Michel Alary

Heterosexual risk of HIV-1 infection per sexual act: systematic review and meta-analysis of observational studies

We did a systematic review and meta-analysis of observational studies of the risk of HIV-1 transmission per heterosexual contact. 43 publications comprising 25 different study populations were identified. Pooled female-to-male (0.04% per act [95% CI 0.01-0.14]) and male-to-female (0.08% per act [95% CI 0.06-0.11]) transmission estimates in high-income countries indicated a low risk of infection in the absence of antiretrovirals. Low-income country female-to-male (0.38% per act [95% CI 0.13-1.10]) and male-to-female (0.30% per act [95% CI 0.14-0.63]) estimates in the absence of commercial sex exposure (CSE) were higher. In meta-regression analysis, the infectivity across estimates in the absence of CSE was significantly associated with sex, setting, the interaction between setting and sex, and antenatal HIV prevalence. The pooled receptive anal intercourse estimate was much higher (1.7% per act [95% CI 0.3-8.9]). Estimates for the early and late phases of HIV infection were 9.2 (95% CI 4.5-18.8) and 7.3 (95% CI 4.5-11.9) times larger, respectively, than for the asymptomatic phase. After adjusting for CSE, presence or history of genital ulcers in either couple member increased per-act infectivity 5.3 (95% CI 1.4-19.5) times versus no sexually transmitted infection. Study estimates among non-circumcised men were at least twice those among circumcised men. Low-income country estimates were more heterogeneous than high-income country estimates, which indicates poorer study quality, greater heterogeneity of risk factors, or under-reporting of high-risk behaviour. Efforts are needed to better understand these differences and to quantify infectivity in low-income countries.

Lack of Effectiveness of Cellulose Sulfate Gel for the Prevention of Vaginal HIV Transmission

BACKGROUND Women make up more than 50% of adults living with human immunodeficiency virus (HIV) infection or the acquired immunodeficiency syndrome (AIDS) in sub-Saharan Africa. Thus, female-initiated HIV prevention methods are urgently needed. METHODS We performed a randomized, double-blind, placebo-controlled trial of cellulose sulfate, an HIV-entry inhibitor formulated as a vaginal gel, involving women at high risk for HIV infection at three African and two Indian sites. The primary end point was newly acquired infection with HIV type 1 or 2. The secondary end point was newly acquired gonococcal or chlamydial infection. The primary analysis was based on a log-rank test of no difference in the distribution of time to HIV infection, stratified according to site. RESULTS A total of 1398 women were enrolled and randomly assigned to receive cellulose sulfate gel (706 participants) or placebo (692 participants) and had follow-up HIV test data. There were 41 newly acquired HIV infections, 25 in the cellulose sulfate group and 16 in the placebo group, with an estimated hazard ratio of infection for the cellulose sulfate group of 1.61 (P=0.13). This result, which is not significant, is in contrast to the interim finding that led to the trial being stopped prematurely (hazard ratio, 2.02 [corrected]; P=0.05 [corrected]) and the suggestive result of a preplanned secondary (adherence-based) analysis (hazard ratio, 2.02; P=0.05). No significant effect of cellulose sulfate as compared with placebo was found on the risk of gonorrheal infection (hazard ratio, 1.10; 95% confidence interval [CI], 0.74 to 1.62) or chlamydial infection (hazard ratio, 0.71; 95% CI, 0.47 to 1.08). CONCLUSIONS Cellulose sulfate did not prevent HIV infection and may have increased the risk of HIV acquisition. (ClinicalTrials.gov number, NCT00153777; and Current Controlled Trials number, ISRCTN95638385.)

Decline in the prevalence of HIV and sexually transmitted diseases among female sex workers in Cotonou, Benin, 1993-1999.

Background Within an ongoing HIV/STD prevention project aimed at female sex workers (FSW) in Cotonou, Benin, we evaluated time trends in HIV and STD prevalences from 1993 to 1999. Design Three serial cross-sectional surveys were conducted in 1993 (n = 374), 1995–1996 (n = 365), and 1998–1999 (n = 591). A questionnaire was administered to the FSW and they were screened for HIV, syphilis, Neisseria gonorrhoeae, and Chlamydia trachomatis. Results The mean percentage of condom use with clients in the week preceding the interview increased from 62.2% in 1993 to 80.7% in 1998–1999 (P = 0.0001). The prevalence of all infections decreased significantly (all P < 0.02; chi-square for trend) over time: HIV from 53.3% in 1993 to 40.6% in 1998–1999; syphilis from 8.9 to 1.5%; gonorrhoea from 43.2 to 20.5%; and chlamydia from 9.4 to 5.1%. However, the mean age of FSW decreased from 31.0 to 28.4 years between 1993 and 1998–1999. Moreover, the country of origin of these women changed dramatically over time: the proportion of Ghanaian women decreased from 66.3% in 1993 to 21.6% in 1998–1999 when the predominant group became Nigerian (38.0%). When controlling for age and country of origin, HIV prevalence was stable over time (P = 0.71), whereas the downward trend remained significant for syphilis and gonorrhoea (both P < 0.001), and was present but not significant for chlamydia (P = 0.13). Conclusion These data suggest that the time trends in HIV and STD prevalences are partly due to the changing sex work milieu, but that the intervention also had an impact. Prevention programmes aimed at FSW should be highly prioritized.

