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Background With advances in cancer diagnosis and treatment, women with early-stage breast cancer (ESBC) are living longer, increasing the number of patients receiving post-treatment follow-up care. Best-practice survivorship models recommend transitioning ESBC patients from oncology-provider (OP) care to community-based care. While developing materials for a future randomized controlled trial (RCT) to test the feasibility of a nurse-led Telephone Survivorship Clinic (TSC) for a smooth transition of ESBC survivors to follow-up care, we explored patients’ and OPs’ reactions to several of our proposed methods. Methods We used a qualitative study design with thematic analysis and a two-pronged approach. We interviewed OPs, seeking feedback on ways to recruit their ESBC patients for the trial, and ESBC patients, seeking input on a questionnaire package assessing outcomes and processes in the trial. Results OPs identified facilitators and barriers and offered suggestions for study design and recruitment process improvement. Facilitators included the novelty and utility of the study and simplicity of methods; barriers included lack of coordination between treating and discharging clinicians, time constraints, language barriers, motivation, and using a paper-based referral letter. OPs suggested using a combination of electronic and paper referral letters and supporting clinicians to help with recruitment. Patient advisors reported satisfaction with the content and length of the assessment package. However, they questioned the relevance of some questions (childhood trauma) while adding questions about trust in physicians and proximity to primary-care providers. Conclusions OPs and patient advisors rated our methods for the proposed trial highly for their simplicity and relevance then suggested changes. These findings document processes that could be effective for cancer-patient recruitment in survivorship clinical trials.

Purpose Early childhood experiences of poverty are associated with adverse developmental outcomes that have impli cations for individual and population health. Low educational attainment and early childbearing are two such important outcomes that can perpetuate childhood poverty into adulthood. Child hunger, or severe food insecurity, is an extreme manifestation of household food insecurity that is associated with the stressful experience of deep family poverty. Life-course theories suggest that childhood experiences of hunger could have adverse effects in the developmental pathway. The objective of this study was to examine the independent contribution of the child hunger experience to subsequent educational attainment and early childbearing in young adult men and women, in consideration of other latent, cumulative or shock effects associated with child poverty. Methods We analyzed National Longitudinal Survey of Children and Youth data using logistic regression based on 15,468 Canadian children followed over 16 years. Results The prevalence of the experience of child hunger was 5.0%. Child hunger was independently predictive of youth leaving high school, yet was not a factor in the achievement of higher educational attainment if youth were able to graduate from high school. Having always lived in rental accommodation and repeated reports of child hunger over time were predictive of early childbearing. Conclusions Interventions directed at children and youth who are at risk of poor developmental outcomes because of severe food insecurity should focus on steering families toward their income entitlements, and providing support for youth to complete high school and to avoid early fertility.

We used longitudinal data to clarify the association between self-report of hunger and subsequent depression risk among youth and young adults, accounting for other risk factors. Youth self-report of ever experiencing hunger data were collected from cycles 4–6 of the National Longitudinal Survey of Children and Youth cohort of Canadian youth 16 years and older (n = 4139). Data on depressive symptoms (CES-D 12) were collected over three cycles (2004–2009, cycles 6–8). We used multivariable regression based on generalized estimating equations (GEE) to examine prior youth hunger on later depression risk, adjusting for time-stable, time-varying, and lagged variables (e.g., depressive symptoms in previous cycle), thereby clarifying the temporal relationship. The prevalence of youth hunger experience and depression risk reached 5.9 and 15.0%, respectively. The adjusted odds ratio of depression for participants reporting hunger was 2.31 (95% CI 1.54, 3.46) and changed little [2.17 (95% CI 1.29, 3.67)] after accounting for previous CES-D 12 scores, suggesting a temporal relationship in which hunger contributes to depression risk. Unlike never-hungry youth, depression in ever-hungry youth remained comparatively elevated over time. Our models support an independent and temporal relationship between youth self-report of hunger and depression in adolescence and young adulthood.

OBJECTIVES: Home ownership as opposed to renting is associated with lower rates of food insecurity, the latter being a marker of household economic deprivation associated with adverse health outcomes. It is unclear whether this relationship persists during a major economic decline, or whether different subgroups of home owners are equally protected. The 2008–2009 recession in Canada was tied to events in the United States related to inappropriate mortgage financing; the impact of the recession on food insecurity among home owners may identify policies to mitigate recessionary outcomes. METHODS: We used a before-and-after natural experimental design using data from the Canadian Community Health Survey (CCHS) cycles 2007/2008 (pre-recession) and 2009/2010 (post-recession) with information on household food insecurity, home ownership versus renting, and socio-demographics. Applying multivariable logistic regression, we examined changes in household food insecurity by housing tenure and sex over the period. RESULTS: Pre-recession, food insecurity affected 3.3% of home owners and 17.1% of renter households. Among home owners, the risk of food insecurity increased post-recession by 10%, which was not statistically significant. Post-recession, and with adjustment, although renters’ higher absolute risk of food insecurity persisted, male-respondent home owners experienced the highest rate of increase in food insecurity prevalence by subgroup (OR = 1.26, 95% CI: 1.06–1.50) versus renters (OR = 1.17, 95% CI: 1.05–1.29). CONCLUSION: Housing policies in Canada protected most home owners from precarity during the 2008–2009 economic recession; however, male-respondent home owners exhibited a unique economic vulnerability during this time. Implications of Canadian home ownership policies are discussed in light of differential vulnerability of home owner groups.

Sexually transmitted infections (STIs) and vaginal dysbiosis (disturbed resident microbiota presenting with abnormal Nugent score or candidiasis) have been associated with mucosal inflammation and risk of HIV-1 infection, cancer and poor reproductive outcomes. To date, the temporal relationships between aberrant cervical innate immunity and the clinical onset of microbial disturbance have not been studied in a large population of reproductive age women. We examined data from a longitudinal cohort of 934 Ugandan and Zimbabwean women contributing 3,274 HIV-negative visits who had complete laboratory, clinical and demographic data. Among those, 207 women later acquired HIV, and 584 women were intermittently diagnosed with C. trachomatis (CT), N. gonorrhoeae (NG), genital herpes (HSV-2), T. vaginalis (TV), candidiasis, and abnormal intermediate (4-6) or high (7-10) Nugent score, i.e. bacterial vaginosis (BV). Immune biomarker concentrations in cervical swabs were analyzed by generalized linear and mixed effect models adjusting for site, age, hormonal contraceptive use (HC), pregnancy, breastfeeding, genital practices, unprotected sex and overlapping infections. High likelihood ratios (1.5-4.9) denoted the values of cervical immune biomarkers to predict onset of abnormal Nugent score and candidiasis at the next visits. When controlling for covariates, higher levels of β-defensin-2 were antecedent to BV, CT and HSV-2, lower anti-inflammatory ratio IL-1RA:IL-1β-to intermediate Nugent scores and candida, lower levels of the serine protease inhibitor SLPI-to candida, lower levels of the adhesion molecule ICAM-1 -to TV, and lower levels of the oxidative stress mitigator and endothelial activation marker VEGF-to NG. Changes in innate immunity following onset of dysbiosis and infections were dependent on HC use when controlling for all other covariates. In conclusion, imminent female genital tract dysbiosis or infection can be predicted by distinct patterns of innate immunity. Future research should characterize biotic and abiotic determinants of this pre-existing innate immunity state.

