Benoit Masse

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.

Effect of family responsibilities and job strain on ambulatory blood pressure among white-collar women.

OBJECTIVE This study was conducted to determine whether large family responsibilities and their combination with high job strain were associated with an increase in ambulatory blood pressure (BP) among white-collar women. METHODS A cross-sectional study was conducted in a stratified random sample of 199 white-collar women with or without children who were employed full time in jobs involving high or low strain. These women were selected from a population of 3183 women of all ages, employed in eight organizations in Quebec City, Canada. Subjects wore an ambulatory BP monitor for 24 hours during a working day. Mean BPs were calculated. Different measures of family responsibilities were used, based on the number of children and their ages, and domestic work. Job strain was measured using the Job Content Questionnaire recommended by Karasek. RESULTS Family responsibility measures were significantly related to diurnal BP among women holding a university degree (N=69). Indeed, women having large family responsibilities had increases in systolic and diastolic BPs of 2.7 to 5.7/1.8 to 4.0 mm Hg (p< or =.05). Among women holding a university degree, increases in diurnal systolic and diastolic BPs reached 8.1 to 10.9/5.5 to 7.1 mm Hg (p< or =.01) among women having both large family responsibilities and high job strain. These results were independent of confounders. There was no significant association among women without a university degree (N=130). CONCLUSIONS Large family responsibilities were associated with significant increases in diurnal systolic and diastolic BPs among white-collar women holding a university degree. In these women, the combined exposure of large family responsibilities and high job strain tended to have a greater effect on BP than the exposure to only one of these factors.

HIV incidence and factors associated with HIV acquisition among injection drug users in St Petersburg, Russia

Background:The Russian HIV-1 epidemic has been driven by injection drug use. Objective:To determine HIV incidence and identify demographic and behavioral correlates of infection to facilitate the development of longitudinal HIV prevention programs. Methods:In 2002, a cohort of 520 injection drug users (IDU) in St Petersburg, Russia were recruited and tested and counseled for HIV-1. HIV-seronegative IDU were enrolled and reevaluated at 6 and 12 months. HIV testing was performed and sociodemographic and behavioral data were collected during each study visit. The relationship of sociodemographic and behavioral factors to HIV-1 incidence was assessed. Results:Most enrolled subjects were young, male, living at home, educated, heroin users, and frequently shared needles and other injection paraphernalia. The retention rate at the 12 month follow-up was 80%. The HIV-1 incidence rate was 4.5/100 person-years. In univariate analysis, psychostimulant use, especially frequent use, three or more sex partners in the past 6 months, and females selling sex were associated with HIV seroconversion. In the multivariate analysis, psychostimulant use three or more times per week was the only factor still associated with HIV seroconversion. Conclusions:The high incidence of HIV infection places St Petersburg among the worst IDU-concentrated epidemics in Europe. Interventions targeting psychostimulant and heroin users and their accompanying behaviors such as frequent injections and increased sexual activity are needed immediately.

Measuring the public-health impact of candidate HIV vaccines as part of the licensing process

The full impact of vaccines against infectious diseases is manifest at both the individual and the community levels. We argue that evaluating the community-level impact of HIV vaccine candidates should be an integral part of the licensing process. We describe a framework for the public-health evaluation of an HIV vaccine, which is based on the interactive use of mathematical models and community randomised clinical trials (C-RCTs) following completion of individual-based clinical trials (I-RCTs). Mathematical models of HIV vaccine can be used to take public-health considerations into account during the licensing process and can also help to select promising vaccine candidates for testing in C-RCTs. We also describe community and individual-based measures useful for defining public-health criteria necessary to guide the licensing process. To move forward, it is crucial to reach a consensus on what should constitute adequate public-health criteria. At the very least, a suitable vaccine would provide some individual benefit to vaccinees and not be detrimental to the population at large. In future I-RCTs and C-RCTs, quantifying each protective vaccine characteristic (eg, reductions in susceptibility or viral load) is important if regulators are to evaluate adequately the potential community-level impact of the vaccine across different settings, populations, and conditions of use.

Incremental role of male circumcision on a generalised HIV epidemic through its protective effect against other sexually transmitted infections: from efficacy to effectiveness to population-level impact.

