Florence Mirembe

Lack of Effectiveness of Cellulose Sulfate Gel for the Prevention of Vaginal HIV Transmission

BACKGROUND Women make up more than 50% of adults living with human immunodeficiency virus (HIV) infection or the acquired immunodeficiency syndrome (AIDS) in sub-Saharan Africa. Thus, female-initiated HIV prevention methods are urgently needed. METHODS We performed a randomized, double-blind, placebo-controlled trial of cellulose sulfate, an HIV-entry inhibitor formulated as a vaginal gel, involving women at high risk for HIV infection at three African and two Indian sites. The primary end point was newly acquired infection with HIV type 1 or 2. The secondary end point was newly acquired gonococcal or chlamydial infection. The primary analysis was based on a log-rank test of no difference in the distribution of time to HIV infection, stratified according to site. RESULTS A total of 1398 women were enrolled and randomly assigned to receive cellulose sulfate gel (706 participants) or placebo (692 participants) and had follow-up HIV test data. There were 41 newly acquired HIV infections, 25 in the cellulose sulfate group and 16 in the placebo group, with an estimated hazard ratio of infection for the cellulose sulfate group of 1.61 (P=0.13). This result, which is not significant, is in contrast to the interim finding that led to the trial being stopped prematurely (hazard ratio, 2.02 [corrected]; P=0.05 [corrected]) and the suggestive result of a preplanned secondary (adherence-based) analysis (hazard ratio, 2.02; P=0.05). No significant effect of cellulose sulfate as compared with placebo was found on the risk of gonorrheal infection (hazard ratio, 1.10; 95% confidence interval [CI], 0.74 to 1.62) or chlamydial infection (hazard ratio, 0.71; 95% CI, 0.47 to 1.08). CONCLUSIONS Cellulose sulfate did not prevent HIV infection and may have increased the risk of HIV acquisition. (ClinicalTrials.gov number, NCT00153777; and Current Controlled Trials number, ISRCTN95638385.)

The dilemma of safe sex and having children: challenges facing HIV sero-discordant couples in Uganda

CONTEXT Contraceptive discontinuation is a common event that may be associated with low motivation to avoid pregnancy. If this is the case, a substantial proportion of pregnancies that follow discontinuation will be reported as intended. METHODS Demographic and Health Survey data from six countries (Bangladesh, the Dominican Republic, Kazakhstan, Kenya, the Philippines and Zimbabwe) over the period 1999-2003 were used to explore the proportions of pregnancies women reported as intended or unintended following various contraceptive behaviors. Multivariate logistic regression analysis was used to examine the characteristics of women who reported births as intended when they followed contraceptive failure or discontinuation for reasons other than a desire for pregnancy. RESULTS The proportion of births reported as intended following contraceptive failure ranged from 16% in Bangladesh to 54% in Kazakhstan, and the proportion reported as intended following discontinuation for reasons other than a desire for pregnancy ranged from 37% in Kenya to 51% in Kazakhstan. In at least half the countries, associations were found between selected womens characteristics and their reports that births following either contraceptive failure or discontinuation were intended: Factors that were positively associated were womens age and the time elapsed between contraceptive discontinuation and the index conception; factors that were negatively associated were increasing number of living children and reporting method failure as opposed to method discontinuation. CONCLUSION These findings suggest that underlying variation in the motivation to avoid pregnancy is an important factor in contraceptive discontinuation.BACKGROUND Sixty percent of new HIV infections in Uganda occur in stable relationships between HIV discordant couples. Given the importance of fertility in Uganda, we hypothesized that unsafe sexual practices may be used to found a family/replace a dead child. Thus, we explored sexual practices to understand to what extent these are influenced by the desire to have children and the implications for HIV transmission among discordant couples. METHODS A cross-sectional survey of 114 HIV discordant couples in Kampala, and in-depth interviews with 15 purposively selected couples. Quantitative data were analysed using STATA. Multivariate logistic regression analysis done to identify factors associated with consistent condom use. Thematic content analysis of qualitative data was done using NVIVO 2. RESULTS Participants wanting children and those with multiple sexual partners were less likely to use condoms (Adj OR 0.51, and 0.36 respectively). Three of the five types of sexual practices used by couples do not allow pregnancy to occur. Main reasons for wanting a child included: ensuring lineage continuity and posterity, securing relationships and pressure from relatives to reproduce. Challenges included: risk of HIV transmission to partner and child, lack of negotiating power for safer sex, failure of health systems to offer safe methods of reproduction CONCLUSIONS HIV sero-discordant couples with strong desire for childbearing have a dilemma of risking HIV infection or infecting their spouse. Some risk transmission of HIV infection to reproduce. We need to address gender issues, risky behaviour and reproductive health services for HIV sero-discordant couples.

