Roselyne Vallo

Association between bacterial vaginosis and Herpes simplex virus type-2 infection : implications for HIV acquisition studies

Objectives: Bacterial vaginosis (BV) and Herpes simplex virus type-2 (HSV-2) have been linked to an increased risk of HIV-1 acquisition. Recent research suggests an association between BV and HSV-2 acquisition, but the converse has not been studied. Here, we investigate whether an association exists between BV and HSV-2 infection Methods: We examined the determinants of BV occurrence in a cohort of female sex workers in Burkina Faso. Participants were followed every 3 months for diagnosis of genital infections and report of sexual behaviours. Factors associated with BV occurrence were assessed using generalised estimating equation models. Results: We enrolled 273 women (mean age, 28 years) and conducted 812 follow-up visits (mean 2.93 visit per woman). Baseline seroprevalence of HIV-1, HSV-2 and recent syphilis were 31.5%, 70.1% and 0.4%, respectively, while baseline prevalence of BV, Trichomonas vaginalis (TV) and Candida albicans were 20.5%, 3.3% and 2.5%, respectively. In multivariable analysis, HSV-2 (relative risk (RR) = 1.73, 95% CI 1.12 to 2.65), HIV-1 (RR = 1.76, 95% CI 1.30 to 2.40), TV (RR = 1.5, 95% CI 1.0 to 2.3), and having ⩾3 sexual partners in the preceding week (RR = 2.2, 95% CI 1.1 to 4.6) were independently associated with BV, while hormonal contraception showed a protective effect (RR = 0.11, 95% CI 0.02 to 0.70). Conclusions: HSV-2 infection was associated with BV occurrence in this population. As HSV-2 is strongly linked to HIV-1 acquisition, studies assessing the cofactor effect of BV on HIV acquisition should control for the presence of HSV-2. Further studies are required to investigate the relative effect of asymptomatic HSV-2 shedding and/or genital ulcerations on BV occurrence.

Extended pre-exposure prophylaxis with lopinavir–ritonavir versus lamivudine to prevent HIV-1 transmission through breastfeeding up to 50 weeks in infants in Africa (ANRS 12174): a randomised controlled trial

BACKGROUND Strategies to prevent postnatal mother-to-child transmission of HIV-1 in Africa, including infant prophylaxis, have never been assessed past 6 months of breastfeeding, despite breastfeeding being recommended up to 12 months after birth. We aimed to compare the efficacy and safety of infant prophylaxis with the two drug regimens (lamivudine or lopinavir-ritonavir) to prevent postnatal HIV-1 transmission up to 50 weeks of breastfeeding. METHODS We did a randomised controlled trial in four sites in Burkina Faso, South Africa, Uganda, and Zambia in children born to HIV-1-infected mothers not eligible for antiretroviral therapy (CD4 count >350 cells per μL). An independent researcher electronically generated a randomisation schedule; we then used sequentially numbered envelopes to randomly assign (1:1) HIV-1-uninfected breastfed infants aged 7 days to either lopinavir-ritonavir or lamivudine (paediatric liquid formulations, twice a day) up to 1 week after complete cessation of breastfeeding or at the final visit at week 50. We stratified the randomisation by country and used permuted blocks of four and six. We used a study label on drug bottles to mask participants, study physicians, and assessors to the treatment allocation. The primary outcome was infant HIV-1 infection between age 7 days and 50 weeks, diagnosed every 3 months with HIV-1 DNA PCR, in the modified intention-to-treat population (all who attended at least one follow-up visit). This trial is registered with ClinicalTrials.gov, number NCT00640263. FINDINGS Between Nov 16, 2009, and May 7, 2012, we enrolled and randomised 1273 infants and analysed 1236; 615 assigned to lopinavir-ritonavir or 621 assigned to lamivudine. 17 HIV-1 infections were diagnosed in the study period (eight in the lopinavir-ritonavir group and nine in the lamivudine group), resulting in cumulative HIV-1 infection of 1.4% (95% CI 0.4-2.5) and 1.5% (0.7-2.5), respectively. Infection rates did not differ between the two drug regimens (hazard ratio [HR] of lopinavir-ritonavir versus lamivudine of 0.90, 95% CI 0.35-2.34; p=0.83). Clinical and biological severe adverse events did not differ between groups; 251 (51%) infants had a grade 3-4 event in the lopinavir-ritonavir group compared with 246 (50%) in the lamivudine group. INTERPRETATION Infant HIV-1 prophylaxis with lopinavir-ritonavir was not superior to lamivudine and both drugs led to very low rates of HIV-1 postnatal transmission for up to 50 weeks of breastfeeding. Infant pre-exposure prophylaxis should be extended until the end of HIV-1 exposure and mothers should be informed about the persistent risk of transmission throughout breastfeeding. FUNDING INSERM/National Agency for Research on AIDS and Viral Hepatitis (including funds from the Total Foundation), European Developing Countries Clinical Trials Partnership, Research Council of Norway.

