Prevalence of syphilis among adults and adolescents in five sub-Saharan African countries: findings from Population-based HIV Impact Assessment surveys.

BACKGROUND: HIV and syphilis are common sexually transmitted infections in sub-Saharan Africa. We aimed to investigate the prevalence and distribution of active syphilis while considering HIV status, demographic characteristics, and behavioural characteristics. METHODS: The Population-based HIV Impact Assessment surveys used a cross-sectional, two-stage, stratified cluster sample design to collect data in Ethiopia, Tanzania, Uganda, Zambia, and Zimbabwe from 2015 to 2018. Eligible participants were aged 15 years and older and provided demographic information, behavioural information, and blood specimens for HIV and syphilis testing. Active syphilis was defined as the presence of both treponemal and non-treponemal antibodies, measured using an antigen-based rapid test. Multivariable logistic regression models with survey weights were applied. The estimated number of participants with active syphilis in each country was calculated by multiplying the survey-weighted syphilis prevalence by the corresponding participant population size from the latest national census data. The total burden across the five countries was obtained by summing these estimates. FINDINGS: 102 831 participants enrolled in the five surveys (54 583 [57·6%] participants were female, 48 248 [42·4%] participants were male, 9036 [9·9%] participants were HIV positive). Population-based syphilis prevalence was 0·9% (95% CI 0·7-1·1) in Tanzania and Zimbabwe, 2·1% (1·9-2·4) in Uganda, and 3·0% (2·7-3·4) in Zambia. Overall, an estimated 1 027 615 (95% CI 877 243-1 158 246) participants had active syphilis across the five countries (266 383 HIV-positive and 761 232 HIV-negative individuals). Syphilis prevalence was higher among people living with HIV (range from 2·6% [95% CI 1·1-4·0] in Ethiopia to 9·6% [8·1-11·0] in Zambia) than among those without HIV (range from 0·8% [0·7-1·0] in Tanzania to 2·1% [1·8-2·4] in Zimbabwe). The odds of active syphilis were higher among people living with HIV than in those who were HIV negative (adjusted odds ratio [aOR] range from 2·5 [95% CI 1·8-3·4] in Uganda to 5·9 [3·8-9·2] in Zimbabwe), among divorced, separated, or widowed individuals (aOR range from 1·5 [1·1-2·0] in Uganda to 2·7 [1·7-4·3] in Zimbabwe), and among those reporting two or more sexual partners in the previous 12 months (aOR range from 1·1 [CI 0·8-1·5] in Uganda to 1·9 [1·1-3·3] in Zimbabwe). INTERPRETATION: This study shows the high burden of syphilis in five sub-Saharan African countries, with a correlation between HIV and active syphilis, underscoring the need for integrated sexual health services and targeted diagnosis, prevention, and treatment strategies to address this public health challenge. FUNDING: The President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention.

Prevalence of monoclonal gammopathy of undetermined significance in Eswatini: a population-based study in Africa.

BACKGROUND: Although monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma disproportionately affect Black individuals, few epidemiological studies have been conducted on these plasma cell disorders in Africa. Here we describe the prevalence of MGUS in Eswatini and compare our results to the landmark Olmsted County, Minnesota study. METHODS: Between 2016 and 2017, 13 339 residents of Eswatini participated in the Swaziland HIV Incidence Measurement Survey, from which a nationally representative biorepository was created. Plasma samples were then randomly selected and analyzed for MGUS. MGUS prevalence in Eswatini was compared with that of Olmsted County. In addition, demographic and HIV-related associations with MGUS were assessed. RESULTS: Of the 515 samples randomly selected, the median age was 50 years (range = 35-80 years); 60% were female; and 38.6% were HIV positive, of whom 82.4% were on antiretroviral therapy. We found that 68 participants had evidence of MGUS, for a prevalence of 13.2%. HIV status was not significantly associated with MGUS (odds ratio = 1.05, 95% confidence interval = 0.62 to 1.77), but among HIV-positive individuals, MGUS was less frequent for patients on antiretroviral therapy (adjusted odds ratio = 0.31, 95% confidence interval = 0.11 to 0.82). The prevalence of conventional MGUS was similar between Eswatini and Olmsted County (3.4% vs 3.2%-3.4%), whereas the incidence of light-chain MGUS was significantly greater in Eswatini (12.3% vs 0.8%). CONCLUSION: Our study suggests that the incidence of MGUS is similar between ethnicities and raises the question of whether the current definition of light-chain MGUS reliably reflects a true monoclonal protein precursor state. Perhaps the current definition of light-chain MGUS may be capturing alternate etiologies, such as untreated HIV infection.

