Impact of training and case manager support for traditional birth attendants in the linkage of care among HIV-positive pregnant women in Southwest Nigeria: a 3-arm cluster randomized control trial.

BACKGROUND: Mother-to-child transmission (MTCT) accounts for 90% of all new paediatric HIV infections in Nigeria and for approximately 30% of the global burden. This study aimed to determine the effectiveness of a training model that incorporated case managers working closely with traditional birth attendants (TBAs) to ensure linkage to care for HIV-positive pregnant women. METHODS: This study was a 3-arm parallel design cluster randomized controlled trial in Ifo and Ado-Odo Ota, Ogun State, Nigeria. The study employed a random sampling technique to allocate three distinct TBA associations as clusters. Cluster 1 received training exclusively; Cluster 2 underwent training in addition to the utilization of case managers, and Cluster 3 served as a control group. In total, 240 TBAs were enrolled in the study, with 80 participants in each of the intervention and control groups. and were followed up for a duration of 6 months. We employed a one-way analysis of variance (ANOVA) statistical test to evaluate the differences between baseline and endline HIV knowledge scores and PMTCT practices. Additionally, bivariate analysis using the chi-square test was used to investigate linkage to care. Furthermore, logistic regression analysis was utilized to identify TBA characteristics associated with various PMTCT interventions, including the receipt of HIV test results and repeat testing at term for HIV-negative pregnant women. The data analysis was performed using Stata version 16.1.877, and we considered results statistically significant when p values were less than 0.05. RESULTS: At the end of this study, there were improvements in the TBAs' HIV and PMTCT-related knowledge within the intervention groups, however, it did not reach statistical significance (p > 0.05). The referral of pregnant clients for HIV testing was highest (93.5%) within cluster 2 TBAs, who received both PMTCT training and case manager support (p ≤ 0.001). The likelihood of HIV-negative pregnant women at term repeating an HIV test was approximately 4.1 times higher when referred by TBAs in cluster 1 (AOR = 4.14; 95% CI [2.82-5.99]) compared to those in the control group and 1.9 times in cluster 2 (AOR = 1.93; 95% CI [1.3-2.89]) compared to the control group. Additionally, older TBAs (OR = 1.62; 95% CI [1.26-2.1]) and TBAs with more years of experience in their practice (OR = 1.45; 95% CI [1.09-1.93]) were more likely to encourage retesting among HIV-negative women at term. CONCLUSIONS: The combination of case managers and PMTCT training was more effective than training alone for TBAs in facilitating the linkage to care of HIV-positive pregnant women, although this effect did not reach statistical significance. Larger-scale studies to further investigate the benefits of case manager support in facilitating the linkage to care for PMTCT of HIV are recommended. TRIAL REGISTRATION: The study was retrospectively registered in the Pan African Clinical Trial Registry, and it was assigned the unique identification number PACTR202206622552114.

Epidemiology and survival outcomes of HIV-associated cervical cancer in Nigeria.

INTRODUCTION: Invasive cervical cancer (ICC) is an HIV-associated cancer that is preventable and precancerous stages including early ICC stages could be detected through screening offering opportunities for treatment and cure. The high incidence in women living with HIV and late presentation often at advanced stages of ICC with limited treatment facilities often result in early mortality. We sought to compare the epidemiologic characteristics and survival differences in HIV status of ICC patients in Nigeria. METHODS: We conducted a cohort study at two federal academic hospital-based research sites in Jos University Teaching Hospital, and Lagos University Teaching Hospital Nigeria, between March 2018 and September 2022. We enrolled women with histologically confirmed ICC with known HIV status, and FIGO staging as part of the United States of America's National Institutes of Health/National Cancer Institute funded project titled 'Epigenomic Biomarkers of HIV-Associated Cancers in Nigeria'. The primary outcome was all-cause mortality with assessment of overall survival (OS) and time to death after ICC diagnosis. OS distribution was estimated using the method of Kaplan-Meier and compared between groups using the log-rank test. RESULTS: A total of 239 women with confirmed ICC were enrolled and included in this analysis, of whom 192 (80.3%) were HIV-negative (HIV-/ICC +), and 47 (19.7%) were HIV-positive (HIV +/ICC +). The HIV +/ICC + patients were younger with median age 46 (IQR: 40-51) years compared to 57 (IQR: 45-66) among HIV-/ICC + (P < 0.001). Squamous cell carcinoma was the commonest histopathologic variant in 80.4% of ICC diagnosis, moderately differentiated tumor grade in 68.1% in both groups. HIV +/ICC + diagnosis was at FIGO advanced stages in 64.9% compared to 47.9% in HIV-/ICC +. The HIV-/ICC + women had better OS compared to HIV +/ICC + participants (p = 0.018), with 12-month OS 84.1% (95%CI 75-90%) and 67.6% (95%CI 42-84%) respectively. CONCLUSION: ICC is diagnosed at a relatively young age in women living with HIV, with a significantly lower overall survival probability compared to women without HIV. The trend of presentation and diagnosis at advanced stages in women living with HIV could partly explain the differences in overall survival.

