Genital tract infections, the vaginal microbiome and gestational age at birth among pregnant women in South Africa : a cohort study protocol

DATA STATEMENT : The research team will prepare datasets used in analyses, in accordance with data sharing requirements of open access journals in which manuscripts are published and in compliance with local Protection of Personal Information Act requirements. These data files will be archived with codebooks as .csv documents or R datasets and stored in REDCap. The final data files will not contain any personal identifying information of participants.INTRODUCTION : Preterm birth complications are the most common cause of death in children under 5 years. The presence of multiple microorganisms and genital tract inflammation could be the common mechanism driving early onset of labour. South Africa has high levels of preterm birth, genital tract infections and HIV infection among pregnant women. We plan to investigate associations between the presence of multiple lower genital tract microorganisms in pregnancy and gestational age at birth. METHODS AND ANALYSIS : This cohort study enrols around 600 pregnant women at one public healthcare facility in East London, South Africa. Eligible women are ≥18 years and at <27 weeks of gestation, confirmed by ultrasound. At enrolment and 30–34 weeks of pregnancy, participants receive on-site tests for Chlamydia trachomatis and Neisseria gonorrhoeae, with treatment if test results are positive. At these visits, additional vaginal specimens are taken for: PCR detection and quantification of Trichomonas vaginalis, Candida spp., Mycoplasma genitalium, M. hominis, Ureaplasma urealyticum and U. parvum; microscopy and Nugent scoring; and for 16S ribosomal RNA gene sequencing and quantification. Pregnancy outcomes are collected from a postnatal visit and birth registers. The primary outcome is gestational age at birth. Statistical analyses will explore associations between specific microorganisms and gestational age at birth. To explore the association with the quantity of microorganisms, we will construct an index of microorganism load and use mixed-effects regression models and classification and regression tree analysis to examine which combinations of microorganisms contribute to earlier gestational age at birth. ETHICS AND DISSEMINATION : This protocol has approvals from the University of Cape Town Research Ethics Committee and the Canton of Bern Ethics Committee. Results from this study will be uploaded to preprint servers, submitted to open access peer-reviewed journals and presented at regional and international conferences. TRIAL REGISTRATION NUMBER : NCT06131749; Pre-results.An MD-PhD scholarship from the Swiss National Science Foundation, the Swiss National Science Foundation and the US National Institutes of Health.http://bmjopen.bmj.comam2024Medical MicrobiologySDG-03:Good heatlh and well-bein

Comparison of Kaposi Sarcoma Risk in Human Immunodeficiency Virus-Positive Adults Across 5 Continents: A Multiregional Multicohort Study

Background. We compared Kaposi sarcoma (KS) risk in adults who started antiretroviral therapy (ART) across the Asia-Pacific, South Africa, Europe, Latin, and North America. Methods. We included cohort data of human immunodeficiency virus (HIV)-positive adults who started ART after 1995 within the framework of 2 large collaborations of observational HIV cohorts. We present incidence rates and adjusted hazard ratios (aHRs). Results. We included 208 140 patients from 57 countries. Over a period of 1 066 572 person-years, 2046 KS cases were diagnosed. KS incidence rates per 100 000 person-years were 52 in the Asia-Pacific and ranged between 180 and 280 in the other regions. KS risk was 5 times higher in South African women (aHR, 4.56; 95% confidence intervals [CI], 2.73-7.62) than in their European counterparts, and 2 times higher in South African men (2.21; 1.34-3.63). In Europe, Latin, and North America KS risk was 6 times higher in men who have sex with men (aHR, 5.95; 95% CI, 5.09-6.96) than in women. Comparing patients with current CD4 cell counts &gt;= 700 cells/mu L with those whose counts were &lt;50 cells/mu L, the KS risk was halved in South Africa (aHR, 0.53; 95% CI,.17-1.63) but reduced by &gt;= 95% in other regions. Conclusions. Despite important ART-related declines in KS incidence, men and women in South Africa and men who have sex with men remain at increased KS risk, likely due to high human herpesvirus 8 coinfection rates. Early ART initiation and maintenance of high CD4 cell counts are essential to further reducing KS incidence worldwide, but additional measures might be needed, especially in Southern Africa

