local HIV incidence and individual risk behaviours. We estimated prevalence of HIV risk behaviours and associated HIV incidence at health district level among AGYW living in 13 countries in sub-Saharan Africa. We analysed 46 geospatially-referenced national household surveys conducted between 1999-2018 across 13 high HIV burden countries in sub-Saharan Africa. Female survey respondents aged 15-29 years were classified into four risk groups (not sexually active, cohabiting, non-regular or multiple partner[s] and female sex workers [FSW]) based on reported sexual behaviour. We used a Bayesian spatio-temporal multinomial regression model to estimate the proportion of AGYW in each risk group stratified by district, year, and five-year age group. Using subnational estimates of HIV prevalence and incidence produced by countries with support from UNAIDS, we estimated new HIV infections in each risk group by district and age group. We then assessed the efficiency of prioritising interventions according to risk group. Data consisted of 274,970 female survey respondents aged 15-29. Among women aged 20-29, cohabiting (63.1%) was more common in eastern Africa than non-regular or multiple partner(s) (21.3%), while in southern countries non-regular or multiple partner(s) (58.9%) were more common than cohabiting (23.4%). Risk group proportions varied substantially across age groups (65.9% of total variation explained), countries (20.9%), and between districts within each country (11.3%), but changed little over time (0.9%). Prioritisation based on behavioural risk, in combination with location- and age-based prioritisation, reduced the proportion of population required to be reached in order to find half of all expected new infections from 19.4% to 10.6%. FSW were 1.3% of the population but 10.6% of all expected new infections. Our risk group estimates provide data for HIV programmes to set targets and implement differentiated prevention strategies outlined in the Global AIDS Strategy. Successfully implementing this approach would result in more efficiently reaching substantially more of those at risk for infections.

Human Immunodeficiency Virus (HIV) Treatment With Antiretroviral Therapy Mitigates the High Risk of Mental Health Disorders Associated With HIV Infection in the US Population.

Background: Whether treatment of human immunodeficiency virus (HIV) with antiretroviral therapy (ART) is associated with lower risk of mental health disorders (MHDs) among people with HIV (PWH) remains unknown. We aim to determine the association between HIV and MHDs and whether ART alters the risk of MHDs among PWH in the US adult population. Methods: We conducted a real-world study using the Merative MarketScan claims database (2016-2020), identifying individuals with HIV (diagnosed using International Classification of Diseases, Tenth Revision, Clinical Modification codes) and those without HIV. A multivariable stratified Cox proportional hazard regression model was conducted to examine the association of HIV treatment status with MHDs, adjusting for potential confounders. Additionally, we sought to determine the effect modification of ART on the relationship between living with HIV and MHDs. Results: A total of 313 539 individuals, with a mean age of 44.2 (standard deviation, 11.4) years, predominantly males (81.2%), residing in the South region of the US (50.9%) were included in the present analysis. During 671 880 person-years of follow-up, 46 235 incident MHD cases occurred. In the multivariable Cox proportional hazard model, living with HIV was associated with higher risk of incident MHDs. Relative to those without HIV, the adjusted hazard ratio was 1.85 (95% confidence interval [CI], 1.79-1.92; P < .001) for those with HIV on treatment, and 2.70 (95% CI, 2.59-2.82; P < .001) for those with HIV without any treatment. Stronger associations between HIV and MHDs were observed in men relative to women, among those aged 18-34 years relative to those aged 55-63 years, and among those with no overweight/obesity relative to obese individuals (Pinteraction < .001 for all). Conclusions: HIV was associated with an increased risk of developing MHDs. However, HIV treatment mitigated the risk.

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.

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.

Evaluating distributional regression strategies for modelling self-reported sexual age-mixing.

The age dynamics of sexual partnership formation determine patterns of sexually transmitted disease transmission and have long been a focus of researchers studying human immunodeficiency virus. Data on self-reported sexual partner age distributions are available from a variety of sources. We sought to explore statistical models that accurately predict the distribution of sexual partner ages over age and sex. We identified which probability distributions and outcome specifications best captured variation in partner age and quantified the benefits of modelling these data using distributional regression. We found that distributional regression with a sinh-arcsinh distribution replicated observed partner age distributions most accurately across three geographically diverse data sets. This framework can be extended with well-known hierarchical modelling tools and can help improve estimates of sexual age-mixing dynamics.

Age patterns of HIV incidence in eastern and southern Africa: a modelling analysis of observational population-based cohort studies.

BACKGROUND: As the HIV epidemic in sub-Saharan Africa matures, evidence about the age distribution of new HIV infections and how this distribution has changed over the epidemic is needed to guide HIV prevention. We aimed to assess trends in age-specific HIV incidence in six population-based cohort studies in eastern and southern Africa, reporting changes in mean age at infection, age distribution of new infections, and birth cohort cumulative incidence. METHODS: We used a Bayesian model to reconstruct age-specific HIV incidence from repeated observations of individuals' HIV serostatus and survival collected among population HIV cohorts in rural Malawi, South Africa, Tanzania, Uganda, and Zimbabwe, in a collaborative analysis of the ALPHA network. We modelled HIV incidence rates by age, time, and sex using smoothing splines functions. We estimated incidence trends separately by sex and study. We used estimated incidence and prevalence results for 2000-17, standardised to study population distribution, to estimate mean age at infection and proportion of new infections by age. We also estimated cumulative incidence (lifetime risk of infection) by birth cohort. FINDINGS: Age-specific incidence declined at all ages, although the timing and pattern of decline varied by study. The mean age at infection was higher in men (cohort mean 27·8-34·6 years) than in women (24·8-29·6 years). Between 2000 and 2017, the mean age at infection per cohort increased slightly: 0·5 to 2·8 years among men and -0·2 to 2·5 years among women. Across studies, between 38% and 63% (cohort medians) of the infections in women were among those aged 15-24 years and between 30% and 63% of infections in men were in those aged 20-29 years. Lifetime risk of HIV declined for successive birth cohorts. INTERPRETATION: HIV incidence declined in all age groups and shifted slightly to older ages. Disproportionate new HIV infections occur among women aged 15-24 years and men aged 20-29 years, supporting focused prevention in these groups. However, 40-60% of infections were outside these ages, emphasising the importance of providing appropriate HIV prevention to adults of all ages. FUNDING: Bill & Melinda Gates Foundation.

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.

Correction: Impact of Age and Sex on CD4+ Cell Count Trajectories following Treatment Initiation: An Analysis of the Tanzanian HIV Treatment Database.

[This corrects the article DOI: 10.1371/journal.pone.0164148.].