Research for Health Care and Policy on HIV/AIDS: proceedings of the third edition of the Cameroon HIV Research (CAM-HERO) 2022, Kribi, Cameroon, from 1st to 3rd December 2022.

Cameroon is committed to reaching HIV epidemic control through coordinated efforts by the Ministry of Public Health, the National AIDS Control Committee, bilateral/multilateral institutions and implementing partners. The third edition of the Cameroon HIV Research Forum (CAM-HERO) was held in Kribi from December 1st to 3rd, 2022, with the theme "Research for Health Care and Policy on HIV/AIDS." The conference brought together local and international scientists and clinicians, policymakers, and regulatory authorities to 1) disseminate HIV research findings and HIV policy; 2) foster operational research collaboration; 3) build research capacity through training on basics of research methods and CAM-HERO young investigator Awards; and 4) initiate a guideline for promoting HIV/AIDS research in Cameroon. The main activities included training on research methodology and basic principles in bioethics, presentations of selected abstracts, and awards for top research. A total of 35 abstracts (16 oral presentations, 16 posters, and 3 late-breaker-abstracts) were selected for presentation following a rigorous review. The conference ended with evidence-based recommendations and a way-forward statement for the development of a National Guide for HIV/AIDS research in Cameroon, with the aim of improving the quality and quantity of research agenda and projects nationwide.

Efficacy of Cipargamin (KAE609) in a Randomized, Phase II Dose-Escalation Study in Adults in Sub-Saharan Africa With Uncomplicated Plasmodium falciparum Malaria.

BACKGROUND: Cipargamin (KAE609) is a potent antimalarial in a phase II trial. Here we report efficacy, pharmacokinetics, and resistance marker analysis across a range of cipargamin doses. These were secondary endpoints from a study primarily conducted to assess the hepatic safety of cipargamin (hepatic safety data are reported elsewhere). METHODS: This phase II, multicenter, randomized, open-label, dose-escalation trial was conducted in sub-Saharan Africa in adults with uncomplicated Plasmodium falciparum malaria. Cipargamin monotherapy was given as single doses up to 150 mg or up to 50 mg once daily for 3 days, with artemether-lumefantrine as control. Key efficacy endpoints were parasite clearance time (PCT), and polymerase chain reaction (PCR)-corrected and uncorrected adequate clinical and parasitological response (ACPR) at 14 and 28 days. Pharmacokinetics and molecular markers of drug resistance were also assessed. RESULTS: All single or multiple cipargamin doses ≥50 mg were associated with rapid parasite clearance, with median PCT of 8 hours versus 24 hours for artemether-lumefantrine. PCR-corrected ACPR at 14 and 28 days was >75% and 65%, respectively, for each cipargamin dose. A treatment-emerging mutation in the Pfatp4 gene, G358S, was detected in 65% of treatment failures. Pharmacokinetic parameters were consistent with previous data, and approximately dose proportional. CONCLUSIONS: Cipargamin, at single doses of 50 to 150 mg, was associated with very rapid parasite clearance, PCR-corrected ACPR at 28 days of >65% in adults with uncomplicated P. falciparum malaria, and recrudescent parasites frequently harbored a treatment-emerging mutation. Cipargamin will be further developed with a suitable combination partner. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov (NCT03334747).

Evidence for an enhanced HIV/AIDS policy and care in Cameroon: proceedings of the second Cameroon HIV Research Forum (CAM-HERO) 2021.

