Exploring Key Challenges for Healthcare Providers and Stakeholders in delivering adolescent sexual and Reproductive Health Services and information during the COVID-19 Pandemic in Malawi, Zambia and Zimbabwe: A Qualitative Study (preprint)

Introduction: This study aimed to explore the direct and indirect influences of COVID-19-related restrictions on adolescents and young people's SRHR in Malawi, Zambia, and Zimbabwe, with a focus on teenage pregnancy and access to and utilization of HIV testing and counselling services. Methods: A qualitative case study in a larger mixed-methods study design was used. Thirty-four interviews and four group discussions were conducted with relevant stakeholders in Malawi, Zambia and Zimbabwe. In Zambia, adolescents and young people were included and asked to describe their experience/perceptions of the impact of COVID-19 on their SRHR. Content and thematic analysis were used to analyze the data, Results: Priority shifts resulted in the focus of service provision to the COVID-19 response, shortages of already insufficient human resources due to infection and/or isolation, supply chain disruptions leading to shortages of important SRH-related commodities and supplies, compromised quality of services such as counselling for HIV and overall limited AYP’s access to SRH information. Suggestions for interventions to improve SRH services include the need for a disaster preparedness strategy, increased funding for ASRHR, the use of community health workers and community-based ASRHR strategies, and the use of technology and social media platforms such as mhealth. Conclusion:Disruption of SRH services for AYP due to pandemic related-restrictions, and diversion of resources/funding has had a ripple effect that may have long-term consequences for AYP throughout the East and Southern African region. This calls for further investment in AYP’s access to SRHR services as progress made may have been deterred.

Accuracy of Anti-SARS-CoV2 Antibody in Comparison with Surrogate Viral Neutralization Test in Person Living with HIV, Systemic Lupus Erythematosus and Chronic Kidney Disease (preprint)

The presence of anti SARS-CoV2-RBD antibody (Anti-RBD) prevents severe COVID-19. We aimed to determine the accuracy of a point-of-care Anti-RBD test implemented in person living with HIV (PLWH), systemic lupus erythematosus (SLE), and chronic kidney disease (CKD). We enrolled 182 non-comorbid subjects and 335 persons with comorbid (PLWH, SLE, CKD) to test anti-RBD assay compared to surrogate viral neutralization (SVNT) as the reference test. We performed linear correlation analysis between anti-RBD vs SVNT and a ROC analyses to ascertain anti-RBD cut-off at 30%, 60%, and 90% inhibition of SVNT to calculate accuracy. Correlations of anti-RBD to SVNT among all groups were excellent with R= 0.7903, R=0.7843, R=0.8153 among non-comorbid, SLE and CKD groups, respectively, with significantly higher correlation among the PLWH group (R=0.8877; p-value=0.0072) compared to non-comorbid group. The accuracy of the anti-RBD test among PLWH and CKD group was similar with the non-comorbid but showed lower sensitivity in the SLE group (p=0.000014). The specificity of the test remained high in all groups. In conclusion, the Anti-RBD test had excellent correlation to SVNT. The persistently high specificity in all groups suggests that this test can be reliably utilized to detect presence of low neutralization capacity, prompting additional vaccination.

Causes of death in people living with HIV in the post 95 -95 -95 era: Lessons from five AIDS Healthcare Foundation clinics in Eswatini (preprint)

Background Eswatini has a high HIV prevalence in adults (24.8%), and despite achieving HIV epidemic control, AIDS-related deaths are still high at 200 per 100,000 population. This study, therefore, describes the causes of death among people living with HIV (PLHIV) receiving care at five clinics in Eswatini. Methods Data of clients receiving antiretroviral therapy (ART) from five AIDS Healthcare Foundation (AHF) Clinics in Eswatini who died was analysed to describe the causes of death. Clients' records were included if they received treatment from any of the five clinics from January 1, 2021, to June 30, 2022. Clients' sociodemographic, clinical, and specific cause of death data were extracted from their clinical records into an Excel spreadsheet for mortality reporting and audits. The different causes of death were categorised and descriptive, and comparative analysis was done using Stata 15 and R. Odds ratio significant at p<0.05 (with 95% confidence interval) to estimate the different associations between the client's characteristics and the four leading causes of death. Results Of 257 clients, 52.5% (n=135) were males, and the median age was 47 years (IQR: 38, 59). The leading causes of death were non-communicable diseases (NCDs) (n=59, 23.0%), malignancies (n=37, 14.4%), Covid-19 (n=36, 14.0%) and advanced HIV disease (AHD) (n=24, 9.3%). Patients aged ≥60 years (OR 0.08; 95% CI: 0.004, 0.44) had lower odds of death from AHD than ≥40 years, and those who had been on ART for 12 – 60 months (OR 0.01; 95% CI: 0.0006, 0.06) and >60 months (OR 0.006; 95% CI: 0.0003, 0.029) had lower odds of death from AHD compared to those on ART for <12 months. Patients aged ≥40 years had higher odds of dying from COVID-19, while females (OR 2.64; 95% CI: 1.29, 5.70) had higher odds of death from malignancy. Conclusion Most patients who died were aged 40 years and above and died from an NCD, malignancy, COVID-19 and AHD-related cause. This indicates a need to expandprevention, screening, and integration of treatment for NCDs and cancers into HIV services. Specific interventions targeting younger PLHIV will limit their risks for AHD.