Persistent high fertility in Uganda: young people recount obstacles and enabling factors to use of contraceptives

BackgroundHigh fertility among young people aged 15-24 years is a public health concern in Uganda. Unwanted pregnancy, unsafe induced abortions and associated high morbidity and mortality among young women may be attributed to low contraceptive use. This study aims at exploring reasons for low contraceptive use among young people.MethodsIn 16 focus group discussions, the views of young people about obstacles and enabling factors to contraceptive use in Mityana and Mubende districts, Uganda were explored. The groups were homogeneously composed by married and unmarried men and women, between the ages of 15-24. The data obtained was analyzed using qualitative content analysis.ResultsYoung men and women described multiple obstacles to contraceptive use. The obstacles were categorized as misconceptions and fears related to contraception, gender power relations, socio-cultural expectations and contradictions, short term planning, and health service barriers. Additionally, young people recounted several enabling factors that included female strategies to overcome obstacles, changing perceptions to contraceptive use, and changing attitude towards a small family size.ConclusionsOur findings suggest changing perceptions and behavior shift towards contraceptive use and a small family size although obstacles still exist. Personalized strategies to young women and men are needed to motivate and assist young people plan their future families, adopt and sustain use of contraceptives. Reducing obstacles and reinforcing enabling factors through education, culturally sensitive behavior change strategies have the potential to enhance contraceptives use. Alternative models of contraceptive service delivery to young people are proposed.

Domestic Violence During Pregnancy and Risk of Low Birthweight and Maternal Complications: A Prospective Cohort Study at Mulago Hospital, Uganda

Objectives  To investigate whether domestic violence during pregnancy is a risk factor for antepartum hospitalization or low birthweight (LBW) delivery.

A randomized trial of misoprostol compared with manual vacuum aspiration for incomplete abortion.

Objective: To compare the safety, efficacy, and acceptability of misoprostol and manual vacuum aspiration for the treatment of incomplete abortion in a hospital setting in Kampala, Uganda. Methods: Three hundred seventeen women with clinically diagnosed incomplete first-trimester abortions were randomized to treatment with either manual vacuum aspiration or 600 &mgr;g misoprostol orally to complete their abortions. All women received antibiotics posttreatment and were followed up 1–2 weeks later. Results: Regardless of treatment allocation, nearly all women in this study successfully completed their abortions with either oral misoprostol or manual vacuum aspiration (96.3% versus 91.5%, relative risk 1.05, 95% confidence interval 0.98–1.14). Complications were less frequent in those receiving misoprostol than those having manual vacuum aspiration (0.9% versus 9.8%, relative risk 0.1, 95% confidence interval 0.01–0.78). In the 6 hours after treatment, women using misoprostol reported heavier bleeding but lower levels of pain than those treated with manual vacuum aspiration. Rates of acceptability were similarly high among women in the 2 treatment groups, with 94.2% and 94.7% of women reporting that their treatment was satisfactory or very satisfactory in the misoprostol and manual vacuum aspiration groups, respectively. Conclusion: For treatment of first-trimester uncomplicated incomplete abortion, both manual vacuum aspiration and 600 &mgr;g oral misoprostol are safe, effective, and acceptable treatments. Based on availability of each method and the wishes of individual women, either option may be presented to women for the treatment of incomplete abortion. Level of Evidence: I

A multicountry evaluation of careHPV testing, visual inspection with acetic acid, and papanicolaou testing for the detection of cervical cancer.

