Is bacterial vaginosis just the tip of the iceberg as to the

risk of HIV related to vaginal flora abnormalities ?

Presenter: Guédou F. A. MD, MSc, PhD Co-authors: Van Damme L, Mirembe F, Solomon S,

Becker M, Deese J, Crucitti T, Taylor D, Alary M

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Afri-Can Forum Entebbe 17-19 January 2013

Overview

BackgroundObjectivesMethods and materialsResultsDiscussionConclusion

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Background(1) Bacterial Vaginosis (BV) is a polymicrobial

infection resulting from the replacement of lactobacilli of the normal vaginal flora by a variety of bacteria, predominantly anaerobic

The main challenge of BV to date is that of the identification of its causative agent so that the current consensus is that a polymicrobial infection

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Background (2)

Conventionally, BV is diagnosed:Clinically on Amsel’s criteria;Biologically with Nugent’score:

normal flora (NS = 0-3);intermediate flora (NS = 4-6);BV (NS = 7-10)

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Background (3)

BV = most common genital infection worldwide

Higher prevalence in developing countries (DC): between 9% and 50%; 70% among female sex workers (FSW)

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But what justifies the present work is that the role of BV in HIV acquisition or transmission has been strongly suggested by some studies

Since BV has such a high prevalence among FSWs, even a modest RR substantial attributable risk for HIV

Background (4)

Background (5)This is of uppermost interest when considering the

role of core group played by FSWs in the dynamic of HIV epidemics in DC and particularly in Sub-Saharan Africa

In addition, most studies that have examined this

association have classified “BV” as (BV vs. non-BV)

Very little attention has been paid to the possible role of intermediate vaginal flora (IVF) in this association

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Objectives

To investigate the association between HIV and respectively IVF and BV, among FSW screened prior to enrolment in the Cellulose sulfate trial

To compare the strengths of these two associations

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ChennaiMudhol/Jhamkandi (India): (2)

Kampala (Uganda): (1)

Durban (South Africa): (1)

Cotonou (Benin): (1)

Uganda

Benin

Settings: Sites of the CS trialMaterials and Methods (1)

Participants selection: Eligibility criteria:Potential participant in the SC trial

18 years or older

HIV high risk woman (≥ 3 different sexual partners in the last 3 months and ≥ 3 sexual acts/week)

Data available for both BV and HIV

Informed consent for screening

Materials and Methods (2)

Data collection

Materials and Methods (3)

Interview: socio-demo. and behavioral data

Gynecological Exam: clinical data

Blood and cervico-vaginal swabs:

HIV: HIV antibodies test

BV: Gram and Nugent score (NS)

Gonorrhea and Chlamydia: SDA (Strand DNA Amplification)

Syphilis: RPR confirmed with TPHA

Trichomoniasis (TV) and Candidiasis: Wet mount

Statistical analyses

Log binomial regression to model HIV prevalence with respect to vaginal flora abnormalities:2 categories: BV vs. Non-BV3 categories : normal (reference), IVF and BV

(Comparison of BV and IVF prevalence ratios)

Bivariate analyses (controlling for site)

Multivariate analyses (adjustment)

Materials and Methods(4)

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Characteristics of 1367 FSW screened at 2 African and 2 Indian sites of a randomized microbicide clinical trial on cellulose sulfate gelCharacteristics n or

median (%) ou

IQR Number of sexual partners /last 3 months 80 [25 –

270] Number of sexual acts / last 7 days 8 [4 – 20] Condom use at the last sexual act 1061 (77.7)Intra-vaginal cleansing 1340 (98.0) Current STI or lower genital infections: HIV Gonorrhea Chlamydia Trichomoniasis Candidiasis Bacterial vaginosis Intermediate vaginal flora Syphilis

369 111 80 92421651262 82

(27.0) (8.1)(5.9)

(6.7)(30.8)(47.6)(19.2)

(6.0)