Canada has episodically discussed guaranteed annual income (GAI) as a poverty reduction strategy, and the idea has garnered renewed attention. We investigate the potential effectiveness of such a strategy by examining food insecurity as an indicator of poverty in unattached low-income adults age 55 to 74 years before and after they become age-eligible for publicly financed pensions at age 65. Results from the Canadian Community Health Survey (2007–2013) showed that Canadians over age 65 have half the prevalence of food insecurity of low-income Canadians under 65. Seniors' public pensions, as an example of GAI, are an effective poverty reduction strategy.

Hormonal contraception (HC), particularly injectable depot-medroxyprogesterone acetate (DMPA), has been associated with increased HIV acquisition and higher levels of cervical regulated upon activation, normal T-cell expressed, and secreted (RANTES), also associated with HIV seroconversion. Longitudinal changes in cervical immunity associated with DMPA and combined oral contraceptives (COCs) have not been studied. Cervical samples from 216 HIV seroconverters in Uganda and Zimbabwe with matched samples from 727 HIV-uninfected controls were collected at two quarterly visits before (t − 2, t − 1), at (t0), and two visits following (t + 1, t + 2) HIV seroconversion and corresponding visits for HIV-negative controls. We measured 10 biomarkers of inflammation and immunity and used generalized linear models to estimate and compare biomarker levels across HIV status, contraceptive, and pregnancy groups. Biomarkers remained relatively stable across visits for controls, while in HIV-infected women cervical immunity started to change before seroconversion with RANTES and BD-2 increased and secretory leukocyte protease inhibitor (SLPI) decreased at t − 1 and continued to change at t0 with ICAM-1 up and IL-8 down and with more biomarkers after seroconversion (IL-1β, IL-6, MIP-3α, VEGF, and IL-1RA down and IL-1RA:IL-1β ratio up). In multivariable analyses, seroconverters had higher BD-2 at t − 1, higher RANTES and lower SLPI from t − 1 through t + 2, and lower IL-8 and IL-1RA at and/or after seroconversion compared to nonseroconverters. Compared to non-HC users, DMPA users had higher RANTES at all visits and lower BD-2 at t − 2 through t0, while COC users and pregnant women had higher IL-8 and SLPI at all visits; COC users also had lower BD-2 preseroconversion; pregnant women had lower RANTES at t0 − t + 2. Longitudinal patterns of cervical immunity differ between HIV seroconverters and HIV-negative women; seroconverters demonstrate increased RANTES and decreased SLPI starting before and continuing postseroconversion. Furthermore, these patterns are differentially regulated by DMPA, COC, and pregnancy.

In the majority of cases, human immunodeficiency virus type 1 (HIV-1) infection is transmitted through sexual intercourse. A single founder virus in the blood of the newly infected donor emerges from a genetic bottleneck, while in rarer instances multiple viruses are responsible for systemic infection. We sought to characterize the sequence diversity at early infection, between two distinct anatomical sites; the female reproductive tract vs. systemic compartment. We recruited 72 women from Uganda and Zimbabwe within seven months of HIV-1 infection. Using next generation deep sequencing, we analyzed the total genetic diversity within the C2-V3-C3 envelope region of HIV-1 isolated from the female genital tract at early infection and compared this to the diversity of HIV-1 in plasma. We then compared intra-patient viral diversity in matched cervical and blood samples with three or seven months post infection. Genetic analysis of the C2-V3-C3 region of HIV-1 env revealed that early HIV-1 isolates within blood displayed a more homogeneous genotype (mean 1.67 clones, range 1–5 clones) than clones in the female genital tract (mean 5.7 clones, range 3–10 clones) (p, Author summary During chronic HIV-1 infection, high viral diversity can be found in the blood and semen of donors. However, a single HIV-1 clone establishes productive infection in the recipient following heterosexual transmission. To investigate the genetic bottleneck occurring at the earliest stages of heterosexual HIV-1 transmission, we characterized the HIV-1 envelope sequence diversity at very early and early stages of infection in the female reproductive tract and matched plasma samples from a cohort of Ugandan and Zimbabwean women. A more diverse viral population was observed in the endocervical swab samples compared to plasma. Endocervical samples harbored a larger number of viral clones, while in the majority of plasma samples only a single clone was present early in infection. Interestingly, these observations were independent of HIV-1 subtype, hormonal contraceptive use or the number of sex acts and partners. Furthermore, in the cases of higher HIV-1 diversity in the blood during early infection, faster CD4 T cell decline were observed during chronic disease suggesting faster disease progression. Our findings provide novel in vivo evidence for the existence of an intra-patient genetic bottleneck restricting the HIV-1 from the vaginal tract to the blood during early heterosexual HIV-1 transmission.

Objective This study analyzes deciduous dental pathology and stable isotopes to investigate the relationship between diet, feeding practices, and oral health in a subadult skeletal sample from the Greek colonial site of Apollonia Pontica, Bulgaria (mid-5th to mid-3rd Centuries BC). Methods Stable carbon and nitrogen isotope analysis was conducted on 74 bone collagen samples, and the deciduous dentitions of 85 individuals aged 8.5 months to 11 years were examined for evidence of caries, calculus, antemortem tooth loss, abscesses, and occlusal tooth wear. Results δ13C and δ15N values of the collagen samples indicate that weaning began between the ages of 6 months and 1 year, and was complete for most individuals by the age of 3. The isotopic data are consistent with a mixed diet of primarily terrestrial C3 resources. The dental pathology data indicate that complementary foods provided to young children had an impact on their oral health early on. Four outliers exhibited elevated δ15N values compared with the adult female range and lower levels of tooth wear than other members of their age groups. Possible explanations include prolonged breastfeeding, the consumption of diets elevated in 15N, and physiological/nutritional stress. Conclusions The deciduous dental data correlate well with the isotopic data and are consistent with later textual sources regarding the timing and duration of weaning, and the composition of complementary foods. The results of this research demonstrate the value of combining isotopic and dental evidence to investigate the dietary practices of infants and young children and the impact of these practices on oral health. Am J Phys Anthropol, 2015. © 2015 Wiley Periodicals, Inc.

To describe pregnancy outcomes among HIV-infected women and examine factors associated with live birth among those receiving and not receiving combination antiretroviral therapy (cART).The present analysis included women with HIV from Uganda and Zimbabwe who participated in a prospective cohort study during 2001-2009. Incident pregnancies and pregnancy outcomes were recorded quarterly. The Kaplan-Meier method was used to estimate incident pregnancy probabilities; factors associated with live birth were evaluated by Poisson regression with generalized estimating equations.Among 306 HIV-infected women, there were 160 incident pregnancies (10.1 per 100 women-years). The pregnancy rate was higher among cART-naïve women than among those receiving cART (10.7 vs 5.5 per 100 women-years; P=0.047), and it was higher in Uganda than in Zimbabwe (14.4 vs 7.7 per 100 women-years; P0.001). Significant associations were noted between a live birth and prenatal care (relative risk 3.9; 95% confidence interval 2.2-6.9) and illness during pregnancy (relative risk 0.8; 95% confidence interval 0.7-1.0).Women not receiving cART have higher pregnancy rates than do those receiving cART, but cART use might not affect the risk of adverse pregnancy outcomes. Timely prenatal care and monitoring of illnesses during pregnancy should be incorporated into treatment services for HIV-infected women.

