Safety and Immunogenicity of Accelerated Heterologous Two-dose Ebola Vaccine Regimens in Adults With and Without HIV in Africa.

BACKGROUND: Shorter prophylactic vaccine schedules may offer more rapid protection against Ebola in resource-limited settings. METHODS: This randomized, observer-blind, placebo-controlled, phase 2 trial conducted in five sub-Saharan African countries included people without HIV (PWOH, n = 249) and people living with HIV (PLWH, n = 250). Adult participants received one of two accelerated Ebola vaccine regimens (MVA-BN-Filo, Ad26.ZEBOV administered 14 days apart [n = 79] or Ad26.ZEBOV, MVA-BN-Filo administered 28 days apart [n = 322]) or saline/placebo (n = 98). The primary endpoints were safety (adverse events [AEs]) and immunogenicity (Ebola virus [EBOV] glycoprotein-specific binding antibody responses). Binding antibody responders were defined as participants with a > 2.5-fold increase from baseline or the lower limit of quantification if negative at baseline. RESULTS: The mean age was 33.4 years, 52% of participants were female, and among PLWH, the median (interquartile range) CD4+ cell count was 560.0 (418.0-752.0) cells/µL. AEs were generally mild/moderate with no vaccine-related serious AEs or remarkable safety profile differences by HIV status. At 21 days post-dose 2, EBOV glycoprotein-specific binding antibody response rates in vaccine recipients were 99% for the 14-day regimen (geometric mean concentrations [GMCs]: 5168 enzyme-linked immunosorbent assay units (EU)/mL in PWOH; 2509 EU/mL in PLWH), and 98% for the 28-day regimen (GMCs: 6037 EU/mL in PWOH; 2939 EU/mL in PLWH). At 12 months post-dose 2, GMCs in PWOH and PLWH were 635 and 514 EU/mL, respectively, for the 14-day regimen and 331 and 360 EU/mL, respectively, for the 28-day regimen. CONCLUSIONS: Accelerated 14- and 28-day Ebola vaccine regimens were safe and immunogenic in PWOH and PLWH in Africa. TRIAL REGISTRATION: NCT02598388.

Perinatal Depressive Symptoms and Viral Non-suppression Among a Prospective Cohort of Pregnant Women Living with HIV in Nigeria, Kenya, Uganda, and Tanzania.

Depression is common during pregnancy and is associated with reduced adherence to HIV-related care, though little is known about perinatal trajectories of depression and viral suppression among women living with HIV (WLHV) in sub-Saharan Africa. We sought to assess any association between perinatal depressive symptoms and viral non-suppression among WLWH. Depressive symptomatology and viral load data were collected every 6 months from WLWH enrolled in the African Cohort Study (AFRICOS; January 2013-February 2020). Generalized estimating equations modeled associations between depressive symptoms [Center for Epidemiological Studies Depression (CES-D) ≥ 16] and viral non-suppression. Of 1722 WLWH, 248 (14.4%) had at least one pregnancy (291 total) and for 61 pregnancies (21.0%), women reported depressive symptoms (13.4% pre-conception, 7.6% pregnancy, 5.5% one-year postpartum). Depressive symptomatology was associated with increased odds of viral non-suppression (aOR 2.2; 95% CI 1.2-4.0, p = 0.011). Identification and treatment of depression among women with HIV may improve HIV outcomes for mothers.

Early sexual debut is associated with drug use and decreased educational attainment among males and females in Kisumu County, Kenya.

Differing global sociocultural contexts of sexual relationships influence age at first sexual intercourse with potentially long-lasting region-specific effects such as increased risk of contracting HIV and other sexually transmitted infections (STIs). In these cross-sectional analyses of data from the screening and enrollment visits for an HIV incidence study in Kisumu County, Kenya, we evaluated factors associated with having experienced an early sexual debut (ESD) among males and females aged 18-35 years. Clinical evaluation was performed and sexual behaviors were assessed via questionnaire. ESD was defined as self-reported age 15 years or younger at first sexual intercourse. Robust Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (95% CIs) for factors associated with ESD. Of 1057 participants, 542 (51.3%) were female. Participants' median age at study screening was 25 years (interquartile range [IQR]: 22-29), and at sexual debut was 16 years (IQR: 14-17). Five hundred and four participants (47.7%) reported ESD. ESD was less common among females (PR 0.78, CI 0.67-0.90) and participants with more than primary education (PR 0.56, CI 0.47-0.66). ESD was more common in participants with a history of drug use (PR 1.28, CI 1.10-1.49). Drug use removed the protective effect of education (some secondary education or less, no drug use: PR 0.72, CI 0.61-0.85; some secondary education or less, drug use: PR 0.94, CI 0.74-1.18). ESD was common in our study and associated with lower educational attainment and increased likelihood of drug use. Interventions are needed early in life, well before 15 years of age, to encourage engagement in schooling and prevent drug use. Comprehensive sexual education and interventions to prevent drug use may be beneficial before the age of 15 years.