Longitudinal effect following initiation of highly active antiretroviral therapy on plasma and cervico-vaginal HIV-1 RNA among women in Burkina Faso

Background: Highly active antiretroviral therapy (HAART) could decrease HIV-1 transmissibility by reducing genital and plasma HIV-1 RNA. Methods: We evaluated the effect of HAART on genital and plasma HIV-1 RNA in a cohort of 39 antiretroviral-naïve women in Burkina Faso. Cervico-vaginal lavages were collected before HAART initiation and at six visits over 28 weeks while on HAART. Blood samples were collected at baseline and at three and four visits for CD4 and plasma HIV-1 RNA measurements, respectively. Results: Before HAART, 72% of women had detectable genital HIV-1 RNA. After 18 weeks on HAART, only one woman (2.5%) had detectable plasma HIV-1 RNA and two women (5.1%) had detectable genital HIV-1 RNA. Similar results were observed at each follow-up visit. However, 16/34 (47%) women with consistently undetectable plasma HIV-1 RNA shed HIV-1 at least once between weeks 18 and 28. In samples with detectable genital HIV-1, the mean quantity of HIV-1 RNA decreased from 3.87 prior to HAART to 3.04 log10 copies/mL at last visit (median 29 weeks; a 6.8-fold decrease in absolute number of copies/mL) (p = 0.04). A significant median CD4 lymphocyte cell gain of 121 cells/μL (interquartile range 59 to 204) was measured between pre-HAART and last visit. Conclusion: These findings suggest that HAART could play a role in reducing HIV transmission in Africa; however, they underscore the need to emphasise safe sex practices with patients taking HAART.

Intravenous heroin use in Haiphong, Vietnam: Need for comprehensive care including methamphetamine use-related interventions

BACKGROUND The aim of this study was to describe patterns among people who inject drugs (PWID), risk-related behaviours and access to methadone treatment, in order to design a large-scale intervention aiming to end the HIV epidemic in Haiphong, Vietnam. METHODS A respondent-driven sampling (RDS) survey was first conducted to identify profiles of drug use and HIV risk-related behaviour among PWID. A sample of PWID was then included in a one-year cohort study to describe access to methadone treatment and associated factors. RESULTS Among the 603 patients enrolled in the RDS survey, 10% were female, all were injecting heroin and 24% were using methamphetamine, including 3 (0.5%) through injection. Different profiles of risk-related behaviours were identified, including one entailing high-risk sexual behaviour (n=37) and another involving drug-related high-risk practices (n=22). High-risk sexual activity was related to binge drinking and methamphetamine use. Among subjects with low sexual risk, sexual intercourse with a main partner with unknown serostatus was often unprotected. Among the 250 PWID included in the cohort, 55.2% initiated methadone treatment during the follow-up (versus 4.4% at RDS); methamphetamine use significantly increased. The factors associated with not being treated with methadone after 52 weeks were fewer injections per month and being a methamphetamine user at RDS. CONCLUSION Heroin is still the main drug injected in Haiphong. Methamphetamine use is increasing markedly and is associated with delay in methadone initiation. Drug-related risks are low but sexual risk behaviours are still present. Comprehensive approaches are needed in the short term.