Traditional healers provide healthcare to a substantial proportion of people living with HIV infection (PLHIV) in high HIV burden countries in sub-Saharan Africa. However, the impact on the health of retained patients visiting traditional healers is unknown. In 2011, a study to asses adherence to anti-retroviral therapy (ART) performed in 18 purposefully selected HIV treatment centers in Tanzania, Zambia and Uganda showed that ‘consulting a traditional healer/herbalist because of HIV’ was an independent risk factor for incomplete ART adherence. To identify characteristics of PLHIV on ART who were also consulting traditional healers, we conducted a secondary analysis of the data from this study. It was found that 260 (5.8%) of the 4451 patients enrolled in the study had consulted a traditional healer during the last three months because of HIV. In multivariable analysis, patients with fewer HIV symptoms, those who had been on ART for >5.3 years and those from Tanzania were more likely to have consulted a traditional healer. However, at the time of the study, there was a famous healer in Manyara district, Loliondo village of Tanzania who claimed his herbal remedy was able to cure all chronic diseases including HIV. HIV treatment programs should be aware that patients with fewer HIV symptoms, those who have been on ART for five or more years, and patients attending ART centers near famous traditional healers are likely to consult traditional healers. Such patients may need more support or counseling about the risks of both stopping ART and poor adherence. Considering the realities of inadequate human resources for health and the burden of disease caused by HIV in sub-Saharan Africa, facilitating a collaboration between allopathic and traditional health practitioners is recommended.

OBJECTIVE:: To estimate whether continuous combined oral contraceptive pill (OCP) use leads to higher continuation and lower pregnancy rates over 12 months than cyclic use in a developing country setting. METHODS:: We enrolled healthy women aged 18 to 30 years in Santo Domingo Dominican Republic. We randomly assigned women to cyclic or continuous use of OCPs. Participants made quarterly clinic visits for 12 months. During follow-up we reviewed OCP adherence and continuation side effects and bleeding and we tested for pregnancy. RESULTS:: We enrolled 358 women (mean age 22.7 years) and 335 (93.6%) completed the study. In intent-to-treat analyses 77.6% of the continuous use group and 71.7% of the cyclic group continued OCPs at 12 months (P=.21). The main reason for OCP discontinuation in both groups was running out of OCPs or forgetting. Across all visits 26.1% of women in the continuous use group and 22.3% of women in the cyclic group ever reported missing three or more OCPs in the past month (P=.43). In multivariable analyses regimen was not associated with discontinuation but both previous birth and perceived ease of use of OCPs decreased risk of discontinuation whereas desire for reduced menstruation increased risk of discontinuation. Although more women reported amenorrhea or infrequent bleeding in the continuous use group more women in the cyclic group found their bleeding patterns acceptable. Bleeding was not associated with discontinuation in multivariable analyses. Pregnancy rates at 12 months were similar (16.2% continuous and 17.4% cyclic). CONCLUSIONS:: Continuous and cyclic OCP regimens were associated with similar 12-month continuation and pregnancy rates. Few factors predicted OCP discontinuation or pregnancy. CLINICAL TRIAL REGISTRATION:: ClinicalTrials.gov www.clinicaltrials.gov NCT00570440. LEVEL OF EVIDENCE:: I.

Little is known about the differences in clinical manifestations between women with various HIV-1 subtypes during acute (AI) and early (EI) HIV infection. In a longitudinal cohort study, clinical signs and symptoms among Uganda and Zimbabwe women with AI and EI were compared with HIV-negative controls; symptoms were assessed quarterly for 15 to 24 months. Early HIV infection was defined as the first visit during which a woman tested HIV antibody positive. Women who were HIV negative serologically but DNA polymerase chain reaction positive were considered AI. In all, 26 women were classified AI and 192 EI, with 654 HIV-negative controls. Primary HIV infection (AI and EI) was associated with unexplained fever ( P

Objective: To evaluate the effect of nevirapine-containing antiretroviral therapy (ART) on combined oral contraceptive (COC) effectiveness. Design: Nonrandomized prospective clinical trial. Methods: We enrolled HIV-infected women aged 18–35 years in South Africa and Uganda who had regular menses were sexually active and had no medical contraindications to COC use. We enrolled 196 women taking nevirapine-containing ART and 206 women not yet eligible for ART as a control group. We treated all participants with low-dose COCs. Our main outcomes were ovulation and pregnancy rates. We estimated ovulation in the first two cycles using weekly serum progesterone and tested for pregnancy monthly for 24 weeks. Results: The median age of participants was 29 and their median CD4þ cell count was 486. In the ART group 43 of 168 (26%) ovulated in cycle 1 30 of 163 (18%) in cycle 2 and 18 of 163 (11%) in both cycles. In the non-ART group 26 of 168 (16%) ovulated in cycle 1 31 of 165 (19%) in cycle 2 and 20 of 165 (12%) in both cycles. We found no significant difference in ovulation rates between groups: unadjusted odds ratio 1.36 (95% confidence interval 0.85–2.18). Pregnancy rates also did not differ: 10.0 per 100- women-years in the ART group and 10.1 per 100-women-years in the non-ART group. Self-reported COC adherence condom use vaginal bleeding and adverse events were similar. Five serious adverse events were reported all in the non-ART group. Conclusion: ART use did not affect risk of ovulation or pregnancy in women taking COCs suggesting that nevirapine-containing ART does not interfere with COC contraceptive effectiveness.

Hormonal contraception (HC) use by HIV-infected women has been identified by the World Health Organization as an important strategy for reducing vertical HIV transmission. Little is known about the factors associated with HC discontinuation among HIV-infected women.We analyzed data from a prospective study of HC use among 231 HIV-infected users with oral contraceptive (OC) or injectable depot medroxyprogesterone acetate (DMPA) in Uganda and Zimbabwe. We used Kaplan-Meier survival curves to estimate the median duration of OC and DMPA use and use of any highly effective contraceptive method. Cox proportional hazards models were used to investigate factors associated with HC discontinuation.Median duration was 36 months [95% confidence interval (CI): 14 to 61] for OC use and 19 months (95% CI: 14 to 24) for DMPA use. Median duration of any highly effective method was 36 months (95% CI: 26 to N/A) for OC users and 22 months (95% CI: 14 to 38) for DMPA users. In multivariable analyses, living in Zimbabwe [hazard ratio (HR): 0.39; 95% CI: 0.18 to 0.83], no partner (HR: 7.18; 95% CI: 3.05 to 16.88), and cervical infection (HR: 1.99; 95% CI: 0.90 to 4.41) were associated with OC discontinuation. No partner (HR: 2.00; 95% CI: 1.12 to 3.58), nausea (HR: 1.84; 95% CI: 1.02 to 3.34), and excessive night sweats (HR: 1.80; 95% CI: 0.95 to 3.40) were associated with DMPA discontinuation.Long-term use of HC methods is acceptable to HIV-infected women. Women discontinue for a variety of reasons, primarily unrelated to HIV. Alternative methods and ongoing contraceptive counseling is essential to reduce unplanned pregnancies and vertical HIV transmission.

Cervicovaginal HIV shedding is associated with increased female-to-male and mother-to-child transmission. Genital inflammation may increase shedding through cytokines/chemokines which recruit and activate HIV target cells. We evaluated whether cervical immune mediators present before seroconversion affected HIV shedding and whether mediators differed between shedders and nonshedders.We used cervical samples from 187 African women with documented HIV seroconversion in the Hormonal Contraception and HIV study. Samples were from the two visits before seroconversion (T-2 and/or T-1), and/or at seroconversion (T0), and/or the two visits (T + 1 and/or T + 2) after seroconversion. We measured interleukin (IL)-1β, IL-1 Receptor Antagonist (IL-1RA), IL-6, IL-8, RANTES (Regulated on Activation, Normal T-Cell Expressed and Secreted), MIP-3α, vascular endothelial growth factor (VEGF), Intercellular Adhesion Molecule-1 (ICAM-1), secretory leukocyte protease inhibitor (SLPI), and BD-2 and used the Wilcoxon test and generalized linear models to evaluate the association between mediators and shedding.The only immune mediator that differed at T-1 was RANTES, which was higher among shedders (p ≤ .05). HIV seroconversion was followed by significant decreases in many mediators, but a significant increase in RANTES. The magnitude of the change was significantly different for shedders versus nonshedders with regard to RANTES (increased in both groups, significantly more so in shedders), SLPI (decreased in both groups, significantly more so in shedders), and MIP-3α (decreased in shedders and increased in nonshedders). At T0, shedders had lower levels of SLPI and MIP-3α than nonshedders.In this study, a specific immune mediator profile was associated with risk of cervical HIV shedding. Higher and increasing levels of RANTES and lower and decreasing levels of SLPI and MIP-3α were associated with increased risk of HIV shedding.