Early sexual debut can be defined as first sexual intercourse at or before 15 years of age. There are many social and cultural factors that influence the age of sexual debut. People who start having sex early in life may exhibit behaviors that increase risk for HIV and other sexually transmitted infections. We conducted a study of men and women aged 18­35 years in Kisumu County, Kenya, which included documentation of medical history, physical examination, laboratory tests, and a questionnaire to assess sexual behaviors. Among the 1057 people studied, the average age of sexual debut was 16.0 years for females and 15.4 years for males. A total of 504 (47.7%) participants reported early sexual debut. The data showed that early sexual debut was less common in females and in participants with more years of education. Early sexual debut was more common in participants with a history of drug use. The findings suggest that interventions to prevent early sexual debut might be improved if they focus on educational attainment and prevention of drug use.

Transitioning women to first-line preferred TLD regimen is lagging in Sub-Saharan Africa.

INTRODUCTION: In 2019, the World Health Organization (WHO) recommended tenofovir disoproxil fumarate-lamivudine-dolutegravir (TLD) as the preferred first line regimen for adults and adolescents regardless of childbearing status. Nevertheless, final eligibility is determined by local policies which may vary from WHO recommendations. We examined TLD transition by gender across five PEPFAR-supported HIV care programs in sub-Saharan Africa. METHODS: The African Cohort Study (AFRICOS) enrolls people living with HIV (PLWH) engaged in care in Uganda, Kenya (South Rift Valley and Kisumu West), Tanzania and Nigeria. PLWH with at least one study visit after the country introduced TLD were included. We generated Kaplan-Meier (KM) curves to compare TLD transition by gender from 1) time countries' introduction of TLD and 2) time of TLD eligibility according to local policies. RESULTS: Among 2.476 participants enrolled through September 2021 at 4 sites in sub-Saharan Africa and eligible to transition to TLD, fewer women (68%) compared to men (80%, p < 0.001) were taking TLD. Kaplan-Meier analysis showed time to transition varied by site, with women in Tanzania transitioning at the same rate as men. In Nigeria, women initially had a slower transition but caught up to men. After adjusting for local policies, women[1] in Kisumu West transitioned at the same rate as men. In South Rift Valley and Uganda, women were less likely to be transitioned. CONCLUSIONS: Despite TLD being the WHO's preferred regimen since 2019, transition of women to potentially lifesaving TLD has been slower than men at certain clinical sites even after accounting for local eligibility criteria.

Predictors of All-Cause Mortality Among People With Human Immunodeficiency Virus (HIV) in a Prospective Cohort Study in East Africa and Nigeria.

BACKGROUND: Introduction of antiretroviral therapy (ART) has been associated with a decline in human immunodeficiency virus (HIV)-related mortality, although HIV remains a leading cause of death in sub-Saharan Africa. We describe all-cause mortality and its predictors in people living with HIV (PLWH) in the African Cohort Study (AFRICOS). METHODS: AFRICOS enrolls participants with or without HIV at 12 sites in Kenya, Uganda, Tanzania, and Nigeria. Evaluations every 6 months include sociobehavioral questionnaires, medical history, physical examination, and laboratory tests. Mortality data are collected from medical records and survivor interviews. Multivariable Cox proportional hazards models were used to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for factors associated with mortality. RESULTS: From 2013 through 2020, 2724 PLWH completed at least 1 follow-up visit or experienced death. Of these 58.4% were females, 25.8% were aged ≥ 50 years, and 98.3% were ART-experienced. We observed 11.42 deaths per 1000 person-years (95% CI: 9.53-13.68) with causes ascertained in 54% of participants. Deaths were caused by malignancy (28.1%), infections (29.7%), and other non-HIV related conditions. Predictors of mortality included CD4 ≤ 350 cells/µL (aHR 2.01 [95% CI: 1.31-3.08]), a log10copies/mL increase of viral load (aHR 1.36 [95% CI: 1.22-1.51]), recent fever (aHR 1.85[95% CI: 1.22-2.81]), body mass index < 18.5 kg/m2 (aHR 2.20 [95% CI: 1.44-3.38]), clinical depression (aHR 2.42 [95% CI: 1.40-4.18]), World Health Organization (WHO) stage III (aHR 2.18 [95% CI: 1.31-3.61]), a g/dL increase in hemoglobin (aHR 0.79 [95% CI: .72-.85]), and every year on ART (aHR 0.67 [95% CI: .56-.81]). CONCLUSIONS: The mortality rate was low in this cohort of mostly virally suppressed PLWH. Patterns of deaths and identified predictors suggest multiple targets for interventions to reduce mortality.