Epidemiology and Survival outcomes of HIV-associated cervical cancer in Nigeria.

Introduction: Invasive cervical cancer (ICC) is an HIV-associated cancer that is preventable and precancerous stages including early ICC stages could be detected through screening offering opportunities for treatment and cure. The high incidence in women living with HIV and late presentation often at advanced stages of ICC with limited treatment facilities often result in early mortality. We sought to compare the epidemiologic characteristics and survival differences in HIV status of ICC patients in Nigeria. Methods: We conducted a cohort study at two federal academic hospital-based research sites in Jos University Teaching Hospital, and Lagos University Teaching Hospital Nigeria, between March 2018 and September 2022. We enrolled women with histologically confirmed ICC with known HIV status, and FIGO staging as part of the United States of America's National Institutes of Health/National Cancer Institute funded project titled 'Epigenomic Biomarkers of HIV-Associated Cancers in Nigeria'. The primary outcome was all-cause mortality with assessment of overall survival (OS) and time to death after ICC diagnosis. OS distribution was estimated using the method of Kaplan-Meier and compared between groups using the log-rank test. Results: A total of 239 women with confirmed ICC were enrolled and included in this analysis, of whom 192 (80.3%) were HIV-negative (HIV-/ICC+), and 47 (19.7%) were HIV-positive (HIV+/ICC+). The HIV+/ICC) patients were younger with median age 46 (IQR: 40-51) years compared to 57 (IQR: 45-66) among HIV-/ICC+) (P<0.001. Squamous cell carcinoma was the commonest histopathologic variant in 80.4% of ICC diagnosis, moderately differentiated tumor grade in 68.1% in both groups. HIV+/ICC+ diagnosis was at FIGO advanced stages in 64.9% compared to 47.9% in HIV-/ICC+. The HIV-/ICC+ women had better OS compared to HIV+/ICC+ participants (p=0.018), with 12-month OS 84.1% (95%CI: 75% - 90%) and 67.6% (95%CI: 42%-84%) respectively. Conclusion: ICC is diagnosed at a relatively young age in women living with HIV, with a significantly lower overall survival probability compared to women without HIV. The trend of presentation and diagnosis at advanced stages in women living with HIV could partly explain the differences in overall survival.

Presence of Burkholderia pseudomallei in Soil, Nigeria, 2019.

Melioidosis, caused by the soil-dwelling bacterium Burkholderia pseudomallei, is predicted to be endemic in Nigeria but is only occasionally reported. This report documents the systematic identification of the presence of B. pseudomallei and B. thailandensis in the soil across multiple states in Nigeria.

Hepatocellular carcinoma presentation and prognosis among Nigerian adults with and without HIV.