Feasibility and acceptability of point of care testing for sexually transmitted infections in outpatient clinics offering integrated services in Eswatini.

BACKGROUND: Lack of point of care testing (POCT) for sexually transmitted infections (STIs) is a continuing missed opportunity in Sub-Saharan Africa. We assessed feasibility and acceptability of STI POCT in Eswatini. METHODS: STI POCT for Chlamydia trachomatis (CT) and Neisseria gonorrhoea (NG) was piloted among sexually active adults 18-45 years attending two urban outpatient clinics offering HIV services. Females were randomized 1:1 to provide urine or vaginal swab and all males provided urine samples for CT/NG testing using Cepheid CT/NG cartridges on existing GeneXpert platforms. Results were returned in-person or by telephone call. We assessed duration of procedures and participant and healthcare worker acceptability of services (5-point Likert scale), time spent on STI POCT services, and correlates of CT/NG infection. RESULTS: Of 250 adults triaged, 99% (248/250) accepted STI POCT, including 44% (109/248) people living with HIV. STI POCT procedures took a median of 3:22 hours. Most adults (90%, 224/248), received results within a day (61% same day, 29% next day). CT/NG was detected among 22% (55/248): 31/55 CT, 21/55 NG and 3/55 coinfections. Youth 18-25 years, history of any sexual intercourse, and condom-less sex within the previous 7 days were significantly associated with CT/NG detected (p < 0.05). Most adults with CT/NG were treated (51/55, 93%). Most participants were satisfied with STI POCT (217/241, 90%), and would accept again/recommend it. All 32 healthcare workers who participated were satisfied with STI POCT. CONCLUSION: STI POCT was feasible, acceptable, and identified a high prevalence of STIs, highlighting the urgent need for this testing.

Trends in mortality in people with HIV from 1999 to 2020: a multi-cohort collaboration.

BACKGROUND: Mortality among people with HIV declined with the introduction of combination antiretroviral therapy. We investigated trends over time in all-cause and cause-specific mortality in people with HIV from 1999-2020. METHODS: Data were collected from the D:A:D cohort from 1999 through January 2015 and RESPOND from October 2017 through 2020. Age-standardized all-cause and cause-specific mortality rates, classified using Coding Causes of Death in HIV (CoDe), were calculated. Poisson regression models were used to assess mortality trends over time. RESULTS: Among 55716 participants followed for a median of 6 years (IQR 3-11), 5263 participants died (crude mortality rate [MR] 13.7/1000 PYFU; 95%CI 13.4-14.1). Changing patterns of mortality were observed with AIDS as the most common cause of death between 1999- 2009 (n = 952, MR 4.2/1000 PYFU; 95%CI 4.0-4.5) and non-AIDS defining malignancy (NADM) from 2010 -2020 (n = 444, MR 2.8/1000 PYFU; 95%CI 2.5-3.1). In multivariable analysis, all-cause mortality declined over time (adjusted mortality rate ratio [aMRR] 0.97 per year; 95%CI 0.96, 0.98), mostly from 1999 through 2010 (aMRR 0.96 per year; 95%CI 0.95-0.97), and with no decline shown from 2011 through 2020 (aMRR 1·00 per year; 95%CI 0·96-1·05). Mortality due all known causes except NADM also declined over the entire follow-up period. CONCLUSION: Mortality among people with HIV in the D:A:D and/or RESPOND cohorts decreased between 1999 and 2009 and was stable over the period from 2010 through 2020. The decline in mortality rates was not fully explained by improvements in immunologic-virologic status or other risk factors.