Helios expressing regulatory T cells are correlated with decreased IL-2 producing CD8 T cells and antibody diversity in Mozambican individuals living chronically with HIV-1.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) causes impairment of T and B cell responses, which begins during the acute phase of infection and is not completely restored by antiretroviral treatment. Regulatory T cell (Tregs) can improve overall disease outcome by controlling chronic inflammation but may also suppress beneficial HIV-1 specific immune responses. We aimed to analyze the profile of Tregs and their correlation with the status of T cells activation, the expression of IL-2 and IFNγ and the profile of HIV-1 specific antibodies response in Mozambican people living chronically with HIV-1 (PLWH-C). RESULTS: In PLWH-C, the proportion of total Tregs was positively correlated with the proportion of IL-2+CD4 T cells (r = 0.647; p = 0.032) and IL-2+IFNγ+CD8 T cells (r = 0.551; p = 0.014), while the proportions of Helios+Tregs correlated inversely with levels of IL-2+CD8 T cells (r = - 0.541; p = 0.017). Overall, PLWH-C, with (82%) or without virologic suppression (64%), were seronegative for at least HIV-1 p31, gp160 or p24, and the breadth of antibody responses was positively correlated with proportions of CD38+HLA-DR+CD8 T cells (r = 0.620; p = 0.012), viral load (r = 0.452; p = 0.040) and inversely with absolute CD4 T cells count (r = - 0.481; p = 0.027). Analysis of all individuals living HIV-1 showed that the breadth of HIV-1 antibody responses was inversely correlated with the proportion of Helios+Tregs (r = - 0.45; p = 0.02). CONCLUSION: Among Mozambican people living with HIV-1, seronegativity to some HIV-1 proteins is common, particularly in virologically suppressed individuals. Furthermore, lower diversity of HIV-specific antibodies is correlated to lower immune activation, lower viral replication and higher CD4 counts, in PLWH-C. Elevation in the proportion of Helios+Tregs is related to a reduction of CD8 T expressing intracellular IL-2, in PLWH-C, but may contribute to impairment of B cell function.

Temporal trends in self-reported HIV stigma and association with adherence and viral suppression in the African Cohort Study.

HIV stigma is a major barrier to HIV care and treatment among people living with HIV (PLWH). Evidence suggests that expansion in antiretroviral therapy (ART) may reduce stigma. However, there are limited longitudinal studies examining temporal trends in HIV stigma in sub-Saharan Africa in the Undetectable = Untransmittable (U = U) era. We longitudinally assessed temporal trends in self-reported experienced stigma and the association of experienced stigma with ART adherence and viral suppression among PLWH enrolled in the African Cohort Study (AFRICOS). AFRICOS is an ongoing cohort study enrolling PLWH in Uganda, Kenya, Tanzania, and Nigeria. As of 1 March 2020, 2937 PLWH enrolled in AFRICOS and had available data. In 2013, 22% of participants reported stigma at the enrollment visit and by 2018 the prevalence decreased to 1% overall and was below 2% for all countries. However, there was not a statistically significant change in stigma prevalence in our longitudinal models. In adjusted models, experiencing stigma was associated with a 0.67 decreased odds of ART Adherence (95% confidence interval (CI): 0.56-0.80) and a 0.64 decreased odds of viral suppression (95% CI: 0.73-0.99). HIV-associated stigma was associated with poor self-reported ART adherence and unsuppressed viral load.

Prevalence and predictors of food insecurity among people living with and without HIV in the African Cohort Study.