Objective This study evaluates the feasibility and performance of careHPV, a novel human papillomavirus (HPV) DNA test, when used for screening women for cervical cancer in low-resource settings. Methods and Materials Clinician-collected (cervical) and self-collected (vaginal) careHPV specimens, visual inspection with acetic acid (VIA), and Papanicolaou test were evaluated among 16,951 eligible women in India, Nicaragua, and Uganda. Women with positive screening results received colposcopy and histologic follow-up as indicated. The positivity of each screening method was calculated overall, by site, and age. In addition, the clinical performance of each screening test was determined for detection of cervical intraepithelial neoplasia (CIN) grade 2 (CIN2+) and CIN grade 3. Results Moderate or severe dysplasia or cancer (taken together as CIN2+) was diagnosed in 286 women. The positivity rate ranged between 2.4% to 19.6% for vaginal careHPV, 2.9% to 20.2% for cervical careHPV, 5.5% to 34.4% for VIA, and 2.8% to 51.8% for Papanicolaou test. Cervical careHPV was the most sensitive for CIN2+ (81.5%; 95% confidence interval [CI], 76.5–85.8) and CIN grade 3 (85.3%; 95% CI, 78.6–90.6) at all sites, followed by vaginal careHPV (69.6% and 71.3%, respectively). The sensitivity of VIA ranged from 21.9% to 73.6% and Papanicolaou test from 40.7% to 73.7%. The pooled specificities of cervical careHPV, vaginal careHPV, VIA, and Papanicolaou test were 91.6%, 90.6%, 84.2%, and 87.7%, respectively. Conclusions careHPV performed well in large multicountry demonstration studies conducted in resource-limited settings that have not previously been conducted this type of testing; its sensitivity using cervical samples or vaginal self-collected samples was better than VIA or Papanicolaou test. The feasibility of using careHPV in self-collected vaginal samples opens the possibility of increasing coverage and early detection in resource-constrained areas.Objective This study evaluates the feasibility and performance of careHPV, a novel human papillomavirus (HPV) DNA test, when used for screening women for cervical cancer in low-resource settings. Methods and Materials Clinician-collected (cervical) and self-collected (vaginal) careHPV specimens, visual inspection with acetic acid (VIA), and Papanicolaou test were evaluated among 16,951 eligible women in India, Nicaragua, and Uganda. Women with positive screening results received colposcopy and histologic follow-up as indicated. The positivity of each screening method was calculated overall, by site, and age. In addition, the clinical performance of each screening test was determined for detection of cervical intraepithelial neoplasia (CIN) grade 2 (CIN2+) and CIN grade 3. Results Moderate or severe dysplasia or cancer (taken together as CIN2+) was diagnosed in 286 women. The positivity rate ranged between 2.4% to 19.6% for vaginal careHPV, 2.9% to 20.2% for cervical careHPV, 5.5% to 34.4% for VIA, and 2.8% to 51.8% for Papanicolaou test. Cervical careHPV was the most sensitive for CIN2+ (81.5%; 95% confidence interval [CI], 76.5–85.8) and CIN grade 3 (85.3%; 95% CI, 78.6–90.6) at all sites, followed by vaginal careHPV (69.6% and 71.3%, respectively). The sensitivity of VIA ranged from 21.9% to 73.6% and Papanicolaou test from 40.7% to 73.7%. The pooled specificities of cervical careHPV, vaginal careHPV, VIA, and Papanicolaou test were 91.6%, 90.6%, 84.2%, and 87.7%, respectively. Conclusions careHPV performed well in large multicountry demonstration studies conducted in resource-limited settings that have not previously been conducted this type of testing; its sensitivity using cervical samples or vaginal self-collected samples was better than VIA or Papanicolaou test. The feasibility of using careHPV in self-collected vaginal samples opens the possibility of increasing coverage and early detection in resource-constrained areas.

Domestic violence as risk factor for unwanted pregnancy and induced abortion in Mulago Hospital, Kampala, Uganda

Objective  To compare pregnancy intention and domestic violence among women with induced and spontaneous abortion.