Estimates of the number of female sex workers in different regions of the world.

Objectives: To collect estimated numbers of female sex workers (FSW) and present proportions of FSW in the female population (FSW prevalence) in different regions of the world. Methods: Subnational and national estimated numbers of FSW reported in published and unpublished literature, as well as from field investigators involved in research or interventions targeted at FSW, were collected. The proportion of FSW in the adult female population was calculated. Subnational estimates were extrapolated to national estimates if appropriate. Population surveys were scanned for proportions of adult women having sex in exchange for money or goods. Results: In sub-Saharan Africa, the FSW prevalence in the capitals ranged between 0.7% and 4.3% and in other urban areas between 0.4% and 4.3%. Population surveys from this same region yielded even higher proportions of women involved in transactional sex. The national FSW prevalence in Asia ranged between 0.2% and 2.6%; in the ex-Russian Federation between 0.1% and 1.5%; in East Europe between 0.4% and 1.4%; in West Europe between 0.1% and 1.4%; and in Latin America between 0.2% and 7.4%. Estimates from rural areas were only available from one country. Conclusions: Although it is well known and accepted that FSW are a highly vulnerable group in the scope of the HIV epidemic, most countries in the world do not know the size of this population group. The estimates of the prevalence of FSW presented in this paper show how important this hard-to-reach population group is in all parts of the world.

Risk of HIV-1 transmission for parenteral exposure and blood transfusion : a systematic review and meta-analysis

Background:The role of iatrogenic transmission within the HIV/AIDS pandemic remains contentious. Estimates of the risk of HIV transmission from injections and blood transfusions are required to inform appropriate prevention policy. Objectives:Systematic review and meta-analysis of the literature on HIV-1 infectivity for parenteral transmission and blood transfusion. Review methods:All identified studies with relevant transmission probability estimates up to May 2005 were included. Statistical methods:When appropriate, summary estimates for accidental percutaneous and blood product exposures were derived. Results:Infectivity estimates following a needlestick exposure ranged from 0.00 to 2.38% [weighted mean, 0.23%; 95% confidence interval (CI), 0.00–0.46%; n = 21]. Three estimates of infectivity per intravenous drug injection ranged from 0.63 to 2.4% (median, 0.8%); a summary estimate could not be calculated. The quality of the only estimate of infectivity per contaminated medical injection (1.9–6.9%) was assessed. Instead we propose a range of 0.24–0.65%. Infectivity estimates for confirmed contaminated blood transfusions range from 88.3 to 100.0% (weighted mean, 92.5%; 95% CI, 89.0–96.1%; n = 6). Conclusions:Infectivity estimates for infected blood transfusions are larger than for other modes of HIV transmission. Few studies on transmission risk per contaminated injection were found. However, transmission risk per needlestick injury, where needles are more likely to be rinsed or disinfected between recipients (especially for medical injections), may be representative of non-intravenous medical injections and lower than the risk from intravenous injections, which are likely to be deeper and to involve more fluids. Further work is needed to better estimate transmission probability related to contaminated injections and its likely contribution to overall HIV transmission.

Role of core and bridging groups in the transmission dynamics of HIV and STIs in Cotonou, Benin, West Africa

The potential for exposure of low and high risk women to HIV and sexually transmitted infections (STI) through unprotected sex with male clients of female sex workers in Cotonou could account for most if not all of the estimated yearly numbers of HIV infections in Cotonou women (∼1000). As ongoing transmission of HIV, and also of the most predominant STIs such as gonorrhoea and HSV-2, appears to be largely fuelled by transmission within core and bridging groups in Cotonou, interventions targeted at both female sex workers and their male clients remain of the utmost importance and could have a significant effect on the evolution of HIV/STI epidemics in Benin.

Management of sexually transmitted diseases and HIV prevention in men at high risk: targeting clients and non-paying sexual partners of female sex workers in Benin.

