Genetic variation that determines TAPBP expression levels associates with the course of malaria in an HLA allotype-dependent manner.

HLA class I (HLA-I) allotypes vary widely in their dependence on tapasin (TAPBP), an integral component of the peptide-loading complex, to present peptides on the cell surface. We identified two single-nucleotide polymorphisms that regulate TAPBP messenger RNA (mRNA) expression in Africans, rs111686073 (G/C) and rs59097151 (A/G), located in an AP-2α transcription factor binding site and a microRNA (miR)-4486 binding site, respectively. rs111686073G and rs59097151A induced significantly higher TAPBP mRNA expression relative to the alternative alleles due to higher affinity for AP-2α and abrogation of miR-4486 binding, respectively. These variants associated with lower Plasmodium falciparum parasite prevalence and lower incidence of clinical malaria specifically among individuals carrying tapasin-dependent HLA-I allotypes, presumably by augmenting peptide loading, whereas tapasin-independent allotypes associated with relative protection, regardless of imputed TAPBP mRNA expression levels. Thus, an attenuated course of malaria may occur through enhanced breadth and/or magnitude of antigen presentation, an important consideration when evaluating vaccine efficacy.

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.

Evidence of Orientia spp. Endemicity among Severe Infectious Disease Cohorts, Uganda.

At 3 severe infection cohort sites in Uganda, Orientia seropositivity was common. We identified 4 seroconversion cases and 1 PCR-positive case. These results provide serologic and molecular support for Orientia spp. circulating in sub-Saharan Africa, possibly expanding its endemic range. Orientia infections could cause severe illness and hospitalizations in this region.

HIV-1 infections with multiple founders associate with the development of neutralization breadth.

Eliciting broadly neutralizing antibodies (bnAbs) is a cornerstone of HIV-1 vaccine strategies. Comparing HIV-1 envelope (env) sequences from the first weeks of infection to the breadth of antibody responses observed several years after infection can help define viral features critical to vaccine design. We investigated the relationship between HIV-1 env genetics and the development of neutralization breadth in 70 individuals enrolled in a prospective acute HIV-1 cohort. Half of the individuals who developed bnAbs were infected with multiple HIV-1 founder variants, whereas all individuals with limited neutralization breadth had been infected with single HIV-1 founders. Accordingly, at HIV-1 diagnosis, env diversity was significantly higher in participants who later developed bnAbs compared to those with limited breadth (p = 0.012). This association between founder multiplicity and the subsequent development of neutralization breadth was also observed in 56 placebo recipients in the RV144 vaccine efficacy trial. In addition, we found no evidence that neutralization breath was heritable when analyzing env sequences from the 126 participants. These results demonstrate that the presence of slightly different HIV-1 variants in acute infection could promote the induction of bnAbs, suggesting a novel vaccine strategy, whereby an initial immunization with a cocktail of minimally distant antigens would be able to initiate bnAb development towards breadth.

Impact of weight gain with dolutegravir on antiretroviral adherence and viral suppression in four African countries.

OBJECTIVE: We hypothesized that total body weight (TBW) gain after switching antiretroviral therapy (ART) regimen to tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD) may negatively impact ART adherence and viral load (VL) and therefore sought to examine these associations. METHODS: The ongoing African Cohort Study (AFRICOS) enrols people with HIV at 12 facilities in Kenya, Nigeria, Tanzania and Uganda supported by The US President's Emergency Plan for AIDS Relief. Among ART-experienced participants who switched to TLD, we used multivariable multinomial logistic regression to examine associations between pre-/post-TLD changes in percentage TBW (≥5% gain, <5% change, ≥5% loss) and changes in self-reported ART adherence (0, 1-2, ≥3 days missed doses in past 30 days) and VL [(<50 copies/mL (undetectable), 50-999 copies/mL (detectable, but suppressed), ≥1000 copies/mL (unsuppressed)]. RESULTS: Among 1508 participants, median time from starting TLD to follow-up was 9 months (interquartile range: 7-11). Overall, 438 (29.1%) participants experienced a TBW gain ≥5%, which was more common among females than among males (32.2% vs 25.2%, p = 0.005) and participants switching from efavirenz [32.0% vs nevirapine (19.9%) and boosted protease inhibitor (20.0%); p < 0.001]. Compared with a TBW change <5% [950 (63.0%) participants], TBW gain ≥5% was not significantly associated with more days with missed ART doses [adjusted odds ratio (aOR) = 0.77, 95% confidence interval (CI): 0.48-1.23] or VL becoming detectable and/or unsuppressed (aOR = 0.69, 95% CI: 0.41-1.16). CONCLUSIONS: Although a substantial proportion of participants experienced weight gain after switching to TLD, we did not identify a significant impact on adherence or virological outcomes.

