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The HIV Research for Prevention (HIVR4P) conference is dedicated to advancing HIV prevention research, responding to a growing consensus that effective and durable prevention will require a combination of approaches as well as unprecedented collaboration among scientists, practitioners, and community workers from different fields and geographic areas. The conference theme in 2018, "From Research to Impact," acknowledged an increasing focus on translation of promising research findings into practical, accessible, and affordable HIV prevention options for those who need them worldwide. HIVR4P 2018 was held in Madrid, Spain, on 21-25 October, with >1,400 participants from 52 countries around the globe, representing all aspects of HIV prevention research and implementation. The program included 137 oral and 610 poster presentations. This article presents a brief summary of highlights from the conference. More detailed information, complete abstracts as well as webcasts and daily Rapporteur summaries may be found on the conference website.

Introduction: Stigma and disclosure concerns have been key barriers to oral pre-exposure prophylaxis (PrEP) adherence for African adolescent girls and young women (AGYW) in efficacy trials. We aimed to understand the impact of these factors among African AGYW in an open-label PrEP study. Methods: HPTN 082 was an open-label PrEP study among AGYW (ages 16 to 24) in Harare, Zimbabwe, and Cape Town and Johannesburg, South Africa from 2016 to 2018. Women starting PrEP were randomized to standard adherence support (counselling, two-way SMS, monthly adherence clubs) or standard support plus drug-level feedback. Serial in-depth interviews were conducted among 67 AGYW after 13-week and 26-week study visits to explore experiences of stigma, disclosure and PrEP adherence. We analysed data by coding transcripts and memo-writing and diagramming to summarize themes. Results: AGYW described stigma related to sexual activity (e.g. 'people say I'm a prostitute') and being perceived to be living with HIV because of taking antiretrovirals (e.g. 'my husband's friends say I'm HIV infected'). Participants who anticipated stigma were reluctant to disclose PrEP use and reported adherence challenges. Disclosure also resulted in stigmatizing experiences. Across all sites, negative descriptions of stigma and disclosure challenges were more common in the first interview. In the second interview, participants often described disclosure as an 'empowering' way to combat community-level PrEP stigma; many said that they proactively discussed PrEP in their communities (e.g. became a 'community PrEP ambassador'), which improved their ability to take PrEP and encourage others to use PrEP. These empowering disclosure experiences were facilitated by ongoing HPTN 082 study activities (e.g. counselling sessions, adherence clubs) in which they could discuss PrEP-related stigma, disclosure and PrEP adherence issues. Conclusions: Stigma and disclosure challenges were initial concerns for African AGYW newly initiating PrEP but many were empowered to disclose PrEP use over their first six months of PrEP use, which helped them cope with stigma and feel more able to take PrEP regularly. PrEP programmes can foster disclosure through community and clinic-based discussion, adherence clubs and activities normalizing sexual behaviour and PrEP use, which can reduce stigma and improve PrEP adherence and thus effectiveness. Keywords: Stigma; disclosure; HIV; pre-exposure prophylaxis; Africa; women, 1 | INTRODUCTION Daily oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) is >90% effective in preventing HIV when taken consistently [ ]. Adherence can be challenging, however, and [...]

Human papillomavirus (HPV) genotype 52 is commonly found in Asian cases of cervical cancer but is rare elsewhere. Analysis of 611 isolates collected worldwide revealed a remarkable geographical distribution, with lineage B predominating in Asia (89.0% vs 0%-5.5%; P(corrected) < .001), whereas lineage A predominated in Africa, the Americas, and Europe. We propose that the name "Asian lineage" be used to denote lineage B, to signify this feature. Preliminary analysis suggested a higher disease risk for lineage B, although ethnogeographical confounders could not be excluded. Further studies are warranted to verify whether the reported high attribution of disease to HPV52 in Asia is due to the high prevalence of lineage B.