Objectives: To evaluate the effect of hormonal contraception including combined oral contraceptives (COCs), and the injectable progestins depo-medroxyprogesterone acetate (DMPA) and norethisterone enanthate (Net-En) on the risk of HIV acquisition among women in South Africa. Design/methods: We analyzed data from 5567 women aged 16-49 years participating in the Carraguard Phase 3 Efficacy Trial. Participants were interviewed about contraceptive use and sexual behaviors and underwent pelvic examinations and HIV testing quarterly. We used marginal structural Cox regression models to estimate the effect of hormonal contraception exposure on HIV acquisition risk among women overall and among young women (16-24 years) in particular. Results: Two hundred and seventy participants became HIV-infected (3.7 per 100 woman-years); HIV incidence was 2.8, 4.6, 3.5 and 3.4 per 100 woman-years in the COC, DMPA, Net-En and nonhormonal contraceptive groups, respectively (P = 0.09). The adjusted hazard ratios (AHRs) were 0.84 [95% confidence interval (CI) 0.51-1.39], 1.28 (95% CI 0.92-1.78) and 0.92 (95% CI 0.64-1.32) among COC, DMPA and Net-En users, respectively, compared with the nonhormonal group controlling for covariates. Age modified the effect of hormonal contraception on HIV acquisition risk; among young women, the AHRs were 1.02 (95% CI 0.46-2.28) for COCs, 1.68 (95% CI 0.96-2.94) for DMPA and 1.36 (95% CI0.78-2.35) for Net-En users. Conclusions: In this study conducted among South African women, hormonal contraception did not significantly increase the risk of HIV acquisition. However, the effect estimate does not rule out a moderate increase in HIV risk associated with DMPA use found in some other recent studies. (C) 2012 Wolters Kluwer Health broken vertical bar Lippincott Williams & Wilkins

Background Bacterial vaginosis, a highly prevalent vaginal condition, is correlated with many adverse reproductive outcomes. In some studies, low vitamin D status (measured as serum 25-hydroxyvitamin D, 25[OH]D) has been associated with increased prevalence of bacterial vaginosis. Objectives We examined the cross-sectional association between vitamin D status and prevalence of bacterial vaginosis, separately for pregnant and nonpregnant women. Using prospectively collected data, we also characterized the effect of time-varying vitamin D status on incident bacterial vaginosis. Study Design We quantified 25(OH)D in stored sera collected quarterly from 571 Zimbabwean women participating in the Hormonal Contraception and Risk of HIV Acquisition Study. The analysis was restricted to women not using hormonal contraception. We characterized associations between vitamin D insufficiency (defined as 25[OH]D ≤ 30 ng/mL vs > 30 ng/mL) and prevalence of bacterial vaginosis among nonpregnant women at the enrollment visit and among pregnant women at the first follow-up visit that pregnancy was detected. Among women who were negative for bacterial vaginosis at enrollment (n = 380), we also assessed the effect of time-varying vitamin D status on incident bacterial vaginosis. We used the Liaison 25(OH)D total assay to measure 25(OH)D. Bacterial vaginosis was diagnosed via Nugent score. Results At enrollment, the prevalence of bacterial vaginosis was 31% and overall median 25(OH)D was 29.80 ng/mL (interquartile range, 24.70–34.30 ng/mL): 29.75 ng/mL (interquartile range, 25.15–33.95 ng/mL) among women with bacterial vaginosis, and 29.90 ng/mL (interquartile range, 24.70–34.50 ng/mL) among women without bacterial vaginosis. Among pregnant women, the prevalence of bacterial vaginosis was 27% and overall median 25(OH)D was 29.90 ng/mL (interquartile range, 24.10–34.00 ng/mL): 30.80 ng/mL (interquartile range, 26.10–36.90 ng/mL) among women with bacterial vaginosis, and 29.10 ng/mL (interquartile range, 23.80–33.45 ng/mL) among women without bacterial vaginosis. Vitamin D levels ≤ 30 ng/mL were not associated with a prevalence of bacterial vaginosis in nonpregnant women (adjusted prevalence ratio, 1.04; 95% confidence interval, 0.81–1.34) or pregnant women (adjusted prevalence ratio, 0.88, 95% confidence interval, 0.51–1.54). Vitamin D levels ≤ 30 ng/mL were similarly not associated with incident bacterial vaginosis (adjusted hazard ratio, 0.98, 95% confidence interval, 0.73–1.31). Our findings were robust to alternative specifications of vitamin D status including using a cut point for vitamin D deficiency of Conclusion Among reproductive-age Zimbabwean women, insufficient vitamin D was not associated with increased bacterial vaginosis prevalence or incidence. Given established associations between bacterial vaginosis and poor reproductive outcomes, identification of factors leading to high bacterial vaginosis prevalence is urgently needed.

OBJECTIVE: Although there is widespread recognition that poverty is a key determinant of health, there has been less research on the impact of poverty reduction on health. Recent calls for a guaranteed annual income (GAI), defined as regular income provided to citizens by the state regardless of work status, raise questions about the impact, relative to the costs, of such a population health intervention. The objective of this study was to determine the impact of Canadian seniors’ benefits (Old Age Security/Guaranteed Income Supplement, analogous to a GAI program) on the self-reported health, self-reported mental health and functional health of age-eligible, low-income seniors. METHODS: We used the 2009–2010 Canadian Community Health Survey to examine unattached adult respondents with an annual income of $20,000 or less, stratified by seniors’ benefits/GAI eligibility (55–64 years: ineligible; 65–74 years: eligible). Using regression, we assessed self-reported health, selfreported mental health and functional health as measured by the Health Utilities Index, as outcomes for seniors’ benefits/GAI-eligible and -ineligible groups. RESULTS: We found that individuals age-eligible for seniors’ benefits/GAI had better health outcomes than recipients of conditional income assistance programs. Eligibility for seniors’ benefits/GAI after age 64 was associated with better self-reported health, functional health and self-reported mental health outcomes, and these effects were observed until age 74. CONCLUSION: Using seniors’ benefits as an example, a GAI leads to significantly better mental health and improved health overall. These improvements are likely to yield reduced health care costs, which may offset the costs associated with program expansion.