To attain the HIV 95-95-95 goals by 2030 in Cameroon, high quality research to inform policy and patient care is of utmost importance. In the context of limited workforce and resources, collaborations, sharing of locally-adapted strategies and other field experience, leveraging on existing and innovative platforms would facilitate a coordinated and optimal AIDS response at country level. The second edition of the Cameroon HIV Research Forum (CAM-HERO) conference took place both physically and virtually on November 18 and 19, 2021 in Kribi, on the theme "Research for Policy and Care". This scientific event brought together Cameroonian HIV/AIDS researchers, experienced clinicians and regulatory authorities to foster i) the dissemination of research findings and facilitate translation into policy, ii) operational research collaboration, iii) identification of new research areas, and iv) capacity building. To achieve the set objectives during this event, a consensus on research priorities for accelerating the achievement of three 95 HIV goals in Cameroon were summarized; meeting sessions included 31 abstract presentations, 13 discussions, and presentations on various aspects of HIV research including ethics, administrative procedures and needs for capacity building; training of young scientists on guidelines for research proposal development toward ethical clearance was done; and a platform for discussion between researchers and regulatory authorities was conducted around the design and setting-up of a national HIV/AIDS research agenda. CAM-HERO 2021 brought together HIV researchers, experts and junior scientists around major programmatic challenges, evidence to translate into practice, research priorities on HIV/AIDS. Collaborations were reinforced, capacities were strengthened, and footprints were established towards a consensus on a national HIV/AIDS research agenda.

Research priorities for accelerating the achievement of three 95 HIV goals in Cameroon: a consensus statement from the Cameroon HIV Research Forum (CAM-HERO).

INTRODUCTION: the Treat-All remains the globally endorsed approach to attain the 95-95-95 targets and end the AIDS pandemic by 2030, but requires some country-level contextualization. In Cameroon, the specific research agenda to inform strategies for improving HIV policy was yet to be defined. METHODS: under the patronage of the Cameroon Ministry of health, researchers, policy makers, implementing partners, and clinicians from 13 institutions, used the Delphi method to arrive at a consensus of HIV research priorities. The process had five steps: 1) independent literature scan by 5 working groups; 2) review of the initial priority list; 3) appraisal of priorities list in a larger group; 4) refinement and consolidation by a consensus group; 5) rating of top research priorities. RESULTS: five research priorities and corresponding research approaches, resulted from the process. These include: 1) effectiveness, safety and active toxicity monitoring of new and old antiretrovirals; 2) outcomes of Antiretroviral Therapy (ART) with focus in children and adolescents; 3) impact of HIV and ART on aging and major chronic diseases; 4) ART dispensation models and impact on adherence and retention; 5) evaluations of HIV treatment and prevention programs. CONCLUSION: the research priorities resulted from a consensus amongst a multidisciplinary team and were based on current data about the pandemic and science to prevent, treat, and ultimately cure HIV. These priorities highlighted critical areas of investigation with potential relevance for the country, funders, and regulatory bodies.

Outcomes of the first meeting of the CAMEROON HIV RESEARCH FORUM (CAM-HERO).

Research is a vital component for the development of any country. In Cameroon, HIV Operational research is rapidly growing, however, it faces some intractable problems which can only be solved through an urgent, strategic, efficient, and collaborative approach involving key stakeholders. The Kribi meeting (09 and 10th December 2020) brought together under the auspices of the Ministry of Public Health leading HIV research organisations and connected HIV researchers and actors from different sectors. These actors disseminated and discussed recent research findings and worked out mechanisms to advance HIV research development, developed new ideas and identified priority research areas, with emphasis on translational research. The official launching and consolidation of Cam-HERO was a critical step and it is hoped that these synergistic efforts will catalyse attainment of the 95-95-95 goals in Cameroon.

Hepatic safety and tolerability of cipargamin (KAE609), in adult patients with Plasmodium falciparum malaria: a randomized, phase II, controlled, dose-escalation trial in sub-Saharan Africa.