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.

Molecular characterisation of human adenoviruses associated with respiratory infections in Uganda.

Human adenoviruses (HAdV) are a diverse group of viruses causing a broad range of infections of the respiratory, urogenital and gastrointestinal tracts and keratoconjunctivitis. There are seven species of human adenoviruses with 113 genotypes which may contain multiple genetic variants. This study characterised respiratory human adenoviruses and associated factors in samples collected from selected hospitals in Uganda. A total of 2,298 nasopharyngeal samples were collected between the period of 2008 to 2016 from patients seeking health care at tertiary hospitals for influenza-like illness. They were screened by polymerase chain reaction (PCR) to determine the prevalence of HAdV. HAdV was cultured in A549 cell lines and the hexon gene was sequenced for genotyping. Of the 2,298 samples tested, 225 (9.8%) were adenovirus-positive by PCR. Age was found to be significantly associated with HAdV infections (p = 0.028) with 98% (220/225) of the positives in children aged 5 years and below and none in adults above 25 years of age. The sequenced isolates belonged to species HAdV-B and HAdV-C with most isolates identified as genotype B3. The results showed a high prevalence and genetic diversity in respiratory HAdV circulating in Ugandan population. Deeper genomic characterization based on whole genome sequencing may be necessary to further elucidate possible transmission and impact of current adenovirus-vectored vaccines in Africa.

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.

Coronavirus Antibody Responses before COVID-19 Pandemic, Africa and Thailand.

Prior immune responses to coronaviruses might affect human SARS-CoV-2 response. We screened 2,565 serum and plasma samples collected from 2013 through early 2020, before the COVID-19 pandemic began, from 2,250 persons in 4 countries in Africa (Kenya, Nigeria, Tanzania, and Uganda) and in Thailand, including persons living with HIV-1. We detected IgG responses to SARS-CoV-2 spike (S) subunit 2 protein in 1.8% of participants. Profiling against 23 coronavirus antigens revealed that responses to S, subunit 2, or subunit 1 proteins were significantly more frequent than responses to the receptor-binding domain, S-Trimer, or nucleocapsid proteins (p<0.0001). We observed similar responses in persons with or without HIV-1. Among all coronavirus antigens tested, SARS-CoV-2, SARS-CoV-1, and Middle East respiratory syndrome coronavirus antibody responses were much higher in participants from Africa than in participants from Thailand (p<0.01). We noted less pronounced differences for endemic coronaviruses. Serosurveys could affect vaccine and monoclonal antibody distribution across global populations.

Safety and immunogenicity of 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccination in children and adolescents in Africa: A randomised, placebo-controlled, multicentre Phase II clinical trial.

BACKGROUND: Reoccurring Ebola outbreaks in West and Central Africa have led to serious illness and death in thousands of adults and children. The objective of this study was to assess safety, tolerability, and immunogenicity of the heterologous 2-dose Ad26.ZEBOV, MVA-BN-Filo vaccination regimen in adolescents and children in Africa. METHODS AND FINDINGS: In this multicentre, randomised, observer-blind, placebo-controlled Phase II study, 131 adolescents (12 to 17 years old) and 132 children (4 to 11 years old) were enrolled from Eastern and Western Africa and randomised 5:1 to receive study vaccines or placebo. Vaccine groups received intramuscular injections of Ad26.ZEBOV (5 × 1010 viral particles) and MVA-BN-Filo (1 × 108 infectious units) 28 or 56 days apart; placebo recipients received saline. Primary outcomes were safety and tolerability. Solicited adverse events (AEs) were recorded until 7 days after each vaccination and serious AEs (SAEs) throughout the study. Secondary and exploratory outcomes were humoral immune responses (binding and neutralising Ebola virus [EBOV] glycoprotein [GP]-specific antibodies), up to 1 year after the first dose. Enrolment began on February 26, 2016, and the date of last participant last visit was November 28, 2018. Of the 263 participants enrolled, 217 (109 adolescents, 108 children) received the 2-dose regimen, and 43 (20 adolescents, 23 children) received 2 placebo doses. Median age was 14.0 (range 11 to 17) and 7.0 (range 4 to 11) years for adolescents and children, respectively. Fifty-four percent of the adolescents and 51% of the children were male. All participants were Africans, and, although there was a slight male preponderance overall, the groups were well balanced. No vaccine-related SAEs were reported; solicited AEs were mostly mild/moderate. Twenty-one days post-MVA-BN-Filo vaccination, binding antibody responses against EBOV GP were observed in 100% of vaccinees (106 adolescents, 104 children). Geometric mean concentrations tended to be higher after the 56-day interval (adolescents 13,532 ELISA units [EU]/mL, children 17,388 EU/mL) than the 28-day interval (adolescents 6,993 EU/mL, children 8,007 EU/mL). Humoral responses persisted at least up to Day 365. A limitation of the study is that the follow-up period was limited to 365 days for the majority of the participants, and so it was not possible to determine whether immune responses persisted beyond this time period. Additionally, formal statistical comparisons were not preplanned but were only performed post hoc. CONCLUSIONS: The heterologous 2-dose vaccination was well tolerated in African adolescents and children with no vaccine-related SAEs. All vaccinees displayed anti-EBOV GP antibodies after the 2-dose regimen, with higher responses in the 56-day interval groups. The frequency of pyrexia after vaccine or placebo was higher in children than in adolescents. These data supported the prophylactic indication against EBOV disease in a paediatric population, as licenced in the EU. TRIAL REGISTRATION: ClinicalTrials.gov NCT02564523.