Human papillomavirus (HPV) 58 accounts for a notable proportion of cervical cancers in East Asia and parts of Latin America, but it is uncommon elsewhere. The reason for such ethnogeographical predilection is unknown. In our study, nucleotide sequences of E6 and E7 genes of 401 HPV58 isolates collected from 15 countries/cities across four continents were examined. Phylogenetic relationship, geographical distribution and risk association of nucleotide sequence variations were analyzed. We found that the E6 genes of HPV58 variants were more conserved than E7. Thus, E6 is a more appropriate target for type-specific detection, whereas E7 is more appropriate for strain differentiation. The frequency of sequence variation varied geographically. Africa had significantly more isolates with E6-367A (D86E) but significantly less isolates with E6-203G, -245G, -367C (prototype-like) than other regions (p ≤ 0.003). E7-632T, -760A (T20I, G63S) was more frequently found in Asia, and E7-793G (T74A) was more frequent in Africa (p < 0.001). Variants with T20I and G63S substitutions at E7 conferred a significantly higher risk for cervical intraepithelial neoplasia grade III and invasive cervical cancer compared to other HPV58 variants (odds ratio = 4.44, p = 0.007). In conclusion, T20I and/or G63S substitution(s) at E7 of HPV58 is/are associated with a higher risk for cervical neoplasia. These substitutions are more commonly found in Asia and the Americas, which may account for the higher disease attribution of HPV58 in these areas.

BackgroundSexually transmitted infections (STIs) such as herpes simplex virus (HSV)-2 are associated with an increased risk of HIV infection. Human papillomavirus (HPV) is a common STI, but little is know about its role in HIV transmission. The objective of this study was to determine whether cervico-vaginal HPV infection increases the risk of HIV acquisition in women independent of other common STIs.Methods and findingsThis prospective cohort study followed 2040 HIV-negative Zimbabwean women (average age 27 years, range 18-49 years) for a median of 21 months. Participants were tested quarterly for 29 HPV types (with L1 PCR primers) and HIV (antibody testing on blood samples with DNA or RNA PCR confirmation). HIV incidence was 2.7 per 100 woman-years. Baseline HPV prevalence was 24.5%, and the most prevalent HPV types were 58 (5.0%), 16 (4.7%), 70 (2.4%), and 18 (2.3%). In separate regression models adjusting for baseline variables (including age, high risk partner, positive test for STIs, positive HSV-2 serology and condom use), HIV acquisition was associated with having baseline prevalent infection with HPV 58 (aHR 2.13; 95% CI 1.09-4.15) or HPV 70 (aHR 2.68; 95% CI 1.08-6.66). In separate regression models adjusting for both baseline variables and time-dependent variables (including HSV-2 status, incident STIs, new sexual partner and condom use), HIV acquisition was associated with concurrent infection with any non-oncogenic HPV type (aHR 1.70; 95% CI 1.02-2.85), any oncogenic HPV type (aHR 1.96; 95% CI 1.16-3.30), HPV 31 (aHR 4.25; 95% CI 1.81-9.97) or HPV 70 (aHR 3.30; 95% CI 1.50-7.20). Detection of any oncogenic HPV type within the previous 6 months was an independent predictor of HIV acquisition, regardless of whether HPV status at the HIV acquisition visit was included (aHR 1.95; 95% CI 1.19-3.21) or excluded (aHR 1.96; 95% CI 1.02-2.85) from the analysis.Conclusions/significanceCervico-vaginal HPV infection was associated with an increased risk of HIV acquisition in women, and specific HPV types were implicated in this association. The observational nature of our study precludes establishment of causation between HPV infection and HIV acquisition. However, given the high prevalence of HPV infection in women, further investigation of the role of HPV in HIV transmission is warranted.