OBJECTIVE: We determined the prevalence and identified predictors of food insecurity in four African countries. DESIGN: Cross-sectional analyses at study enrolment. SETTING: From January 2013 to March 2020, people living with HIV (PLWH) and without HIV were enrolled at twelve clinics in Kenya, Uganda, Tanzania and Nigeria. PARTICIPANTS: Participants reporting not having enough food to eat over the past 12 months or receiving <3 meals/d were defined as food insecure. Robust Poisson regression models were used to estimate unadjusted and adjusted prevalence ratios (aPR) and 95 % CI for predictors of food insecurity among all participants and separately among PLWH. RESULTS: 1694/3496 participants (48·5 %) reported food insecurity at enrolment, with no difference by HIV status. Food insecurity was more common among older participants (50+ v. 18-24 years aPR 1·35, 95 % CI 1·15, 1·59). Having 2-5 (aPR 1·14, 95 % CI 1·01, 1·30) or >5 dependents (aPR 1·17, 95 % CI 1·02, 1·35), and residing in Kisumu West, Kenya (aPR 1·63, 95 % CI 1·42, 1·87) or Nigeria (aPR 1·20, 95 % CI 1·01, 1·41) was associated with food insecurity. Residing in Tanzania (aPR 0·65, 95 % CI 0·53, 0·80) and increasing education (secondary/above education v. none/some primary education aPR 0·73, 95 % CI 0·66, 0·81) was protective against food insecurity. Antiretroviral therapy (ART)-experienced PLWH were more likely to be food secure irrespective of viral load. CONCLUSION: Food insecurity was highly prevalent in our cohort though not significantly associated with HIV. Policies aimed at promoting education, elderly care, ART access in PLWH and financial independence could potentially improve food security in Africa.

Routine HIV clinic visit adherence in the African Cohort Study.

BACKGROUND: Retention in clinical care is important for people living with HIV (PLWH). Evidence suggests that missed clinic visits are associated with interruptions in antiretroviral therapy (ART), lower CD4 counts, virologic failure, and overlooked coinfections. We identified factors associated with missed routine clinic visits in the African Cohort Study (AFRICOS). METHODS: In 2013, AFRICOS began enrolling people with and without HIV in Uganda, Kenya, Tanzania, and Nigeria. At enrollment and every 6 months thereafter, sociodemographic questionnaires are administered and clinical outcomes assessed. Missed clinic visits were measured as the self-reported number of clinic visits missed in the past 6 months and dichotomized into none or one or more visits missed. Logistic regression with generalized estimating equations was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between risk factors and missed visits. RESULTS: Between January 2013 and March 2020, 2937 PLWH were enrolled, of whom 2807 (95.6%) had initiated ART and 2771 had complete data available for analyses. Compared to PLWH 50+, missed clinic visits were more common among those 18-29 years (aOR 2.33, 95% CI 1.65-3.29), 30-39 years (aOR 1.59, 95% CI 1.19-2.13), and 40-49 years (aOR 1.42, 95% CI 1.07-1.89). As compared to PLWH on ART for < 2 years, those on ART for 4+ years were less likely to have missed clinic visits (aOR 0.72, 95% CI 0.55-0.95). Missed clinic visits were associated with alcohol use (aOR 1.34, 95% CI 1.05-1.70), a history of incarceration (aOR 1.42, 95% CI 1.07-1.88), depression (aOR 1.47, 95% CI 1.13-1.91), and viral non-suppression (aOR 2.50, 95% CI 2.00-3.12). As compared to PLWH who did not miss any ART in the past month, missed clinic visits were more common among those who missed 1-2 days (aOR 2.09, 95% CI 1.65-2.64) and 3+ days of ART (aOR 7.06, 95% CI 5.43-9.19). CONCLUSIONS: Inconsistent clinic attendance is associated with worsened HIV-related outcomes. Strategies to improve visit adherence are especially needed for young PLWH and those with depression.

Transient Reductions in Human Immunodeficiency Virus (HIV) Clinic Attendance and Food Security During the Coronavirus Disease 2019 (COVID-19) Pandemic for People Living With HIV in 4 African Countries.

The coronavirus disease 2019 (COVID-19) pandemic and associated public health responses have disrupted daily living activities with economic and health consequences globally. We observed transient decreases in human immunodeficiency virus (HIV) clinic visit adherence and food security among persons living with HIV early in the pandemic, and an increase in viral suppression later in the pandemic.

Pretreatment and Acquired Antiretroviral Drug Resistance Among Persons Living With HIV in Four African Countries.