Cervical cancer risk in women living with HIV across four continents: A multicohort study

We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and 2014. We analyzed cohort data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. We used flexible parametric survival models to determine regional ICC rates and risk factors for incident ICC. We included 64,231 women from 45 countries. During 320,141 person-years (pys), 356 incident ICC cases were diagnosed (Europe 164, South Africa 156, North America 19 and Latin America 17). Raw ICC incidence rates per 100,000 pys were 447 in South Africa (95% confidence interval [CI]: 382-523), 136 in Latin America (95% CI: 85-219), 76 in North America (95% CI: 48-119) and 66 in Europe (95% CI: 57-77). Compared to European women ICC rates at 5 years after ART initiation were more than double in Latin America (adjusted hazard ratio [aHR]: 2.43, 95% CI: 1.27-4.68) and 11 times higher in South Africa (aHR: 10.66, 95% CI: 6.73-16.88), but similar in North America (aHR: 0.79, 95% CI: 0.37-1.71). Overall, ICC rates increased with age (&gt;50 years vs. 16-30 years, aHR: 1.57, 95% CI: 1.03-2.40) and lower CD4 cell counts at ART initiation (per 100 cell/mu l decrease, aHR: 1.25, 95% CI: 1.15-1.36). Improving access to early ART initiation and effective cervical cancer screening in women living with HIV should be key parts of global efforts to reduce cancer-related health inequities. What’s new? Invasive cervical cancer (ICC) is a significant burden among women living with human immunodeficiency virus (HIV). Little is known, however, about geographical differences in ICC rates in women living with HIV. Here, ICC incidence rates in women who received antiretroviral therapy (ART) were compared across geographic regions. ICC incidence was notably high among women living with HIV in South Africa and Latin America. Five years after ART initiation, ICC incidence remained elevated for women in these two regions, compared with women in Europe and North America. Reduced CD4 cell count and older age at ART initiation were associated with increased ICC risk

Non-Hodgkin lymphoma risk in adults living with HIV across five continents The AIDS-defining Cancer Project Working Group of leDEA and COHERE in EuroCoord

Objective: To compare non-I lodgkin lymphoma (NHL) incidence rates in adults who started antiretroviral therapy (ART) across the Asia-Pacific, South Africa, Europe, Latin, and North America. Methods: We included cohort data of adults living with HIV who started ART after 1995 within the framework of the International epidemiology Databases to Evaluate AIDS (leDEA) and (he Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). We used flexible parametric survival models to compare regional NHL rates at 2 years after ART start and to identify risk factors for NHL. Results: We included 210898 adults with 1.1 million person-years (pys) of follow-up and 1552 incident NHL cases (raw overall incidence rate 142/100000 pys). After adjusting for age at ART start, first-line ART regimen, calendar period of ART start, and especially current CD4(+) cell count, NHL rates were similar across regions for most population groups. However, South African women remained at increased risk of developing NHL compared with their European counterparts [adjusted hazard ratio [aHR] 1.79, 95% CI 1.19-2.701. In Europe, Latin, and North America, NHL risk was highest in MSM (aHR 1.30, 95% CI 1.14-1.48), followed by heterosexual men (referent), and women (aHR 0.66, 95% CI 0.57-0.78). Conclusion: The risk of developing NHL is higher in women in South Africa than in Europe and higher in MSM compared with heterosexual men and women. Reasons for these differences remain unclear. Early ART access and regular patient monitoring to avert low CD4(+) cell counts remain key for NHL prevention. copyright (C) 2018 WolLers Kluwer Health, Inc. All rights reserved