HIV prevalence and awareness among adults presenting for enrolment into a study of people at risk for HIV in Kisumu County, Western Kenya.

INTRODUCTION: Despite declines in new HIV diagnoses both globally and in Kenya, parts of Western Kenya still report high HIV prevalence and incidence. We evaluated HIV prevalence to inform the development of policies for strategic and targeted HIV prevention interventions. METHODS: Adult participants aged 18-35 years were recruited in Kisumu County and screened for HIV for a prospective HIV incidence cohort. Questionnaires assessed HIV-associated risk behaviors. Participants who tested positive for HIV were disaggregated into groups based on prior knowledge of their HIV status: previously-diagnosed and newly-diagnosed. In separate analyses by prior knowledge, robust Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for factors potentially associated with a positive HIV test in each group, as compared to participants without HIV. RESULTS: Of 1059 participants tested for HIV, 196 (18.5%) had a positive HIV test. Among PLWH, 78 (39.8%) were newly diagnosed with HIV at screening. After adjusting for other variables, previously-diagnosed HIV was more common among females than males (PR 2.70, 95%CI 1.69-4.28), but there was no observed sex difference in newly-diagnosed HIV prevalence (PR 1.05, 95%CI 0.65-1.69). Previously-diagnosed HIV was also more common among people reporting consistent use of condoms with primary sexual partners as compared to inconsistent condom use (PR 3.19, 95%CI 2.09-4.86), but newly-diagnosed HIV was not associated with such a difference between consistent and inconsistent condom use (PR 0.73, 95%CI 0.25-2.10). CONCLUSION: Prevalence of newly-diagnosed HIV was high, at approximately 8% of participants, and not statistically different between genders, highlighting the need for improved HIV case finding regardless of sex. The higher prevalence of previously-diagnosed HIV in female participants may reflect higher rates of HIV testing through more encounters with the healthcare system. Higher prevalence of consistent condom use amongst those previously-diagnosed suggests behavioral change to reduce HIV transmission, a potential benefit of policies to facilitate earlier HIV diagnosis.

Young at risk-people in Maputo City, Mozambique, present a high willingness to participate in HIV trials: Results from an HIV vaccine preparedness cohort study.

INTRODUCTION: Vaccine efficacy testing requires engagement of willing volunteers with high disease incidence. We evaluated factors associated with willingness to participate in potential future HIV vaccine trials in Maputo, Mozambique. METHODS: Adults aged 18-35 years without HIV and who reported at least two sexual partners in the 3 months prior to screening were enrolled into a 24-month observational study. They were asked at screening and exit if they would be willing to participate in a theoretical HIV vaccine study. Bivariate and multivariate logistic regression analyses were done between willingness to participate, demographic, sexual behavior, and motivational factors for screening visit data. Logistic regression with generalized estimating equations (GEE) was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors potentially associated with willingness to participate for data from both visits. RESULTS: A total of 577 participants without HIV were eligible, including 275 (48%) women. The mean age was 22.2 (SD ± 3.9) years. At screening 529 (92%) expressed willingness to participate and the proportion remained stable at 378 (88%) of the 430 participants retained through the exit visit (p = 0.209). Helping the country (n = 556) and fear of needles (n = 26) were the top motive and barrier for willingness to participate, respectively. Results from the GEE binary logistic regression (screening visit and exit visit) showed that wanting to learn how to avoid risk behaviors (aOR 3.33, 95% CI: 1.61-6.86) and feeling protected against HIV infection (aOR 2.24, 95% CI: 1.07-4.7) were associated with willingness to participate in HIV vaccine studies. CONCLUSION: The majority of our study population in Mozambique expressed willingness to participate in a theoretical HIV vaccine trial. Participation in a HIV vaccine trial was seen as a way to contribute to the fight against HIV but was associated with some unrealistic expectations such as protection against HIV. This reinforces the need for continuous mobilization and awareness of potential participants to HIV vaccine trial.

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

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

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

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

Clinical laboratory reference values in adults in Kisumu County, Western Kenya; hematology, chemistry and CD4.

