Zvavahera M. Chirenje

Safety and effectiveness of BufferGel and 0.5% PRO2000 gel for the prevention of HIV infection in women

Objective:To determine the safety and effectiveness of BufferGel and 0.5% PRO2000 microbicide gels for the prevention of male-to-female HIV transmission. Design:Phase II/IIb, randomized, placebo-controlled trial with three double-blinded gel arms and an open-label no gel arm. Methods:Study participants from Malawi, South Africa, Zambia, Zimbabwe, and the USA were instructed to apply study gel up to 1 h before each sex act and safety, sexual behavior, pregnancy, gel adherence, acceptability, and HIV serostatus were assessed during follow-up. Results:The 3101 enrolled women were followed for an average of 20.4 months with 93.6% retention and 81.1% self-reported gel adherence. Adverse event rates were similar in all study arms. HIV incidence rates in the 0.5% PRO2000 gel, BufferGel, placebo gel, and no gel arms were 2.70, 4.14, 3.91, and 4.02 per 100 women-years, respectively. HIV incidence in the 0.5% PRO2000 gel arm was lower than the placebo gel arm (hazard ratio = 0.7, P = 0.10) and the no gel arm (hazard ratio = 0.67, P = 0.06). HIV incidence rates were similar in the BufferGel and both placebo gel (hazard ratio = 1.10, P = 0.63) and no gel control arms (hazard ratio = 1.05, P = 0.78). HIV incidence was similar in the placebo gel and no gel arms (hazard ratio = 0.97, P = 0.89). Conclusion:The 0.5% PRO2000 gel demonstrated a modest 30% reduction in HIV acquisition in women. However, these results were not statistically significant and subsequent findings from the Microbicide Development Programme (MDP) 301 trial have confirmed that 0.5% PRO2000 gel has little or no protective effect. BufferGel did not alter the risk of HIV infection. Both products were well tolerated.

Intravaginal Practices, Vaginal Flora Disturbances, and Acquisition of Sexually Transmitted Diseases in Zimbabwean Women

One hundred sixty-nine Zimbabwean women were studied to determine whether the use of intravaginal practices (cleaning with the fingers, wiping the vagina, and inserting traditional substances) are associated with disturbances of vaginal flora and acquisition of sexually transmitted diseases (STDs). Subjects were interviewed and received counseling and a pelvic examination at enrollment, 1 month, and 6 months, and vaginal specimens were collected at enrollment and at 6 months. Users were more likely than nonusers to have vaginal flora disturbances but were not more likely to acquire an STD (relative risk [RR], 2.15; P=.188). Certain vaginal flora disturbances were associated with increased STD incidence and HIV prevalence. The absence of lactobacilli from the vaginal flora was associated with being positive for human immunodeficiency virus in baseline (odds ratio [OR], 0.24; P=.001) and 6-month transition multivariate models (OR, 0.39; P=.025). The presence of clue cells at baseline was associated with a higher incidence of STDs (RR, 1. 94; P=.025).

Adjunctive testing for cervical cancer in low resource settings with visual inspection, HPV, and the Pap smear

Objective: To test whether the performance of visual inspection using acetic acid (VIA) could be improved through adjunctive testing and to determine whether the combination of visual inspection of the cervix and HPV testing could prove useful for identifying those at highest risk of cervical precancer. Methods: Between October 1995 and August 1997, 2199 women willing to be screened for cervical cancer in peri‐urban clinics in Harare, Zimbabwe received VIA, Pap smear and HPV as screening tests. The presence or absence of (pre)cancer was confirmed via colposcopy with biopsy as indicated for >97% of all women. Computerized simulations of sequential testing scenarios provided estimates of the joint (net) test qualities of different paired combinations of the three tests and allowed for comparisons with the individual test qualities. Results: Using HGSIL/CIN II‐III as the reference threshold of disease, the net sensitivity and specificity of VIA and HPV when used sequentially were 63.6 and 81.9%, respectively, compared to 43.3 and 91%, respectively, when Pap smears were followed by HPV testing. VIA followed by the Pap smear yielded a net sensitivity of 37.5% and net specificity of 94.3%. Conclusions: For programs with limited resources but with the capacity for HPV testing, sequential testing involving the use of VIA followed by HPV could yield fewer false positives than the use of VIA alone at a cost of relatively few additional false negatives.