Background: Substantial heterogeneity in HIV prevalence has been observed within sub‐Saharan Africa. It is not clear which factors can explain these differences. Our aim was to identify risk factors that could explain the large differences in HIV‐1 prevalence among pregnant women in Harare, Zimbabwe, and Moshi, Tanzania. Methods: Cross‐sectional data from a two‐centre study that enrolled pregnant women in Harare (N = 691) and Moshi (N = 2654) was used. Consenting women were interviewed about their socio‐demographic background and sexual behaviour, and tested for presence of sexually transmitted infections and reproductive tract infections. Prevalence distribution of risk factors for HIV acquisition and spread were compared between the two areas. Results: The prevalence of HIV‐1 among pregnant women was 26% in Zimbabwe and 7% in Tanzania. The HIV prevalence in both countries rises constantly with age up to the 25‐30 year age group. After that, it continues to rise among Zimbabwean women, while it drops for Tanzanian women. Risky sexual behaviour was more prominent among Tanzanians than Zimbabweans. Mobility and such infections as HSV‐2, trichomoniasis and bacterial vaginosis were more prevalent among Zimbabweans than Tanzanians. Reported male partner circumcision rates between the two countries were widely different, but the effect of male circumcision on HIV prevalence was not apparent within the populations. Conclusions: The higher HIV‐1 prevalence among pregnant women in Zimbabwe compared with Tanzania cannot be explained by differences in risky sexual behaviour: all risk factors tested for in our study were higher for Tanzania than Zimbabwe. Non‐sexual transmission of HIV might have played an important role in variation of HIV prevalence. Male circumcision rates and mobility could contribute to the rate and extent of spread of HIV in the two countries., Background There is substantial heterogeneity in HIV‐1 prevalence within sub‐Saharan Africa, a region that contains more than a third of the world's HIV‐1 infections [1]. Sub‐Saharan Africa's epidemics vary significantly [...]

Introduction: African adolescent girls and young women (AGYW) eligible for HIV pre‐exposure prophylaxis (PrEP) experience high levels of depressive symptoms. Depression can reduce PrEP adherence among adults, although analyses have considered depression as a time‐varying exposure rather than modelling distinct patterns of symptoms. The association between depressive symptoms and PrEP adherence has not been explored for AGYW. To address these gaps, we sought to understand depressive symptom trajectories among African AGYW initiating PrEP and the impact of time‐varying depressive symptoms and symptom trajectories on PrEP adherence. Methods: HPTN 082 was an open‐label PrEP study among AGYW (ages 16 to 24) in Zimbabwe and South Africa from 2016 to 2018. Depressive symptoms were measured at enrolment and Weeks 13, 26 and 52, using the 10‐item Center for Epidemiologic Studies scale; a score ≥10 is indicative of elevated depressive symptoms. PrEP adherence was defined as any detectable tenofovir diphosphate (TFV‐DP) levels. Group‐based trajectory modelling was used to model longitudinal patterns of depressive symptoms. We assessed psychosocial and behavioural predictors of depressive symptom trajectory membership (e.g. PrEP stigma, intimate partner violence [IPV], sexual behaviour). We modelled associations between (1) group trajectory membership and PrEP adherence at Week 52 and (2) time‐varying depressive symptoms and PrEP adherence through follow‐up. Results: At enrolment, 179 (41.9%) participants had elevated depressive symptoms. Group‐based trajectory models revealed persistent elevated depressive symptoms in 48.5%, declining symptoms in 9.4% and no consistent or mild depressive symptoms in 43.3%. AGYW who engaged in transactional sex, reported IPV, or had traumatic stress symptoms were more likely to be assigned to the persistent elevated symptom group compared with the consistent no/mild symptom group (Wald test p‐value all <0.01). Participants assigned to the persistent elevated depressive symptom trajectory had a significantly lower risk of detectable TFV‐DP at Week 52 than those in the no/mild symptom trajectory (adjusted prevalence ratio = 0.89; 95% CI: 0.80 to 0.98). Elevated depressive symptoms were significantly inversely associated with PrEP use throughout follow‐up (adjusted relative risk = 0.73; 95% CI = 0.53 to 0.99). Conclusions: Persistent depressive symptoms were common among African AGYW seeking PrEP. Integration of depressive symptom screening and treatment into PrEP programmes may improve PrEP effectiveness among African women. [ABSTRACT FROM AUTHOR]