BACKGROUND: Clinical laboratory reference intervals (RIs) are essential for diagnosing and managing patients in routine clinical care as well as establishing eligibility criteria and defining adverse events in clinical trials, but may vary by age, gender, genetics, nutrition and geographic location. It is, therefore, critical to establish region-specific reference values in order to inform clinical decision-making. METHODS: We analyzed data from a prospective observational HIV incidence cohort study in Kombewa, Kenya. Study participants were healthy males and females, aged 18-35 years, without HIV. Median and 95% reference values (2.5th percentile to 97.5th percentile) were calculated for laboratory parameters including hematology, chemistry studies, and CD4 T cell count. Standard Deviation Ratios (SDR) and Bias Ratios (BR) are presented as measures of effect magnitude. Findings were compared with those from the United States and other Kenyan studies. RESULTS: A total of 299 participants were analyzed with a median age of 24 years (interquartile range: 21-28). Ratio of males to females was 0.9:1. Hemoglobin range (2.5th-97.5th percentiles) was 12.0-17.9 g/dL and 9.5-15.3 g/dL in men and women respectively. In the cohort, MCV range was 59-95fL, WBC 3.7-9.2×103/µL, and platelet 154-401×103/µL. Chemistry values were higher in males; the creatinine RI was 59-103 µmol/L in males vs. 46-76 µmol/L in females (BRUL>.3); and the alanine transferase range was 8.8-45.3 U/L in males vs. 7.5-36.8 U/L in females (SDR>.3). The overall CD4 T cell count RI was 491-1381 cells/µL. Some parameters including hemoglobin, neutrophil, creatinine and ALT varied with that from prior studies in Kenya and the US. CONCLUSION: This study not only provides clinical reference intervals for a population in Kisumu County but also highlights the variations in comparable settings, accentuating the requirement for region-specific reference values to improve patient care, scientific validity, and quality of clinical trials in Africa.

False reactive HIV-1 diagnostic test results in an individual from Kenya on multiple testing platforms-A case report.

BACKGROUND: Rapid diagnostic tests (RDT) are routinely used in screening for HIV infection. More complex diagnostic algorithms incorporating fourth-generation screening and confirmatory HIV-1/HIV-2 differentiation immunoassays (IA) may be used to confirm HIV infection. Co-infections and autoimmune diseases may lead to falsely reactive HIV diagnostic test results. CASE PRESENTATION: A Kenyan man with asymptomatic schistosomiasis and low risk factors for HIV infection demonstrated an inconsistent and discordant pattern of reactivity on HIV RDT, repeated reactivity on fourth-generation IA and positive at a single time-point for HIV-1 on the Geenius HIV1/HIV2 confirmatory assay during the course of a prospective cohort study with HIV repeat testing. The individual initiated antiretroviral therapy following HIV diagnosis. However, his bi-annual behavioral questionnaire suggested low-risk factors for infection. Supplementary confirmatory serologic and nucleic acid tests were performed and gave discordant results. The participant was determined to be HIV uninfected using cell-associated HIV-1 DNA/RNA testing and antiretroviral therapy was discontinued. DISCUSSION AND CONCLUSIONS: Sole reliance on diagnostic test results may result in misdiagnosis of HIV infection, social harm and potential antiretroviral induced drug toxicity. Interpretation of HIV test results should incorporate multiple parameters.

Determining hematological, biochemical and immunological reference values in healthy adults with high-risk for HIV acquisition in Mozambique.

INTRODUCTION: In many African countries, laboratory reference values are not established for the local healthy adult population. In Mozambique, reference values are known for young adults (18-24yo) but not yet established for a wider age range. Our study aimed to establish hematological, biochemical and immunological reference values for vaccine trials in Mozambican healthy adults with high-risk for HIV acquisition. METHODS: A longitudinal cohort and site development study in Mozambique between November 2013 and 2014 enrolled 505 participants between 18 to 35 years old. Samples from these healthy participants, were analyzed to determine reference values. All volunteers included in the analysis were clinically healthy and human immunodeficiency virus (HIV), hepatitis B and C virus, and syphilis negative. Median and reference ranges were calculated for the hematological, biochemical and immunological parameters. Ranges were compared with other African countries, the USA and the US National Institute of Health (NIH) Division of AIDS (DAIDS) toxicity tables. RESULTS: A total of 505 participant samples were analyzed. Of these, 419 participants were HIV, hepatitis B and C virus and syphilis negative including 203 (48.5%) females and 216 (51.5%) males, with a mean age of 21 years. In the hematological parameters, we found significant differences between sex for erythrocytes, hemoglobin, hematocrit, MCV, MCH and MCHC as well as white blood cells, neutrophils and platelets: males had higher values than females. There were also significant differences in CD4+T cell values, 803 cells/µL in men versus 926 cells/µL in women. In biochemical parameters, men presented higher values than women for the metabolic, enzymatic and renal parameters: total and direct bilirubin, ALT and creatinine. CONCLUSION: This study has established reference values for healthy adults with high-risk for HIV acquisition in Mozambique. These data are helpful in the context of future clinical research and patient care and treatment for the general adult population in the Mozambique and underline the importance of region-specific clinical reference ranges.

Determining hematological, biochemical and immunological reference values in healthy adults with high-risk for HIV acquisition in Mozambique

n many African countries, laboratory reference values are not established for the local healthy adult population. In Mozambique, reference values are known for young adults (18- 24yo) but not yet established for a wider age range. Our study aimed to establish hematological, biochemical and immunological reference values for vaccine trials in Mozambican healthy adults with high-risk for HIV acquisition.