Situation analysis for cervical cancer diagnosis and treatment in East, Central and Southern African countries

OBJECTIVE To determine the factors influencing cervical cancer diagnosis and treatment in countries of East, Central and Southern Africa (ECSA). METHODS Data were collected from randomly selected primary health care centres, district and provincial hospitals, and tertiary hospitals in each participating country. Health care workers were interviewed, using a questionnaire; the facilities for screening, diagnosing, and treating cervical cancer in each institution were recorded, using a previously designed checklist. FINDINGS Although 95% of institutions at all health care levels in ECSA countries had the basic infrastructure to carry out cervical cytology screening, only a small percentage of women were actually screened. Lack of policy guidelines, infrequent supply of basic materials, and a lack of suitable qualified staff were the most common reasons reported. CONCLUSIONS This study demonstrates that there is an urgent need for more investment in the diagnosis and treatment of cervical cancer in ECSA countries. In these, and other countries with low resources, suitable screening programmes should be established.

phase 1 Trial of the Topical Microbicide Buffergel: Safety Results From Four International Sites

Aim: To evaluate the safety of BufferGel (ReProtect LLC, Baltimore, MD), a spermicidal microbicide that acidifies semen and maintains the protective acidity of the vagina, in a high‐dose tolerance trial. Methods: HIV/STD negative, sexually abstinent, and sexually active women in India, Thailand, Malawi, and Zimbabwe were asked to insert one applicator (˜5 ml) of BufferGel vaginally twice per day for 14 days. Sexually active women agreed to have sex (while using BufferGel and nonlubricated condoms) at least twice per week. Results: In total, 98 women (30 sexually abstinent and 68 sexually active) were enrolled. Overall compliance with product use was 93%. Epithelial abnormalities detected by pelvic examination or colposcopy were uncommon (8 cases in 271 examinations). Irritation was reported by approximately one quarter of the women (0.58 events per woman‐week) but was generally mild and of short duration. The prevalence of bacterial vaginosis (BV) fell significantly, from 30% at enrollment to 6% at one week, and 7% at two weeks of BufferGel use. Thirty‐two women acquired microscopically detectable yeast during BufferGel exposure, but only 3 developed symptomatic vaginitis. Conclusion: BufferGel appears to be safe and well tolerated by the cervicovaginal epithelium. Its effect on BV and yeasts merits further study.

A randomised clinical trial of loop electrosurgical excision procedure (LEEP) versus cryotherapy in the treatment of cervical intraepithelial neoplasia

The objective of the treatment of cervical intraepithelial neoplasia (CIN) is the prevention of invasive carcinoma of the cervix, which still remains the most common cancer in Zimbabwean women, as in most other low-resource countries where screening facilities are grossly inadequate. We conducted a randomised prospective study to compare CIN treatment outcome after cryotherapy and loop electrosurgical excision procedure (LEEP) in 400 women with histologically confirmed high grade squamous intra-epithelial lesions (HGSIL). Treatment outcome measures were immediate complications, persistent disease and recurrent disease evaluated at follow-up visits. Eighty-two per cent of the women (159 cryotherapy, 168 LEEP) completed their 6-month and 12-month follow-up visits. LEEP had a significantly higher overall cure rate of 96·4% (absence of persistant or recurrent disease) compared to 88·3% cryotherapy ( P =0·026). Although cryotherapy was not superior to LEEP, its cure rate (88·3%) is acceptable and therefore provides a viable treatment option for low resource countries such as Zimbabwe where the majority of women at risk for cervical cancer reside in rural areas.The objective of the treatment of cervical intraepithelial neoplasia (CIN) is the prevention of invasive carcinoma of the cervix, which still remains the most common cancer in Zimbabwean women, as in most other low-resource countries where screening facilities are grossly inadequate. We conducted a randomised prospective study to compare CIN treatment outcome after cryotherapy and loop electrosurgical excision procedure (LEEP) in 400 women with histologically confirmed high grade squamous intra-epithelial lesions (HGSIL). Treatment outcome measures were immediate complications, persistent disease and recurrent disease evaluated at follow-up visits. Eighty-two per cent of the women (159 cryotherapy, 168 LEEP) completed their 6-month and 12-month follow-up visits. LEEP had a significantly higher overall cure rate of 96.4% (absence of persistent or recurrent disease) compared to 88.3% cryotherapy (P=0.026). Although cryotherapy was not superior to LEEP, its cure rate (88.3%) is acceptable and therefore provides a viable treatment option for low resource countries such as Zimbabwe where the majority of women at risk for cervical cancer reside in rural areas.

Effect of intravaginal practices on the vaginal and cervical mucosa of Zimbabwean women.