Abstract Background Cervix cancer, preventable, continues to be the third most common cancer in women worldwide, especially in lowest income countries. Prophylactic HPV vaccination should help to reduce the morbidity and mortality associated with cervical cancer. The purpose of the study was to describe the results of and key concerns in eight HPV vaccination programs conducted in seven lowest income countries through the Gardasil Access Program (GAP). Methods The GAP provides free HPV vaccine to organizations and institutions in lowest income countries. The HPV vaccination programs were entirely developed, implemented and managed by local institutions. Institutions submitted application forms with institution characteristics, target population, communication delivery strategies. After completion of the vaccination campaign (3 doses), institutions provided a final project report with data on doses administered and vaccination models. Two indicators were calculated, the program vaccination coverage and adherence. Qualitative data were also collected in the following areas: government and community involvement; communication, and sensitization; training and logistics resources, and challenges. Results A total of eight programs were implemented in seven countries. The eight programs initially targeted a total of 87,580 girls, of which 76,983 received the full 3-dose vaccine course, with mean program vaccination coverage of 87.8%; the mean adherence between the first and third doses of vaccine was 90.9%. Three programs used school-based delivery models, 2 used health facility-based models, and 3 used mixed models that included schools and health facilities. Models that included school-based vaccination were most effective at reaching girls aged 9-13 years. Mixed models comprising school and health facility-based vaccination had better overall performance compared with models using just one of the methods. Increased rates of program coverage and adherence were positively correlated with the number of vaccination sites. Qualitative key insights from the school models showed a high level of coordination and logistics to facilitate vaccination administration, a lower risk of girls being lost to follow-up and vaccinations conducted within the academic year limit the number of girls lost to follow-up. Conclusion Mixed models that incorporate both schools and health facilities appear to be the most effective at delivering HPV vaccine. This study provides lessons for development of public health programs and policies as countries go forward in national decision-making for HPV vaccination.

Abstract Background Expensive CD4 count and viral load tests have failed the intended objective of enabling access to HIV therapy in poor resource settings. It is imperative to develop simple, affordable and non-subjective disease monitoring tools to complement clinical staging efforts of inexperienced health personnel currently manning most healthcare centres because of brain drain. Besides accurately predicting HIV infection, sequential appearance of specific bands of WB test offers a window of opportunity to develop a less subjective tool for monitoring disease progression. Methods HIV type characterization was done in a cohort of infected pregnant women at 36 gestational weeks using WB test. Student-t test was used to determine maternal differences in mean full blood counts and viral load of mothers with and those without HIV gag antigen bands. Pearson Chi-square test was used to assess differences in lack of bands appearance with vertical transmission and lymphadenopathy. Results Among the 64 HIV infected pregnant women, 98.4% had pure HIV-1 infection and one woman (1.7%) had dual HIV-1/HIV-2 infections. Absence of HIV pol antigen bands was associated with acute infection, p = 0.002. All women with chronic HIV-1 infection had antibody reactivity to both the HIV-1 envelope and polymerase antigens. However, antibody reactivity to gag antigens varied among the women, being 100%, 90%, 70% and 63% for p24, p17, p39 and p55, respectively. Lack of antibody reactivity to gag p39 antigen was associated with disease progression as confirmed by the presence of lymphadenopathy, anemia, higher viral load, p = 0.010, 0.025 and 0.016, respectively. Although not statistically significant, women with p39 band missing were 1.4 times more likely to transmit HIV-1 to their infants. Conclusion Absence of antibody reactivity to pol and gag p39 antigens was associated with acute infection and disease progression, respectively. Apart from its use in HIV disease diagnosis, WB test could also be used in conjunction with simpler tests like full blood counts and patient clinical assessment as a relatively cheaper disease monitoring tool required prior to accessing antiretroviral therapy for poor resource settings. However, there is also need to factor in the role of host-parasite genetics and interactions in disease progression.

