Optimised prevention of postnatal HIV transmission in Zambia and Burkina Faso (PROMISE-EPI): a phase 3, open-label, randomised controlled trial.

BACKGROUND: Transmission through breastfeeding accounts for more than half of the unacceptably high number of new paediatric HIV infections worldwide. We hypothesised that, in addition to maternal antiretroviral therapy (ART), extended postnatal prophylaxis with lamivudine, guided by point-of-care assays for maternal viral load, could reduce postnatal transmission. METHODS: We did a phase 3, open-label, randomised controlled trial at four health-care facilities in Zambia and four health-care facilities in Burkina Faso. Mothers with HIV and their breastfed infants without HIV attending the second visit of the Expanded Programme of Immunisation (EPI-2; infant age 6-8 weeks) were randomly assigned 1:1 to intervention or control groups. In the intervention group, maternal viral load was measured using Xpert HIV viral load assay at EPI-2 and at 6 months, with results provided immediately. Infants whose mothers had a viral load of 1000 copies per mL or higher were started on lamivudine syrup twice per day for 12 months or 1 month after breastfeeding discontinuation. The control group followed national guidelines for prevention of postnatal transmission of HIV. The primary outcome assessed by modified intention to treat was infant HIV infection at age 12 months, with HIV DNA point-of-care testing at 6 months and at 12 months. This trial is registered with ClinicalTrials.gov (NCT03870438). FINDINGS: Between Dec 12, 2019 and Sept 30, 2021, 34 054 mothers were screened for HIV. Among them, 1506 mothers with HIV and their infants without HIV, including 1342 mother and infant pairs from Zambia and 164 from Burkina Faso, were eligible and randomly assigned 1:1 to the intervention (n=753) or control group (n=753). At baseline, the median age of the mothers was 30·6 years (IQR 26·0-34·7), 1480 (98·4%) of 1504 were receiving ART, and 169 (11·5%) of 1466 had a viral load ≥1000 copies/mL. There was one case of HIV transmission in the intervention group and six in the control group, resulting in a transmission incidence of 0·19 per 100 person-years (95% CI 0·005-1·04) in the intervention group and 1·16 per 100 person-years (0·43-2·53) in the control group, which did not reach statistical significance (p=0·066). HIV-free survival and serious adverse events were similar in both groups. INTERPRETATION: Our intervention, initiated at EPI-2 and based on extended single-drug postnatal prophylaxis guided by point-of-care maternal viral load could be an important strategy for paediatric HIV elimination. FUNDING: The EDCTP2 programme with the support of the UK Department of Health & Social Care.

Prevention of mother-to-child transmission of HIV at the second immunization visit: a cross-sectional study, Burkina Faso.

Objective: To evaluate the performance of the cascade of activities for prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) at the second immunization visit in Burkina Faso. Methods: In a cross-sectional study, we recruited mothers attending the second immunization visit for their infant in 20 health centres of Bobo-Dioulasso city, Burkina Faso over 12 months (2019-2020). We administered a short questionnaire to 14 176 mothers and performed HIV serological tests on mothers who had not been tested in the last 3 months. All mothers were asked about their attendance for antenatal care and HIV rapid testing. HIV-infected mothers were also asked about the timing of their HIV diagnosis, antiretroviral therapy, pre-exposure prophylaxis initiation at birth and infant diagnosis of HIV. Findings: Of 14 136 respondents, 13 738 (97.2%) had at least one HIV serological test in their lifetime. Of 13 078 mothers who were never tested or were HIV-negative, 12 454 (95.2%) were tested during or after their last pregnancy. Among HIV-infected mothers already aware of their status, 110/111 (99.1%) women were on antiretroviral therapy. Among HIV-exposed infants, 84/101 (83.2%) babies received 6 weeks of antiretroviral prophylaxis at birth and 58/110 (52.7%) had a blood sample collected for early infant diagnosis. Only two mothers received their child's test results at the time of the second immunization visit. Four mothers were newly diagnosed as HIV-positive during the study. Conclusion: Collecting data at the second immunization visit, a visit rarely missed by mothers, could be useful for identifying gaps in the PMTCT cascade in settings where mothers are difficult to reach, such as in low-income countries with intermediate or low HIV prevalence.