BACKGROUND: The novel anti-malarial cipargamin (KAE609) has potent, rapid activity against Plasmodium falciparum. Transient asymptomatic liver function test elevations were previously observed in cipargamin-treated subjects in two trials: one in malaria patients in Asia and one in volunteers with experimentally induced malaria. In this study, the hepatic safety of cipargamin given as single doses of 10 to 150 mg and 10 to 50 mg once daily for 3 days was assessed. Efficacy results, frequency of treatment-emerging mutations in the atp4 gene and pharmacokinetics have been published elsewhere. Further, the R561H mutation in the k13 gene, which confers artemisinin-resistance, was associated with delayed parasite clearance following treatment with artemether-lumefantrine in Rwanda in this study. This was also the first study with cipargamin to be conducted in patients in sub-Saharan Africa. METHODS: This was a Phase II, multicentre, randomized, open-label, dose-escalation trial in adults with uncomplicated falciparum malaria in five sub-Saharan countries, using artemether-lumefantrine as control. The primary endpoint was ≥ 2 Common Terminology Criteria for Adverse Events (CTCAE) Grade increase from baseline in alanine aminotransferase (ALT) or aspartate transaminase (AST) during the 4-week trial. RESULTS: Overall, 2/135 patients treated with cipargamin had ≥ 2 CTCAE Grade increases from baseline in ALT or AST compared to 2/51 artemether-lumefantrine patients, with no significant difference between any cipargamin treatment group and the control group. Cipargamin exposure was comparable to or higher than those in previous studies. Hepatic adverse events and general safety and tolerability were similar for all cipargamin doses and artemether-lumefantrine. Cipargamin was well tolerated with no safety concerns. CONCLUSIONS: This active-controlled, dose escalation study was a detailed assessment of the hepatic safety of cipargamin, across a wide range of doses, in patients with uncomplicated falciparum malaria. Comparison with previous cipargamin trials requires caution as no clear conclusion can be drawn as to whether hepatic safety and potential immunity to malaria would differ with ethnicity, patient age and or geography. Previous concerns regarding hepatic safety may have been confounded by factors including malaria itself, whether natural or experimental infection, and should not limit the further development of cipargamin. Trial registration ClinicalTrials.gov number: NCT03334747 (7 Nov 2017), other study ID CKAE609A2202.

Longitudinal interrelationship between HIV viral suppression, maternal weight change, breastfeeding, and length in HIV-exposed and uninfected infants participating in the Kabeho study in Kigali, Rwanda.

PURPOSE: The health of infants that are HIV-exposed and -uninfected (HEU) is a major public health concern as HIV becomes a chronic condition. We investigate the interrelationship between maternal viral suppression, maternal weight status, breastfeeding, and infants that are HEU. METHODS: The Kabeho study followed 502 HEU infants in Kigali, Rwanda, for 24 months from 2013 to 2014. We use a structural equation modeling approach to investigate the dynamic relationships between viral suppression, maternal weight change, breastfeeding, and infant length-for-age z-score (LAZ) as defined by the WHO. RESULTS: Older mothers are more likely to be virally suppressed and to breastfeed. Viral suppression and the mother being on antiretroviral treatment for longer were related to lower infant LAZ at three months. A more positive maternal weight change was related to higher infant LAZ at the end of each period. At 12 months, a higher infant LAZ was related to increased probability of continued breastfeeding. At 18 months, continued breastfeeding was related to lower LAZ, and food shortages were related to higher LAZ. CONCLUSION: There is a complex interrelationship between viral suppression, maternal weight change, breastfeeding, and infant LAZ. These relationships demonstrate the link between maternal and infant health in the context of HIV.

Presentation of Pediatric Unintentional Injuries at Rural Hospitals in Rwanda: A Retrospective Study.

Background: Injuries are a leading cause of mortality among children globally, with children in low- and middle-income countries more likely to die if injured compared to children in high-income countries. Timely and high-quality care are essential to reduce injury-related morbidity and mortality. Objectives: This study describes patterns, management, and outcomes of children 0-15 years presenting with unintentional injuries at three district hospitals in rural Rwanda between January 1 and December 31, 2017. Methods: Using a retrospective cross-sectional study design, we assessed the demographic and clinical characteristics, care provided, and outcomes of the children using data extracted from patient medical charts. We describe the patient population using frequencies and proportions as well as median and interquartile ranges. Findings: Of the 449 injured children who sought care at the three rural district hospitals, 66.2% (n = 297) were boys. The main causes of injury were falls (n = 261, 58.1%), burns (n = 101, 22.5%), and road traffic injuries (n = 67, 14.9%). Burns were the most common injury among children aged 0-5 years while falls were the leading injury type among the 5-15 years age group. Vital signs were inconsistently completed ranging between 23.8-89.1% of vital sign items. Of the injured children, 37.0% (n = 166) received surgery at the district hospital, general practitioners performed 80.9% (n = 114) of surgeries, 87.4% (n = 145) of operated patients received no anesthesia, and 69.3% (n = 311) were admitted to the district hospital, while 2.7% (n = 12) were transferred to tertiary facilities for higher-level care. Conclusions: The presentation of child injuries-namely falls, burns, and road traffic accidents-is similar to what has been reported in other sub-Saharan African countries. However, more needs to be done to improve the completion and documentation of vital signs and increase availability of surgical specialists. Finally, targeted strategies to prevent burns and motorcycle-related injuries are recommended prevention interventions for this rural population.