The 10-year health impact, economic impact, and return on investment of the South African molecular diagnostics programme for HIV, Tuberculosis and SARS-CoV-2 (preprint)

To ensure there is adequate investment into diagnostics, an understanding of the magnitude of impact and return on investment is necessary. We therefore sought to understand the health and economic impacts of the molecular diagnostic programme in South Africa, to deepen the under-standing on the broad value of diagnostics and guide future healthcare investments. We calcu-lated the 10-year (where data were available) total cost and DALYs averted associated with molecular diagnosis of molecular TB testing (2013-2022), HIV viral load monitoring (2013-2022), early infant diagnosis of HIV infection (2013-2022), and SARS-CoV-2 testing (2020-2022). We then calculated the economic value associated with those health gains and subsequent return on investment. Since the inception of the molecular diagnostics programme in South Africa, 3,035,782 DALYs have been averted as a direct consequence of this pro-gramme. This has generated an estimated $20.5 billion in economic value due to these health gains. The return on investment varied by specific diagnostic test (19.0 for tuberculosis, 1.4 for HIV viral load testing, 64.8 for early infant diagnosis of HIV, and 2.5 for SARS-CoV-2), for an average of 9.9 for the entire molecular diagnostics programme between 2013 and 2022- or $9.9 of value for each $1 invested. The molecular diagnostics programme in South Africa gen-erated a significant amount of health gains and economic value associated with these health gains, and the return-on-investment rivals other high-impact public health interventions such as childhood vaccination. Consequently, the molecular diagnostics programme in South Africa is highly impactful, and will continue to be an excellent investment of South African public health expenditure.

Changes in the senescence profile and immune checkpoints in HIV-infected individuals after COVID-19 (preprint)

Background: Both SARS-CoV-2 and HIV infection exhibit alterations in the senescence profile and immune checkpoint (IC) molecules. However, the midterm impact of SARS-CoV-2 on these profiles in people with HIV (PWH) remains unclear. This study aimed to evaluate differences in plasma biomarker levels related to ICs, the senescence-associated secretory phenotype (SASP), and pro- and anti-inflammatory cytokines in PWH following recovery from SARS-CoV-2 infection. Methods: We conducted a cross-sectional study of 95 PWH receiving antiretroviral therapy, stratified by SARS-CoV-2 infection status: a) 48 previously infected (HIV/SARS) and b) 47 controls without previous infection (HIV). Plasma biomarkers (n=44) were assessed using Procartaplex Multiplex Immunoassays. Differences were analyzed using a generalized linear model adjusted for sex and ethnicity and corrected for the false discovery rate. Significant values were defined as an adjusted arithmetic mean ratio [≥]1.2 or [≤]0.8 and a qvalue<0.1. Spearman correlation evaluated relationships between plasma biomarkers (significant correlations, rho[≥]0.3 and q value<0.1). Results: The median age of the PWH was 45 years, and 80% were men. All SARS-CoV-2-infected PWH experienced symptomatic infection; 83.3% had mild symptomatic infection, and sample collection occurred at a median of 12 weeks postdiagnosis. The HIV/SARS group showed higher levels of ICs (CD80, PDCD1LG2, CD276, PDCD1, CD47, HAVCR2, TIMD4, TNFRSF9, TNFRSF18, and TNFRSF14), SASP (LTA, CXCL8, and IL13), and inflammatory plasma biomarkers (IL4, IL12B, IL17A, CCL3, CCL4, and INF1A) than did the HIV group. Conclusions: SARS-CoV-2 infection in PWH causes significant midterm disruptions in plasma ICs and inflammatory cytokine levels, highlighting SASP-related factors, which could be risk factors for the emergence of complications in PWH.

