Joseph Vyankandondera

Safety, tolerability, and systemic absorption of dapivirine vaginal microbicide gel in healthy, HIV-negative women.

Objectives:To assess the local and systemic safety of dapivirine vaginal gel vs. placebo gel as well as the systemic absorption of dapivirine in healthy, HIV-negative women. Methods:Two prospective, randomized, double-blind, placebo-controlled phase I/II studies were conducted at five research centers, four in Africa and one in Belgium. A total of 119 women used dapivirine gel (concentrations of 0.001, 0.002, 0.005, or 0.02%), and 28 used placebo gel twice daily for 42 days. The primary endpoints were colposcopic findings, adverse events, Division of AIDS grade 3 or grade 4 laboratory values, and plasma levels of dapivirine. Results:Safety data were similar for the dapivirine and placebo gels. None of the adverse events with incidence more than 5% occurred with greater frequency in the dapivirine than placebo groups. Similar percentages of placebo and dapivirine gel users had adverse events that were considered by the investigator to be related to study gel. A total of five serious adverse events occurred in the two studies, and none was assessed as related to study gel. Mean plasma concentrations of dapivirine were approximately dose proportional, and, within each dose group, mean concentrations were similar on days 7, 28, and 42. The maximum observed mean concentration was 474 pg/ml in the 0.02% gel group on day 28. Two weeks after the final application of study gel, mean concentrations decreased to 5 pg/ml or less. Conclusion:Twice daily administration of dapivirine vaginal gel for 42 days was safe and well tolerated with low systemic absorption in healthy, HIV-negative women suggesting that continued development is warranted.

High human immunodeficiency virus incidence in a cohort of Rwandan female sex workers

Background: Measurement of human immunodeficiency virus (HIV) incidence among female sex workers in Rwanda is a key part of preparing for HIV prevention trials. Methods: HIV-negative, nonpregnant female sex workers (N = 397) were tested for HIV-1, sexually transmitted infections, and pregnancy quarterly for 12 months, and again at a 1-time year 2 visit. Additional women (N = 156) were tested for HIV at baseline and 6 to 12 months thereafter in a parallel study. Results: A total of 19 participants seroconverted during follow-up, with 13 in the first 12 months. The 12-month HIV incidence rate (IR) was 3.5 (95% confidence interval: 1.6, 5.4) per 100 person-years (PY). There was a nonsignificant downward trend from 4.6/100 PY (1.6, 7.7) in the first 6 months to 2.2 (0.1, 4.4) in the second 6 months (IR ratio: 2.1 [95% confidence interval: 0.7, 7.8]). The year 2 IR was 2.1 (0.4, 3.7), and the HIV IR in the parallel study (in the absence of frequent study visits) was 3.3/100 PY (0, 7.0). HIV testing history, lifetime pregnancies, recent initiation of sex work, gonorrhea, syphilis, and change in reproductive intentions were associated with incident HIV infection. Incidence of pregnancy, herpes simplex virus-type 2, trichomoniasis, gonorrhea, chlamydia, and syphilis per 100 PY were as follows: 26.3 (21.9, 30.7), 8.7 (4.0, 13.4), 16.9 (12.7, 21.1), 12.1 (8.2, 15.9), 8.1 (5.1, 11.2), and 6.2 (3.7, 8.7). Conclusions: The HIV/sexually transmitted infections burden in this group was high. HIV IR was highest in the first 6 months of the cohort, and in the parallel study in which there were no risk-reduction procedures. HIV prevention and family planning interventions are needed.

Living Situation Affects Adherence to Combination Antiretroviral Therapy in HIV-Infected Adolescents in Rwanda: A Qualitative Study

Introduction Adherence to combination antiretroviral therapy (cART) is vital for HIV-infected adolescents for survival and quality of life. However, this age group faces many challenges to remain adherent. We used multiple data sources (role-play, focus group discussions (FGD), and in-depth interviews (IDI)) to better understand adherence barriers for Rwandan adolescents. Forty-two HIV positive adolescents (ages 12–21) and a selection of their primary caregivers were interviewed. All were perinatally-infected and received (cART) for ≥12 months. Topics discussed during FGDs and IDIs included learning HIV status, disclosure and stigma, care and treatment issues, cART adherence barriers. Results Median age was 17 years, 45% female, 45% orphaned, and 48% in boarding schools. We identified three overarching but inter-related themes that appeared to influence adherence. Stigma, perceived and experienced, and inadvertent disclosure of HIV status hampered adolescents from obtaining and taking their drugs, attending clinic visits, carrying their cARTs with them in public. The second major theme was the need for better support, in particular for adolescents with different living situations, (orphanages, foster-care, and boarding schools). Lack of privacy to keep and take medication came out as major barrier for adolescents living in congested households, as well the institutionalization of boarding schools where privacy is almost non-existent. The third important theme was the desire to be ‘normal’ and not be recognized as an HIV-infected individual, and to have a normal life not perturbed by taking a regimen of medications or being forced to disclose where others would treat them differently. Conclusions We propose better management of HIV-infected adolescents integrated into boarding school, orphanages, and foster care; training of school-faculty on how to support students and allow them privacy for taking their medications. To provide better care and support, HIV programs should stimulate caregivers of HIV-infected adolescents to join them for their clinic visits.