Factors Associated with Loss to Follow-up among Cervical Cancer Patients in Rwanda.

Background: Cervical cancer is among the most common cancers affecting women globally. Where treatment is available in low- and middle-income countries, many women become lost to follow-up (LTFU) at various points of care. Objective: This study assessed predictors of LTFU among cervical cancer patients in rural Rwanda. Methods: We conducted a retrospective study of cervical cancer patients enrolled at Butaro Cancer Center of Excellence (BCCOE) between 2012 and 2017 who were either alive and in care or LTFU at 12 months after enrollment. Patients are considered early LTFU if they did not return to clinic after the first visit and late LTFU if they did not return to clinic after the second visit. We conducted two multivariable logistic regressions to determine predictors of early and late LTFU. Findings: Of 652 patients in the program, 312 women met inclusion criteria, of whom 47 (15.1%) were early LTFU, 78 (25.0%) were late LTFU and 187 (59.9%) were alive and in care. In adjusted analyses, patients with no documented disease stage at presentation were more likely to be early LTFU vs. patients with stage 1 and 2 when controlling for other factors (aOR: 14.93, 95% CI 6.12-36.43). Patients who travel long distances (aOR: 2.25, 95% CI 1.11, 4.53), with palliative care as type of treatment received (aOR: 6.65, CI 2.28, 19.40) and patients with missing treatment (aOR: 7.99, CI 3.56, 17.97) were more likely to be late LTFU when controlling for other factors. Patients with ECOG status of 2 and higher were less likely to be late LTFU (aOR: 0.26, 95% CI 0.08, 0.85). Conclusion: Different factors were associated with early and later LTFU. Enhanced patient education, mechanisms to facilitate diagnosis at early stages of disease, and strategies that improve patient tracking and follow-up may reduce LTFU and improve patient retention.

Postoperative Rheumatic Heart Disease Follow-Up: Creating a National Registry and First Results from Rwanda.

Background: In many developing countries, rheumatic heart disease (RHD) is diagnosed at an advanced stage and requires surgery for patient survival. However, access to cardiac surgery in this context is limited and often provided through partnerships, requiring centralized patient data systems for monitoring and follow-up. Objectives: This study used data from a national postoperative RHD registry to analyze clinical outcomes of Rwandan patients who received surgery between 2006 and 2017. Methods: The RHD registry was created in 2017 using data compiled from Rwanda Ministry of Health and RHD surgery partners. We extracted pre- and post-operative data on patients who were alive and in care. We excluded patients who died or were lost to follow-up, as their data was not collected in the registry. We evaluated the association between demographic, surgical, and follow-up characteristics and most recent patient symptoms, categorized by New York Heart Association (NYHA) class. Findings: Among the 191 patients eligible for inclusion in this study, 107(56.0%) were female, 110(57.6%) were adults at the time of surgery (>15 years), and 128(67.4%) had surgery in Rwanda. Most patients (n = 166, 86.9%) were on penicillin prophylaxis. Of the patients with mechanical valves, 47(29.9%) had therapeutic International Normalized Ratio values. 90% of patients were asymptomatic (NYHA I) at the time of most recent visit. NYHA class was not significantly associated with any of the considered variables. The median length of follow-up for patients was four years (IQR: 2, 5 years). Conclusion: This study shows both the feasibility and challenges of creating a RHD registry 11 years after the national initiation of RHD surgeries. Most patients captured in the registry are asymptomatic; however, collecting details on patients who had died or were lost to follow-up has proven difficult. Implementing strategies to maintain a complete and up-to-date registry will facilitate follow-up for pre- and postoperative patients.