Clinical outcomes of coronavirus disease 2019 in people living with human immunodeficiency virus in South Korea: A nationwide population-based cohort study (preprint)

Background: We aimed to compare the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) in people living with human immunodeficiency virus (HIV) (PLWH) with those in the general population. Methods: This nationwide descriptive epidemiological study was conducted in South Korea between January 2020 and February 2022. The National Health Insurance claims data covering the whole nation were collected through the Health Insurance Review and Assessment Service. Results: Among 3,653,808 individuals who were diagnosed with COVID-19, 1,311 (0.04%) were PLWH. All the PLWH received antiretroviral therapy, and 26.47% had more than one underlying disease other than HIV infection. The overall in-hospital mortality rates of PLWH and the general population were 0.76% and 0.25%, respectively (P=0.002). According to the Cox proportional hazard model, no significant difference was observed in the in-hospital mortality rate [hazard ratio (HR): 1.80, 95% confidence interval (CI): 0.70–4.67] between PLWH and the general population. However, progression to severe or critical COVID-19 was more common in PLWH (HR: 2.70, 95% CI: 1.37–5.33). In PLWH diagnosed with COVID-19, a multivariable Cox regression analysis found old age (≥60 years old) (HR: 6.9; 95% CI 2.57–18.56) and diabetes mellitus (HR: 5.13; 95% CI: 2.02–13.00) as the independent risk factors for severe or critical COVID-19. Conclusions: PLWH had a significantly higher risk of severe or critical COVID-19 than that of the general population. Our findings suggest the need for applying differentiated strategies to decrease the impact of COVID-19 on PLWH.

Dynamics of T cell responses to COVID-19 vaccines and breakthrough infection in people living with HIV receiving antiretroviral therapy (preprint)

Introduction: People living with HIV (PLWH) can exhibit impaired immune responses to vaccines. Accumulating evidence indicates that PLWH, particularly those receiving antiretroviral therapy, mount strong antibody responses to COVID-19 vaccination, but fewer studies have examined cellular immune responses to vaccination. We measured SARS-CoV-2 spike-specific CD4+ and CD8+ T cell responses generated by two and three doses of COVID-19 vaccine in PLWH receiving antiretroviral therapy, compared to control participants without HIV. We also quantified T cell responses after post-vaccine breakthrough infection, and receipt of fourth vaccine doses, in a subset of PLWH. Methods: We quantified CD4+ and CD8+ T cells reactive to overlapping peptides spanning the ancestral SARS-CoV-2 spike protein in 50 PLWH and 87 controls without HIV, using an activation induced marker (AIM) assay. All participants remained SARS-CoV-2 naive until at least one month after their third vaccine dose. SARS-CoV-2 infection was determined by seroconversion to nucleocapsid (N) antigen, which occurred in 21 PLWH and 38 controls post-third dose. Multivariable regression analyses were used to investigate relationships between sociodemographic, health and vaccine-related variables and vaccine-induced T cell responses, as well as breakthrough infection risk. Results: A third vaccine dose boosted spike-specific CD4+ and CD8+ T cell frequencies significantly above those measured after the second dose (all p<0.0001). Median T cell frequencies did not differ between PLWH and controls after the second dose (p>0.1), but CD8+ T cell responses were modestly lower in PLWH after the third dose (p=0.02), an observation that remained significant after adjustment for sociodemographic, health and vaccine-related variables (p=0.045). In PLWH who experienced breakthrough infection, median T cell frequencies increased even higher than those observed after three vaccine doses (p<0.03), and CD8+ T cell responses in this group remained higher even after a fourth vaccine dose (p=0.03). In multivariable analysis, the only factor associated with increased breakthrough infection risk was younger age, consistent with the rapid increases in SARS-CoV-2 seropositivity among younger adults in Canada after the initial appearance of the Omicron variant. Conclusion: PLWH receiving antiretroviral therapy mount strong T cell responses to COVID-19 vaccines that can be enhanced by booster doses or breakthrough infection.