Objectives: Lesions on the vaginal and cervical mucosa may facilitate transmission of HIV and other sexually transmitted diseases (STDs). We evaluated the relationship between intravaginal practices and the presence of colposcopic lesions in Zimbabwean women. Methods: Users and nonusers of intravaginal practices were seen at enrollment, and at 1 and 6 months. Interviewing, counseling, and pelvic and colposcopic examinations were performed at each study visit. Specimens were collected at enrollment and 6 months. Results: Colposcopic lesions were found at least once in 83% of the participants (n = 162), and in 66% of all exams (n = 430). Most lesions were classified as related to infection with human Papillomavirus (HPV) (58%) or another pathogen (20%), but 11% of lesions could have been caused by intravaginal practices (signal lesions). Intravaginal practices were not associated with an increased incidence in signal lesions (95 and 124 lesions per 100 person‐years of follow‐up for users and nonusers respectively; p = .290), nor with the presence of signal lesions in multivariate baseline (odds ratio [OR], 1.32; 95% confidence interval [CI], 0.37‐4.72; p = .666) and six month transition models (OR, 1.67; 95% CI, 0.59‐4.70; p = .333). Conclusions: No associations between intravaginal practices and colposcopic lesions were found in this study. However, the potential effect of intravaginal practices on the cervical and vaginal mucosa, and on subsequent HIV and STD transmission, warrants further study. The usefulness of colposcopy as a research tool in areas with high prevalences of HIV and HPV is questioned.

Acceptability of Heat Treating Breast Milk to Prevent Mother-to-Child Transmission of Human Immunodeficiency Virus in Zimbabwe: A Qualitative Study

Although heat treatment of human milk is an official infant-feeding recommendation for human immunodeficiency virus (HIV)-positive mothers in Zimbabwe, its implementation has not been adequately addressed, because knowledge about the safety of this method is rudimentary and its acceptability is poorly understood. To address this knowledge gap, the authors conducted focus group discussions among mothers, grandmothers, midwives, and husbands in various regions of Zimbabwe. Although the practice of heat treating expressed human milk was initially met with skepticism because of potential obstacles, including time constraints and social and cultural stigma, a pattern of opinion reversal emerged in all groups. By the end of each discussion, participants believed that, given its affordability and its potential to protect infants from HIV infection, heat-treated human milk may be a feasible infant-feeding option for HIV-positive mothers in Zimbabwe. These findings merit further investigation so that appropriate behavioral strategies can be designed.

Impact of a Single Session of Counseling on Partner Referral for Sexually Transmitted Disease Treatment, Harare, Zimbabwe

Counseling patients with sexually transmitted diseases (STD) to refer their partners to treatment is considered a means of preventing reinfection and controlling the spread of STD and is standard practice throughout the world. We conducted a randomized controlled trial to assess the impact of an enhanced counseling session on partner referral in Harare, Zimbabwe. The intervention consisted of an individualized confidential session with a trained counselor; standard care (control) relied on the treating clinician to discuss partner referral. A consecutive sample of 272 patients (135 men, 137 women) was randomly assigned to the intervention or control group; 137 (50%) completed follow- up. By intent-to-treat analysis, persons in the intervention arm were more likely to report notifying any partner compared to controls (92% vs. 67%, adjusted odds ratio 4.1, 95% confidence interval 1.3–13.2, p < .001). Across both study arms, women and married persons were more likely to notify partners, particularly spouses. Few persons notified casual partners. Qualitative data at follow-up identified diverse motivating factors and barriers to partner referral. A short, low-cost counseling session may increase the number of spouses referred to STD treatment in resource-poor, high-morbidity areas of sub-Saharan Africa. New methods of treating or notifying casual partners need to be evaluated.

Age-Disparate Partnerships and Risk of HIV-1 Acquisition among South African Women Participating in the VOICE Trial

Abstract:A recent analysis from South Africa reported no association between age-disparate relationships and HIV-1 acquisition. We assessed the association between male partner age and HIV-1 acquisition among South African women participating in the VOICE trial. Of 4077 women enrolled, 3789 had complete data; 26% and 5% reported having a partner >5 and >10 years older at enrollment, respectively. Reporting a partner >5 years older (hazard ratio = 1.00; 95% confidence interval: 0.74 to 1.35) or >10 older (hazard ratio = 0.92; 95% confidence interval: 0.49 to 1.74) was not associated with HIV-1 acquisition. These data corroborate recent reports and may suggest a shift in local epidemiology of heterosexual HIV-1 transmission.