BACKGROUND: Emerging HIV drug resistance (HIVDR) could jeopardize the success of standardized HIV management protocols in resource-limited settings. We characterized HIVDR among antiretroviral therapy (ART)-naive and experienced participants in the African Cohort Study (AFRICOS). METHODS: From January 2013 to April 2019, adults with HIV-1 RNA >1000 copies/mL underwent ART history review and HIVDR testing upon enrollment at 12 clinics in Uganda, Kenya, Tanzania, and Nigeria. We calculated resistance scores for specific drugs and tallied major mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) using Stanford HIVDB 8.8 and SmartGene IDNS software. For ART-naive participants, World Health Organization surveillance drug resistance mutations (SDRMs) were noted. RESULTS: HIVDR testing was performed on 972 participants with median age 35.7 (interquartile range [IQR] 29.7-42.7) years and median CD4 295 (IQR 148-478) cells/mm3. Among 801 ART-naive participants, the prevalence of SDRMs was 11.0%, NNRTI mutations 8.2%, NRTI mutations 4.7%, and PI mutations 0.4%. Among 171 viremic ART-experienced participants, NNRTI mutation prevalence was 83.6%, NRTI 67.8%, and PI 1.8%. There were 90 ART-experienced participants with resistance to both efavirenz and lamivudine, 33 (36.7%) of whom were still prescribed these drugs. There were 10 with resistance to both tenofovir and lamivudine, 8 (80.0%) of whom were prescribed these drugs. CONCLUSIONS: Participants on failing ART regimens had a high burden of HIVDR that potentially limited the efficacy of standardized first- and second-line regimens. Management strategies that emphasize adherence counseling while delaying ART switch may promote drug resistance and should be reconsidered.

Prevalence and risk factors associated with HIV and syphilis co-infection in the African Cohort Study: a cross-sectional study.

BACKGROUND: Each year, 5.6 million new syphilis cases are diagnosed globally. Guidelines for people living with HIV (PLWH) in low-income countries (LIC) recommend STI testing for symptomatic persons and those newly diagnosed with HIV; routine STI testing is less clear. Here we provide updated syphilis prevalence and identify co-infection risk factors in PLWH in the African Cohort Study (AFRICOS) to understand these rates as they relate to syndromic treatment. METHODS: AFRICOS is a study enrolling PLWH and HIV-uninfected individuals in four African countries. Participant study enrollment information was used to determine syphilis prevalence and co-infection risk factors. Inclusion criteria consisted of adults 18 years or older receiving care at a participating clinic as a long-term resident who consented to data and specimen collection. Exclusion criteria consisted of pregnancy and/or imprisonment. Screen-positive syphilis was defined as a reactive rapid plasma regain (RPR) upon study enrollment whereas confirmed syphilis included a reactive RPR followed by reactive treponemal test. Multivariate analyses was performed to determine HIV and syphilis co-infection risk factors. RESULTS: Between 2013 and March 1, 2020, 2939 PLWH enrolled and 2818 were included for analysis. Screen-positive and confirmed syphilis prevalence were 5.3% (151/2818) and 3.1% (87/2818), respectively. When the analysis was restricted to PLWH with an RPR titer of greater than, or equal to, 1:8, 11/87 (12.6%) participants were included. No PLWH and confirmed syphilis had documented genital ulcers. In the multivariate model, participants with confirmed syphilis co-infection were more likely to have none or some primary education [aOR 3.29 (1.60, 6.74)] and consume alcohol [aOR 1.87 (1.16, 3.03)] compared to those without syphilis. Antiretroviral therapy (ART) with suppressed viral load (VL) was protective in the unadjusted model but not adjusted multivariate model. CONCLUSIONS: Our findings show that syphilis rates in sub-Saharan Africa remain elevated where diagnosis remains challenging, and that both lower education level and alcohol consumption are significantly associated with HIV/syphilis co-infection in AFRICOS. Based on our analysis, current STI guidelines targeting testing for African individuals with either new HIV diagnosis or syndromic symptoms may be inadequate, highlighting the need for increased testing and treatment strategies in resource-limited settings.

Assessing the impact of HIV support groups on antiretroviral therapy adherence and viral suppression in the African cohort study.

BACKGROUND: Support groups for people living with HIV (PLWH) may improve HIV care adherence and outcomes. We assessed the impact of support group attendance on antiretroviral therapy (ART) adherence and viral suppression in four African countries. METHODS: The ongoing African Cohort Study (AFRICOS) enrolls participants at 12 clinics in Kenya, Uganda, Tanzania, and Nigeria. Self-reported attendance of any support group meetings, self-reported ART adherence, and HIV RNA are assessed every 6 months. Logistic regression models with generalized estimating equations were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) for support group attendance and other factors potentially associated with ART adherence and viral suppression. RESULTS: From January 2013 to December 1, 2019, 1959 ART-experienced PLWH were enrolled and 320 (16.3%) reported any support group attendance prior to enrollment. Complete ART adherence, with no missed doses in the last 30 days, was reported by 87.8% while 92.4% had viral suppression <1000copies/mL across all available visits. There was no association between support group attendance and ART adherence in unadjusted (OR 1.01, 95% CI 0.99-1.03) or adjusted analyses (aOR 1.00, 95% CI 0.98-1.02). Compared to PLWH who did not report support group attendance, those who did had similar odds of viral suppression in unadjusted (OR 0.99, 95% CI 0.978-1.01) and adjusted analyses (aOR 0.99, 95% CI 0.97-1.01). CONCLUSION: Support group attendance was not associated with significantly improved ART adherence or viral suppression, although low support group uptake may have limited our ability to detect a statistically significant impact.

