Nienke J. Veldhuijzen

Factors affecting transmission of mucosal human papillomavirus

Human papillomavirus (HPV) is the most common sexually transmitted infection. The effect of HPV on public health is especially related to the burden of anogenital cancers, most notably cervical cancer. Determinants of exposure to HPV are similar to those for most sexually transmitted infections, but determinants of susceptibility and infectivity are much less well established. Gaps exist in understanding of interactions between HPV, HIV, and other sexually transmitted infections. The roles of mucosal immunology, human microbiota at mucosal surfaces, host genetic factors and hormonal concentrations on HPV susceptibility and infectivity are poorly understood, as are the level of effectiveness of some primary or secondary preventive measures other than HPV vaccination (such as condoms, male circumcision, and combination antiretroviral therapy for HIV). Prospective couples studies, studies focusing on mucosal immunology, and in-vitro raft culture studies mimicking HPV infection might increase understanding of the dynamics of HPV transmission.

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.

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.

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.

HIV diagnosis, linkage to HIV care, and HIV risk behaviors among newly diagnosed HIV-positive female sex workers in Kigali, Rwanda

Objective:To evaluate linkage-to-care, sexual behavior change, and psychosocial experiences among newly HIV-diagnosed female sex workers (FSWs) in Rwanda. Methods:FSWs (n = 800) with unknown serostatus were screened for HIV during 2007/2008. Women testing HIV positive (n = 192) were referred to care and asked to return for interviews and laboratory testing 12-36 months postdiagnosis. One hundred fourty-one women (73%) returned for the postdiagnosis visit. Results:Median CD4 count at diagnosis was 460 cells per microliter [interquartile range (IQR): 308-628], with 32% eligible for antiretroviral therapy (ART) per national CD4 criteria (median CD4: 235, IQR: 152-303). Postdiagnosis, 92% of women reported having disclosed their HIV status to a friend or relative, 85% reported having enrolled in HIV care (median 30 days after diagnosis, IQR: 7-360), including 89% among ART-eligible women. Among ART-eligible women in care, 87% had initiated ART, with a median follow-up CD4 count of 354 cells per microliter (IQR: 213-456). Women who did not initiate ART experienced a 6-month CD4 count change of −14 cells per microliter (IQR: −41 to 13). Three-quarters of women reported reduced sexual risk behavior postdiagnosis, with only 64% continuing to identify as FSWs. However, 53% reported past month condom use only “sometimes.” Conclusions:Timely linkage to care and ART uptake were high in this group of Rwandan FSWs. However, risky sexual behaviors remained common after enrollment in care. HIV-positive FSWs are an important and receptive group for targeted efforts to increase HIV diagnosis and linkage to care/treatment. Once in care, intensified and sustained HIV prevention education is necessary.

Anal intercourse among female sex workers in East Africa is associated with other high-risk behaviours for HIV.

INTRODUCTION Epidemiological and HIV prevention studies in sub-Saharan Africa have almost exclusively focussed on vaginal transmission of HIV, the primary mode of transmission in the region. Little is known about the prevalence of heterosexual anal intercourse (AI), its correlates and its role in the spread of HIV. Prevention messaging seldom, if ever, includes AI. METHODS Sexual and other risk behaviours (including frequency of AI) were assessed in two cross-sectional surveys of female sex workers (FSW) in Kigali, Rwanda (n=800) and Mombasa, Kenya (n=820). In addition, a subset of FSW surveyed in Kigali attended seven focus group discussions and four in-depth interviews. RESULTS AI was reported by 5.5% and 4.3% of FSW in the cross-sectional surveys, in Kigali and Mombasa, respectively. FSW practising AI reported multiple risk factors for HIV transmission: inconsistent condom use (odds ratio (OR) Kigali 5.9 (95% CI 1.4-24.7); OR Mombasa 2.1 (1.1-4.2)); more than five sexual partners in the past week (OR Kigali 4.3 (1.5-12.4); OR Mombasa 2.2 (1.1-4.3)); alcohol use before sex (OR Kigali 2.8 (1.4-5.8)); more than 5 years of female sex work (OR Mombasa 2.4 (1.2-4.9)); and history of genital symptoms in the past year (OR Mombasa 3.6 (1.7-7.9)). AI was, however, not associated with HIV prevalence (OR Kigali 0.9 (0.5-1.9); OR Mombasa 0.5 (0.2-1.2)). Negative connotations and stigma associated with AI were expressed during qualitative interviews. CONCLUSIONS AI was associated with several indicators of sexual risk behaviour. Prevalence of AI was probably underreported due to social desirability bias. Stigma associated with AI poses methodological challenges in obtaining valid data.

Joining and leaving sex work: experiences of women in Kigali, Rwanda

Although sex work can bring significant economic benefit there are serious downsides, not least vulnerability to adverse sexual health outcomes. Focus-groups discussions and in-depth interviews were conducted with 70 female sex workers to explore the context in which they started sex work, their motivations to leave, and their experiences of trying to leave. The pathway to becoming a sex worker was underscored by poverty, with disruptive events leading to increasing vulnerability and increasingly difficult life choices. A sizeable minority of women became sex workers while working as house-girls, a position associated with financial, physical and sexual vulnerability. The majority of participants were still working as sex workers, citing financial reasons for not leaving. Motivations to leave sex work included experiencing a frightening incident, peer pressure and concerns about dependent children. Those who left often described a change in their financial circumstances that enabled them to leave. Some had left but had returned to sex work following a financial crisis or because they found their new life too hard. House-girls are particularly vulnerable and therefore an appropriate focus for prevention. Programmes assisting women to leave need to include financial safety nets so that a time of financial difficulty does not necessitate a return to sex work.