Follow-up after post-exposure prophylaxis before and during the COVID-19 pandemic in Brazil (preprint)

Although post-exposure prophylaxis (PEP) is a powerful tool to abort HIV infection within 72 hours of exposure, blocking the establishment of chronic infection, follow-up metrics of this intervention are scarce. As antiretroviral use delays diagnosis biomarkers, the moment to perform serological evaluations must be considered this to avoid missed diagnosis opportunities. We assessed the return adherence after PEP dispensation in service in the Sao Paulo metropolitan area and reviewed the literature, both showing limited adherence to current protocols and leading to difficulties in diagnosing early HIV infection. The current proposed date for the first return after PEP is associated with low adherence and may have limited capability to detect antibodies if the infection is present. Guidelines should allow a longer time after PEP discontinuation along with message reminders to encourage adherence and avoid false negative results that can be detrimental both to the patient and to the community.

Regional Health Divides: Understanding Inequities in Late Diagnosis of HIV in Tajikistan (preprint)

HIV early detection (CD4 counts ≥350 cells/μL) is correlated with higher life expectancy among people living with HIV (PLHIV). Several factors including physical, cultural, structural, and financial barriers have contributed to HIV late detection. This is the first-of-its-kind study on the regional differences in early detection of HIV within Tajikistan and any country in the Central Asia region. Utilizing Tajikistan Ministry of Health's national HIV data (N=10,700) spanning 2010 to 2023, we developed median regression models with median CD4 cell count as the outcome and as predictors: time (years), region, age, gender, and area (urban/rural status). Individuals younger than 19 years old are more likely to be detected early for HIV, whereas those older than 39 years are more prone to late detection. Given their active engagement in age-related and sexual activities, those older than 39 years face a higher risk of HIV transmission to others if diagnosed late. Therefore, they require further attention and targeted interventions. Females are detected earlier compared to their male counterparts, regardless of region of residence. Rural populations are detected earlier in most years compared to their urban counterparts. The COVID-19 pandemic accelerated HIV early detection in 2021 but most regions have returned to near pre-pandemic levels of detection in 2022 and 2023. These fluctuations in early detection may signify a shift in attention and resource allocation, potentially affecting efforts to address access gaps during the initial year of the COVID-19 pandemic. There are significant health inequities among different demographic and geographic groups which warrant further attention.

Time-dependent enhancement of mRNA vaccines by 4-1BB costimulation (preprint)

mRNA vaccines have demonstrated efficacy against COVID-19. However, concerns regarding waning immunity and breakthrough infections have motivated the development of next-generation vaccines with enhanced efficacy. In this study, we investigated the impact of 4-1BB costimulation on immune responses elicited by mRNA vaccines in mice. We first vaccinated mice with an mRNA vaccine encoding the SARS-CoV-2 spike antigen like the Moderna and Pfizer-BioNTech vaccines, followed by administration of 4-1BB costimulatory antibodies at various times post-vaccination. Administering 4-1BB costimulatory antibodies during the priming phase did not enhance immune responses. However, administering 4-1BB costimulatory antibodies after 96 hours elicited a significant improvement in CD8 T cell responses, leading to enhanced protection against breakthrough infections. A similar improvement in immune responses was observed with multiple mRNA vaccines, including vaccines against common cold coronavirus, human immunodeficiency virus (HIV), and arenavirus. These findings demonstrate a time-dependent effect by 4-1BB costimulation and provide insights for developing improved mRNA vaccines.

Prospective Clinical Surveillance for Severe Acute Respiratory Illness in Kenyan Hospitals during the COVID-19 pandemic (preprint)