Background We examined hormonal contraceptive (HC) discontinuation and factors associated with discontinuation among HIV-uninfected women and the effect of HIV diagnosis on subsequent contraceptive use. Study Design We analyzed 4461 HIV-uninfected women from a prospective study of HC and HIV acquisition in Uganda, Zimbabwe and Thailand. Participants were ages 18–35 years, not pregnant, and using oral contraceptives (OCs) or injectable depot medroxyprogesterone acetate (DMPA) for at least 3 months before enrollment (median duration of OC and DMPA use before enrollment was 11.7 and 8.9 months, respectively). We compared the probability of OC and DMPA discontinuation using survival analysis and factors related to discontinuation using Cox regression. We also analyzed contraceptive patterns among 194 women who became infected with HIV. Results Median duration of use after study enrollment was 15.6 months for OCs and 18.5 months for DMPA. Continuation rates for both methods were highest in Thailand. Factors associated with OC discontinuation included, nausea, breast tenderness, condom use, and no sex. Factors associated with DMPA discontinuation included young age, breast tenderness, nausea, irregular bleeding, high-risk sexual behaviors, partner risk, condom use, and no sex. Following an HIV diagnosis, 135 (98.5%) of 137 hormonal users continued HC and 14 (25%) of 57 nonusers began using HC. Conclusions Contraceptive continuation for OCs and DMPA was relatively high over 2 years. Young women, those reporting side effects, and those using condoms are more likely to discontinue and need ongoing contraceptive counseling. Many women receiving HIV-positive diagnoses desire effective contraception.

Background Progestin-only injectable contraceptives continue to gain in popularity, but uncertainty remains about pregnancy risk among women late for reinjection. The World Health Organization (WHO) recommends a “grace period” of 2 weeks after the scheduled 13-week reinjection. Beyond 2 weeks, however, many providers send late clients home to await menses. Study design A prospective cohort study in Uganda, Zimbabwe and Thailand followed users of depot-medroxyprogesterone acetate (DMPA) for up to 24 months. Users were tested for pregnancy at every reinjection, allowing analysis of pregnancy risk among late comers. Results The analysis consists of 2290 participants contributing 13,608 DMPA intervals. The pregnancy risks per 100 women-years for “on time” [0.6; 95% confidence interval (CI), 0.33–0.92], “2-week grace” (0.0; 95% CI, 0.0–1.88) and “4-week grace” (0.4; 95% CI, 0.01–2.29) injections were low and virtually identical. Conclusion Extending the current WHO grace period for DMPA reinjection from 2 to 4 weeks does not increase pregnancy risk and could increase contraceptive continuation.

Background. Trichomoniasis vaginalis is the most common nonviral sexually transmitted infection (STI) worldwide, with a particularly high prevalence in regions of human immunodeficiency virus (HIV) endemicity. However, its impact as a cofactor for HIV acquisition is poorly understood. Methods. Samples from 213 women who experienced HIV seroconversion (cases) during a longitudinal study involving 4450 women in Uganda and Zimbabwe were matched with samples from HIV-uninfected women (controls). All samples underwent polymerase chain reaction (PCR) analysis for Trichomonas vaginalis DNA. For cases, analyzed samples were from the visit in which HIV seroconversion was detected and the visit preceding detection of seroconversion; for controls, one analyzed sample was from the visit matched by follow-up duration to the cases' seroconversion visit, and the other sample was from the visit immediately preceding the matched visit. Results. The prevalence of T. vaginalis infection before HIV infection was 11.3% in cases and 4.5% in controls (P = .002). In multivariable analysis controlling for hormonal contraception, other STIs, behavioral, and demographic factors, the adjusted odds ratio for HIV acquisition was 2.74 (95% confidence interval, 1.25-6.00) for T. vaginalis-positive cases. The presence of behavioral risk factors for HIV infection, study recruitment from a referral population at high-risk for HIV, primary sex partner-associated risk for HIV infection, and herpes simplex virus type 2 seropositivity were also predictive of incident HIV infection. Conclusions. T. vaginalis infection is strongly associated with an increased risk for HIV infection in this general population of African women. Given the high prevalence of T. vaginalis infection in HIV-endemic areas, T. vaginalis control may have a substantial impact on preventing HIV acquisition among women

The objective was to estimate the probability of pregnancy for oral contraceptive pill (OCP) injectable contraceptive and condom users in Uganda Thailand and Zimbabwe. This study is a secondary analysis of 5224 women who participated in a prospective study evaluating the association between hormonal contraception and human immunodeficiency virus (HIV) acquisition. The overall 12-month cumulative probability of pregnancy of injectable contraceptive users was 0.6% (95% confidence interval [CI] 0.3-1.0) with similar risks in Uganda (0.3% 95% CI 0-0.7) Thailand (0.6% 95% CI 0-1.2) and Zimbabwe (1.0% 95% CI 0.3-1.7). The 12-month cumulative probability of pregnancy for OCP users was 9.5% (95% CI 8.1-11.0%) with similar risks of pregnancy in Uganda and Zimbabwe (14.6% 95% CI 11.7-17.4; and 10.2% 95% CI 8.0 -12.5 respectively) but substantially lower risk in Thailand (0.5% 95% CI 0-1.2). The overall 12-month cumulative probability of pregnancy for women intending to use a given method at baseline was 2.0% (95% CI 1.4-2.6%) for injectable contraceptives 15.7% (95% CI 14.1-17.3%) for OCPs and 25.8% (95% CI 23.2-28.4) for condoms. Women in Thailand experienced lower pregnancy risk with condoms (18.4% 95% CI 11.1-25.7) than in Uganda (29.5% 95% CI 25.7-33.4) and Zimbabwe (23.3% 95% CI 19.4-27.2). The overall risk of pregnancy for injectable contraceptive users was substantially lower than for oral contraceptive pill users. However Thai participants had similarly low cumulative pregnancy probabilities for both methods. Women receiving contraceptive counseling should be informed that their experience with a given method may differ from the average or typical-use pregnancy rates often discussed during contraceptive counseling. Tailored counseling is necessary for women to make informed choices. (authors)

In 1960 few in the developing world used contraceptives. Fifteen years later it was common and now the majority of couples use some method of contraception. During those early years a quiet social innovation occurred: the official national program to implement contraceptive practice throughout the entire country. That innovation spread across much of the developing world becoming a new determinant of fertility and did much to reverse traditional pro-natalist attitudes. The story of that revolution deserves a new examination as undertaken in this volume. The 23 case studies presented here were the earliest national efforts to establish organized family planning programs for entire populations. Useful accounts of the history of the family planning movement are available but the wealth of early country studies and analyses has been largely forgotten. Much of the history behind the creation of national programs has vanished and young people entering the field have limited awareness of it. Planners of related reproductive health programs lack ready access to the lessons gained from the formative years of nationally oriented family planning efforts. It is useful therefore to fill these gaps by providing accounts of those experiences and their implications for todays concerns. (excerpt)