Evaluation of the prevention of mother-to-child transmission of HIV programs at the second immunization visit in Burkina Faso and Zambia.

OBJECTIVE: Our study aimed to assess the PMTCT indicators in Burkina Faso and Zambia using a patient-orientated innovative strategy based on the second visit in the Expanded Program on Immunization (EPI-2) visit at 6-8 weeks. DESIGN: This was a cross sectional study. METHODS: We assessed women attending EPI-2 at primary healthcare facilities in Burkina Faso and Zambia with their children about their exposure to PMTCT interventions. For women living with HIV (WLHIV), viral load was measured and their children were tested for HIV DNA using point of care devices. RESULTS: Overall, 25 093 were enrolled from Burkina Faso and 8961 women from Zambia. Almost, all women attended at least one antenatal care visit. Among those aware of their HIV-positive status, 95.8 and 99.2% were on antiretroviral therapy (ART) in Burkina Faso and Zambia, respectively. Among WLHIV on ART, 75 and 79.2% achieved a viral load suppression (viral load <1000 copies/ml) in Burkina Faso and Zambia, respectively. Infant postnatal prophylaxis was administered from birth until EPI-2 to 60.9 and 89.7% of HIV-exposed children in Burkina Faso and Zambia, respectively. In Burkina Faso, only 60 of 192 (31.3%) of HIV-exposed children were sampled at day 42 for early infant diagnosis (EID) and 3 (1.6%) received a result by EPI-2. In Zambia, these figures were 879 of 1465 (64.0%) and 9.9% (145/1465), respectively for HIV-exposed children sampled at birth. CONCLUSION: This evaluation strategy at EPI-2 visit could strengthen program monitoring and help identifying gaps to be addressed on the last mile towards elimination of MTCT of HIV.

Development of a checklist of quality indicators for clinical trials in resource-limited countries: the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) experience.

BACKGROUND: Since 1994, the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) has funded research sites in resource-limited countries (RLCs). These sites implement research on human immunodeficiency virus (HIV) infection and Hepatitis C. In parallel, international regulations and recommendations for clinical trials have evolved and proliferated. However, little guidance exists on how these should be interpreted and applied within academic trials and in the context of RLCs. After developing a specific Ethical Charter for research in developing countries in 2002, ANRS developed a set of quality indicators (QIs) as a monitoring tool for assessing compliance to international guidelines. PURPOSE: We describe here the development process, QIs adopted, and areas for improvement. METHODS: In 2008, a group of experts was convened that included a researcher representing each ANRS site (Cote d'Ivoire, Senegal, Cameroun, Burkina Faso, Egypt, and Cambodia). Our structuring interaction development process combined evidence and expert opinion in two nominal group meetings to identify (1) clinical trial processes involved, (2) issues specific to RLCs in terms of Good Clinical Practice (GCP) and the application of ethical recommendations, and (3) checklists of QIs adapted to clinical trials conducted in RLCs. RESULTS: The trial process reviewed and proposed for RLCs was mostly similar to the one produced in wealthier countries. The scheme generated by our work group added two further processes: 'drug management' and 'biological investigations'. Specific issues regarding trial management in RLCs were therefore described for eight trial steps (1) protocol conception and seeking authorizations, (2) participant enrollment and follow-up, (3) site monitoring, (4) drug management, (5) biological investigations, (6) record management, (7) data management, and (8) site closeout. A total of 58 indicators were identified with at least one indicator for each trial process. LIMITATIONS: Some trial activities require further consideration, that is, in the case of vulnerable participants (children, pregnant women). Proposed indicators are the result of expert consensus and reflect their experience in the HIV field. Relevance to existing trials and extrapolation to other fields must be assessed. CONCLUSIONS: This innovative program allowed ANRS sites located in RLCs to share their GCP implementation experiences in order to build a list of relevant indicators for clinical trials. The next step is to collect data from ongoing HIV and hepatitis C trials in these settings and will assess the relevance of these indicators to document current quality of performance among trials in resource-limited settings.