HIV prevalence and risk behavior among male and female adults screened for enrolment into a vaccine preparedness study in Maputo, Mozambique.

INTRODUCTION: Mozambique continues to have a significant burden of HIV. Developing strategies to control the HIV epidemic remains a key priority for the Mozambican public health community. The primary aim of this study was to determine HIV prevalence and risk behavior among males and females screened for a HIV vaccine preparedness study in Maputo, Mozambique. METHODS: Male and female participants between 18-35 years old were recruited from the general community and from female sex worker (FSW) and lesbian, gay, bisexual, and transgender (LGBT) associations in Maputo. All participants were screened for HIV and a questionnaire was administered to each participant to assess HIV risk behavior. RESULTS: A total of 1125 adults were screened for HIV infection, among whom 506 (45%) were male. Among men, 5.7% reported having had sex with men (MSM) and 12% of female participants reported having exchanged sex for money, goods or favors in the past 3 months. The overall HIV prevalence was 10.4%; 10.7% of women, and 10.1% of men were HIV infected; 41.4% of MSM were seropositive. HIV infection was associated with older age (25-35 years old) (OR: 6.13, 95% CI: 3.01, 12.5), MSM (OR: 9.07, 95% CI: 3.85, 21.4), self-perception of being at high-risk for HIV (OR: 3.99, 95% CI: 1.27, 12.5) and self-report of a history of a diagnosis of sexually transmitted infection (OR: 3.75, 95% CI: 1.57, 8.98). CONCLUSION: In our cohort, HIV prevalence was much higher among MSM compared to the overall prevalence. Behavioral factors were found to be more associated with HIV prevalence than demographic factors. The study findings demonstrate the critical importance of directing services to minority communities, such as MSM, when prevention strategies are being devised for the general population.

Association Between Maternal-Perceived Psychological Stress and Fetal Telomere Length.

OBJECTIVE: Our study aimed to investigate the association between maternal-perceived psychological stress and fetal telomere length. METHODS: We recruited women in labor upon hospital delivery admission. Based on responses to the Perceived Stress Scale, we categorized participants as having "high," "normal," or "low" perceived stress. We collected umbilical cord blood samples (N = 71) and isolated genomic DNA from cord blood leukocytes using quantitative polymerase chain reaction. We used a ratio of relative telomere length derived by telomere-to-single-copy gene ratio (T/S ratio). We applied analysis of variance and bootstrapping statistical procedures. RESULTS: Sixteen (22.5%) women were classified as having low perceived stress, 42 (59.2%) were classified as having normal perceived stress, and 13 (18.3%) were classified as having high perceived stress. Fetal telomere length differed significantly across the three stress groups in a dose-response pattern (T/S ratio of those with low perceived stress was greater than those with normal perceived stress, which was greater than those with high perceived stress [P < 0.05]). CONCLUSIONS: Our findings support our hypothesis that maternal-perceived psychological stress during pregnancy is associated with shorter fetal telomere length and suggest maternal stress as a possible marker for early intrauterine programming for accelerated chromosomal aging.

Impact of intrauterine tobacco exposure on fetal telomere length.

OBJECTIVE: We sought to investigate whether maternal smoking during pregnancy affects telomere length of the fetus. STUDY DESIGN: Pregnant women were recruited on hospital admission at delivery. A self-report questionnaire and salivary cotinine test were used to confirm tobacco exposure. Neonatal umbilical cord blood samples were collected, and genomic DNA was isolated from cord blood leukocytes and was analyzed for fetal telomere length based on quantitative polymerase chain reaction. A ratio of relative telomere length was determined by telomere repeat copy number and single copy gene copy number (T/S ratio) and used to compare the telomere length of active, passive, and nonsmokers. Bootstrap and analysis of variance statistical methods were used to evaluate the relationship between prenatal smoking status and fetal telomere length. RESULTS: Of the 86 women who were included in this study, approximately 69.8% of the participants were covered by Medicaid, and 55.8% of the participants were black or Hispanic. The overall mean T/S ratio was 0.8608 ± 1.0442. We noted an inverse relationship between smoking and fetal telomere length in a dose-response pattern (T/S ratio of nonsmokers that was more than passive smokers that was more than active smokers). Telomere length was significantly different for each pairwise comparison, and the greatest difference was between active and nonsmokers. CONCLUSION: Our results provide the first evidence to demonstrate a positive association between shortened fetal telomere length and smoking during pregnancy. Our findings suggest the possibility of early intrauterine programming for accelerated aging that is the result of tobacco exposure.