There are limited data from sub-Saharan Africa describing the pattern of admissions to public hospitals with severe acute respiratory infections during the COVID-19 pandemic. We conducted a prospective longitudinal hospital-based sentinel surveillance between May 2020 and December 2022 at 16 public hospitals in Kenya. All patients aged above 18 years admitted to adult medical wards in the participating hospitals were included. Demographic and clinical characteristics, COVID-19 infection and vaccination status and outcome data were collected. Of the 52,714 patients included in the study, 18,001 (35%) were admitted with severe acute respiratory illness (SARI). The mean age was 51 years. Patients were equally distributed across sexes. Pneumonia was the most common diagnosis at discharge. Hypertension, HIV and diabetes mellitus were the most common comorbidities. COVID-19 test results were positive in 2,370 (28%) of the 8,517 (47%) patients that underwent testing. Overall inpatient case fatality for SARI was 21% (n=3,828). After adjusting for age, sex and presence of a comorbidity, SARI patients had higher inpatient mortality compared to non-SARI patients regardless of their COVID-19 status (aHR 1.31, 95% CI 1.19 - 1.46). COVID-19 positive SARI patients had a higher inpatient mortality rate compared to their negative counterparts (aHR 1.31, 95% CI 1.12 - 1.54, p value < 0.0001). COVID-19 vaccine effectiveness against mortality due to SARI after adjusting for age, sex and presence of a comorbidity was 34% (95% CI 11% - 51%). We have provided a comprehensive description of the pattern of admissions with respiratory illnesses in Kenyan hospitals during the COVID-19 pandemic period. We have demonstrated the utility of routine surveillance activities within public hospitals in low-income settings which if strengthened can enhance the response to emerging health threats.

End-user feedback of rapid diagnostics in rural Kenya (preprint)

Underserved communities in low-resource countries are disproportionately impacted by communicable diseases when compared to those in developed countries. These communities have limited access to life saving diagnostic laboratory tests making it difficult to treat communicable diseases like SARS-CoV-2 and Human Immunodeficiency Virus (HIV). Rapid diagnostic tests, like the COVID-19 antigen (Ag) test, play a crucial role in underserved communities by enabling fast and inexpensive diagnosis in low-resource settings. Unfortunately, these rapid test platforms often lack the accuracy and precision of their laboratory-based analogs, resulting in a need for improved rapid diagnostics. The World Health Organization’s (WHO) ASSURED (Affordable, Sensitive, Specific, User-friendly, Rapid and robust, Equipment-free, and Deliverable to end-users) criteria are often referenced in the development of diagnostic tests. In this work, we aim to provide guidance to the “user-friendly” component of ASSURED through end-user surveys taken in rural Kenya. In these surveys, we examine the user-friendliness of two of the most commonly used rapid diagnostic tests, the COVID-19 Ag test and pregnancy test, by assessing participants’ familiarity with the tests, their opinion of test appearance, and the perceived complexity of the operator’s workflow. We also examine community acceptance and desire for a self-test for the highly stigmatized HIV. We intend these results to help guide developers of future rapid diagnostic tests intended for low-resource communities.

Neurosyphilis with Concomitant Cryptococcal Meningitis in a Patient with AIDS after COVID-19: a case report (preprint)

Background The common infections agents causing meningitis in patients with human immunodeficiency virus (HIV) include Cryptococcus neoformans and Treponema pallidum. Furthermore, there is an elevated risk of meningitis in patients with HIV concomitantly infected with SARS-CoV-2.Case presentation: A 38-year-old male presented with headache and dizziness. After hospitalization, polymerase chain reaction test for SARS-CoV-2 in nasopharyngeal swab was positive, and lumbar puncture revealed neurosyphilis with concomitant cryptococcal meningitis. He underwent Paxlovid, penicillin, antifungal and antiretroviral treatment. The patient had no other neurological symptoms and was stable during the 6-month follow-up period.Conclusions During the COVID-19 pandemic, patients with HIV, particularly those not underwent antiretroviral therapy, are at higher risk for severe infections, including central nervous system complications, due to their compromised immune systems.

Difference of Omicron variant infection and influence factors between people with and without HIV infection (preprint)

Background There are mixed findings in the literature regarding the association between HIV status and the risk of COVID-19 infection. Thus, we aimed to estimate the association between characteristics of HIV infection and the risk of COVID-19 Infection in a Chinese sample.Methods We conducted a cross-sectional survey of 1995 people living with HIV (PLWH) and 3503 HIV-negative adults in Ningbo, China. We compared the prevalence rates of the SARS-CoV-2 infection and the long nucleic acid conversion time (more than 2 weeks) among PLWH and HIV-negative participants, respectively. In addition, we explored the risk factors associated with SARS-CoV-2 infection and the long nucleic acid conversion time among the two groups.Results Overall, 1485/1995 (74.4%) PLWH and 2864/3503 (81.8%) HIV-negative people were infected with SARS-CoV-2. Among the SARS-CoV-2-infected participants, 437/1485 (29.4%) PLWH and 649/2864 (22.7%) HIV-negative people had the long nucleic acid conversion time. After controlling for the potential confounders, the rate of the SARS-CoV-2 infection was lower among the PLWH than the HIV-negative group (adjusted OR = 0.836, 95% CI = 0.706–0.990). However, PLWH had a significantly higher risk of the long nucleic acid conversion time after the SARS-CoV-2 infection (adjusted OR = 1.417, 95% CI = 1.176–1.707) than the HIV negative participants. Compared with those who did not receive ART, PLWH adults who received ART significantly had the increased risk of SARS-CoV-2 infection. Furthermore, HIV-negative participants receiving COVID-19 vaccines significantly displayed the decreased likelihood of the long nucleic acid conversion time after the SARS-CoV-2 infection.Conclusions Our study indicates that different HIV Infection status was significantly and differently associated with the SARS-CoV-2 infection and the long nucleic acid conversion time. However, the further studies are needed to confirm the effect of ART and COVID-19 vaccines on SARS-CoV-2 infection in PLWH.