Implementation of blood glucose self-monitoring among insulin-dependent patients with type 2 diabetes in three rural districts in Rwanda: 6 months open randomised controlled trial.

INTRODUCTION: Most patients diagnosed with diabetes in sub-Saharan Africa (SSA) present with poorly controlled blood glucose, which is associated with increased risks of complications and greater financial burden on both the patients and health systems. Insulin-dependent patients with diabetes in SSA lack appropriate home-based monitoring technology to inform themselves and clinicians of the daily fluctuations in blood glucose. Without sufficient home-based data, insulin adjustments are not data driven and adopting individual behavioural change for glucose control in SSA does not have a systematic path towards improvement. METHODS AND ANALYSIS: This study explores the feasibility and impact of implementing self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes in rural Rwandan districts. This is an open randomised controlled trial comprising of two arms: (1) Intervention group-participants will receive a glucose metre, blood test strips, logbook, waste management box and training on how to conduct SMBG in additional to usual care and (2) Control group-participants will receive usual care, comprising of clinical consultations and routine monthly follow-up. We will conduct qualitative interviews at enrolment and at the end of the study to assess knowledge of diabetes. At the end of the study period, we will interview clinicians and participants to assess the perceived usefulness, facilitators and barriers of SMBG. The primary outcomes are change in haemoglobin A1c, fidelity to SMBG protocol by patients, appropriateness and adverse effects resulting from SMBG. Secondary outcomes include reliability and acceptability of SMBG and change in the quality of life of the participants. ETHICS AND DISSEMINATION: This study has been approved by the Rwanda National Ethics Committee (Kigali, Rwanda No.102/RNEC/2018). We will disseminate the findings of this study through presentations within our study settings, scientific conferences and publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: PACTR201905538846394; pre-results.

Predominance of the heterozygous CCR5 delta-24 deletion in African individuals resistant to HIV infection might be related to a defect in CCR5 addressing at the cell surface.

INTRODUCTION: The chemokine receptor CCR5 is the main co-receptor for R5-tropic HIV-1 variants. We have previously described a novel 24-base pair deletion in the coding region of CCR5 among individuals from Rwanda. Here, we investigated the prevalence of hCCR5Δ24 in different cohorts and its impact on CCR5 expression and HIV-1 infection in vitro. METHODS: We screened hCCR5Δ24 in a total of 3232 individuals which were either HIV-1 uninfected, high-risk HIV-1 seronegative and seropositive partners from serodiscordant couples, Long-Term Survivors, or HIV-1 infected volunteers from Africa (Rwanda, Kenya, Guinea-Conakry) and Luxembourg, using a real-time PCR assay. The role of the 24-base pair deletion on CCR5 expression and HIV infection was assessed in cell lines and PBMC using mRNA quantification, confocal analysis, flow and imaging cytometry. RESULTS AND DISCUSSION: Among the 1661 patients from Rwanda, 12 individuals were heterozygous for hCCR5Δ24 but none were homozygous. Although heterozygosity for this allele may not confer complete resistance to HIV-1 infection, the prevalence of the mutation was 2.41% (95%CI: 0.43; 8.37) in 83 Long-Term Survivors (LTS) and 0.99% (95%CI: 0.45; 2.14) in 613 HIV-1 exposed seronegative members as compared with 0.35% (95% Cl: 0.06; 1.25) in 579 HIV-1 seropositive members. The prevalence of hCCR5Δ24 was 0.55% (95%CI: 0.15; 1.69) in 547 infants from Kenya but the mutation was not detected in 224 infants from Guinea-Conakry nor in 800 Caucasian individuals from Luxembourg. Expression of hCCR5Δ24 in cell lines and PBMC showed that the hCCR5Δ24 protein is stably expressed but is not transported to the plasma membrane due to a conformational change. Instead, the mutant receptor was retained intracellularly, colocalized with an endoplasmic reticulum marker and did not mediate HIV-1 infection. Co-transfection of hCCR5Δ24 and wtCCR5 did not indicate a transdominant negative effect of CCR5Δ24 on wtCCR5. CONCLUSIONS: Our findings indicate that hCCR5Δ24 is not expressed at the cell surface. This could explain the higher prevalence of the heterozygous hCCR5Δ24 in LTS and HIV-1 exposed seronegative members from serodiscordant couples. Our data suggest an East-African localization of this deletion, which needs to be confirmed in larger cohorts from African and non-African countries.