INTRODUCTION: Hepatocellular carcinoma (HCC) is an increasing cause of mortality in Nigeria among persons with HIV (PLH), as access to antiretroviral therapy (ART) improves. In this study we describe clinical, radiological, and laboratory characteristics in Nigerian adults with HCC, with and without HIV, and examine how HIV impacts survival. METHODS: This prospective observational study was conducted between August 2018 and November 2021 at two Nigerian hospitals [Jos University Teaching Hospital (JUTH) and Lagos University Teaching Hospital (LUTH)]. Subjects ≥18 years with HCC diagnosed according to American Association for the Study of Liver Diseases (AASLD) criteria were included. Baseline characteristics were compared, and Kaplan-Meier curves were generated to estimate survival. RESULTS: 213 subjects [177 (83%) without HIV and 36 (17%) with HIV (PLH)] were enrolled. Median age was 52 years (IQR 42,60) and most subjects were male (71%). 83% PLH were on antiretroviral therapy (ART). Hepatitis B surface antigen (HBsAg) positivity was similar between the two groups [91/177 (51%) without HIV vs. 18/36 (50%) with HIV; p = 0.86]. 46/213 (22%) subjects had active hepatitis C (anti-HCV+/HCV RNA>10 IU/mL). Cirrhosis was more common in PLH but there were no other significant differences in clinical and tumor characteristics between the groups. Overall, 99% subjects were symptomatic and 78% in late-stage HCC. Median overall survival was significantly shorter in PLH vs. without HIV (0.98 months vs 3.02 months, HR = 1.55, 95%CI 1.02, 2.37, p = 0.04). This association was not significant after adjusting for known risk factors including gender, current alcohol use, alpha-fetoprotein (AFP), albumin, and total bilirubin (HR = 1.38, 95%CI 0.84, 2.29, p = 0.21). CONCLUSION: HCC presented late with an extremely poor overall prognosis, highlighting the urgent need for more intensive surveillance in Nigeria to diagnose HCC at earlier stages. Early diagnosis and management of viral hepatitis, and access to HCC therapies, could prevent early mortality among persons with HCC, especially among PLH.

Comparative Assessment of p16/Ki-67 Dual Staining Technology for cervical cancer screening in women living with HIV (COMPASS-DUST)-Study protocol.

The risk of progression of low-grade (CIN1) to high-grade cervical intraepithelial neoplasia (CIN2/3) is 3-5 times higher for women living with HIV (WLHIV) than for HIV-negative women. Evidence suggests that the current cervical cancer screening methods perform less effectively in WLHIV. An emerging screening method-p16/Ki-67 dual staining technology (DUST) is a safe and rapid assay that could be used to detect CIN2/3 with higher sensitivity and specificity. The study in this protocol will evaluate the performance of DUST in cervical cancer screening among WLHIV. We will conduct an intra-participant comparative study (Phase 1) to enrol n = 1,123 sexually active WLHIV aged 25-65 years at two accredited adult HIV treatment centres in Lagos, Nigeria to compare the performance of DUST to the currently used screening methods (Pap smear, hr-HPV DNA, or VIA testing) in detecting high-grade CIN and cancer (CIN2+). Subsequently, a prospective cohort study (Phase 2) will be conducted by enrolling all the WLHIV who are diagnosed as having low-grade CIN (CIN1) in Phase 1 for a 6-monthly follow-up for 2 years to detect the persistence and progression of CIN1 to CIN2+. The findings of this study may provide evidence of the existence of a better performance screening method for the primary and triage detection of CIN2+ in WLHIV. It may also demonstrate that this high-performance test can improve the long-term predictive accuracy of screening by extending the intervals between evaluations and thus decrease the overall cost and increase screening uptake and follow-up compliance in WLHIV.

Cervical Epithelial Abnormalities and Associated Factors among HIV-Infected Women in Lagos, Nigeria: A Cytology-Based Study.

INTRODUCTION: As it may not be feasible to provide cervical cancer screening services to all HIV-infected women in most resource-limited settings, there is a need to identify those who are most at risk. We determined the prevalence, patterns, and associated factors of cervical cytological abnormalities among HIV-infected women in Lagos, Nigeria. METHODS: This descriptive cross-sectional study was conducted among HIV-infected women at the adult HIV treatment and colposcopy clinics of a university teaching hospital in Lagos, Nigeria, between October 2018 and December 2019. A cervical sample was collected from each woman to detect cervical cytological abnormalities. RESULTS: Of the 593 enrolled women, cervical cytological abnormalities were present in 40 (6.7%). Most (37.5%) of the women with cytological abnormalities had atypical squamous cells of undetermined significance. Age at coitarche (<20 vs. ≥20 years: adjusted odds ratio, 2.42; 95% confidence interval, 1.21-4.83, p = 0.01) was the only factor that was independently associated with cervical epithelial abnormalities. CONCLUSION: The prevalence of cervical cytological abnormalities in our study is lower than most previous reports in Africa. Sexual debut at an early age was significantly associated with cytological abnormalities. It is necessary to confirm the findings of this study through a well-designed and adequately powered longitudinal study.