Clot Twist - D-dimer analysis of healthy adults receiving heterologous or homologous booster COVID-19 vaccine after a single prime dose of Ad26.COV2.S in a phase II randomised open-label trial, BaSiS. (preprint)

BaSiS (Booster After Sisonke Study) is a prospectively enrolled open-label trial in which healthy adults, with controlled co-morbidities and no prior thrombosis, who received a single Ad26.COV2.S prime vaccination primarily through the Sisonke phase IIIB open label implementation study in South Africa. An exploratory objective evaluated the clotting profiles of participants who were enrolled across 4 sites in South Africa and randomised 1:1:1:1 to receive one of full-dose Ad26.COV2.S, half-dose Ad26.COV2.S, full-dose Comirnaty or half-dose Comirnaty booster. D-dimer testing (INNOVANCE D-Dimer Assay), as a coagulopathy marker, was conducted pre-booster (baseline) and 2 weeks post-booster. The median age among 285 participants was 42.2 years (IQR:35.5-48.7), 235/285 (82.5%) were female, 269/285 (94.4%) were Black African. Of the 40.4% (115/285) people living with HIV (PLHIV), 79.1% (91/115) were well-controlled on antiretroviral therapy. At baseline, 39.3% (112/285) had elevated d-dimers; all asymptomatic. Females and obese participants were significantly more likely to have elevated baseline d-dimers (OR=4.17; 95% CI:1.88 to 9.26 and OR=2.64; 95% CI:1.57 to 4.43, respectively). Of 169 with normal baseline d-dimers, 29 (17.2%) became elevated 2 weeks post-booster: median increase 0.23ug/ml (IQR:0.15-0.42); those receiving full-dose Comirnaty exhibited lower risk of d-dimer elevation post vaccination, compared to other booster vaccination arms (OR:0.26; 95% CI:0.07 to 0.98). PLHIV experienced significantly higher median increases compared to HIV uninfected participants (0.43 vs 0.17, p=0.004). Elevated d-dimers in asymptomatic, low-risk adults were unexpectedly common but were not associated with thromboembolism, supporting the rationale of using d-dimers only if clinically indicated. Trial Registration: South African Clinical Trails Register number DOH-27-012022-7841.

Socio-demographic determinants of COVID-19 vaccination status among people living with HIV; A cross-sectional study in selected regions in Tanzania (preprint)

