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.

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.

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.

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.

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.

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.

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.].

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

OBJECTIVE: New guidelines recommend that all HIV-infected individuals initiate antiretroviral treatment (ART) immediately following diagnosis. This study describes how immune reconstitution varies by gender and age to help identify poorly reconstituting subgroups and inform targeted testing initiatives. DESIGN: Longitudinal data from the outpatient monitoring system of the National AIDS Control Program in Tanzania. METHODS: An asymptotic nonlinear mixed effects model was fit to post-treatment CD4+ cell count trajectories, allowing for fixed effects of age and sex, and an age by sex interaction. RESULTS: Across 220,544 clinic visits from 32,069 HIV-infected patients, age- and sex-specific average CD4+ cell count at ART initiation ranged from 83-136 cells/mm3, long term asymptotic CD4+ cell count ranged from 301-389 cells/mm3, and time to half of maximal CD4+ reconstitution ranged from 3.57-5.68 months. CD4+ cell count at ART initiation and asymptotic CD4+ cell count were 1.28 (95% CI: 1.18-1.40) and 1.25 (95% CI: 1.20-1.31) times higher, respectively, for females compared to males in the youngest age group (19-29 years). Older patients started treatment at higher CD4+ counts but experienced slower CD4+ recovery than younger adults. Treatment initiation at greater CD4+ cell counts was correlated with greater asymptotic CD4+ cell counts within all sex and age groups. CONCLUSION: Older adults should initiate care early in disease progression because total immune reconstitution potential and rate of reconstitution appears to decrease with age. Targeted HIV testing and care linkage remains crucial for patient populations who tend to initiate treatment at lower CD4+ cell counts, including males and younger adults.