Epidemiological and clinical implications of asymptomatic malaria and schistosomiasis co-infections in a rural community in western Kenya.

BACKGROUND: Malaria and schistosomiasis present considerable disease burden in tropical and sub-tropical areas and severity is worsened by co-infections in areas where both diseases are endemic. Although pathogenesis of these infections separately is well studied, there is limited information on the pathogenic disease mechanisms and clinical disease outcomes in co-infections. In this study, we investigated the prevalence of malaria and schistosomiasis co-infections, and the hematologic and blood chemistry abnormalities in asymptomatic adults in a rural fishing community in western Kenya. METHODS: This sub-study used samples and data collected at enrollment from a prospective observational cohort study (RV393) conducted in Kisumu County, Kenya. The presence of malaria parasites was determined using microscopy and real-time-PCR, and schistosomiasis infection by urine antigen analysis (CCA). Hematological analysis and blood chemistries were performed using standard methods. Statistical analyses were performed to compare demographic and infection data distribution, and hematologic and blood chemistry parameters based on different groups of infection categories. Clinically relevant hematologic conditions were analyzed using general linear and multivariable Poisson regression models. RESULTS: From February 2017 to May 2018, we enrolled 671 participants. The prevalence of asymptomatic Plasmodium falciparum was 28.2% (157/556) and schistosomiasis 41.2% (229/562), with 18.0% (100/556) of participants co-infected. When we analyzed hematological parameters using Wilcoxon rank sum test to evaluate median (IQR) distribution based on malarial parasites and/or schistosomiasis infection status, there were significant differences in platelet counts (p = 0.0002), percent neutrophils, monocytes, eosinophils, and basophils (p < 0.0001 each). Amongst clinically relevant hematological abnormalities, eosinophilia was the most prevalent at 20.6% (116/562), whereas thrombocytopenia was the least prevalent at 4.3% (24/562). In univariate model, Chi-Square test performed for independence between participant distribution in different malaria parasitemia/schistosomiasis infection categories within each clinical hematological condition revealed significant differences for thrombocytopenia and eosinophilia (p = 0.006 and p < 0.0001, respectively), which was confirmed in multivariable models. Analysis of the pairwise mean differences of liver enzyme (ALT) and kidney function (Creatinine Clearance) indicated the presence of significant differences in ALT across the infection groups (parasite + /CCA + vs all other groups p < .003), but no differences in mean Creatinine Clearance across the infection groups. CONCLUSIONS: Our study demonstrates the high burden of asymptomatic malaria parasitemia and schistosomiasis infection in this rural population in Western Kenya. Asymptomatic infection with malaria or schistosomiasis was associated with laboratory abnormalities including neutropenia, leukopenia and thrombocytopenia. These abnormalities could be erroneously attributed to other diseases processes during evaluation of diseases processes. Therefore, evaluating for co-infections is key when assessing individuals with laboratory abnormalities. Additionally, asymptomatic infection needs to be considered in control and elimination programs given high prevalence documented here.

Persons living with HIV in sero-discordant partnerships experience improved HIV care engagement compared with persons living with HIV in sero-concordant partnerships: a cross-sectional analysis of four African countries.