Background Public Health and Social Measures are among the commonly used methods to prevent the spread of COVID-19. Vaccination has also been an integral component of infectious disease prevention and control and it has been used widely to protect humans against some of the very serious diseases such as COVID-19. People living with HIV (PLHIV) are known to be more vulnerable to the severest form of COVID-19 than the general population. Other groups of people likely to get the severe form of COVID-19 include the elderly and those with co-morbidities such as cancers, cardiovascular diseases, diabetes, etc.Objectives The main objective of the study was to establish socio-demographic factors that determine COVID-19 vaccination status among PLHIV in selected regions in mainland Tanzania and to provide insight into ways to enhance COVID-19 vaccine coverage in Tanzania.Methods A facility-based cross-sectional study was conducted in March-April 2022 among PLHIV in selected regions of Tanzania namely Kagera, Tabora, Geita, and Dar es Salaam. A total of 25 Care and Treatment Centres (CTCs) were randomly selected with a probability proportion of size in each region. In each CTC, 11 PLHIV eligible for vaccination were systematically selected to participate in the study. Face-to-face interviews were conducted using a structured questionnaire and Open Data Kit (ODK) software was used to record and transfer data to a designated server. Data cleaning and analysis were done using Stata version 14.0. A chi-square test was used to assess the association between socio-demographic characteristics and COVID-19 vaccination status. A generalized linear mixed-effects model was fitted to determine factors associated with COVID-19 vaccination status.Results Out of 1,100 PLHIV interviewed, 696 (63.3%) were found to be vaccinated against COVID-19. Level of education, age, occupation, employment status, location, and level of health facilities were found to be significant determinants of COVID-19 vaccination status among PLHIV in the study areas. PLHIV who had college and university education, elderly, farmers, and those employed and living in a rural setting were found to be more likely to be vaccinated than other comparison groups in the categories analyzed.Conclusion The study established that the COVID-19 vaccination status among PLHIV attending health facilities in the study area was higher than in the general population, this could be attributed to the effort by the public and private sectors to encourage PLHIV to vaccinate. To be able to attain the target of vaccination coverage of 60% as suggested by the WHO, the study emphasizes different interventions including an increase in the number of vaccination centers, support to those willing to vaccinate but unable to access vaccination services, emphasis on not only elderly people but also members of the community who are middle-aged and younger to take COVID-19 vaccine and more effort and engagement of higher levels of health service provision including health centers and hospitals.

Long-term symptoms after SARS-CoV-2 infection in a cohort of people living with HIV (PLWH): a real-life study (preprint)

Background Our Hospital in Northern Italy assists 3817 people living with HIV (PLWH) and has faced the impact of COVID-19. Little is known about the impact of HIV infection on the risk of post-COVID-19 conditions (PCCs) onset. We aim to assess the incidence of PCC in PLWH and the factors associated with its occurrence.Methods We performed a retrospective, observational study including all PLWH > 18 years registered in the Brescia Health Protection Agency database, assessing SARS-CoV-2 burden, vaccination status, socio-demographic, and viro-immunological parameters from February 2020 until May 2022. Persistence of self-reported symptoms (clustered into gastrointestinal, respiratory, osteo-muscular, and neuro-behavioral symptoms) was evaluated after 3 months by a telephone-administered questionnaire. We estimated the associations between all variables and outcomes through univariate and multivariable logistic models.Results In the study period, 653 PLWH were diagnosed with SARS-CoV-2 infection (17.1%). We observed 19 (2.9%) reinfections, 71 (10.9%) hospitalizations, and 3 (0.5%) deaths. We interviewed 510/653 PLWH (78%), and 178 (PCCs prevalence 34.9%; CI95% 30.7–39.2) reported persistent symptoms. Asthenia/fatigue was the most reported symptom (60/178), followed by muscular pain (54/178). In the multivariate regression model, male sex was protective (adjusted OR = 0.64; CI95% 0.99–3.66), while hospitalization during acute infection was associated with an increased the risk of PCCs (adjusted OR = 1.9; CI95% 0.99–3.66). Notably, no viro-immunological variable modified the PCCs risk onset.Conclusions Our study highlights a substantial prevalence of PCCs among PLWH, three months post-SARS-CoV-2 infection, independent of viro-immunological features or vaccination status.

Mathematical Modelling Indicates Th-cell Targeted Antibody-Dependent Cellular Cytotoxic Is a Crucial Obstacle Hurdling HIV Vaccine Development (preprint)

HIV poses a significant threat to human health. Although some progress has been made in the development of an HIV vaccine, there is currently no reported success in achieving an effective and fully functional vaccine for HIV. This highlights the challenges involved in HIV vaccine development. Through mathematical modeling, we have conducted a systematic study on the impact of antibody-dependent cellular cytotoxicity (ADCC) on HIV-specific immune responses. Unlike other viral infections, the ADCC effect following HIV infection may cause significant damage to the follicular center Th cells, leading to apoptosis of follicular center cells and rapid death of effector Th cells. This impedes the generation of neutralizing antibodies and creates barriers to viral clearance, thereby contributing to long-term infection. Another challenge posed by this effect is the substantial reduction in vaccine effectiveness, as effective antigenic substances such as gp120 bind to Th cell surfaces, resulting in the apoptosis of follicular center Th cells due to ADCC, hindering antibody regeneration. To address this issue, we propose the concept of using bispecific antibodies. By genetically editing B cells to insert the bispecific antibody gene, which consists of two parts targeting the CD4 binding site of HIV, such as the broadly neutralizing antibody 3BNC117, and the other targeting antibodies against other viruses, such as the spike protein of SARS-CoV-2. We can simultaneously enhance the levels of two pathogen-specific antibodies through stimulation with non-HIV-antigens corresponding to the other part of the chimeric antibody, such as the spike protein. This study contributes to the elucidation of the pathophysiology of HIV, while also providing a theoretical framework for the successful development of an HIV vaccine.