Limited Evidence for a Relationship between HIV-1 Glycan Shield Features in Early Infection and the Development of Neutralization Breadth.

Identifying whether viral features present in acute HIV-1 infection predetermine the development of neutralization breadth is critical to vaccine design. Incorporating such features in vaccine antigens could initiate cross-reactive antibody responses that could sufficiently protect vaccinees from HIV-1 infection despite the uniqueness of each founder virus. To understand the relationship between Env determinants and the development of neutralization breadth, we focused on 197 individuals enrolled in two cohorts in Thailand and East Africa (RV144 and RV217) and followed since their diagnosis in acute or early HIV-1 infection. We analyzed the distribution of variable loop lengths and glycans, as well as the predicted density of the glycan shield, and compared these envelope features to the neutralization breadth data obtained 3 years after infection (n = 121). Our study revealed limited evidence for glycan shield features that associate with the development of neutralization breadth. While the glycan shield tended to be denser in participants who subsequently developed breadth, no significant relationship was found between the size of glycan holes and the development of neutralization breadth. The parallel analysis of 3,000 independent Env sequences showed no evidence of directional evolution of glycan shield features since the beginning of the epidemic. Together, our results highlight that glycan shield features in acute and early HIV-1 infection may not play a role determinant enough to dictate the development of neutralization breadth and instead suggest that the glycan shield's reactive properties that are associated with immune evasion may have a greater impact. IMPORTANCE A major goal of HIV-1 vaccine research is to design vaccine candidates that elicit potent broadly neutralizing antibodies (bNAbs). Different viral features have been associated with the development of bNAbs, including the glycan shield on the surface of the HIV-1 Envelope (Env). Here, we analyzed data from two cohorts of individuals who were followed from early infection to several years after infection spanning multiple HIV-1 subtypes. We compared Env glycan features in HIV-1 sequences obtained in early infection to the potency and breadth of neutralizing antibodies measured 1 to 3 years after infection. We found limited evidence of glycan shield properties that associate with the development of neutralization breadth in these cohorts. These results may have important implications for antigen design in future vaccine strategies and emphasize that HIV-1 vaccines will need to rely on a complex set of properties to elicit neutralization breadth.

Molecular dating and viral load growth rates suggested that the eclipse phase lasted about a week in HIV-1 infected adults in East Africa and Thailand.

Most HIV-1 infected individuals do not know their infection dates. Precise infection timing is crucial information for studies that document transmission networks or drug levels at infection. To improve infection timing, we used the prospective RV217 cohort where the window when plasma viremia becomes detectable is narrow: the last negative visit occurred a median of four days before the first detectable HIV-1 viremia with an RNA test, referred below as diagnosis. We sequenced 1,280 HIV-1 genomes from 39 participants at a median of 4, 32 and 170 days post-diagnosis. HIV-1 infections were dated by using sequence-based methods and a viral load regression method. Bayesian coalescent and viral load regression estimated that infections occurred a median of 6 days prior to diagnosis (IQR: 9-3 and 11-4 days prior, respectively). Poisson-Fitter, which analyzes the distribution of hamming distances among sequences, estimated a median of 7 days prior to diagnosis (IQR: 15-4 days) based on sequences sampled 4 days post-diagnosis, but it did not yield plausible results using sequences sampled at 32 days. Fourteen participants reported a high-risk exposure event at a median of 8 days prior to diagnosis (IQR: 12 to 6 days prior). These different methods concurred that HIV-1 infection occurred about a week before detectable viremia, corresponding to 20 days (IQR: 34-15 days) before peak viral load. Together, our methods comparison helps define a framework for future dating studies in early HIV-1 infection.