Particular types of hormonal contraceptives (HCs) and genital tract infections have been independently associated with risk of HIV-1 acquisition. We examined whether immunity in women using injectable depot medroxyprogesterone acetate (DMPA), combined oral contraceptives (COC), or no HCs differs by the presence of cervicovaginal infections. Immune mediators were quantified in cervical swabs from 832 HIV-uninfected reproductive-age Ugandans and Zimbabweans. Bacterial infections and HIV were diagnosed by PCR, genital herpes serostatus by enzyme-linked immunosorbent assay (ELISA), altered microflora by Nugent score, and Trichomonas vaginalis and Candida albicans infection by wet mount. Generalized linear models utilizing Box-Cox-Power transformation examined associations between levels of mediators, infection status, and HCs. In no-HC users, T. vaginalis was associated with broadest spectrum of aberrant immunity (higher interleukin 1β [IL-1β], IL-8, macrophage inflammatory protein 3α [MIP-3α], β-defensin 2 [BD2], and IL-1 receptor antigen [IL-1RA]). In women with a normal Nugent score and no genital infection, compared to the no-HC group, COC users showed higher levels of IL-1β, IL-6, IL-8, and IL-1RA, while DMPA users showed higher levels of RANTES and lower levels of BD2, both associated with HIV seroconversion. These effects of COC were blunted in the presence of gonorrhea, chlamydia, trichomoniasis, candidiasis, and an abnormal Nugent score; however, RANTES was increased among COC users with herpes, chlamydia, and abnormal Nugent scores. The effect of DMPA was exacerbated by lower levels of IL-1RA in gonorrhea, chlamydia, or herpes, SLPI in gonorrhea, and IL-1β, MIP-3α, and IL-1RA/IL1β ratio in trichomoniasis. Thus, the effects of HC on cervical immunity depend on the genital tract microenvironment, and a weakened mucosal barrier against HIV may be a combined resultant of genital tract infections and HC use., IMPORTANCE In this article, we show that in young reproductive-age women most vulnerable to HIV, hormonal contraceptives are associated with altered cervical immunity in a manner dependent on the presence of genital tract infections. Through altered immunity, hormones may predispose women to bacterial and viral pathogens; conversely, a preexisting specific infection or disturbed vaginal microbiota may suppress the immune activation by levonorgestrel or exacerbate the suppressed immunity by DMPA, thus increasing HIV risk by their cumulative action. Clinical studies assessing the effects of contraception on HIV susceptibility and mucosal immunity may generate disparate results in populations that differ by microbiota background or prevalence of undiagnosed genital tract infections. A high prevalence of asymptomatic infections among HC users that remain undiagnosed and untreated raises even more concerns in light of their combined effects on biomarkers of HIV risk. The molecular mechanisms of the vaginal microbiome’s simultaneous interactions with hormones and HIV remain to be elucidated.

This study analyzes deciduous dental pathology and stable isotopes to investigate the relationship between diet, feeding practices, and oral health in a subadult skeletal sample from the Greek colonial site of Apollonia Pontica, Bulgaria (mid-5th to mid-3rd Centuries BC).Stable carbon and nitrogen isotope analysis was conducted on 74 bone collagen samples, and the deciduous dentitions of 85 individuals aged 8.5 months to 11 years were examined for evidence of caries, calculus, antemortem tooth loss, abscesses, and occlusal tooth wear.δ(13) C and δ(15) N values of the collagen samples indicate that weaning began between the ages of 6 months and 1 year, and was complete for most individuals by the age of 3. The isotopic data are consistent with a mixed diet of primarily terrestrial C3 resources. The dental pathology data indicate that complementary foods provided to young children had an impact on their oral health early on. Four outliers exhibited elevated δ(15) N values compared with the adult female range and lower levels of tooth wear than other members of their age groups. Possible explanations include prolonged breastfeeding, the consumption of diets elevated in (15) N, and physiological/nutritional stress.The deciduous dental data correlate well with the isotopic data and are consistent with later textual sources regarding the timing and duration of weaning, and the composition of complementary foods. The results of this research demonstrate the value of combining isotopic and dental evidence to investigate the dietary practices of infants and young children and the impact of these practices on oral health.

Severe acute respiratory syndrome (SARS) was imported into Singapore in late February 2003 by a local resident who returned from a holiday in Hong Kong and started an outbreak in the hospital where she was admitted on 1 March 2003. The disease subsequently spread to 4 other healthcare institutions and a vegetable wholesale centre. During the period between March and May 2003, 238 probable SARS cases, including 8 imported cases and 33 deaths, were reported. Transmission within the healthcare and household settings accounted for more than 90% of the cases. Factors contributing to the spread of infection included the failure to recognise the high infectivity of this novel infection, resulting in a delay in isolating initial cases and contacts and the implementation of personal protective measures in healthcare institutions; and the super-spreading events by 5 index cases, including 3 with co-morbid conditions presenting with atypical clinical manifestations of SARS. Key public health measures were directed at prevention and control within the community and hospitals, and the prevention of imported and exported cases. An isolated laboratory-acquired case of SARS was reported on 8 September 2003. Based on the lessons learnt, Singapore has further strengthened its operational readiness and laboratory safety to respond to SARS, avian flu and other emerging diseases.

OBJECTIVE: Hormonal contraception (HC) younger age and pregnancy have been associated with increased HIV risk in some studies. We sought to elucidate the biological mechanisms for these associations. DESIGN: Case-control selection of specimens from a large prospective clinical study. METHODS: We enrolled and followed 4531 HIV-negative women from Uganda and Zimbabwe using either the injectable depo-medroxyprogesterone acetate (DMPA) combined oral contraception or no HC (NH). Innate immunity mediators were measured in cervical samples collected from women at their visit before HIV seroconversion (n = 199) and matched visits from women remaining HIV uninfected (n = 633). Generalized linear models were applied after Box-Cox power transformation. RESULTS: Higher RANTES and lower secretory leukocyte protease inhibitor (SLPI) levels were associated with HIV seroconversion. DMPA users had higher RANTES and lower BD-2 levels. Most inflammation-promoting and/or inflammation-inducible mediators were higher [interleukin (IL)-1beta IL-6 IL-8 MIP-3alpha vascular endothelial growth factor and SLPI] and the protective BD-2 and IL-1RA:IL-1beta ratio were lower among combined oral contraception users. Pregnant women showed a similar cervical immunity status (higher IL-1beta IL-6 IL-8 vascular endothelial growth factor SLPI and IL-1RA; lower IL-1RA:IL-1beta). Age

Objective To assess whether the risk of complications is higher in HIV-1-infected women compared with non-infected women in the two years following insertion of the intrauterine contraceptive device. Design Prospective cohort study. Population Six hundred and forty-nine women (156 HIV-1-infected, 493 non-infected) in Nairobi, Kenya who requested an intrauterine contraceptive device and met local eligibility criteria. Methods We gathered information on complications related to the use of the intrauterine contraceptive device, including pelvic inflammatory disease, removals due to infection, pain or bleeding, expulsions, and pregnancies at one, four, and 24 months after insertion by study physicians masked to participants’ HIV-1 status. Cox regression was used to estimate hazard ratios. Results Complications were identified in 94 of 636 women returning for follow up (14.7% of HIV-1-infected, 14.8% of non-infected). The incidence of pelvic inflammatory disease was rare in both infected (2.0%) and non-infected (0.4%) groups. Multivariate analyses suggested no association between HIV-1 infection and increased risk of overall complications (hazard ratio=1.0; 95% CI 0.6-1.6). Infection-related complications (e.g. any pelvic tenderness, removal for infection or pain) were also similar between groups (10.7% of HIV-1-infected, 8.8% of non-infected; P=0.50), although there was a non-significant increase in infection-related complications among HIV-1-infected women with use of the intrauterine contraceptive device longer than five months (hazard ratio=1.8; 95% CI 0.8-4.4). Neither overall nor infection-related complications differed by CD4 (immune) status. Conclusions HIV-1-infected women often have a critical need for safe and effective contraception. The intrauterine contraceptive device may be an appropriate contraceptive method for HIV-1-infected women with ongoing access to medical services.