Prevalence and Genotype Distribution of Potential High-Risk and High-Risk Human Papillomavirus among Women attending Selected Reproductive Health Clinics in Lake Victoria Basin-Kenya: A Cross-sectional Study (preprint)

Background Persistent human papillomavirus (HPV) infection is considered the primary etiological factor for invasive cervical cancer. Understanding the epidemiology of circulating potential high-risk (HR) and HR HPV strains is essential in updating epidemiological knowledge and recommendations on genotype-specific vaccination development. In Lake Victoria Basin-LVB (Kisumu and Siaya Counties, Kenya), both the HIV burden, the post-COVID-19 pandemic environment and the population growth point to the need to study the current circulating strains. This study determined the prevalence and factors associated with Potential HR/HR HPV among women attending selected reproductive health clinics in LVB. The prevalence of Potential HR/HR HPV, genotype-specific distributions, and implications to the current HPV vaccination ongoing within Kenya are discussed. Methods A cross-sectional facility-based survey made up of 434 women aged 16-68 years was carried out in two selected facilities in the Urban-Kisumu County (Jaramogi Oginga Odinga Teaching and Referral Hospital-[JOOTRH] and rural-Siaya County (Gobei Health Center). Structured questionnaires were conducted to collect participant clinical and social characteristics. Cervical specimens were collected by registered reproductive health nurses and HPV genotyping was carried out using RIATOL HPV genotyping qPCR assay. Descriptive statistics followed by logistic binary regression was done using R version 4.3.2 Results The overall prevalence of potential HR/HR HPV among women attending the selected reproductive health clinics was reported at 36.5% (158/434). Specifically, in the rural setting, Gobei Health Center, the prevalence was 41.4% (41/99) while in the urban setting-JOOTRH, it was 34.6% (117/335). The most prevalent potential HR/HR HPV are 52, 67, 16, 31, 39, 45, and 31 for both HIV-positive and negative women and either in rural-Gobei Health Centre and Urban-JOOTRH. In this study, HIV status was not associated with potential HR/HR HPV among women attending. Age was the main factor associated with HPV infection among HIV-positive and negative women attending the selected reproductive health clinics in rural-urban Lake Victoria Basin, with women between the age of 30-39 having the highest risk (AOR=0.3, CI:0.2-0.7, p<0.001). Conclusion In both rural and urban regions, potential HR/HR HPV infection among individuals attending reproductive health clinics at the selected facilities remains common. The study identifies the need for effective implementation and clinical follow-up process of cervical cancer control program in the Lake Victoria Basin.

Traditional uses and pharmacological activities of Tetracera alnifolia (Wild) Drake (preprint)

Ethnopharmacological relevance: Tetracera alnifolia (Wild) Drake, is well used in traditional Guinean medicine for the treatment of infectious skin diseases. The present aim was to contribute to the valorization of Tetracera alnifolia leaves, focused on ethnomedical, biological and phytochemical investigations. Materials and methods: we conducted an ethnomedical survey across several markets of the city of Conakry to identify 39 healers. Chloroform, methanol, dichloromethane, and aqueous extracts were tested for activities against protozoa, bacteria, fungi, HIV, and SARS-CoV-2. Results: the traditional healers indicated that T. alnifolia is used in the treatment of more than 15 pathologies including Fassa (marasmus/malnutrition), Soukhou kouye (white discharge in women), and Temou bankhi (sexual weakness in men). Leaves were the most used part. The modes of preparation included decoction and powder. Data from biological activities identicatied good activities of the methanolic extract against Leishmania infantum (MIC = 8.11 g / ml) and a moderate activity on Trypanosoma brucei (MIC = 28.15 g / ml) and Staphylococcus aureus (MIC = 29.91 g/ ml), while dichloromethane extracts acted on live SARS-CoV-2 replication with up to 53.4% inhibition at 50 g/mL. Conclusion: these results explain at least in part the traditional use of T. alnifolia