Abstract Background HIV incidence is a useful tool for improving the targeting of populations for interventions and assessing the effectiveness of prevention strategies. A study in Harare, Zimbabwe reported cumulative incidences of 3.4% (3.0-3.8) and 6.5% (5.7-7.4) among post-partum women followed for 12 and 24 months respectively between 1997 and 2001. According to a Government report on HIV the prevalence of HIV fell from about 30% in 1999 to 14% in 2008. The purpose of this study was to determine the incidence of HIV-1 among women enrolled during late pregnancy and followed for six years after childbirth and to identify risk factors associated with acquisition of HIV. Methods HIV-uninfected pregnant women around 36 weeks gestation were enrolled from primary health care clinics in peri-urban settlements around Harare and followed-up for up to six years after childbirth. At every visit a questionnaire was interview-administered to obtain socio-demographic data and sexual history since the previous visit. A genital examination was performed followed by the collection of biological samples. Results Of the 552 HIV-uninfected women 444 (80.4%) were seen at least twice during the six years follow-up and 39 acquired HIV, resulting in an incidence (95% CI) of 2.3/100 woman-years-at-risk (wyar) (1.1-4.1). The incidence over the first nine months post-partum was 5.7/100 wyar (3.3-8.1). A greater proportion of teenagers (15.3%) contributed to a high incidence rate of 2.9/100 (0.6-8.7) wyar. In multivariate analysis lower education of participant, RR 2.1 (1.1-4.3) remained significantly associated with HIV acquisition. Other risk factors associated with acquisition of HIV-1 in univariate analysis were young age at sexual debut, RR 2.3, (1.0-5.6) and having children with different fathers, RR 2.7(1.3-5.8). Women that knew that their partners had other sexual partners were about four times more likely to acquire HIV, RR 3.8 (1.3-11.2). Conclusion The incidence of HIV was high during the first nine months after childbirth. Time of seroconversion, age and educational level of seroconverter are important factors that must be considered when designing HIV intervention strategies.

Abstract Objective To determine HIV-1 RNA load during the third trimester of pregnancy and evaluate its effect on in utero and intra-partum/postpartum transmissions in a breastfeeding population. Design A nested case-control study within a PMTCT cohort of antiretroviral therapy naive pregnant women and their infants. Methods A case was a mother who transmitted HIV-1 to her infant (transmitter) who was matched to one HIV-1 positive but non-transmitting mother (control). Results From a cohort of 691 pregnant women, 177 (25.6%) were HIV-1 positive at enrolment and from these 29 (23%) transmitted HIV-1 to their infants, 10 and 19 during in utero and intra-partum/postpartum respectively. Twenty-four mothers sero-converted after delivery and three transmitted HIV-1 to their infants. Each unit increase in log10 viral load was associated with a 178 cells/mm3 and 0.2 g/dL decrease in TLC and hemoglobin levels, p = 0.048 and 0.021 respectively, and a 29% increase in the risk of transmission, p = 0.023. Intra-partum/postpartum transmitters had significantly higher mean viral load relative to their matched controls, p = 0.034. Conclusion Antenatal serum HIV-1 RNA load, TLC and hemoglobin levels were significantly associated with vertical transmission but this association was independent of transmission time. This finding supports the rationale for preventive strategies designed to reduce vertical transmission by lowering maternal viral load.

Abstract Background Sexually transmitted infections (STIs) and Reproductive tract infections (RTIs) are responsible for high morbidity among women. We aim to quantify the magnitude of the burden and risk factors of STI/RTI s among pregnant women in Zimbabwe. Methods A cross sectional study of pregnant women enrolled at 36 weeks of gestation from the national PMTCT program. Study was conducted from three peri-urban clinics around Harare Zimbabwe offering maternal and child health services. Results A total of 691 pregnant women were enrolled. Prevalence of HSV was (51.1%), HIV (25.6%) syphilis (1.2%), Trichomonas vaginalis (11.8%), bacterial vaginosis (32.6%) and Candidiasis (39.9%). Seven percent of the women had genital warts, 3% had genital ulcers and 28% had an abnormal vaginal discharge. Prevalence of serological STIs and vaginal infections were 51% and 64% respectively. Risk factors for a positive serologic STI were increasing age above 30 years, polygamy and multigravid; adjusted OR (95% CI) 2.61(1.49-4.59), 2.16(1.06-4.39), 3.89(1.27-11.98) respectively, partner taking alcohol and number of lifetime sexual partners. For vaginal infections it was age at sexual debut; OR (95% CI) 1.60(1.06-2.42). More than 25% of the women reported previous STI treatment. Fifty two percent reported ever use of condoms and 65% were on oral contraceptives. Mean age gap for sexual partners was 6.3 years older. Conclusions There is a high morbidity of STI/RTIs in this cohort. There is need to continuously screen, counsel, treat and monitor trends of STI/RTIs to assess if behaviour changes lead to reduction in infections and their sustainability.