Voluntary HIV testing and risky sexual behaviours among health care workers: a survey in rural and urban Burkina Faso.

BACKGROUND: Voluntary counselling and testing (VCT) together with a safe sexual behaviour is an important preventive strategy in the control of HIV. Although Health care workers (HCWs) are critical in the response to HIV, little is known about VCT and high risk behaviours (HRB) among this group in West Africa. This study aims to assess the prevalence of VCT and HRB among HCWs in Burkina Faso. METHODS: We collected data through a questionnaire in urban areas (Ouagadougou and Bobo-Dioulasso) and rural areas (Poni and Yatenga) among HCWs from 97 health care facilities. Urine samples were collected, screened for HIV using a Calypte(®) test kit and confirmed by Western Blot. Multiple logistic regression analysis was performed to identify factors associated with the use of VCT services and with high-risk sex behaviour. RESULTS: About 92.5% of eligible HCWs participated (1570 out of 1697). Overall, 38.2% of them (34.6% of women and 42.6% of men) had ever used VCT services. About 40% of HCWs reported that fear of knowing the test result was the main reason for not doing the HIV test. Male HCWs (p = 0.001), laboratory workers (p < 0.001), those having two years or more experience (p = 0.03), and those who had multiple partners (p = 0.001) were more likely to have tested for HIV. One fifth of HCWs reported multiple partners. Of these, thirteen percent did not use condoms. HCWs who had multiple partners were significantly more likely to be men, single, living in rural areas, and under the age of 29 years. CONCLUSION: VCT was still very low among HCWs in Burkina Faso, while HRB was high.These findings suggest that 'HCW-friendly' VCT centres should be implemented, securing confidentiality among colleagues. In addition, refreshment courses on HIV risk reduction, counselling and testing are certainly required during the professional career of HCWs.

Low seroprevalence of syphilis in Burkina Faso.

BACKGROUND: Little information is available on the epidemiology of syphilis in West Africa, where this infection is routinely screened in antenatal clinics to prevent congenital infection. In order to inform control programmes, the burden of active syphilis was estimated among pregnant women and adults in Burkina Faso. METHODS: This study enrolled 2136 pregnant women from 98 healthcare facilities and 1679 consenting women and men from the general population of Ouagadougou, the capital city. After a face-to-face interview on demographic characteristics, blood samples were collected and tested for syphilis. Active syphilis was defined by a dually positive result on rapid plasma reagin and Treponema pallidum haemagglutination antibody tests. RESULTS: The overall seroprevalence of active syphilis was 1.7% (95% CI 1.3 to 2.2), with similar rates between women (1.2%, 95% CI 0.7 to 2.3) and men (1.8%, 95% CI 1.0 to 3.0) in Ouagadougou, and a trend for higher prevalence among pregnant women from semi-urban areas (2.2%, 95% CI 1.0 to 4.5) compared with rural areas (1.7%, 95% CI 1.2 to 2.4, p = 0.06). The prevalence tended to be higher among women aged 20-24 years (2.6%, 95% CI 1.3 to 7.6) and men aged 30-34 years (3.9%, 95% CI 0.8 to 11.0) than at other ages. However, age, marital status, location and education were not associated with syphilis. CONCLUSION: The low prevalence of syphilis among pregnant women and the adult general population is very encouraging but should not challenge the amount of resources dedicated to sexually transmitted infection and HIV prevention.