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Multivariate analysis between vaginal flora abnormalities and HIVFactors HIV

prevalence by exposition level

Ajusted prevalence ratio (aPR)*

ni/Ni (%)

aPR (95%CI) p-value

Vaginal flora abnormalities (in 2 cat.):Bacterial vaginosis (NS= 7-10)Non-Bacterial vaginosis (NS= 0-6)

192/651 (29.5)177/716 (24.7)

1.21 (1.03-1.44) 1.00 –

0.02 –

Vaginal flora abnormalities (in 3 cat.):Bacterial vaginosis (NS= 7-10)Intermediate vaginal flora (NS= 4-6)Normal vaginal flora (NS= 0-3)

192/651 (29.5) 84/262 (32.1) 93/454 (20.5)

1.48 (1.20-1.84)1.56 (1.22-1.98)1.00 –

0.00030.0003–

*The aPR from the 2 types of categorisation were obtained from separate multivarite models but including the same covariates (site, education level, STI history, occupation other than Sex work, oral sex, female sterilisation, gonorrhea and vaginal candidiasis)

Discussion (1)• The aPR obtained using women with NVF as

reference was substantially higher than that obtained using women without BV as reference

• This is due to the fact that HIV prevalence among women with IVF was significantly higher than that of women with NVF: aPR = 1.56 (95% CI = 1.22-1.98, p = 0.0003)

• The use of all women without BV (NVF/IVF) as a reference to measure the increase in HIV risk associated with BV could lead to its underestimation

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Discussion (2)

In addition, the strength of the association obtained with IVF was similar to that obtained with the BV (p = 0.6347)

This is in contrast with the trend of monotonic increase found in most studies that have examined the association between HIV and vaginal flora abnormalities

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Discussion (3): Direction of the association?

BV may increase the risk of HIVMobilization of HIV target cellsWeakening of the vaginal epithelial barrier

HIV may increase the risk of BVImmunosuppression? But no significant association between HIV and other STIs!

A risk factor common to HIV and BV (not / insufficiently controlled by analysis)

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Discussion (4): the study limits

Cross-sectional design124 eligible FSW excluded (lack of data

on BV)Inability to control for HSV-2, alcoholPossibility of inaccuracy for some data:

Vaginal douching (quantification)Number of sexual partners (memory)Condom use (social desirability)

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Discussion (5): Strenghts of the study

Clinical trial settings:

Large sample size

An international quality control system

Use of the current gold standard for BV

diagnosis

Use of log-binomial regression: which

enabled a better approximation of the

relative risk19

ConclusionsThe results of this study suggest that:

BV represents only a part of the vaginal flora abnormalities associated with an increased risk of HIV;

IVF is associated with HIV as stronger as BV

Need of prospective studies to confirm findings

Implication for HIV prevention:Controlling vaginal flora abnormalities (not just BV) among FSWs may be an untapped strategy to curb HIV epidemic, particularly in countries with concentrated epidemic

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Acknowledgments (1)Trial participantsCotonou Team (Benin):

Clinical team: I. Minani; N. Geraldo; G. Ainan; C. Assogba; C. Gbenafa

Lab team: M. Loembe; E. Goma; G. Ahotin; L. Djossou; N. Tata Sociology team: O. Azonnadou, J. Agonmounon, F. Mito-Yobo Field team: G. Batona et coll.

Canada Team(CHU of Quebec) : M. Belleau, J. Leroux, J. Begin, L. Pagé

Other sites: Lusaka (Ouganda): F. Mirembe et al. Chennai (Inde): S. Solomon et al. Mudhol/Jhamkandi (Inde): M. Becker et al.

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Aknowledgments (2)

International Team: CONRAD (VA, USA): L. Van Damme (PI); FHI (NC, USA): J. Deese; D. Taylor; ITM (Antwerrp, Belgium) : T. Crucitti

Sponsor: CONRAD (USA)

Funders: USAID Fondation Bill Gates & Melinda

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Thanks for your kind attention