Decreased consumption of common weaning foods is associated with poor linear growth among HIV-exposed infants participating in the Kigali antiretroviral and breastfeeding assessment for the elimination of HIV (Kabeho) study.

OBJECTIVE: The World Health Organization recommends that complementary foods that are adequate, safe, and appropriate be introduced to infants at age 6 months. Using an innovative modeling technique, we examine patterns of nutrient intake in HIV-exposed and uninfected (HEU) infants and establish their relationship with growth. METHODS: Single-day dietary recalls and anthropometrics were collected every two to 3 months from 543 infants living in Kigali, Rwanda, and attending clinics for the prevention of mother-to-child HIV transmission. A common weaning food index (CWFI) was calculated in grams and nutrient density for infants to reflect the extent to which the infants consumed the weaning foods typical of this population at ages 6 to 10, 11 to 15, and 16 to 20 months. Regressions among the CWFI, length-for-age z-scores (LAZ), and weight-for-length z-scores (WLZ) were conducted to estimate the relationship between the dietary patterns and growth. RESULTS: Mean absolute intake of zinc and calcium from complementary foods was insufficient. Increasing CWFI was related to increasing cow milk consumption. The density CWFI showed a decrease in the density of iron and folate as infants consume more of the weaning foods typical of this population. Density CWFI, breastfeeding, and caloric intake act on early LAZ and WLZ and interact with one another. Among breastfed infants, those who consume little of the common weaning foods and have a high caloric intake develop deficits in LAZ and have an elevated WLZ. CONCLUSIONS: A diet that is more dominated by the typical weaning foods of this population may support a healthy growth pattern.

Using Trials of Improved Practices to identify practices to address the double burden of malnutrition among Rwandan children.

OBJECTIVE: Low- and middle-income countries (LMIC) are increasingly experiencing the double burden of malnutrition. Studies to identify 'double-duty' actions that address both undernutrition and overweight in sub-Saharan Africa are needed. We aimed to identify acceptable behaviours to achieve more optimal feeding and physical activity practices among both under- and overweight children in Rwanda, a sub-Saharan LMIC with one of the largest recent increases in child overweight. DESIGN: We used the Trials of Improved Practices (TIPs) method. During three household visits over 1·5 weeks, we used structured interviews and unstructured observations to collect data on infant and young child feeding practices and caregivers' experiences with testing recommended practices. SETTING: An urban district and a rural district in Rwanda. PARTICIPANTS: Caregivers with an under- or overweight child from 6 to 59 months of age (n 136). RESULTS: We identified twenty-five specific recommended practices that caregivers of both under- and overweight children agreed to try. The most frequently recommended practices were related to dietary diversity, food quantity, and hygiene and food handling. The most commonly cited reason for trying a new practice was its benefits to the child's health and growth. Financial constraints and limited food availability were common barriers. Nearly all caregivers said they were willing to continue the practices and recommend them to others. CONCLUSIONS: These practices show potential for addressing the double burden as part of a broader intervention. Still, further research is needed to determine whether caregivers can maintain the behaviours and their direct impact on both under- and overweight.

Determinants of growth in HIV-exposed and HIV-uninfected infants in the Kabeho Study.