Prevalence of Histoplasmosis among Persons with Advanced HIV Disease, Nigeria.

We sought to determine the prevalence of probable disseminated histoplasmosis among advanced HIV disease (AHD) patients in Nigeria. We conducted a cross-sectional study in 10 sites across 5 of 6 geopolitical zones in Nigeria. We identified patients with urinary samples containing CD4 cell counts <200 cells/mm3 or World Health Organization stage 3 or 4 disease who also had >2 clinical features of disseminated histoplasmosis, and we tested them for Histoplasma antigen using a Histoplasma enzyme immune assay. Of 988 participants we recruited, 76 (7.7%) were antigen-positive. The 76 Histoplasma antigen-positive participants had significantly lower (p = 0.03) CD4 counts; 9 (11.8%) were also co-infected with tuberculosis. Most antigen-positive participants (50/76; 65.8%; p = 0.015) had previously received antiretroviral treatment; 26/76 (34.2%) had not. Because histoplasmosis is often a hidden disease among AHD patients in Nigeria, Histoplasma antigen testing should be required in the AHD package of care.

The impact of dolutegravir-based combination antiretroviral therapy on the spermatozoa and fertility parameters of men living with human immunodeficiency virus.

The factors responsible for this reported fertility decline among human immunodeficiency virus (HIV) positive men is yet to be determined. This study is aimed at investigating the impact of HIV or combination antiretroviral therapy (cART) on sperm cells, reproductive hormones, oxidative stress markers, apoptosis, and sperm DNA fragmentation of men living with HIV. Twenty-one men living with HIV gave their written informed consent to participate in this study. Only 11 of the participants successfully donated blood and semen before and after 3 months of their treatment with cART. Semen, reproductive hormones, oxidative stress biomarkers, and DNA fragmentation were analysed. Data were subjected to Wilcoxon matched pairs signed rank test (ethical approval: CMUL/HREC/09/19/614). There was a significant decrease in viral load of HIV (p < 0.01), and a marked increase in progressive and total sperm motility. Total sperm count, morphology, and vitality had no significant change after 3 months of treatment with cART however, there was a significant increase (p < 0.05) in testosterone from 2.48 to 3.68 ng/ml, but luteinizing hormone decreased significantly (p < 0.05) from 9.6 to 6.5 mIU/ml. In addition, sperm DNA fragmentation increased significantly (p < 0.01). Conversely, viral load, and catalase decreased significantly, but no significant difference in malondialdehyde. This study showed that HIV depleted testosterone and impaired sperm motility which may negatively affect the fertility potential of men living with HIV. It also showed that adherence to cART (a combination of tenofovir, lamivudine, and dolutegravir) reduces the viral load and reverses the deleterious effects of cART albeit, cART appears to be toxic at subcellular spermatogenic levels.

A Qualitative Study Exploring Factors Associated with Retention in HIV Care among Women with HIV in a Large HIV Clinic in Lagos, Nigeria, after Implementing the Test and Treat Policy.

Background: In Nigeria, various sociocultural and economic factors may prevent women from being retained in HIV care. This study explores the factors associated with retention in care among women with HIV in a large HIV clinic in Lagos, Nigeria, under the Test and Treat policy. Methods: Women living with HIV/AIDS (n = 24) enrolled in an HIV study at the AIDS Prevention Initiative in Nigeria (APIN) clinic in Lagos, Nigeria, were interviewed from April 1 to October 31, 2021, using a semistructured interview guide. Interviews were audio-taped, transcribed verbatim, and the themes were analyzed using the framework of Andersen and Newman's Behavioural Model for Healthcare Utilization. Results: The mean age of the respondents was 37.4 ± 9.27 years. The identified themes were as follows: being aware of the antiretroviral medications and their benefits, the household's awareness of the respondents' HIV status, and the presence of social support. Other themes were the presence of a dependable source of income and the ability to overcome the challenges encountered in obtaining income, ease of travel to and from the clinic (length of travel time and transportation costs), securing support from the clinic, challenges encountered in the process of accessing care at the clinic, and the ability to overcome these challenges. Also mentioned were self-perception of being HIV positive, motivation to remain in care, linkage to care, and intention to stay in care. Conclusion: Several deterring factors to retention in HIV care, such as nondisclosure of status, absence of social support, and clinic barriers, persist under the Test and Treat policy. Therefore, to achieve the "treatment as prevention" for HIV/AIDS, especially in sub-Saharan Africa, it is essential to employ strategies that address these barriers and leverage the facilitators for better health outcomes among women with HIV/AIDS.