Epigenetic aging in older people living with HIV in Eswatini: a pilot study of HIV and lifestyle factors and epigenetic aging.

BACKGROUND: People living with HIV (PLHIV) on effective antiretroviral therapy are living near-normal lives. Although they are less susceptible to AIDS-related complications, they remain highly vulnerable to non-communicable diseases. In this exploratory study of older PLHIV (OPLHIV) in Eswatini, we investigated whether epigenetic aging (i.e., the residual between regressing epigenetic age on chronological age) was associated with HIV-related parameters, and whether lifestyle factors modified these relationships. We calculated epigenetic aging focusing on the Horvath, Hannum, PhenoAge and GrimAge epigenetic clocks, and a pace of biological aging biomarker (DunedinPACE) among 44 OPLHIV in Eswatini. RESULTS: Age at HIV diagnosis was associated with Hannum epigenetic age acceleration (EAA) (ß-coefficient [95% Confidence Interval]; 0.53 [0.05, 1.00], p = 0.03) and longer duration since HIV diagnosis was associated with slower Hannum EAA (- 0.53 [- 1.00, - 0.05], p = 0.03). The average daily dietary intake of fruits and vegetables was associated with DunedinPACE (0.12 [0.03, 0.22], p = 0.01). The associations of Hannum EAA with the age at HIV diagnosis and duration of time since HIV diagnosis were attenuated when the average daily intake of fruits and vegetables or physical activity were included in our models. Diet and self-perceived quality of life measures modified the relationship between CD4+ T cell counts at participant enrollment and Hannum EAA. CONCLUSIONS: Epigenetic age is more advanced in OPLHIV in Eswatini in those diagnosed with HIV at an older age and slowed in those who have lived for a longer time with diagnosed HIV. Lifestyle and quality of life factors may differentially affect epigenetic aging in OPLHIV. To our knowledge, this is the first study to assess epigenetic aging in OPLHIV in Eswatini and one of the few in sub-Saharan Africa.

Cancer genetic mutation prevalence in sub-Saharan Africa: A review of existing data.

BACKGROUND: Cancer represents a leading cause of death worldwide. Germline mutations in several genes increase the risk of developing several cancers, including cancers of the breast, ovary, pancreas, colorectum, and melanoma. An understanding of the population prevalence of pathogenic germline variants can be helpful in the design of public health interventions, such as genetic testing, which has downstream implications for cancer screening, prevention, and treatment. While population-based studies of pathogenic germline variants exist, most such studies have been conducted in White populations. Limited data exist regarding the prevalence of germline mutations within sub-Saharan African populations. MATERIALS AND METHODS: We identified countries defined as sub-Saharan Africa by the World Bank and conducted a scoping literature review using PubMed. For each country, we identified and summarized studies that focused on the prevalence of germline genetic mutations with sample sizes >10 and in a population directly from sub-Saharan Africa, either with or without diseases associated with the relevant genetic mutations. Studies that evaluated the prevalence of somatic or likely benign variants were excluded. RESULTS: Within the 48 countries in sub-Saharan Africa, we identified 34 studies which meet the inclusion criteria. Twenty studies were conducted in South Africa, Nigeria, or Burkina Faso; four countries had more than two published papers. We found that 33 of 48 countries in sub-Saharan Africa lacked any genetic studies. Notably, there has been an increase in relevant studies starting in 2020. Importantly, of the 34 studies identified, 29 included data on BRCA1 or BRCA2. Data on the prevalence of mutations contributing to familial cancer syndromes other than BRCA1 and BRCA2 was limited. CONCLUSIONS: While some progress has been made towards understanding the prevalence of germline mutations in cancer susceptibility genes, the characterization of genetic mutations among sub-Saharan African populations remains strikingly incomplete. Given the genetic diversity in the region, there remains a great need for large-scale, population-based studies to understand the prevalence of germline pathogenic variants and adequately capture all the subpopulations in this part of the world.