Factors influencing estimates of HIV-1 infection timing using BEAST.

While large datasets of HIV-1 sequences are increasingly being generated, many studies rely on a single gene or fragment of the genome and few comparative studies across genes have been done. We performed genome-based and gene-specific Bayesian phylogenetic analyses to investigate how certain factors impact estimates of the infection dates in an acute HIV-1 infection cohort, RV217. In this cohort, HIV-1 diagnosis corresponded to the first RNA positive test and occurred a median of four days after the last negative test, allowing us to compare timing estimates using BEAST to a narrow window of infection. We analyzed HIV-1 sequences sampled one week, one month and six months after HIV-1 diagnosis in 39 individuals. We found that shared diversity and temporal signal was limited in acute infection, and insufficient to allow timing inferences in the shortest HIV-1 genes, thus dated phylogenies were primarily analyzed for env, gag, pol and near full-length genomes. There was no one best-fitting model across participants and genes, though relaxed molecular clocks (73% of best-fitting models) and the Bayesian skyline (49%) tended to be favored. For infections with single founders, the infection date was estimated to be around one week pre-diagnosis for env (IQR: 3-9 days) and gag (IQR: 5-9 days), whilst the genome placed it at a median of 10 days (IQR: 4-19). Multiply-founded infections proved problematic to date. Our ability to compare timing inferences to precise estimates of HIV-1 infection (within a week) highlights that molecular dating methods can be applied to within-host datasets from early infection. Nonetheless, our results also suggest caution when using uniform clock and population models or short genes with limited information content.

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.

Safety and immunogenicity of 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccination in healthy and HIV-infected adults: A randomised, placebo-controlled Phase II clinical trial in Africa.

BACKGROUND: We investigated safety, tolerability, and immunogenicity of the heterologous 2-dose Ebola vaccination regimen in healthy and HIV-infected adults with different intervals between Ebola vaccinations. METHODS AND FINDINGS: In this randomised, observer-blind, placebo-controlled Phase II trial, 668 healthy 18- to 70-year-olds and 142 HIV-infected 18- to 50-year-olds were enrolled from 1 site in Kenya and 2 sites each in Burkina Faso, Cote d'Ivoire, and Uganda. Participants received intramuscular Ad26.ZEBOV followed by MVA-BN-Filo at 28-, 56-, or 84-day intervals, or saline. Females represented 31.4% of the healthy adult cohort in contrast to 69.7% of the HIV-infected cohort. A subset of healthy adults received booster vaccination with Ad26.ZEBOV or saline at Day 365. Following vaccinations, adverse events (AEs) were collected until 42 days post last vaccination and serious AEs (SAEs) were recorded from signing of the ICF until the end of the study. The primary endpoint was safety, and the secondary endpoint was immunogenicity. Anti-Ebola virus glycoprotein (EBOV GP) binding and neutralising antibodies were measured at baseline and at predefined time points throughout the study. The first participant was enrolled on 9 November 2015, and the date of last participant's last visit was 12 February 2019. No vaccine-related SAEs and mainly mild-to-moderate AEs were observed among the participants. The most frequent solicited AEs were injection-site pain (local), and fatigue, headache, and myalgia (systemic), respectively. Twenty-one days post-MVA-BN-Filo vaccination, geometric mean concentrations (GMCs) with 95% confidence intervals (CIs) of EBOV GP binding antibodies in healthy adults in 28-, 56-, and 84-day interval groups were 3,085 EU/mL (2,648 to 3,594), 7,518 EU/mL (6,468 to 8,740), and 7,300 EU/mL (5,116 to 10,417), respectively. In HIV-infected adults in 28- and 56-day interval groups, GMCs were 4,207 EU/mL (3,233 to 5,474) and 5,283 EU/mL (4,094 to 6,817), respectively. Antibody responses were observed until Day 365. Ad26.ZEBOV booster vaccination after 1 year induced an anamnestic response. Study limitations include that some healthy adult participants either did not receive dose 2 or received dose 2 outside of their protocol-defined interval and that the follow-up period was limited to 365 days for most participants. CONCLUSIONS: Ad26.ZEBOV, MVA-BN-Filo vaccination was well tolerated and immunogenic in healthy and HIV-infected African adults. Increasing the interval between vaccinations from 28 to 56 days improved the magnitude of humoral immune responses. Antibody levels persisted to at least 1 year, and Ad26.ZEBOV booster vaccination demonstrated the presence of vaccination-induced immune memory. These data supported the approval by the European Union for prophylaxis against EBOV disease in adults and children ≥1 year of age. TRIAL REGISTRATION: ClinicalTrials.gov NCT02564523.

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.