The epidemiology of human papillomavirus infection in HIV-positive and HIV-negative high-risk women in Kigali, Rwanda

BackgroundThe prevalence, incidence and persistence of human papillomavirus (HPV) types in sub-Saharan Africa are not well established. The objectives of the current study are to describe (predictors of) the epidemiology of HPV among high-risk women in Kigali, Rwanda.MethodsHIV-negative, high-risk women were seen quarterly for one year, and once in Year 2. HIV serostatus, clinical, and behavioral information were assessed at each visit, HPV types at Month 6 and Year 2, and other sexually transmitted infections (STI) at selected visits. HPV prevalence was also assessed in HIV-positive, high-risk women.ResultsPrevalence of any HPV was 47.0% in HIV-negative women (median age 25 years) compared to 72.2% in HIV-positive women (median age 27 years; OR 2.9, 95% CI 1.9-4.6). Among HIV-negative women, cumulative incidence of high-risk (HR)-HPV was 28.0% and persistence 32.0% after a mean period of 16.6 and 16.9 months, respectively. Prior Chlamydia trachomatis and Neisseria gonorrhoeae infection, concurrent low-risk (LR)-HPV infection and incident HSV-2 were associated with HR-HPV prevalence among HIV-negative women; prior C. trachomatis infection and co-infection with LR-HPV and HPV16-related HPV types with HR-HPV acquisition. HPV16-related types were the most prevalent and persistent.ConclusionsHigh HPV prevalence, incidence and persistence were found among high-risk women in Kigali. HPV52 had the highest incidence; and, together with HPV33 and HPV58, were strongly associated with acquisition of other HR-HPV types in HIV-negative women.

Dual Testing Algorithm of BED-CEIA and AxSYM Avidity Index Assays Performs Best in Identifying Recent HIV Infection in a Sample of Rwandan Sex Workers

Background To assess the performance of BED-CEIA (BED) and AxSYM Avidity Index (Ax-AI) assays in estimating HIV incidence among female sex workers (FSW) in Kigali, Rwanda. Methodology and Findings Eight hundred FSW of unknown HIV status were HIV tested; HIV-positive women had BED and Ax-AI testing at baseline and ≥12 months later to estimate assay false-recent rates (FRR). STARHS-based HIV incidence was estimated using the McWalter/Welte formula, and adjusted with locally derived FRR and CD4 results. HIV incidence and local assay window periods were estimated from a prospective cohort of FSW. At baseline, 190 HIV-positive women were BED and Ax-AI tested; 23 were classified as recent infection (RI). Assay FRR with 95% confidence intervals were: 3.6% (1.2–8.1) (BED); 10.6% (6.1–17.0) (Ax-AI); and 2.1% (0.4–6.1) (BED/Ax-AI combined). After FRR-adjustment, incidence estimates by BED, Ax-AI, and BED/Ax-AI were: 5.5/100 person-years (95% CI 2.2–8.7); 7.7 (3.2–12.3); and 4.4 (1.4–7.3). After CD4-adjustment, BED, Ax-AI, and BED/Ax-AI incidence estimates were: 5.6 (2.6–8.6); 9.7 (5.0–14.4); and 4.7 (2.0–7.5). HIV incidence rates in the first and second 6 months of the cohort were 4.6 (1.6–7.7) and 2.2 (0.1–4.4). Conclusions Adjusted incidence estimates by BED/Ax-AI combined were similar to incidence in the first 6 months of the cohort. Furthermore, false-recent rate on the combined BED/Ax-AI algorithm was low and substantially lower than for either assay alone. Improved assay specificity with time since seroconversion suggests that specificity would be higher in population-based testing where more individuals have long-term infection.

HIV acquisition is associated with prior high-risk human papillomavirus infection among high-risk women in Rwanda.

As part of a prospective cohort study to assess HIV incidence among high-risk women in Kigali, Rwanda, we evaluated the association between high-risk human papillomavirus (HPV) infection and subsequent HIV acquisition. Women who seroconverted for HIV between the first and second HPV measurement visit were 4.9 times [95% confidence interval = 1.2–19.7] more likely to have HR-HPV detected at the first visit compared with women who remained HIV-negative.

High Burden of Prevalent and Recently Acquired HIV among Female Sex Workers and Female HIV Voluntary Testing Center Clients in Kigali, Rwanda