Risk Behaviors for HIV and HCV Infection Among People Who Inject Drugs in Hai Phong, Viet Nam, 2014

We examined the potential for HIV and hepatitis C (HCV) transmission across persons who inject drugs (PWID), men-who-have-sex-with-men (MSM) and female commercial sex workers (CSW) PWID and the potential for sexual transmission of HIV from PWID to the general population in Hai Phong, Viet Nam. Using respondent driven and convenience sampling we recruited 603 participants in 2014. All participants used heroin; 24% used non-injected methamphetamine. HIV prevalence was 25%; HCV prevalence was 67%. HIV infection was associated with HCV prevalence and both infections were associated with length of injecting career. Reported injecting risk behaviors were low; unsafe sexual behavior was high among MSM-PWID and CSW-PWID. There is strong possibility of sexual transmission to primary partners facilitated by methamphetamine use. We would suggest future HIV prevention programs utilize multiple interventions including “treatment as prevention” to potential sexual transmission of HIV among MSM and CSW-PWID and from PWID to the general population.

Increased Methamphetamine Use among Persons Who Inject Drugs in Hai Phong, Vietnam, and the Association with Injection and Sexual Risk Behaviors

ABSTRACT Methamphetamine use has increased significantly in Southeast Asia in the last 5–10 years, but there is little research on risk behaviors associated with the increase in this region. We evaluate injection and sexual risk behaviors associated with current methamphetamine use among heterosexual persons who inject drugs (PWID) in Hai Phong, Vietnam. We recruited 1336 PWID and assessed associations between methamphetamine use, injection and sexual risk behaviors, stratified by HIV serostatus. There were several statistically significant associations between methamphetamine use and sexual risk behaviors among HIV-positive PWID, but we did not find any associations between methamphetamine use and injection risk behaviors. Methamphetamine may increase the likelihood of PWID transmitting HIV to non-injecting primary sexual partners, as it can reduce ART adherence and can lead to weakening of the immune system and increased HIV viral loads. All participants were injecting heroin, and methamphetamine use may interfere with opiate use treatment. Public health efforts should focus on the large increase in methamphetamine use and the associated sexual risk behaviors. Emphasis on sexual risk behavior, particularly among those who are HIV-positive, in conjunction with continued monitoring of ART adherence and HIV viral loads, is critical.

High-risk HPV detection and associated cervical lesions in a population of French menopausal women

BACKGROUND With population ageing, post-menopausal women represent a new group to be considered in cervical cancer screening strategies, including the significance of High Risk (HR)-HPV detection. OBJECTIVES A retrospective analysis was conducted in a cohort of 406 menopausal women attending routine gynaecological consultation at the Hospital of Montpellier (France). STUDY DESIGN All women benefited from a cervical smear and HR-HPV detection using Hybrid Capture 2 (HC2) test. The prevalence of cytological abnormalities, HR-HPV detection and risk factors associated with HR-HPV detection were analyzed. Evolution of both tests was evaluated in a sub-group of women with adequate follow-up. RESULTS Five women (1.2%) had an abnormal cervical smear at baseline. HR-HPV was detected in 40 women (9.9%), including 36 women with normal cytology (9%). Risk factors associated with HR-HPV detection at enrolment were a previous history of Cervical Intraepithelial Neoplasia and a high socio-economic level, but not hormone replacement therapy. When cytology and HR-HPV detection were negative at enrolment, both remained negative for 95% (230/241) of women during follow-up (median duration of follow-up: 60 months). HR-HPV persistence was observed for 55% (18/33) of women with normal cytology and positive HR-HPV test. Finally, all women with a final diagnosis of high-grade (CIN2+) cervical lesion (N = 7) had a positive HR-HPV test with or without abnormal cytology. CONCLUSIONS HR-HPV was detected in 9.9% of menopausal women. HR-HPV detection was a better predictor of CIN2+ lesions than cytology in this population. Women with previous CIN history should benefit from HR-HPV testing and need long term follow-up.