Objective: Mycoplasma genitalium is an emerging sexually transmitted infection (STI) and has been associated with reproductive tract infections and HIV in cross-sectional studies. In this longitudinal study, we assess whether M. genitalium is associated with risk of acquiring HIV-1 infection. Design: Nested case-control study within a large prospective study in Zimbabwe and Uganda Methods: A total of 190 women who seroconverted to HIV-1 during follow-up (cases) were matched with up to two HIV-negative controls. Mycoplasma genitalium testing was performed by PCR-ELISA, using archived cervical samples from the HIV-1 detection visit and the last HIV-negative visit for cases, and equivalent visits in follow-up time for controls. Risk factors for HIV-1 acquisition were analyzed using conditional logistic regression, with M. genitalium as the primary exposure. Results: Mycoplasma genitalium was a common infection in these populations (14.8 and 6.5% prevalence among cases and controls, respectively, at the visit prior to HIV-1 detection), and more prevalent than other nonviral STIs. We found a greater than two-fold independent increased risk of HIV-1 acquisition among women infected with M. genitalium at the visit prior to HIV-1 acquisition [ adjusted odds ratio (AOR) = 2.42; 95% confidence interval (CI) 1.01-5.80), and at time of HIV-1 acquisition (AOR 2.18; 95% CI 0.98-4.85). An estimated 8.7% (95% CI 0.1-12.2%) of incident HIV-1 infections were attributable to M. genitalium. Conclusion: This is the first longitudinal study to assess the relationship between M. genitalium and HIV-1 acquisition. If findings from this research are confirmed, M. genitalium screening and treatment among women at high risk for HIV-1 infection may be warranted as part of an HIV-1 prevention strategy. (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

BACKGROUND: Individuals who acquire human immunodeficiency virus (HIV) may experience an immediate disruption of genital tract immunity altering the ability to mount a local and effective immune response. This study examined the impact of early HIV infection on new detection of human papillomavirus (HPV). METHODS: One hundred fifty-five Zimbabwean women with observation periods before and after HIV acquisition and 486 HIV-uninfected women were selected from a cohort study evaluating hormonal contraceptive use and risk of HIV acquisition. Study visits occurred at 3-month intervals. Cervical swab samples available from up to 6 months before at and up to 6 months after the visit when HIV was first detected were typed for 37 HPV genotypes or subtypes. RESULTS: We observed approximately 5-fold higher odds of multiple (>/=2) new HPV detections only after HIV acquisition relative to HIV-negative women after adjusting for sexual behavior and concurrent genital tract infections. We also observed approximately 2.5-fold higher odds of single new HPV detections at visits before and after HIV acquisition relative to HIV-uninfected women in multivariable models. CONCLUSIONS: These findings suggest that HIV infection has an immediate impact on genital tract immunity as evidenced by the high risk of multiple new HPV detections immediately after HIV acquisition. (c) The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

The effect of combined oral contraceptives (COCs) and depot-medroxyprogesterone acetate (DMPA) on the area of cervical ectopy is not well understood.From 1996 to 1999, we recruited women not using hormonal contraception from two family planning centers in Baltimore, MD. Upon study entry and 3, 6 and 12 months after the initial visit, participants were interviewed and received visual cervical examinations with photography. Ectopy was measured from digitized photographs and was analyzed both continuously and categorically (small [≤0.48 cm(2)] vs. large [0.48 cm(2)]).Of 1003 enrolled women, 802 returned for at least one follow-up visit. At 12 months, the numbers of women using COCs, DMPA or no hormonal method at least 50% of the time since the prior visit were 230, 76 and 229, respectively. After multivariable adjustment, COC use (vs. no hormonal use) was associated with large area of ectopy (odds ratio [OR]: 1.8, 95% confidence interval [CI]: 1.0-3.3). No significant relationship was observed between DMPA and large area of ectopy (OR: 0.5, 95% CI: 0.2-1.3). The incidence of large area of ectopy by contraceptive exposure (COC, DMPA or no hormonal method) was 17.4 (CI: 11.8-24.6), 10.9 (CI: 4.4-22.4) and 4.6 (CI: 2.2-8.4) per 100 woman-years, respectively.Use of COCs, but not DMPA, was associated with large area of cervical ectopy. Area of ectopy at baseline was the strongest predictor of area of ectopy at follow-up.

During the HC-HIV Study more than 30% of participants switched their contraceptive method. The decision to switch contraceptive use was found to be associated with participants’ use of condoms, their sexual behavioral risk, and their partners’ behavioral risks – all risk factors for HIV acquisition in the HC-HIV Study dataset. Furthermore, these HIV risk factors changed over time and may both predict subsequent hormonal contraceptive use and be predicted by past hormonal contraceptive exposure and thus were found to be time-dependent confounders. Use of conventional Cox proportional hazard regression modeling as applied in the original analysis [1] cannot satisfactorily adjust for

We conducted a cross-sectional study with 208 HIV-uninfected and 188 HIV-infected women in Uganda and Zimbabwe to investigate differences in median CD4 counts. Absolute CD4 counts were determined by flow cytometry. Multivariate analyses were used to examine the association of country and HIV-infection status on CD4 counts. Median CD4 counts were significantly lower in Zimbabwe than in Uganda overall (649 and 783 cells/mm3, P = 0.009) and among HIV-infected women (470 and 614 cells/mm3, P = 0.003). In separate multivariable models, CD4 counts were significantly lower in Zimbabwe in HIV-uninfected ( P = 0.014) and infected ( P < 0.001) women, controlling for age, contraceptive method, education and living with partner status. In a model combining HIV-uninfected and infected women, there was no significant interaction between country and HIV infection status ( P = 0.344), suggesting that the relationship between country and CD4 count was not significantly modified by HIV infection status. This study reinforces the importance of establishing country-specific reference CD4 levels as CD4 count continues to be used as a key biomarker in clinical decision-making for HIV-infected individuals in sub-Saharan Africa.

Early HIV infection represents a dynamic period during which infection disseminates from local lymph nodes and HIV viremia initially climbs to very high levels followed by a decline to an equilibrium (viral setpoint). The high viremia levels in peripheral blood during early infection appear associated with high levels of HIV transmission [1]. In addition, the level of viral setpoint is an important predictor of subsequent HIV disease progression [2-4]. While this dynamic period has been well-documented in the peripheral blood, little is known about the dynamic of genital viral loads during early infection (first 6 months). Genital viral loads, the biologic mediator between plasma viral loads and HIV transmission, are important to understand particularly during the early infection period. Two recent studies conducted in men [5] and women [6] have documented high genital viral loads during this period. However, it is unclear if and when a setpoint is attained in the genital compartment. It is also unclear whether there are modifiable risk factors that influence genital viral loads during the early infection period. Few studies have examined factors associated with plasma viral setpoint. A study conducted among Kenyan sex workers [7] found that use of the injectable-progestin contraceptive depot-medroxyprogesterone acetate (DMPA) at the time of HIV infection was associated with a higher plasma viral load setpoint while the presence of genital ulcer disease (GUD) during early HIV infection was associated with higher subsequent plasma viral loads. However, these findings have not been corroborated. HIV-1 genital shedding among women can be affected by both systemic (pregnancy, hormonal contraceptive use, CD4 lymphocyte levels, plasma viral loads, HAART, HIV-1 subtype) [8-15] and local factors (menstruation, genital inflammation, cervical and vaginal infections, abnormal vaginal flora) [6;8-9;13;16-20]. However, factors associated with HIV-1 genital shedding during early HIV-1 infection have not been reported. We studied the relationship between plasma and genital HIV viral loads among Ugandan and Zimbabwean women during acute and early (first 6 months) HIV infection and examine factors, including hormonal contraceptive use, that may be associated with plasma and genital viral loads during this period and could impact subsequent HIV-1 disease progression or transmission. Data was drawn from a prospective cohort study of contraception and HIV acquisition – the Hormonal Contraception and the Risk of HIV Acquisition (HC-HIV) Study [21] and a subsequent study conducted among the women who became HIV-infected – the Hormonal Contraception and HIV-1 Genital Shedding and Disease Progression among Women with Primary HIV Infection (GS) Study.