ObjectivesMale clients of female sex workers have rarely been specific targets for HIV/sexually transmitted diseases (STD) interventions in sub-Saharan Africa. We assessed the effectiveness of outreach methodology for contacting sexual partners of female sex workers for purposes of HIV/STD prevention in Cotonou, Benin. Design and methodsIn collaboration with owners/managers, outreach personnel and female sex workers, 404 clients were recruited on-site at prostitution venues, and provided urine samples for leukocyte esterase dipstick (LED), STD and HIV testing before having sex with female sex workers. After having sex they underwent an interview and physical examination. No payment was made for study participation. Prostitution site personnel (n = 41) and boyfriends of female sex workers (n = 56) were also recruited. ResultsIn all 68% of the clients approached agreed to participate. On-site LED testing and free STD treatment were important factors in participation. HIV-1 prevalence was several-fold higher than in the general population in Cotonou, at 8.4, 12.2 and 16.1% in clients, personnel and boyfriends respectively, and was associated with increasing age and lack of condom use with female sex workers. Condom use rates by clients with female sex workers were non-negligible but sub-optimal, and low with regular partners. Approximately one-third of clients with regular partners also had other non-female sex worker sex partners. Boyfriends of female sex workers are of particular concern due to high numbers of partners, very low condom use rates and high HIV prevalence. ConclusionsStudy findings indicate that male sex partners of female sex workers form a ‘bridging population’ for HIV/STD transmission both to female sex workers, as well as from female sex workers to the general population of women, particularly regular female partners.

Evaluation design for large-scale HIV prevention programmes: the case of Avahan, the India AIDS initiative

Background:Closing the HIV prevention gap to prevent HIV infections requires rapid, worldwide rollout of large-scale national programmes. Evaluating such programmes is challenging and complex, requiring clarity of evaluation purpose and evidential approaches substantively different to those employed for pilots and small programmes. Objectives:This paper describes the evaluation design for the implementation phase of Avahan, the India AIDS initiative, a large HIV prevention programme funded by the Bill and Melinda Gates Foundation. Avahan, which began in December 2003, has a 10-year charter to impact the Indian epidemic and its response by implementing an HIV prevention programme targeting core and bridge groups in 83 districts of six Indian states, transferring the programme to the Government of India, and disseminating programme learning. Methods:The foundation commissioned an external process to design Avahans evaluation framework. An independent advisory group oversees and guides course corrections in the execution of this framework. Results:Avahans evaluation framework comprises: trend and synthetic analysis of data from core, bridge and household biobehavioural surveys in a subset of intervention districts, denominator estimates and programme monitoring from all intervention districts, and governments antenatal surveillance (two sites per district in all districts); bespoke transmission dynamics modelling to estimate infections averted (subset of districts); cost effectiveness studies (subset of districts). In addition, there are other knowledge-building and quality-monitoring activities. Conclusion:Rather than a small set of monofocal outcome measures, scaled programmes require nuanced evaluations that approximate programmatic scale by collecting data with different levels of geographical scope, synthesize multiple data and methods to arrive at a composite picture, and can cope with continuous environmental and programme evolution.

Mycoplasma genitalium: an organism commonly associated with cervicitis among west African sex workers

Objectives: To identify the contribution of Mycoplasma genitalium to the aetiology of cervicitis in sub-Saharan Africa and its relative importance in the overall burden of sexually transmitted infections among female sex workers (FSW). Methods: The study population consisted of FSW recruited in Ghana and Bénin during the initial visit of a randomised controlled trial. A questionnaire was administered, a pelvic examination carried out, and cervical samples obtained for detection of M genitalium, Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis. Clinical signs potentially indicating cervicitis were cervical discharge, pus on the cervical swab, bleeding after sampling, and inflammatory cervix. Results: Among 826 FSW, 26.3% were infected with M genitalium. N gonorrhoeae was strongly and independently associated with each of the four signs of cervicitis (adjusted odds ratios (AOR): 4.1 to 6.0). The AOR for C trachomatis were intermediate (1.3–4.1) and the AOR for M genitalium were lower (between 1.6 and 1.8) but statistically significant (p⩽0.05) for each sign. Conclusions:M genitalium is weakly associated with signs of cervicitis in west African FSW but is highly prevalent.

The impact of HIV epidemic phases on the effectiveness of core group interventions: insights from mathematical models

Mathematical models have highlighted the disproportionate contribution of core group transmitters to the spread of sexually transmitted diseases. Because the effectiveness of interventions varies with time, it has been suggested that epidemic phases should be considered in the design of prevention strategies. This study aimed to examine the impact of HIV epidemic phases on the effectiveness of HIV interventions based on gonorrhoea screening and condom use, targeted to core groups. The results are based on a mathematical model of gonorrhoea and HIV transmission in a relatively slow spreading HIV epidemic using Cotonou (Benin) as an example. For epidemics with a low reproductive potential modest core group interventions can significantly reduce HIV incidence and prevalence. As the epidemic matures, effective interventions should also incorporate core and non-core populations. For epidemics with a high reproductive potential, core group interventions are necessary but not sufficient to have a rapid and large scale impact. A more general population approach is also needed early in the epidemic. Epidemic phases are also important in the evaluation of prevention strategies.