Accelerated Epigenetic Age Among Women with Invasive Cervical Cancer and HIV-Infection in Nigeria.

Background: Invasive cervical cancer (ICC) is a serious public health burden in Nigeria, where human immunodeficiency virus (HIV) remains highly prevalent. Previous research suggested that epigenetic age acceleration (EAA) could play a role in detection of HIV-associated ICC. However, little research has been conducted on this topic in Africa where the population is most severely affected by HIV-associated ICC. Here, we investigated the association between ICC and EAA using cervical tissues of ICC-diagnosed Nigerian women living with HIV. Methods: We included 116 cervical tissue samples from three groups of Nigerian women in this study: (1) HIV+/ICC+ (n = 39); (2) HIV+/ICC- (n = 53); and (3) HIV-/ICC + (n = 24). We utilized four DNA methylation-based EAA estimators; IEAA, EEAA, GrimAA, and PhenoAA. We compared EAA measurements across the 3 HIV/ICC groups using multiple linear regression models. We also compared EAA between 26 tumor tissues and their surrounding normal tissues using paired t-tests. We additionally performed a receiver operating characteristics (ROC) curve analysis to illustrate the area under the curve (AUC) of EAA in ICC. Results: We found the most striking associations between HIV/ICC status and PhenoAge acceleration (PhenoAA). Among HIV-positive women, PhenoAA was on average 13.4 years higher in women with ICC compared to cancer-free women (P = 0.005). PhenoAA was 20.7 and 7.1 years higher in tumor tissues compared to surrounding normal tissues among HIV-positive women (P = 0.009) and HIV-negative women (P = 0.284), respectively. We did not find substantial differences in PhenoAA between HIV-positive and HIV-negative women with ICC. Conclusion: PhenoAA is associated with ICC in HIV-infected women in our study. Our findings suggest that PhenoAA may serve as a potential biomarker for further risk stratification of HIV-associated ICC in Nigeria and similar resource-constrained settings.

Melioidosis in Africa: Time to Raise Awareness and Build Capacity for Its Detection, Diagnosis, and Treatment.

Melioidosis is a tropical infectious disease caused by the soil-dwelling bacterium Burkholderia pseudomallei with a mortality of up to 50% in low resource settings. Only a few cases have been reported from African countries. However, studies on the global burden of melioidosis showed that Africa holds a significant unrecognized disease burden, with Nigeria being at the top of the list. The first World Health Organization African Melioidosis Workshop was organized in Lagos, Nigeria, with representatives of health authorities, microbiology laboratories, and clinical centers from across the continent. Dedicated hands-on training was given on laboratory diagnostics of B. pseudomallei. This report summarises the meeting objectives, including raising awareness of melioidosis and building capacity for the detection, diagnosis, biosafety, treatment, and prevention across Africa. Further, collaboration with regional and international experts provided a platform for sharing ideas on best practices.

Derangement of protein S and C4b-binding protein levels as acquired thrombophilia in HIV-infected adult Nigerians.

BACKGROUND: HIV is a chronic inflammatory state with the production of many acute-phase-reactant proteins. Some of these proteins have procoagulant activities that predispose HIV-infected patients to thrombosis. OBJECTIVES: The aim of the study was to evaluate the effects of HIV infection on the serum levels of C4b-binding protein (C4BP) and protein S as markers of predisposition to thrombosis in HIV-infected adults. METHODS: The study population comprised of 61 HIV-infected adults on antiretroviral treatment (ART) who had achieved virological suppression, 58 HIV-infected adults not yet on ART and 59 HIV-negative healthy controls. The serum levels of free protein S, C4BP and the euglobulin clot lysis time (ECLT) were determined. RESULTS: The mean plasma-free protein S level of HIV-infected patients on ART (86.9% ± 25.8%) was significantly higher than that of treatment-naïve HIV-infected patients (75.7% ± 27.3%) (p = 0.005). Conversely, there was no statistically significant difference between the protein S levels of the HIV-infected subjects on ART (86.9% ± 25.8%) and those of the controls (94.9% ± 7.9%) (p = 0.119). The mean C4BP was significantly higher in the treatment-naïve HIV-infected subjects (36.7 ± 1.7 ng/dL) than that in those on ART (30.7 ± 2.6 ng/dL) and that in the controls (22.4 ± 2.4 ng/dL) (p < 0.0001). Protein S deficiency was more prevalent among the subjects with elevated C4BP (p = 0.023). The mean ECLT was significantly more prolonged in the treatment-naïve HIV-infected subjects (241.9 ± 34.7 s) than controls (189.5 ± 40.7 s) (p < 0.0001). CONCLUSION: HIV infection causes elevated levels of C4BP and diminishes the serum levels of free protein S. We infer that the risk of thrombosis (as measured by these biomarkers) decreases with the use of antiretroviral drugs.