Objective : To determine if women receiving intrauterine devices (IUCDs) outside of menses have an acceptable rate of insertion problems and subsequent IUCD-related complications. Design : Cross-sectional and prospective cohort study of insertions at times other than during menses. Setting : The study was carried out in two government family planning (FP) clinics in Nairobi,Kenya. Subjects : After appropriate pre-test and post-test HIV counselling, 1686 women requesting IUCDs at two FP clinics between 1994 and 1995 in Nairobi were enrolled at baseline into a study examining the effect of human complications. Six hundred and forty nine women (156 HIV-infected and 493 HIVuninfected) were selected for the four month follow up study. They were classified according to their menstrual cycle status at time of IUCD insertion. Main outcome measures : Problems at the time of insertion (pain, bleeding, immediate expulsion) and IUCD-related complications through four months. Results : Rates of immediate insertion problems were low in the women who had insertions during menses (7.0%), outside of menses (4.0%) or had oligomenorrhea/amenorrhea (2.6%). The adjusted odds ratios for IUCD insertion problems outside of menses and in oligomenorrhea/ amenorrhea (versus women with insertion during menses) were 0.54 (95% CI 0.18 -1.59) and 0.39 (95% CI 0.12 -1.29) respectively. IUCD-related complications were higher in the iligomenorrhea/amenorrhea (11.5%) or insertion outside of menses (6.9%), than the within menses (4.3%) groups. However, the differences were not statistically significant. Adjusted odds ratios for IUCD outside of menses and oligomenorrhoea/amenorrhea groups were 1.65 (95% CI 0.21 - 12.91) and 2.72 (95% CI 0.34 - 21.71) respectively. Conclusion : The results confirm that the IUCD can be safely inserted outside of menses with minimal insertion difficulties and subsequent complications. Availability of IUCDs outside of menses may enhance IUCD acceptance in Kenya and create better opportunity for visual screening of the cervix for sexually transmitted infections.

Objective: To estimate the effects of reproductive tract infections (RTIs) on HIV acquisition among Zimbabwean and Ugandan women. Methods: A multicenter prospective observational cohort study enrolled 4439 HIV-uninfected women aged 18 to 35 attending family planning clinics in Zimbabwe and Uganda. Participants, were interviewed, and tested for HIV and RTIs every 3 months for 15 to 24 months. They received HIV risk reduction counseling, male condoms, and treatment for curable RTIs. Results: Despite HIV risk reduction counseling and regular screening and treatment for RTIs, the HIV incidence did not decline during the study. Positive HSV-2 serostatus at baseline (hazard ratio [HR] = 3.69, 95% confidence interval = 2.45-5.55), incident HSV-2 (HR = 5.35, 3.06-9.36), incident Neisseria gonorrhoeae (HR = 5.46, 3.41-8.75), and altered vaginal flora during the study (bacterial vaginosis [BV]: HR = 2.12, 1.50-3.01; and intermediate flora: HR = 2.02, 1.39-2.95) were independently associated with HIV acquisition after controlling for demographic and behavioral covariates and other RTIs (Treponema pallidum, Chlamydia trachomatis, Trichomonas vaginalis, and vaginal yeasts). For N. gonorrhoeae, C. trachomatis, T vaginalis, and vaginal yeasts,. the risk of HIV acquisition increased when the infection was identified at the visit before the HIV-detection visit or with the duration of infection. Population attributable risk percent (PAR%) calculations show that HSV-2 contributes most to acquisition of new HIV infections (50.4% for baseline HSV-2 and 7.9% for incident HSV-2), followed by altered vaginal flora (17.2% for bacterial vaginosis and 11.8% for intermediate flora). Conclusions: A substantial proportion of new HIV infections in Zimbabwean and Ugandan women are attributable to RTIs, particularly HSV-2 and altered vaginal flora

Background The IUD is a highly effective, safe, inexpensive and long-lasting contraceptive. However, IUDs may increase PID risk during the early postinsertion period when inserted in women with cervical infections. We developed a simple algorithm to identify women at low risk of current sexually transmitted infection (STI) who are appropriate IUD candidates in regions with moderate or high STI prevalence. Methods We used data sets from family planning populations in Kenya, Zimbabwe, Jamaica and the United States to develop optimum algorithms. We then validated these algorithms using data sets from family planning populations in Thailand and Uganda. Results A simple unweighted algorithm based on age, living with partner, education, bleeding between periods and a behavioral risk score (number of sex partners, condom use) was the most useful. Adding clinical signs did not improve algorithm performance. Women categorized at low risk by this algorithm were at substantially reduced risks of cervical infection. Women identified at high STI risk had at least twice the risk as the overall clinic populations. Women in the moderate-risk group had STI risks similar to the overall clinic populations. Conclusion Women categorized as low risk by the algorithm can be referred for IUD insertion while women categorized at high risk should not receive an IUD without further testing or treatment. Women in the moderate-risk group should be triaged based on the STI prevalence of the overall clinic population. A simple checklist has been developed to help providers estimate a client's risk of current STI and to guide appropriate triage.

Objective This study evaluated the effect of the so-called universal placebo compared to the polystyrene sulfonate (PSS) placebo on genital irritation. Design A single-center, Phase I, randomized, closed-label study was performed to evaluate the genital irritation of microbicide placebo gels. Thirty healthy, sexually abstinent women were randomly assigned to apply 3.5 mL of either the universal placebo or the PSS placebo gel intravaginally twice daily for 14 days. Methods Genital irritation was assessed by signs as seen on pelvic examination and colposcopy and reports of symptoms. Vaginal health was assessed by wet mounts, Gram stains for Nugent score and polymorphonuclear leukocytes, and semiquantitative vaginal cultures. Acceptability was assessed as reported on the follow-up questionnaire. Results The universal placebo was less irritating than the PSS placebo with a lower proportion of women experiencing signs and/or symptoms of genital irritation throughout follow-up (36% compared to 80%, p=.0253). The universal placebo was associated with few and mild genital symptoms, few and minor colposcopic findings and good vaginal health with no clinically significant changes in genital flora. Most participants found the feel of the universal placebo gel neutral or pleasant, and all participants found it odorless. Conclusions The universal placebo appeared safe and acceptable when used twice daily for 14 days. The strategy of creating a de novo inert universal placebo is a successful approach. The universal placebo is appropriate for use as a placebo gel in HIV prevention trials with microbicide candidates.

Background and Objectives: Several previous studies have suggested that hormonal contraception could be associated with increased risk of cervical infections. However, few high-quality prospective studies have examined this relationship. Goal: The goal of this study was to measure the effect of oral contraceptives (OC) and depot-medroxyprogesterone acetate (DMPA) on the acquisition of cervical chlamydial and gonococcal infections. Study: Women attending 2 reproductive health centers in Baltimore, MD, were enrolled into a prospective cohort study. Participants were 15 to 45 years and were initiating OCs or DMPA or not using hormonal contraception. Interviews, physical examinations, and testing for incident cervical infections were conducted at 3, 6, and 12 months. Results: The analysis included 819 women. Most were single (77%) and nulliparous (75%); 43% were black. Median age was 22 years. During the study, 45 women acquired a chlamydial or gonococcal infection (6.2 per 100 women-years). DMPA use (hazard ratio [HR], 3.6; 95% confidence interval [CI], 1.6 ‐ 8.5), but not OC use (HR, 1.5; 95% CI, 0.6 ‐3.5), was significantly associated with increased acquisition of cervical infections after adjusting for other risk factors. Cervical ectopy was not an important mediator of cervical infection risk. Conclusions: DMPA use, but not OC use, appeared to be significantly associated with increased acquisition of cervical chlamydial and gonococcal infections.