Nurse-led HIV services and quality of care at health facilities in Kenya

Objective:To develop a novel measure to characterize human immunodeficiency virus (HIV) programme quality at health facilities in Kenya and explore its associations with patient- and facility-level characteristics.Methods:We developed a composite indicator to measure quality of HIV care, comprising: assessment of eligibility for antiretroviral therapy(ART); initiation of ART; and retention on ART or in care, if ineligible for ART, for 12 months. We applied the comprehensive retention indicator to routinely collected clinical data from 13 331 patients enrolled in HIV care and treatment at 63 health facilities in the Eastern and Nyanza regions of Kenya from 1 January 2014 to 31 March 2016. We explored the association between facility- andpatient-level characteristics and the primary outcome: appropriate staging and management of HIV, and retention in care over 12 months.Findings:Of the enrolled patients, 8404 (63%) achieved comprehensive retention 12 months after enrolment in care. In univariate analyses, patients at facilities where nurses delivered HIV treatment services (including eligibility assessment, initiation and follow up of ART) had significantly higher comprehensive retention rates at 12 months. In multivariate analyses, after adjusting for both facility- and patient-level characteristics, patients at facilities where nurses initiated ART had significantly higher comprehensive retention in care at 12 months (relative risk, RR: 1.22; 95% confidence interval, CI: 1.00­1.48).Conclusion:Nurse-led HIV services were significantly associated with quality of care, confirming the central role of nurses in the achievement of global health goals, and the need for further investment in nursing education, training and mentoring

Factors Associated with Late Antiretroviral Therapy Initiation among Adults in Mozambique

Despite recent changes to expand the ART eligibility criteria in sub-Saharan Africa, many patients still initiate ART in the advanced stages of HIV infection, which contributes to increased early mortality rates, poor patient outcomes, and onward transmission. To evaluate individual and clinic-level factors associated with late ART initiation in Mozambique, we conducted a retrospective sex-specific analysis of data from 36,411 adult patients who started ART between January 2005 and June 2009 at 25 HIV clinics in Mozambique. Late ART initiation was defined as CD4 count<100 cells/µL or WHO stage IV. Mixed effects models were used to identify patient- and clinic-level factors associated with late ART initiation. The proportion of patients initiating ART late decreased from 46% to 37% during 2005­2007, but remained constant (between 37­33%) from 2007­2009. Of those who initiated ART late (median CD4 = 57 cells/µL), 5% were known to have died and 54% were lost to clinic within 6 months of ART initiation (compared with 2% and 47% among other patients starting ART [median CD4 = 192 cells/µL]). In multivariate analysis, female sex and pregnancy at ART initiation (AORfemale_not_pregnant_vs._male = 0.66, 95%CI [0.62­0.69]; AORpregnant_vs._non_pregnant = 0.60, 95%CI [0.49­0.73]), younger and older age (AOR15­25_vs.26­30 = 0.86, 95%CI [0.79­0.94], AOR>45_vs.26­30 = 0.72, 95%CI [0.67­0.77]), entry into care via PMTCT (AORentry_through_PMTCT_vs.VCT = 0.42, 95%CI [0.35­0.50]), marital status (AORmarried/in union_vs.single = 0.87, 95%CI [0.83­0.92]), education (AORsecondary_or_higher_vs.primary = 0.87, 95%CI [0.83­0.93]) and year of ART initiation were associated with a lower likelihood of late ART initiation. Clinic-level factors independently associated with a lower likelihood of late ART initiation included CD4 machine on-site (AORCD4_machine_onsite_vs.offsite = 0.83, 95%CI [0.74­0.94]) and presence of PMTCT services onsite (AOR = 0.85, 95%CI [0.77­0.93]). The risk of starting ART late remained persistently high. Efforts are needed to ensure identification and enrollment of patients at earlier stages of HIV disease. Individual and clinic level factors identified may provide clues for upstream structural interventions.