Prevalence of Factor V Leiden G1691A and Prothrombin G20210A Gene Mutation Among Pregnant Women: Experience from a Multi-Center Study in Nigeria.

INTRODUCTION: Inherited thrombophilia and venous thromboembolism (VTE) have been closely linked to adverse pregnancy outcomes such as preeclampsia/eclampsia contributing to increased maternal and perinatal morbidity and mortality. There is, however, little genetic data from Africa including Nigeria that explores the prevalence of common VTE genetic risk markers such as factor V Leiden mutation (FVL G1691A) and prothrombin gene mutation (F2 G20210A) among pregnant women in Nigeria. PURPOSE: To determine the prevalence and distribution of FVL G1691A and F2 G20210A in pregnant women in Lagos, Nigeria. PATIENTS AND METHODS: This hospital-based cross-sectional pilot study was conducted among pregnant women between 1 July 2019 and 31 August 2020. The genotype of interest was determined through amplification by polymerase chain reaction using G1691A of FV and prothrombin A20210G specific primers. Descriptive data were presented using Stata version 15 (Stata Corp) statistical software. RESULTS: Of the 400 recruited participants, 397 and 389 samples were successfully processed for FVL G1691A and F2 G20210A mutations, respectively. Three participants had FVL heterozygous mutation; thus, the prevalence of heterozygous mutation of FVL among the study participants was 0.76%, 95% CI: 0.002-0.023%, n=3/397. There was no F2 G20210A mutation detected among the study participants. CONCLUSION: This study indicates that screening for factor V Leiden mutation and prothrombin gene mutation in pregnancy might not be of any clinical significance among Nigerian women. However, carrying out a genome-wide associated study is recommended to determine the true impact of these two common inherited thrombophilias in this population.

High Acceptability of Donating Hair and Other Biological Samples for Research Among People Living with HIV in an Outpatient Clinic in Lagos, Nigeria.

Willingness to donate hair samples is a rate-limiting step for assaying antiretroviral (ARV) concentrations in hair, an emerging technique for HIV prevention and treatment monitoring. We surveyed ethnically diverse Nigerians to determine their willingness to donate hair for biomedical research. A cross-sectional survey of people living with HIV on ARV therapy (ART) was conducted at the HIV clinic of Nigerian Institute of Medical Research, using systematic sampling. The researcher-administered questionnaire was designed to capture sociodemographic data, length of time on ART, and willingness to donate hair. Univariate analysis was performed on sociodemographic characteristics, and independent-samples t-test and chi-square tests were used for bivariate analysis. Multivariable logistic regression analysis was performed to assess factors associated with willingness to donate hair samples, with a significance level of 0.05. Of the 398 participants enrolled in the study, 258 (64.8%) were female, the average age was 40 years (±9.8), and the average time spent on ART was 7.3 years (±4.2). More than half (64.8%) of the respondents were willing to donate hair samples for biomedical research and they were 1.5 times more likely to donate hair than blood. For one-third of the participants, the anticipated benefit from the eventual research findings was the primary motivation to donate hair samples. Fear of use of hair for rituals was the most common stated reason for unwillingness to donate hair samples (21.2%). In an ethnically diverse, urban-based Nigerian study population, nearly two-thirds of the participants were willing to donate hair samples for biomedical research. These findings support the feasibility of hair sampling for future HIV clinical research conducted within Nigeria.

Development and evaluation of mucoadhesive bigel containing tenofovir and maraviroc for HIV prophylaxis.