Epidemiology of herpes simplex virus type 2 infection in rural and urban Burkina Faso.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) infection enhances human immunodeficiency virus (HIV) susceptibility and may increase sexual transmission, but few data on HSV-2 prevalence are available from West Africa. The main objective of this study was to describe the prevalence and determinants of HSV-2 among adults in urban and rural Burkina Faso. METHODS: We conducted (i) a 2-stage clustered population-based survey among adults aged 15 to 49 years in Ouagadougou (N = 883 women and 791 men), the capital city of Burkina Faso, and (ii) a cross-sectional study among attendees (N = 2018) of all 98 antenatal clinics from 4 provinces of the country. HSV-2 infection was diagnosed using a specific IgG2 enzyme-linked immunosorbent assay test (Kalon). RESULTS: The prevalence of HSV-2 among pregnant women was 18.0% (95% confidence interval (CI): 16.3%-19.7%), with a trend for lower rates in rural (17.3%; CI: 15.5%-19.2%) versus semiurban areas (21.4%; CI: 17.2%-26.2%) (P = 0.08), whereas the prevalence of HSV-2 was 23.7% (CI: 20.9%-26.6%) among women in Ouagadougou (N = 883), and 15.3% (CI: 12.9%-18.0%) among men (N = 791). Using multivariable logistic regression analysis among women, older age, being married, contraceptives, bacterial vaginosis (BV), and HIV infection were significantly associated with HSV-2 infection. Among men, only increased age and HIV were independently associated with HSV-2. CONCLUSION: The prevalence of HSV-2 infection was high among young women, including in rural areas, with a strong association with BV. Therefore, rural areas should not be neglected in prevention programs. New potent BV, hormonal contraceptives, and HSV control strategies may be helpful for HIV control.

Design and challenges of a large HIV prevention clinical study on mother-to-child transmission: ANRS 12397 PROMISE-EPI study in Zambia and Burkina Faso.

Post-natal HIV infection through breastfeeding remains a challenge in many low and middle-income countries, particularly due to non-availability of alternative infant feeding options and the suboptimal Prevention of Mother to Child Transmission of HIV-1 (PMTCT) cascade implementation and monitoring. The PROMISE-EPI study aims to address the latter by identifying HIV infected mothers during an almost never-missed visit for their infant, the second extended program on immunization visit at 6-8 weeks of age (EPI-2). The study is divided into 3 components inclusive of an open-label randomized controlled trial aiming to assess the efficacy of a responsive preventive intervention compared to routine intervention based on the national PMTCT guidelines for HIV-1 uninfected exposed breastfeeding infants. The preventive intervention includes: a) Point of care testing for early infant HIV diagnosis and maternal viral load; b) infant, single-drug Pre-Exposure Prophylaxis (PrEP) (lamivudine) if mothers are virally unsuppressed. The primary outcome is HIV-transmission rate from EPI-2 to 12 months. The study targets to screen 37,000 mother/infant pairs in Zambia and Burkina Faso to identify 2000 mother/infant pairs for the clinical trial. The study design and challenges faced during study implementation are described, including the COVID-19 pandemic and the amended HIV guidelines in Zambia in 2020 (triple-drug PrEP in HIV exposed infants guided by quarterly maternal viral load). The changes in the Zambian guidelines raised several questions including the equipoise of PrEP options, the standard of care-triple-drug (control arm in Zambia) versus the study-single-drug (intervention arm). Trial registration number (www.clinicaltrials.gov): NCT03869944. Submission category: Study Design, Statistical Design, Study Protocols.

Low prevalence rate of indeterminate serological human immunodeficiency virus results among pregnant women from Burkina Faso, West Africa.

Rapid human immunodeficiency virus (HIV) antibody tests have been adopted into national guidelines for HIV testing in many countries in sub-Saharan Africa. One goal of HIV rapid testing is to minimize the occurrence of indeterminate results. From January 2005 to December 2007, plasma (or serum) samples from pregnant women in Bobo-Dioulasso (Burkina Faso, West Africa) were screened for HIV by using two rapid tests (the Determine HIV1/2 test [Abbott] and Genie II HIV-1/HIV-2 [Bio-Rad]) through a sequential algorithm prior to enrollment of HIV-1-infected women in a prevention of mother-to-child transmission (PMTCT) trial (WHO/ANRS 1289 Kesho Bora trial). Samples exhibiting indeterminate results (Determine positive and Genie II negative) were further tested with a fourth-generation HIV enzyme immunoassay (EIA) (Murex HIV Ag/Ab combination in 2005 and 2006 and Vironostika HIV Uni-Form II Ag/Ab in 2007). If positive, they were finally assessed for HIV-1 RNA (Generic HIV-1 RNA viral load assay; Biocentric). From a total of 44,653 samples tested, 597 (1.3%) showed indeterminate results. Of these, 367 could be analyzed by EIA. Only 15 (15/367, 4.1%) samples were found EIA reactive. Of these, 11 could be tested for HIV-1 RNA. All were HIV-1 RNA negative. In our clinical practice, pregnant women with such indeterminate results are now reassured during posttest counseling that they are very unlikely to be infected with HIV-1. As a consequence, such women with indeterminate results can reliably be considered negative when urgent clinical decisions (such as providing PMTCT prophylaxis) need to be taken.