BACKGROUND: Persons living with HIV (PLWH) who are members of sero-discordant and sero-concordant relationships may experience psychological stressors or motivators that affect HIV care. We assessed the association between sero-discordance status, antiretroviral therapy (ART) uptake, and viral suppression in the African Cohort Study (AFRICOS). METHODS: AFRICOS enrolls PLWH and HIV-uninfected individuals at 12 sites in Uganda, Kenya, Tanzania, and Nigeria. At enrollment, we determined ART use through self-report. Viral suppression was defined as HIV RNA < 1000 copies/mL. We analyzed PLWH who were index participants within two types of sexual dyads: sero-discordant or sero-concordant. Binomial regression models were used to estimate prevalence ratios (PRs) and 95% confidence intervals (95% CIs) for factors associated with ART use and viral suppression at study enrollment. RESULTS: From January 2013 through March 2018, 223 index participants from sero-discordant dyads and 61 from sero-concordant dyads were enrolled. The majority of the indexes were aged 25-34 years (50.2%), female (53.4%), and married (96.5%). Sero-discordant indexes were more likely to disclose their status to partners compared with sero-concordant indexes (96.4% vs. 82.0%, p < 0.001). After adjustment, sero-discordant index participants were more likely to be on ART (aPR 2.8 [95% CI 1.1-6.8]), but no more likely to be virally suppressed. Results may be driven by unique psycho-social factors and global implementation of treatment as prevention. CONCLUSIONS: PLWH in sero-discordant sexual partnerships demonstrated improved uptake of ART compared with those in sero-concordant partnerships. Interventions are needed to increase care engagement by individuals in sero-concordant relationships to improve HIV outcomes.

The pregnancy factor: the prevalence of depression among women living with HIV enrolled in the African Cohort Study (AFRICOS) by pregnancy status.

Among Sub-Saharan African women living with HIV (WLWH), pregnancy creates unique stressors that may cause depression. We describe the prevalence of depression among WLWH enrolled in the African Cohort Study (AFRICOS) by pregnancy status and describe factors associated with depression. WLWH < 45 years of age underwent six-monthly visits with depression diagnosed using the Center for Epidemiological Studies-Depression scale. Visits were categorized as "pregnant;" "postpartum" (the first visit made after the last pregnancy visit), and "non-pregnant." The prevalence of depression was calculated for each visit type and compared using prevalence odds ratios (POR) with 95% confidence intervals (CI). Logistic regression with generalized estimating equations was used to evaluate sociodemographic factors associated with depression. From January 2013 to March 1, 2020, 1333 WLWH were enrolled, and 214 had pregnancies during follow-up. As compared to the prevalence of depression during "non-pregnant" visits (9.1%), depression was less common at "pregnant" (6.3%; POR = 0.68 [CI: 0.42, 1.09]) and "postpartum" (3.4%; POR = 0.36 [CI: 0.17, 0.76]) visits. When controlling for other factors, the visit category was not independently associated with depression. Visit number, study site, employment status, and food security were independently associated with decreased odds of depression. We observed a lower prevalence of depression during pregnancy and the postpartum period than has been previously described among WLWH during similar time points. We observed protective factors against depression which highlight the impact that holistic and consistent health care at HIV-centered clinics may have on the well-being of WLWH in AFRICOS.

Hepatitis and tuberculosis testing are much less common than HIV testing among adults in Kisumu, Kenya: results from a cross-sectional assessment.

BACKGROUND: Kenya has a high burden of HIV, viral hepatitis, and tuberculosis. Screening is necessary for early diagnosis and treatment, which reduces morbidity and mortality across all three illnesses. We evaluated testing uptake for HIV, viral hepatitis, and tuberculosis in Kisumu, Kenya. METHODS: Cross-sectional data from adults aged 18-35 years who enrolled in a prospective HIV incidence cohort study from February 2017 to May 2018 were analyzed. A questionnaire was administered to each participant at screening for study eligibility to collect behavioral characteristics and to assess prior testing practices. Among participants without a history of previously-diagnosed HIV, multivariable robust Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for factors potentially associated with HIV testing in the 12 months prior to enrollment. A hierarchical model was used to test for differential access to testing due to spatial location. RESULTS: Of 671 participants, 52 (7.7%) were living with HIV, 308 (45.9%) were female, and the median age was 24 (interquartile range 21-28) years. Among 651 (97.0%) who had ever been tested for HIV, 400 (61.2%) reported HIV testing in the past 6 months, 129 (19.7%) in the past 6-12 months, and 125 (19.1%) more than one year prior to enrollment. Any prior testing for viral hepatitis was reported by 8 (1.2%) participants and for tuberculosis by 51 (7.6%). In unadjusted models, HIV testing in the past year was more common among females (PR 1.08 [95% CI 1.01, 1.17]) and participants with secondary education or higher (PR 1.10 [95% CI 1.02, 1.19]). In the multivariable model, only secondary education or higher was associated with recent HIV testing (adjusted PR 1.10 [95% CI 1.02, 1.20]). Hierarchical models showed no geographic differences in HIV testing across Kisumu subcounties. CONCLUSIONS: Prior HIV testing was common among study participants and most had been tested within the past year but testing for tuberculosis and viral hepatitis was far less common. HIV testing gaps exist for males and those with lower levels of education. HIV testing infrastructure could be leveraged to increase access to testing for other endemic infectious diseases.