BACKGROUND: Sexual transmission of HIV is the most common means of acquiring the disease. Topical microbicides have been investigated to prevent transmission. This study will use a specific entry inhibitor, maraviroc, and a nucleotide reverse transcriptase inhibitor (NRTI), tenofovir, a dual combination which will provide a synergist effect that can enhance the efficacy of HIV microbicides via a mucoadhesive dual compartment bigel. Bigel formulation via hydrogel organogel linkages were developed and evaluated for their physicochemical characteristics, safety, and anti-HIV efficacy. In vitro diffusion studies were performed with Franz diffusion cells having effective diffusion surface area of 1.76cm2 and receiver chamber volume of 15mL. RESULT: The bigel formulations showed a viscosity ranging from 14179 to 14560 cPs and had a good spreadability and acidic pH in the range of 4.0 ± 0.34 to 5.2 ± 0.18. The bigel formulations showed good anti-HIV activity at a concentration of 0.1 µg/mL. The in vitro release study of maraviroc from the bigel formulations showed a release rate ranging from 2.675 to 3.838 µg/cm2/min½ while the release rate for tenofovir ranged from 3.475 to 3.825 µg/cm2/min½. The bigel formulations were non-toxic to the human vagina as there was < 1 log10 change in Lactobacilli crispatus viability. CONCLUSION: This study successfully developed a dual compartment bigel containing maraviroc and tenofovir. BG C was found to be stable and safe towards vaginal and rectal epithelium, and it actively prevented HIV transmission. This bigel has the potential for long-term pre-exposure prophylaxis prevention of HIV transmission.

Absence of human leukocyte antigen-B*57:01 amongst patients on antiretroviral therapy in Nigeria: Implications for use of abacavir.

Background: The presence of human leukocyte antigen (HLA) B*57:01 allele predicts hypersensitivity reaction (HSR) to abacavir (ABC), a nucleoside reverse-transcriptase inhibitor used for human immunodeficiency virus (HIV) treatment. However, the prevalence of this allele amongst Nigerians with HIV is yet to be established. We aimed to determine the prevalence of HLA-B*57:01 allele amongst Nigerians with HIV infection. Methods: We conducted a multicentre cross-sectional epidemiologic survey. Between April 2016 and April 2017, patients were enrolled across five HIV treatment facilities in Nigeria. Participants' demographic information and their history of ABC exposure were obtained, and venous blood was obtained for HLA typing. Results: One thousand five hundred and four (1504) adults were enrolled, with a mean age of 44.6 ± 10.7 years, 1078 (71.7%) were female. 1463 (97.3%) were on antiretroviral therapy. ABC use was reported by 12 (0.8%) participants and none reported HSR. Of 1500 blood samples that were processed, 1458 (97.2%) were successfully typed. Of these, 132 (9.1%) were HLA-B*57 positive using non-specific low-resolution HLA-B*5701 primer mix. On further analysis, none of the 132 samples (0%) had the HLA-B*5701 allele. Conclusion: HLA-B*5701allele is rare amongst Nigerians.

Assessment of ultrasound flow-mediated dilation of brachial artery in regular blood donors in a Nigerian Tertiary Hospital

Background: Iron is a pro-oxidant cofactor that may be linked to cardiovascular disease (CVD) progression and reduction of body iron stores have been hypothesized to reduce the risk of CV disease. Aim: The aim of this study is to assess reduction in CVD risk susceptibility among regular blood donors compared with nondonors using ultrasound brachial artery flow-mediated dilation (BAFMD). Settings and Design: A prospective comparative study designed to establish the difference between mean flow-mediated dilatation (FMD) in the patients who are regular blood donors compared with nondonors recruited from a Teaching Hospital donor clinic. Materials and Methods: Data were collected over 7 months from December 2014 to June 2015. 100 eligible regular male blood donors, aged 21­50 years, were selected from a Teaching Hospital blood donor records and their BAFMD assessed. 50 nondonors/ first time donors, of equivalent age group, consecutively were assessed for comparison. Serum markers of iron stores, markers of oxidative stress and other related cardiac risk factors were also assessed in all patients. Results: BAFMD was significantly greater in regular blood donors when compared with nondonors (13.95% ± 7.02% vs. 8.20% ± 4.19%, P = 0.000). Serum ferritin was significantly decreased in regular blood donors when compared with nondonors (mean value 41.92 ng/ml ± 23.12 ng/ml vs. 61.97 ± 30.19 ng/ml, P = 0.000), but Hb did not differ between the groups. High FMD was significantly associated with high C-high-density lipoprotein and low C-LDL (r = −0.215*, P = 0.032, r = 0.188, P = 0.031, r = 0.193, P = 0.027, r = 0.0279, P = 0.002, r = 0.139, P = 0.084). LDL was decreased in regular blood donors compared with nondonors. Conclusion: The study provides prognostic information for assessing ultrasound BAFMD as a cardiac risk marker. Regular blood donors have enhanced cardiovascular function with increased flow-mediated dilation, decreased body iron stores, and decreased oxidative stress compared with nondonors