HIV-exposed and HIV-uninfected (HEU) infants may be at increased risk of poor health and growth outcomes. We characterized infant growth trajectories in a cohort of HEU infants to identify factors associated with healthy growth. HIV-positive women participating in prevention of mother-to-child HIV transmission programmes in Kigali, Rwanda, were followed until their infants were 2 years old. Infant anthropometrics were regularly collected. Latent class analysis was used to categorize infant growth trajectories. Multiple logistic regression was used to estimate the odds of infants belonging to each growth trajectory class. On average, this population of HEU infants had moderate linear growth faltering, but only modest faltering in weight, resulting in mean weight-for-length z-score (WLZ) above the World Health Organization (WHO) median. Mean WLZ was 0.53, and mean length-for-age z-score (LAZ) was -1.14 over the first 2 years of life. We identified four unique WLZ trajectories and seven trajectories in LAZ. Low neonatal weight-for-age and a high rate of illness increased the likelihood that infants were in the lightest WLZ class. Shorter mothers were more likely to have infants with linear growth faltering. Female infants who were older at the end of exclusive breastfeeding were more likely to be in the second tallest LAZ class. In conclusion, the current WHO recommendations of Option B+ and extended breastfeeding may induce higher WLZ and lower LAZ early in infancy. However, there is considerable heterogeneity in growth patterns that is obscured by simply analysing average growth trends, necessitating the analysis of growth in subpopulations.

A longitudinal analysis of the vaginal microbiota and vaginal immune mediators in women from sub-Saharan Africa.

In cross-sectional studies increased vaginal bacterial diversity has been associated with vaginal inflammation which can be detrimental for health. We describe longitudinal changes at 5 visits over 8 weeks in vaginal microbiota and immune mediators in African women. Women (N = 40) with a normal Nugent score at all visits had a stable lactobacilli dominated microbiota with prevailing Lactobacillus iners. Presence of prostate-specific antigen (proxy for recent sex) and being amenorrhoeic (due to progestin-injectable use), but not recent vaginal cleansing, were significantly associated with microbiota diversity and inflammation (controlled for menstrual cycle and other confounders). Women (N = 40) with incident bacterial vaginosis (Nugent 7-10) had significantly lower concentrations of lactobacilli and higher concentrations of Gardnerella vaginalis, Atopobium vaginae, and Prevotella bivia, at the incident visit and when concentrations of proinflammatory cytokines (IL-1ß, IL-12p70) were increased and IP-10 and elafin were decreased. A higher 'composite-qPCR vaginal-health-score' was directly associated with decreased concentrations of proinflammatory cytokines (IL-1α, IL-8, IL-12(p70)) and increased IP-10. This longitudinal study confirms the inflammatory nature of vaginal dysbiosis and its association with recent vaginal sex and progestin-injectable use. A potential role for proinflammatory mediators and IP-10 in combination with the vaginal-health-score as predictive biomarkers for vaginal dysbiosis merits further investigation.

Understanding Antiretroviral Treatment Adherence Among HIV-Positive Women at Four Postpartum Time Intervals: Qualitative Results from the Kabeho Study in Rwanda.

As lifelong antiretroviral therapy (ART) for pregnant women is implemented, it is important to understand the attitudes and norms affecting women's postpartum ART adherence. This is a qualitative cross-sectional study of HIV-positive postpartum women (n = 112) enrolled in a 2-year observational prospective cohort in Rwanda. Informed by the Theory of Reasoned Action (TRA), we conducted in-depth interviews with women whose children were 0-6, 7-12, 13-18, or 21-24 months of age to describe factors contributing to adherence and changes over time. Positive ART attitudes reported by women included mothers' health promotion, prevention of infant HIV infection, higher CD4 count, and improved physical appearance. Negative attitudes were few, but included side effects and the lifelong nature of treatment. Learning from people living with HIV (PLHIV) was identified as a norm facilitating adherence; ART adherence was inhibited by fear of disclosure or stigmatization in communities and clinics. Poor adherence behaviors were common immediately after HIV diagnosis, not necessarily during prevention of mother-to-child transmission (PMTCT). Women with older children, most of whom stopped breastfeeding by 13-18 months, reported more barriers and missed doses than women with younger children. The TRA was useful in identifying the collective influence of attitudes, norms, and intentions on behavior. Findings suggest that HIV-positive women are vulnerable to poor adherence following HIV diagnosis and around the time of breastfeeding cessation. Lifelong treatment adherence can be supported through PLHIV exemplifying long-term ART use, fewer and less stigmatizing clinic visits, and counseling messages highlighting the benefits of drugs on appearance and illness prevention and incorporating biological feedback.