Factors associated with sexually transmitted infections among care-seeking adults in the African Cohort Study.

OBJECTIVES: Sexually transmitted infections (STIs) are a major cause of morbidity. Understanding drivers of transmission can inform effective prevention programs. We describe STI prevalence and identify factors associated with STIs in four African countries. METHODS: The African Cohort Study is an ongoing, prospective cohort in Kenya, Nigeria, Tanzania and Uganda. At enrollment, a physical exam was conducted and STI diagnosis made by a clinician using a syndromic management approach. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) for factors associated with an STI diagnosis. RESULTS: As of June 2020, 3544 participants were enrolled. STI prevalence was 7.7% and did not differ by HIV status (p = 0.30). Prevalence differed by syndrome (3.5% vaginal discharge, 1.5% genital ulcer, 2.1% lower abdominal pain, 0.2% inguinal bubo). The odds of having an STI were higher at all sites compared to Kisumu West, Kenya, and among those with a primary level education or below compared to those with secondary or higher (aOR: 1.77; 95% CI: 1.32-2.38). The odds of an STI diagnosis was higher among participants 18-29 years (aOR: 2.29; 95% CI: 1.35-3.87), females (aOR: 2.64; 95% CI: 1.94-3.59), and those with depression (aOR: 1.78; 95% CI: 1.32-2.38). Among PLWH, similar factors were independently associated with an STI diagnosis. Viral suppression was protective against STIs (aOR: 2.05; 95% CI: 1.32-3.20). CONCLUSIONS: Prevalence of STIs varied by site with young people and females most at risk for STIs. Mental health is a potential target area for intervention.

Militaries and global health: peace, conflict, and disaster response.

Many countries show a growing willingness to use militaries in support of global health efforts. This Series paper summarises the varied roles, responsibilities, and approaches of militaries in global health, drawing on examples and case studies across peacetime, conflict, and disaster response environments. Militaries have many capabilities applicable to global health, ranging from research, surveillance, and medical expertise to rapidly deployable, large-scale assets for logistics, transportation, and security. Despite this large range of capabilities, militaries also have limitations when engaging in global health activities. Militaries focus on strategic, operational, and tactical objectives that support their security and defence missions, which can conflict with humanitarian and global health equity objectives. Guidelines-both within and outside militaries-for military engagement in global health are often lacking, as are structured opportunities for military and civilian organisations to engage one another. We summarise policies that can help close the gap between military and civilian actors to catalyse the contributions of all participants to enhance global health.

Impact of age on CD4 recovery and viral suppression over time among adults living with HIV who initiated antiretroviral therapy in the African Cohort Study.

INTRODUCTION: With increased use of antiretroviral therapy (ART), HIV mortality rates are declining and people living with HIV (PLWH) are surviving longer. We characterized CD4 recovery and viral suppression among adults aged < 50 and ≥ 50 years living with HIV who initiated ART in the African Cohort Study (AFRICOS). METHODS: Beginning in January 2013, PLWH at twelve clinics in Kenya, Uganda, Tanzania and Nigeria underwent medical history review, CD4 and viral load testing as part of the ongoing African Cohort Study (AFRICOS). ART-naïve PLWH who initiated ART within 30 days of enrollment and had at least one year of follow-up were included in these analyses. To compare ART response in participants < 50 years and ≥ 50 years old, changes in CD4 count and viral load suppression after ART initiation were examined at different time points using linear and binomial regression with generalized estimating equations. Variables for time since ART initiation and the interaction between age group and time on ART were included in the model to evaluate longitudinal changes in CD4 recovery and viral suppression by age. RESULTS: Between January 2013 and September 2019, 2918 PLHV were enrolled in the cohort. Of these, 443 were ART naïve and initiated on ART within 30 days of enrollment, with 90% (n = 399) aged < 50 years old at ART initiation. At ART initiation, participants aged 50 and older had a higher median CD4 count compared to participants younger than 50 years of age although it did not reach statistical significance (306 cells/mm3, IQR:130-547 vs. 277cells/mm3, IQR: 132-437). In adjusted models examining CD4 recovery and viral suppression there were no significant differences by age group over time. By the end of follow-up viral suppression was high among both groups of adults (96% of adults ≥ 50 years old and 92% of adults < 50 years old). CONCLUSION: This study found no difference in long-term CD4 recovery or viral suppression by age at ART initiation. We found that particularly among younger adults participants had lower median CD4 counts at ART initiation, suggesting the importance of identifying and putting this population on treatment earlier in the disease course.