Objectives To estimate HIV prevalence and risk factors in population-based samples of female sex workers (FSW) and female voluntary counseling and testing (VCT) clients in Rwanda. Methods We conducted a cross-sectional survey of 800 FSW and 1,250 female VCT clients in Rwanda, which included interviewing and testing for HIV-1/2, HSV-2 and pregnancy, and BED-CEIA and Avidity Index (AI) to identify recent infections among HIV-infected women. Results Prevalence of HIV-1, HSV-2, and pregnancy were 24% (95% CI: 21.0–27.0), 59.8% (56.4–63.2), and 7.6% (5.8–9.5) among FSW, and 12.8% (10.9–14.6), 43.2% (40.4–46.0), and 11.4% (9.7–13.3) among VCT clients, respectively. Thirty-five percent of FSW and 25% of VCT clients had never been HIV tested. Per national guidelines, 33% of newly HIV-diagnosed FSW and 36% of VCT clients were already eligible for ART based on CD4<350 cells/µl. Condom use at last sex was higher among FSW (74%) than VCT clients (12%). In age and district of residence-adjusted models, HIV-1 seropositivity was associated with HSV-2 co-infection; recent treatment for sexually transmitted infection (STI); genital symptoms; forced sex; imprisonment; widowhood; and alcohol consumption. Eleven percent of FSW and 12% of VCT clients had recently acquired HIV-1 per BED-CEIA and AI. HSV-2 infection and recent STI treatment were associated with recent HIV infection in both groups, and being married and vaginal cleansing were associated with recent infection before last sex among VCT clients. Conclusions This population-based survey reveals a high HIV prevalence and incidence among FSW and female VCT clients in Kigali, the scale of which is masked by the low general-population HIV prevalence in Rwanda. HIV/STI and family planning services should be strengthened.

Gender differences and factors associated with treatment-seeking behaviour for infertility in Rwanda

BACKGROUND This study examines perceptions of infertility causes, treatment-seeking behaviour and factors associated with seeking medical care in an urban infertile population in Rwanda, as well as the response of health providers. METHODS Between November 2007 and May 2009 a hospital based survey was conducted among 312 women and 254 male partners in an infertile relationship. RESULTS Infertility causes based on a medical diagnosis were mentioned by 24% of women and 17% of men. Male infertility awareness was low in both sexes with 28% of men and 10% of women reporting male-related causes. Seventy-four per cent of women and 22% of men had sought care for their infertility in the past. Seeking treatment in the formal medical sector was associated with higher income, being married and infertility duration of more than 5 years in both sexes. In women, higher education and being nulliparous and in men blaming oneself for the infertility was also associated with seeking formal medical care. Participants reported a wide array of treatments they received in the past, often including ineffective or even harmful interventions. CONCLUSION Health authorities should invest in improving information, education and counselling on issues pertaining to causes and treatments of infertility, and in drawing up guidelines for the management of infertility at all levels of health care.

Antiretroviral therapy drug adherence in Rwanda: Perspectives from patients and healthcare workers using a mixed-methods approach

Rwanda has achieved high enrollment into antiretroviral therapy (ART) programs but data on adherence after enrollment are not routinely collected. We used a mixed-methods approach (standardized questionnaires, pill counts, focus group discussions, and in-depth interviews) to determine levels of and barriers to ART adherence from the perspective of both patients and healthcare workers (HCW). Data were available from 213 patients throughout the first year on ART; 58 of them and 23 HCW participated in a qualitative sub-study. Self-reported adherence was high (96% of patients reporting more than 95% adherence), but adherence by pill count was significantly lower, especially in the first 3 months. In the standardized interviews, patients mostly reported that they “simply forgot” or “were away from home” as reasons for nonadherence. The qualitative research identified three interrelated constructs that appeared to negatively influence adherence: stigma, difficulty coming to terms with illness, and concealment of illness. Both standardized questionnaires and the qualitative research identified poverty, disruption to daily routines, factors related to regimen complexity and side effects, and service-related factors as barriers to adherence. We conclude that regular triangulation of different sources of adherence data is desirable to arrive at more realistic estimates. We propose that program monitoring and evaluation cycles incorporate more in-depth research to better understand concerns underlying reasons for nonadherence reported in routine monitoring.

Effects of Nevirapine, Compared with Lamivudine, on Lipids and Lipoproteins in HIV-1—Uninfected Newborns: The Stopping Infection from Mother-to-Child via Breast-Feeding in Africa Lipid Substudy

BACKGROUND The objective of the present study was to assess whether the high-density lipoprotein cholesterol (HDL-c)-increasing effect of nevirapine (NVP), as observed in human immunodeficiency virus type 1 (HIV-1)-infected subjects, at least in part may relate to intrinsic properties of NVP. METHODS At 2, 6, and 12 weeks after birth, complete lipid profiles as well as plasma apolipoproteins levels were assessed in 80 HIV-uninfected newborns, half of whom received NVP and half lamivudine (3TC), respectively. Newborns were randomly selected from a randomized trial in which NVP or 3TC had been administered to HIV-uninfected infants born to HIV-infected mothers to try and prevent HIV-1 transmission from occurring during breast-feeding. RESULTS After 6 weeks of therapy, the expected physiological decline in HDL-c levels in the newborns was attenuated in infants treated with NVP, compared with levels in those treated with 3TC. Apolipoprotein A-I (apoA-I) levels were higher at all time points in the NVP arm than they were in the 3TC arm (P=.02), reaching peak levels at 6 weeks. The difference in HDL-c was no longer significant at 12 weeks. CONCLUSIONS apoA-I levels and HDL-c were elevated in HIV-1-uninfected newborns receiving NVP, compared with those receiving 3TC. These data support that NVP may indeed have intrinsic apoA-I and HDL-c elevating properties in humans.