24-month HIV-free survival among infants born to HIV-positive women enrolled in Option B+ program in Kigali, Rwanda: The Kabeho Study.

Lifelong antiretroviral therapy (ART) provision to all pregnant HIV-positive women ("Option B+") has been recommended by the World Health Organization since 2013, but there remain limited data on the effects of Option B+ on long-term HIV-free survival in breastfeeding HIV-exposed infants. The Kigali Antiretroviral and Breastfeeding Assessment for the Elimination of HIV (Kabeho) study enrolled HIV-positive women from the third trimester of pregnancy to 2 weeks postpartum in 14 heath facilities implementing Option B+ in Kigali, Rwanda. Mother-child pairs in the longitudinal observational cohort were followed until 24 months postpartum, with HIV diagnostic testing at 6 weeks, and 9, 18 and 24 months. The Kaplan-Meier method was used to estimate HIV transmission, survival, and HIV-free survival through 24 months. We enrolled 608 HIV-positive women in 2013-2014; birth outcome data were available for 600 women and 597 live-born infants. By 6 weeks, 11 infants had died and 3 infants had confirmed HIV infection (0.5% transmission; 95% confidence interval [CI] 0.2-1.6). At 9 months, there were 9 additional deaths and 2 new infections (cumulative transmission 0.9%, 95% CI 0.4-2.2). At 18 months, there were 6 additional deaths and no new infant infections. At 24 months, there were no additional child deaths and 1 new infection (cumulative 2.2%, 95% CI 0.7-7.0), for an overall 24-month HIV-free survival of 93.2% (95% CI 89.5-95.6). Low transmission rates and high HIV-free survival at 24 months were achieved in breastfeeding infants of HIV-positive mothers receiving universal ART in urban health facilities in Rwanda, though vigilance on maintaining viral suppression for ART-experienced women is needed.

Detectable Viral Load in Late Pregnancy among Women in the Rwanda Option B+ PMTCT Program: Enrollment Results from the Kabeho Study.

There are limited viral load (VL) data available from programs implementing "Option B+," lifelong antiretroviral treatment (ART) to all HIV-positive pregnant and postpartum women, in resource-limited settings. Extent of viral suppression from a prevention of mother-to-child transmission of HIV program in Rwanda was assessed among women enrolled in the Kigali Antiretroviral and Breastfeeding Assessment for the Elimination of HIV (Kabeho) Study. ARV drug resistance testing was conducted on women with VL>2000 copies/ml. In April 2013-January 2014, 608 pregnant or early postpartum HIV-positive women were enrolled in 14 facilities. Factors associated with detectable enrollment VL (>20 copies/ml) were examined using generalized estimating equations. The most common antiretroviral regimen (56.7%, 344/607) was tenofovir/lamivudine/efavirenz. Median ART duration was 13.5 months (IQR 3.0-48.8); 76.1% of women were on ART at first antenatal visit. Half of women (315/603) had undetectable RNA-PCR VL and 84.6% (510) had <1,000 copies/ml. Detectable VL increased among those on ART > 36 months compared to those on ART 4-36 months (72/191, 37.7% versus 56/187, 29.9%), though the difference was not significant. The odds of having detectable enrollment VL decreased significantly as duration on ART at enrollment increased (AOR = 0.99, 95% CI: 0.9857, 0.9998, p = 0.043). There was a higher likelihood of detectable VL for women with lower gravidity (AOR = 0.90, 95% CI: 0.84, 0.97, p = 0.0039), no education (AOR = 2.25, (95% CI: 1.37, 3.70, p = 0.0004), nondisclosure to partner (AOR = 1.97, 95% CI: 1.21, 3.21, p = 0.0063) and side effects (AOR = 2.63, 95% CI: 1.72, 4.03, p<0.0001). ARV drug resistance mutations were detected in all of the eleven women on ART > 36 months with genotyping available. Most women were receiving ART at first antenatal visit, with relatively high viral suppression rates. Shorter ART duration was associated with higher VL, with a concerning increasing trend for higher viremia and drug resistance among women on ART for >3 years.