Relationship between mortality and feeding modality among children born to HIV-infected mothers in a research setting: the Kesho Bora study.

OBJECTIVE: To assess the relationship between infant feeding practices and mortality by 18 months of age among children born to HIV-infected mothers in the Kesho Bora trial (Burkina-Faso, Kenya and South Africa). METHODS: Enrolled HIV-infected women were counseled to choose between breastfeeding up to 6 months or replacement feeding from delivery. Multivariable Cox models were used to compare the infant mortality risks according to feeding practices over time defined as never breastfed, weaned or still breastfed. The category 'still breastfed' was disaggregated as exclusively, predominantly or partially breastfed to compare modes of breastfeeding. The relationship between weaning and mortality was also assessed using marginal structural models to control for time-dependent confounders, such as maternal or infant morbidity (reverse causality). RESULTS: Among 795 mothers, 618 (77.7%) initiated breastfeeding. Mortality rates by 18 months among uninfected and infected children were 6 and 38%, respectively. Never breastfed and weaned children were at greater risk of death compared with those still breastfed. Adjusted hazard ratios were 6.7 [95% confidence interval (CI)=2.5-17.9; P<0.001] and 6.9 (CI=2.8-17.2; P<0.001) for never breastfed and weaned children, respectively. Estimation of the effect of weaning using marginal structural models led to similar results. No statistically significant differences were observed according to mode of breastfeeding (exclusive, predominant or partial). CONCLUSION: Within 6 months after birth, weaned or never breastfed children were at about seven-fold higher risk of dying compared with children who were still breastfed despite a context in which interventions were provided to reduce risks associated with replacement feeding.

Are teachers at higher risk of HIV infection than the general population in Burkina Faso?

In order to assess the human immunodeficiency virus (HIV) prevalence among teachers in Burkina Faso, we carried out a national survey in 336 primary and secondary schools from urban and rural areas. Among 2088 teachers who agreed to participate, 1498 (71.7%) provided urine for HIV testing. The crude prevalence of HIV among teachers was 2.8% (95% confidence interval [CI]: 2.0-3.6), with no difference between teachers from primary schools (2.9%, 95%CI: 2.1-4.0) and those from secondary schools (2.5%, 95%CI: 0.5-4.5). Age- and area-standardized HIV prevalence was 1.0% (95%CI: 0.4-1.2) in male teachers, 2.5 times lower than among men in the general population (as assessed from a concomitant Demographic Health Survey), and it was 3.5% (95%CI: 2.5-5.2) in female teachers, 1.7 times higher than in Demographic Health Survey women. This finding calls for the implementation of specific HIV prevention programmes in the education sector targeting women more specifically.

Who Is Going for VCT? A Case Study in Urban Burkina Faso.

Introduction. Voluntary HIV counselling and testing (VCT) is a key element of treatment and is essential for prevention of vertical HIV transmission. Little information is available on the uptake of VCT in Burkina Faso. This study aims to assess the prevalence of VCT in urban Burkina Faso, where the epidemic is still highly concentrated. Methods. We conducted a two-stage clustered population-based survey among 1,694 subjects living in Ouagadougou, Burkina Faso. After informed consent was obtained, a behavioural questionnaire was administered to participants. Results. Overall, 10.2% of individuals had used VCT, while 9% were women. Among women who had a child after the launch of the programme to prevent mother-to-child transmission (PMTCT), only 10.4% have been tested for HIV. Almost all participants (99.3%) were aware of HIV/AIDS, and 65% knew the main methods of prevention. In multivariate analysis, older age and being married and better educated were independent factors associated with VCT. Conclusions. Despite high public knowledge and awareness about HIV, VCT uptake was still very low and PMTCT coverage was poor. New strategies are required to increase VCT uptake in urban areas, in particular among the youngest age.