Slow Acceptance of Universal Antiretroviral Therapy (ART) Among Mothers Enrolled in IMPAACT PROMISE Studies Across the Globe.

The PROMISE trial enrolled asymptomatic HIV-infected pregnant and postpartum women not eligible for antiretroviral treatment (ART) per local guidelines and randomly assigned proven antiretroviral strategies to assess relative efficacy for perinatal prevention plus maternal/infant safety and maternal health. The START study subsequently demonstrated clear benefit in initiating ART regardless of CD4 count. Active PROMISE participants were informed of results and women not receiving ART were strongly recommended to immediately initiate treatment to optimize their own health. We recorded their decision and the primary reason given for accepting or rejecting the universal ART offer after receiving the START information. One-third of participants did not initiate ART after the initial session, wanting more time to consider. Six sessions were required to attain 95% uptake. The slow uptake of universal ART highlights the need to prepare individuals and sensitize communities regarding the personal and population benefits of the "Treat All" strategy.

Prevalence, predictors and challenges of gestational diabetes mellitus screening among pregnant women in northern Tanzania.

OBJECTIVES: To determine the prevalence and predictors of gestational diabetes mellitus (GDM) as well as acceptability of returning for glucose tolerance testing among pregnant women in Moshi municipality, northern Tanzania. METHODS: Cross-sectional study from October 2015 to April 2016 among women with gestation age of 24-28 weeks of pregnancy attending at Kilimanjaro Christian Medical Centre (KCMC) referral hospital, Majengo and Pasua Health Centres. Women were interviewed and requested to return the next day (window within a month, depending on gestational age) for fasting plasma glucose (FPG) testing, followed immediately by a 75 g oral glucose tolerance test (OGTT). GDM was diagnosed using the 2013 WHO criteria. Logistic regression was conducted to reveal independent predictors for GDM. RESULTS: Of 433 interviewed women, 100 (23%) did not return for FPG and OGTT testing. The prevalence of GDM among the 333 screened women was 19.5%, and 3% had diabetes in pregnancy (DIP). GDM was significantly associated with age ≥35 years (adjusted OR 6.75), pre-pregnancy obesity (AOR 2.22) and history of abortion (AOR 2.36). CONCLUSION: Prevalence of GDM is high in Moshi. We recommend introduction of routine screening for hyperglycaemia during pregnancy along with strategies for follow-up to prevent long-term effects of GDM and DIP in women and their children.

PEG1/MEST and IGF2 DNA methylation un CIN and in cervical cancer

INTRODUCTION: Although most invasive cervical cancer (ICC) harbor <20 human papillomavirus (HPV) genotypes, use of HPV screening to predict ICC from HPV has low specificity, resulting in multiple and costly follow-up visits and overtreatment. We examined DNA methylation at regulatory regions of imprinted genes in relation to ICC and its precursor lesions to determine if methylation profiles are associated with progression of HPV-positive lesions to ICC. MATERIALS AND METHODS: We enrolled 148 controls, 38 CIN and 48 ICC cases at Kilimanjaro Christian Medical Centre from 2008 to 2009. HPV was genotyped by linear array and HIV-1 serostatus was tested by two rapid HIV tests. DNA methylation was measured by bisulfite pyrosequencing at regions regulating eight imprinted domains. Logistic regression models were used to estimate odd ratios. RESULTS: After adjusting for age, HPV infection, parity, hormonal contraceptive use, and HIV-1 serostatus, a 10 % decrease in methylation levels at an intragenic region of IGF2 was associated with higher risk of ICC (OR 2.00, 95 % CI 1.14-3.44) and cervical intraepithelial neoplasia (CIN) (OR 1.51, 95 % CI 1.00-2.50). Methylation levels at the H19 DMR and PEG1/MEST were also associated with ICC risk (OR 1.51, 95 % CI 0.90-2.53, and OR 1.44, 95 % CI 0.90-2.35, respectively). Restricting analyses to women >30 years further strengthened these associations. CONCLUSIONS: While the small sample size limits inference, these findings show that altered DNA methylation at imprinted domains including IGF2/H19 and PEG1/MEST may mediate the association between HPV and ICC risk (AU)

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PEG1/MEST and IGF2 DNA methylation in CIN and in cervical cancer.

INTRODUCTION: Although most invasive cervical cancer (ICC) harbor <20 human papillomavirus (HPV) genotypes, use of HPV screening to predict ICC from HPV has low specificity, resulting in multiple and costly follow-up visits and overtreatment. We examined DNA methylation at regulatory regions of imprinted genes in relation to ICC and its precursor lesions to determine if methylation profiles are associated with progression of HPV-positive lesions to ICC. MATERIALS AND METHODS: We enrolled 148 controls, 38 CIN and 48 ICC cases at Kilimanjaro Christian Medical Centre from 2008 to 2009. HPV was genotyped by linear array and HIV-1 serostatus was tested by two rapid HIV tests. DNA methylation was measured by bisulfite pyrosequencing at regions regulating eight imprinted domains. Logistic regression models were used to estimate odd ratios. RESULTS: After adjusting for age, HPV infection, parity, hormonal contraceptive use, and HIV-1 serostatus, a 10 % decrease in methylation levels at an intragenic region of IGF2 was associated with higher risk of ICC (OR 2.00, 95 % CI 1.14-3.44) and cervical intraepithelial neoplasia (CIN) (OR 1.51, 95 % CI 1.00-2.50). Methylation levels at the H19 DMR and PEG1/MEST were also associated with ICC risk (OR 1.51, 95 % CI 0.90-2.53, and OR 1.44, 95 % CI 0.90-2.35, respectively). Restricting analyses to women >30 years further strengthened these associations. CONCLUSIONS: While the small sample size limits inference, these findings show that altered DNA methylation at imprinted domains including IGF2/H19 and PEG1/MEST may mediate the association between HPV and ICC risk.

Prevalence and severity of cervical squamous intraepithelial lesion in a tertiary hospital in northern Tanzania.

Cervical cancer is the second most common cancer in women worldwide and the leading cause of cancer deaths in Tanzanian women. Prevention of cervical cancer relies on the detection and treatment of Squamous Intraepithelial Lesion (SIL), a premalignant disease stage. Worldwide there are overwhelming reports associating SIL and HIV infection, however in Tanzania such reports are limited. A cross-sectional hospital-based descriptive study was conducted to determine the prevalence and severity of SIL in 234 HIV seropositive and seronegative women aged 18-68 years old at Kilimanjaro Christian Medical Centre in northern Tanzania. A structured questionnaire was used to collect sociodemographic data. In addition, blood was collected for rapid HIV antibody testing and CD4+ T-lymphocyte counts to associate with prevalence and severity of SIL from the cervical smear collections. A total of 214 subjects had smear results regarded as valid for interpretation, of which 46.3% were HIV seropositive. Overall rate of SIL was 17%. Proportion of SIL among HIV seropositive subjects was 32% versus 4% in seronegative subjects (OR = 13.3, 95% CI = 4.2-46.4). Low CD4+ T-lymphocyte cell count was associated with higher prevalence of SIL (P = 0.001). The relationship between CD4+ T-lymphocyte cell counts and the severity of cervical SIL was significant (P = 0.007). Marital status and number of lifetime sex partners were risk factors significantly associated with SIL (P = 0.004 and 0.005, respectively). SIL was not associated with age, education level, parity or age at sex debut. The prevalence and severity of cervical SIL was significantly associated with HIV infection and immunologic disease progression. These findings underscore the need for HIV screening among women with SIL, and the need for cervical cancer screening in HIV-infected women. Marital status and number of lifetime sex partners were significant risk factors associated with SIL.