HIV-1 disease progression in immune-competent HIV-1-infected and breastfeeding mothers participating in the ANRS 12174 clinical trial in Burkina Faso, South Africa, Uganda and Zambia: a cohort study

Objective We have assessed HIV-1 disease progression among HIV-1-positive mothers in relation to duration of any or exclusive breast feeding in the context of ANRS 12174 trial. Methods The analysis was completed on 203, 212, 272 and 529 HIV-1-positive and lactating mothers with CD4 count >350 cells/µL from Burkina Faso, South Africa, Uganda and Zambia, respectively. The trial compared lamivudine and lopinavir/ritonavir as a peri-exposure prophylaxis during a 50-week follow-up time. A multiple logistic regression model was run with the mothers’ weight, CD4 count and HIV-1 viral load as separate dependent variables, then combined into a dependent composite endpoint called HIV-1 disease progression where HIV-1 viral load was replaced by the HIV-1 clinical stage. Exclusive or predominant breast feeding (EPBF) and any breastfeeding duration were the key explanatory variables. Results In the adjusted model, the associations between EPBF duration and weight change, CD4 cell count and the HIV-1 viral load were consistently insignificant. The CD4 cell count was associated with a significantly higher mothers’ body mass index (BMI; a mean increase of 4.9 (95% CI 2.1 to 7.7) CD4 cells/µL per each additional kilogram per square metre of BMI) and haemoglobin concentration (19.4 (95% CI 11.4 to 27.4) CD4 cells/µL per each additional gram per decilitre of haemoglobin concentration). There was no significant association between EPBF duration and HIV-1 disease progression. A higher education level was a factor associated with a slower HIV-1 disease progression. Conclusion Breast feeding was not a risk factor for a faster progression of HIV-1 disease in mothers of this cohort with a baseline CD4 cell count >350 cells/µL. Trial registration number NCT0064026; Post-results.

Changes in body mass index and hemoglobin concentration in breastfeeding women living with HIV with a CD4 count over 350: Results from 4 African countries (The ANRS 12174 trial).

Introduction Breastfeeding is recommended for infants born to HIV-infected women in low-income settings. Both breastfeeding and HIV-infection are energy demanding. Our objective was to explore how exclusive and predominant breastfeeding changes body mass index (BMI) among breastfeeding HIV1-positive women participating in the ANRS12174 trial (clinical trial no NCT0064026). Methods HIV-positive women (n = 1 267) with CD4 count >350, intending to breastfeed HIV-negative infants were enrolled from Burkina Faso, South Africa, Uganda and Zambia and counselled on breastfeeding. N = 1 216 were included in the analysis. The trial compared Lamivudine and Lopinavir/Ritonavir as a peri-exposure prophylaxis. We ran a linear mixed-effect model with BMI as the dependent variable and exclusive or predominant breastfeeding duration as the key explanatory variable. Results Any breastfeeding or exclusive/predominant) breastfeeding was initiated by 99.6% and 98.6% of the mothers respectively in the first week after birth. The median (interquartile range: IQR) duration of the group that did any breastfeeding or the group that did exclusive /predominant breastfeeding were 9.5 (7.5; 10.6) and 5.8 (5.6; 5.9)) months, respectively. The median (IQR) age, BMI, CD4 count, and HIV viral load at baseline (day 7) were 27 (23.3; 31) years, 23.7 (21.3; 27.0) kg/m2, 530 (432.5; 668.5) cells/μl and 0.1 (0.8; 13.7)1000 copies/mL, respectively. No major change in mean BMI was seen in this cohort over a 50-week period during lactation. The mean change between 26 and 50 weeks after birth was 0.7 kg/m2. Baseline mean BMI (measured on day 7 postpartum) and CD4 count were positively associated with maternal BMI change, with a mean increase of 1.0 kg/m2 (0.9; 1.0) per each additional baseline-BMI kilogram and 0.3 kg/m2 (0.2; 0.5) for each additional CD4 cell/μl, respectively. Conclusion Breastfeeding was not negatively correlated with the BMI of HIV-1 infected Sub-Saharan African mothers. However, a higher baseline BMI and a CD4 count >500 cells/μl were associated with maternal BMI during the exclusive/ predominant breastfeeding period. Considering the benefits of breast milk for the infants and the recurrent results from different studies that breastfeeding is not harmful to the HIV-1-infected mothers, this study also supports the WHO 2016 guidelines on infant feeding that mothers living with HIV should breastfeed where formula is not safe for at least 12 months and up to 24 months, given that the right treatment or prophylaxis for the infection is administered. These findings and conclusions cannot be extrapolated to women who are immune-compromised or have AIDS.