A survey of genetic fetal-haemoglobin modifiers in Nigerian patients with sickle cell anaemia.

Genetic variants at three quantitative trait loci (QTL) for fetal haemoglobin (HbF), BCL11A, HBS1L-MYB and the ß-globin gene cluster, have attracted interest as potential targets of therapeutic strategies for HbF reactivation in sickle cell anaemia (SCA). We carried out the first systematic evaluation of critical single nucleotide polymorphisms at these disease modifier loci in Nigerian patients with SCA. Common variants for BCL11A and HBS1L-MYB were strongly associated with HbF levels. At both loci, secondary association signals were detected, illustrating the mapping resolution attainable in this population. For BCL11A, the two independent sites of association were represented by rs1427407 (primary site, p = 7.0 x 10(-10)) and rs6545816 (secondary site, conditioned on rs1427407: p = 0.02) and for HBS1L-MYB by rs9402686 (HMIP-2B, p = 1.23 x 10(-4)) and rs66650371 (HMIP-2A, p = 0.002). Haplotype analysis revealed similarities in the genetic architecture of BCL11A and HBS1L-MYB in Nigerian patients. Variants at both loci also alleviated anaemia. The variant allele for the γ globin gene promoter polymorphism XmnI-HBG2 was too infrequent in our patients to be evaluated in this relatively small study. Studying the large and diverse SCA patient populations in African countries such as Nigeria will be key for a clearer understanding of how these loci work and for the discovery of new disease modifier genes.

A modified anthrax toxin-based enzyme-linked immunospot assay reveals robust T cell responses in symptomatic and asymptomatic Ebola virus exposed individuals.

BACKGROUND: Ebola virus (EBOV) caused more than 11,000 deaths during the 2013-2016 epidemic in West Africa without approved vaccines or immunotherapeutics. Despite its high lethality in some individuals, EBOV infection can produce little to no symptoms in others. A better understanding of the immune responses in individuals who experienced minimally symptomatic and asymptomatic infection could aid the development of more effective vaccines and antivirals against EBOV and related filoviruses. METHODOLOGY/PRINCIPLE FINDINGS: Between August and November 2017, blood samples were collected from 19 study participants in Lagos, Nigeria, including 3 Ebola virus disease (EVD) survivors, 10 individuals with documented close contact with symptomatic EVD patients, and 6 control healthcare workers for a cross-sectional serosurvey and T cell analysis. The Lagos samples, as well as archived serum collected from healthy individuals living in surrounding areas of the 1976 Democratic Republic of Congo (DRC) epidemic, were tested for EBOV IgG using commercial enzyme-linked immunosorbent assays (ELISAs) and Western blots. We detected antibodies in 3 out of 3 Lagos survivors and identified 2 seropositive individuals not known to have ever been infected. Of the DRC samples tested, we detected antibodies in 9 out of 71 (12.7%). To characterize the T cell responses in the Lagos samples, we developed an anthrax toxin-based enzyme-linked immunospot (ELISPOT) assay. The seropositive asymptomatic individuals had T cell responses against EBOV nucleoprotein, matrix protein, and glycoprotein 1 that were stronger in magnitude compared to the survivors. CONCLUSION/SIGNIFICANCE: Our data provide further evidence of EBOV exposure in individuals without EVD-like illness and, for the first time, demonstrate that these individuals have T cell responses that are stronger in magnitude compared to severe cases. These findings suggest that T cell immunity may protect against severe EVD, which has important implications for vaccine development.