Prevalence and concordance of HPV, HIV, and HSV-2 in heterosexual couples in Kigali, Rwanda.

Background: In the absence of prospectively collected transmission data, the transmission potential of a sexually transmissible infection (STI) can be estimated by its proxy of concordance in sexual partners. Here we report concordance data of 3 viral STIs: human papillomavirus (HPV), HIV, and herpes simplex virus type 2 (HSV-2) among heterosexual couples in Kigali, Rwanda. Methods: Cervical and penile HPV typing was performed among 166 community-sampled fertile couples in Kigali, Rwanda (median sampling interval 10 days (interquartile range: 5–36). HIV and HSV-2 serostatus, curable STIs, and sociobehavioral and clinical characteristics were also assessed. Results: Concordance rates for all 3 viral STIs were higher than expected by chance alone. Positive concordance among couples was 25% for HSV-2, 15.7% for any HPV, 8.4% for high-risk (HR)-HPV, and 6% for HIV. HR-HPV prevalence among women and men was 19.9% and 26.5%, respectively. Partners HIV status was more strongly associated with HR-HPV detection in men (OR: 8.5; confidence interval: 2.9–24.6) than in women (OR: 1.9; confidence interval 0.5–6.7). Conclusion: More than half of the couples were discordant for HIV, HPV, and/or HSV-2, indicating that prevention strategies directed to infected cases are important to protect their uninfected sexual partners.

The Age Distribution of Type-Specific High-Risk Human Papillomavirus Incidence in Two Population-Based Screening Trials

Background: Age- and type-specific high-risk human papillomavirus (hrHPV) incidence estimates in screen-eligible women are relevant from a public health perspective because they provide an indication of the effect of vaccination on the occurrence of screen-positives in HPV-based screening. However, limited data from women over 25 years of age are available. Methods: In 24,105 hrHPV-negative women participating in Dutch (Population-Based Screening Study Amsterdam: POBASCAM) and Italian (New Technologies for Cervical Cancer: NTCC) population-based randomized controlled screening trials the age- and type-specific distribution of incident hrHPV infections detected at the next screening round was assessed. HPV types were grouped into vaccine (bivalent: HPV16/18; polyvalent HPV16/18/31/33/45/52/58) and nonvaccine types. Results: The incidence of screen-detected hrHPV among women ages 29 to 56 years was 2.54% (95% confidence interval, 2.30–2.78) in POBASCAM and 2.77% (2.36–3.19) in NTCC. In both studies, the incidence of bivalent, polyvalent, and nonpolyvalent infections decreased with age (P < 0.0001). Among women with incident infection(s), vaccine-type positivity changed quadratically with age, in particular for the polyvalent vaccine (P values: POBASCAM: bivalent 0.264, polyvalent 0.038; NTCC bivalent 0.039, polyvalent 0.005). However, more than 20% and 50% of women with incident hrHPV were positive for bivalent and polyvalent vaccine types, respectively, in all ages in both studies. Conclusions: We observed decreasing age trends of hrHPV vaccine and nonvaccine type incidences and age-related differences in the vaccine-type positivity among women with incident infections. Most importantly, hrHPV infections continued to be detected in all ages and the contribution of vaccine types remained substantial. Impact: Our results indicate a considerable reduction of new hrHPV infections in vaccinated cohorts, ensuing revision of screening guidelines. Cancer Epidemiol Biomarkers Prev; 24(1); 111–8. ©2014 AACR.

Willingness to participate in future HIV prevention trials in Beira, Mozambique

In preparation for trials of new HIV prevention methods, willingness to participate (WTP) was assessed in Beira, Mozambique. A totla of 1 019 women participating in an HIV incidence study, and 97 men participating in a separate WTP survey, were interviewed. When comparing the answers to questions that were identical in the two studies, WTP was higher among women than men for all prevention methods. Among women, WTP was highest for trials evaluating daily oral pre-exposure prophylaxis (PrEP; 84.4% reporting very likely to participate), followed by vaccination (77.8%), daily vaginal gel use (67.7%), coital vaginal gel use (67.1%) and monthly vaginal ring use (47.7%). Among men, WTP was highest for trials evaluating vaccination (57.6%), followed by daily vaginal gel use for female sexual partners (52.5%), daily oral PrEP (49.5%), coital vaginal gel use for female sexual partners (46.4%) and monthly vaginal ring use for female sexual partners (39.4%). Among men, the most important motivators for trial participation were social benefits, whereas personal risks (most notably receiving injections and/or blood draws) were deterrents; this was not assessed in women. Other important lessons learnt are that male circumcision and antiretroviral drugs were not generally recognised as ways to prevent HIV, that having to use hormonal contraception during trial participation will likely reduce WTP, and that evening clinics are not likely to be popular. The barriers reported in this and other studies may be challenging but are not impossible to overcome.