Abstract Background Herpes simplex virus type 2 (HSV-2) is the leading cause of genital ulcer disease worldwide. The virus can be transmitted to neonates and there are scarce data regarding incidence of HSV-2 among women in pregnancy and after childbirth. The aim of this study is to measure the incidence and risk factors for HSV-2 infection in women followed for 9 months after childbirth. Methods Pregnant women were consecutively enrolled late in pregnancy and followed at six weeks, four and nine months after childbirth. Stored samples were tested for HSV-2 at baseline and again at nine months after childbirth and HSV-2 seropositive samples at nine months after childbirth (seroconverters) were tested retrospectively to identify the seroconversion point. Results One hundred and seventy-three (50.9%) of the 340 consecutively enrolled pregnant women were HSV-2 seronegative at baseline. HSV-2 incidence rate during the 10 months follow up was 9.7 (95% CI 5.4-14.4)/100 and 18.8 (95% CI 13.9-26.1)/100 person years at risk (PYAR) at four months and nine months after childbirth respectively. Analysis restricted to women reporting sexual activity yielded higher incidence rates. The prevalence of HSV-2 amongst the HIV-1 seropositive was 89.3%. Risk factors associated with HSV-2 seropositivity were having other sexual partners in past 12 months (Prevalence Risk Ratio (PRR) 1.8 (95% CI 1.4-2.4) and presence of Trichomonas vaginalis (PRR 1.7 95% CI 1.4-2.1). Polygamy (Incidence Rate Ratio (IRR) 4.4, 95% CI 1.9-10.6) and young age at sexual debut (IRR 3.6, 95% CI 1.6-8.3) were associated with primary HSV-2 infection during the 10 months follow up. Conclusions Incidence of HSV-2 after childbirth is high and the period between late pregnancy and six weeks after childbirth needs to be targeted for prevention of primary HSV-2 infection to avert possible neonatal infections.

Several studies indicate that HIV-infected women continue to have children. We set out to determine the trend in HIV transmission at subsequent pregnancies. From 2002-2003, pregnant women were enrolled in a single dose nevirapine-based Prevention of Mother-to-Child Transmission of HIV (PMTCT) programme. Six years later, women with subsequent children in this cohort were identified and their children's HIV status determined. From 330 identified HIV-infected mothers, 73 had second/subsequent children with HIV results. Of these, nine (12.3%, 95% confidence interval [CI]: 4.6-20.1%) children were HIV-infected. Of the 73 second children, 51 had older siblings who had been initially enrolled in the study with definitive HIV results with an infection rate of 17/51 (33.3%, 95% CI: 19.9-46.7). About 35% of the women had been on antiretroviral drugs. These results demonstrate lower subsequent HIV transmission rates in women on a national PMTCT programme in a resource-poor setting with the advent of antiretroviral therapy. [ABSTRACT FROM AUTHOR]

Objective: To determine HIV-1 RNA load during the third trimester of pregnancy and evaluate its effect on in utero and intra-partum/postpartum transmissions in a breastfeeding population. Design: A nested case-control study within a PMTCT cohort of antiretroviral therapy naive pregnant women and their infants. Methods: A case was a mother who transmitted HIV-1 to her infant (transmitter) who was matched to one HIV-1 positive but non-transmitting mother (control). Results: From a cohort of 691 pregnant women, 177 (25.6%) were HIV-1 positive at enrolment and from these 29 (23%) transmitted HIV-1 to their infants, 10 and 19 during in utero and intra-partum/postpartum respectively. Twenty-four mothers sero-converted after delivery and three transmitted HIV-1 to their infants. Each unit increase in log10 viral load was associated with a 178 cells/mm³ and 0.2 g/dL decrease in TLC and hemoglobin levels, p = 0.048 and 0.021 respectively, and a 29% increase in the risk of transmission, p = 0.023. Intra-partum/postpartum transmitters had significantly higher mean viral load relative to their matched controls, p = 0.034. Conclusion: Antenatal serum HIV-1 RNA load, TLC and hemoglobin levels were significantly associated with vertical transmission but this association was independent of transmission time. This finding supports the rationale for preventive strategies designed to reduce vertical transmission by lowering maternal viral load. [ABSTRACT FROM AUTHOR]