Uptake of family planning methods and unplanned pregnancies among HIV-infected individuals: a cross-sectional survey among clients at HIV clinics in Uganda

BackgroundPrevention of unplanned pregnancies among HIV-infected individuals is critical to the prevention of mother to child HIV transmission (PMTCT), but its potential has not been fully utilized by PMTCT programmes. The uptake of family planning methods among women in Uganda is low, with current use of family planning methods estimated at 24%, but available data has not been disaggregated by HIV status. The aim of this study was to assess the utilization of family planning and unintended pregnancies among HIV-infected people in Uganda.MethodsWe conducted exit interviews with 1100 HIV-infected individuals, including 441 men and 659 women, from 12 HIV clinics in three districts in Uganda to assess the uptake of family planning services, and unplanned pregnancies, among HIV-infected people. We conducted multivariate analysis for predictors of current use of family planning among women who were married or in consensual union and were not pregnant at the time of the interview.ResultsOne-third (33%, 216) of the women reported being pregnant since their HIV diagnoses and 28% (123) of the men reported their partner being pregnant since their HIV diagnoses. Of these, 43% (105) said these pregnancies were not planned: 53% (80) among women compared with 26% (25) among men. Most respondents (58%; 640) reported that they were currently using family planning methods. Among women who were married or in consensual union and not pregnant, 80% (242) were currently using any family planning method and 68% were currently using modern family planning methods (excluding withdrawal, lactational amenorrhoea and rhythm). At multivariate analysis, women who did not discuss the number of children they wanted with their partners and those who did not disclose their HIV status to sexual partners were less likely to use modern family planning methods (adjusted OR 0.40, range 0.20-0.81, and 0.30, range 0.10-0.85, respectively).ConclusionsThe uptake of family planning among HIV-infected individuals is fairly high. However, there are a large number of unplanned pregnancies. These findings highlight the need for strengthening of family planning services for HIV-infected people.

Nonimmune immunoglobulin binding and multiple adhesion characterize Plasmodium falciparum-infected erythrocytes of placental origin

The harmful effects of pregnancy-associated malaria (PAM) are engendered by the heavy sequestration of Plasmodium falciparum-parasitized RBCs in the placenta. It is well documented that this process is mediated by interactions of parasite-encoded variant surface antigens and placental receptors. A P. falciparum erythrocyte membrane protein 1 variant, VAR2CSA, and the placental receptor chondroitin sulfate A (CSA) are currently the focus of PAM research. A role for immunoglobulins (IgG and IgM) from normal human serum and hyaluronic acid as additional receptors in placental sequestration have also been suggested. We show here (i) that CSA and nonimmune IgG/IgM binding are linked phenotypes of in vitro-adapted parasites, (ii) that a VAR2CSA variant shown to bind CSA also harbors IgG- and IgM-binding domains (DBL2-X, DBL5-ε, and DBL6-ε), and (iii) that IgG and IgM binding and adhesion to multiple receptors (IgG/IgM/HA/CSA) rather than the exclusive binding to CSA is a characteristic of fresh Ugandan placental isolates. These findings are of importance for the understanding of the pathogenesis of placental malaria and have implications for the ongoing efforts to develop a global PAM vaccine.

Expanded Phase I safety and acceptability study of 6% cellulose sulfate vaginal gel.

Background:An expanded Phase I trial was performed to assess the safety and acceptability of 6% cellulose sulfate gel (CS) in comparison with K-Y Jelly. Methods:Sexually abstinent (cohort I) and sexually active (cohort II) women in India, Nigeria and Uganda applied 3.5 ml of either 6% CS gel or K-Y Jelly for seven consecutive days. Safety was assessed by symptoms and signs (including colposcopy) of genital irritation, review of adverse events, and by changes in vaginal health as assessed by microscopy. Results:One hundred and eighty women (90 on CS and 90 on K-Y Jelly) were enrolled. Baseline characteristics of women in both gel groups were similar. In cohort I, six (14%) women on CS and 12 (27%) on K-Y Jelly reported genital symptoms, two (in K-Y Jelly group) of whom withdrew from the study. New colposcopy findings or findings showing deterioration were detected in four (9%) women on CS and nine (21%) women on K-Y Jelly in cohort I. Two women on CS and three on K-Y Jelly in cohort II reported genital symptoms. Five women (11%) in each gel group in cohort II had new colposcopy findings or findings showing deterioration. The differences between the gel groups were not statistically significant. The majority of women had no problem with their assigned product. Conclusion:A vaginal application of 6% cellulose sulfate twice daily for seven consecutive days is as safe and well tolerated as a similar regimen of K-Y Jelly. Further development of 6% CS for prevention of HIV and pregnancy is recommended.