Background: Male circumcision (MC) can reduce HIV acquisition. However, a better understanding of the indirect protective effect of MC on sexually transmitted infections (STIs) is required. Objective: To assess the incremental benefits conferred by MC on HIV infection at the individual level in circumcision trials (no herd immunity effect) and at the population level (with herd immunity effect) owing to its protective effect against other STIs. Methods: A dynamic stochastic model of HIV and STI infections in a Kenyan population was used to simulate the impact of MC offered to a few trial participants or to a large proportion of men in order to study the protective role of MC on HIV infection at the individual and population levels. Results: Fewer than 20% of the HIV infections prevented in the circumcised arm of the circumcision trials (individual level) could be attributable to the efficacy of MC against STIs rather than against HIV. At the population level, MC can significantly reduce the prevalence of HIV, especially among men and women in the longer term. However, even at the population level, the long-term incremental impact of MC on HIV due to the protection against STI is modest (even if MC efficacy against the STI and STI prevalence was high). Conclusions: The protection of MC against STI contributes little to the overall effect of MC on HIV. Additional work is needed to determine whether, and under what conditions, the protective effect of MC efficacy against STIs can have a significant incremental benefit on the HIV epidemic.

Modeling the gender-specific impact of vaginal microbicides on HIV transmission

Vaginal microbicides (VMB) are currently among the few women-initiated biomedical interventions for preventing heterosexual transmission of HIV. In this paper we use a deterministic model of HIV transmission to assess the public-health benefits of a VMB intervention and evaluate its gender-specific impact over short (initial) and extended periods of time. We define two distinct quantitative benefit ratios (QBRs) based on infections prevented in men and women to create and study regions of male advantage in different parameter spaces. Our analysis exposes complicated temporal correlations between the QBRs and series of pre-intervention (e.g., HIV acquisition risks per act) and intervention parameters (e.g., VMB efficacy mechanisms, rates of resistance development and reversion) and indicates that different QBRs may often disagree on the gender distribution of the benefits from a VMB intervention. We also outline the strong influence of some modeling assumptions on the reported results and conclude that the assessment of VMB and other biomedical interventions must be based on more comprehensive analyses than calculations of infections prevented over a fixed period of time.

Psychologic distress in postmyocardial infarction patients who have returned to work.

Objective: To assess the prevalence of psychologic distress in women and men returning to work after a myocardial infarction (MI) and to compare this prevalence with the prevalence observed among men and women of the general working population. Methods: The study population was composed of 990 post-MI patients (106 women and 884 men) recruited in 30 hospitals who had returned to work after their first MI. Psychologic distress was measured with the French version of the Psychiatric Symptom Index (PSI). Adjusted mean PSI score and prevalence of psychologic distress were compared with those observed in 8829 other workers (3823 women and 5006 men), representative of the general working population. Results: Mean PSI score was higher in post-MI women (30.3) than in post-MI men (20.3). This score was also higher in the post-MI population than in the general working population, both for women (30.3 compared with 17.0) and men (20.3 compared with 14.1). Psychologic distress was more prevalent in post-MI women than in post-MI men (prevalence ratio [PR], 1.62; confidence interval [CI], 1.27–2.07). This score was also higher in post-MI women and post-MI men than in the general working population (PR, 2.18; CI, 1.75–2.71 and 1.76; CI, 1.48–2.08, respectively). Conclusions: Among the presumably fittest post-MI patients, namely those who had returned to work, psychologic distress was significantly more prevalent than in the general working population, particularly among women. Further research is needed to shed light on prognosis in post-MI workers experiencing psychologic distress and on adequate intervention before and after their return to work. PR = prevalence ratio; CI = confidence interval; MI = myocardial infarction; PSI = Psychiatric Symptom Index.

Who will Benefit from a Wide-Scale Introduction of Vaginal Microbicides in Developing Countries?

Vaginal microbicides (VMB) are currently among the few biomedical interventions designed to help women reduce their risk of acquiring HIV infection. However, the microbicide containing antiretroviral (ARV-VMB) may lead to the development of antiretroviral resistance and could paradoxically become more beneficial to men at the population level.We developed a mathematical model to study the impact of a wide-scale population usage of VMB in a heterosexual population. Gender ratios of prevented infections and prevalence reduction are evaluated in 63 different intervention schedules including continuous and interrupted ARV-VMB use by HIV-positive women. The influence of different factors on population-level benefits is also studied through Monte Carlo simulations using parameters sampled from primary ranges representative of developing countries.Our analysis indicates that women are more likely than men to benefit from ARV-VMB use since 78-80% of the total 63,000 simulations investigated (under different parameter sets) showed a female advantage whether benefit is measured as cumulative number of infections prevented, the percentage of cumulative infections prevented, or the expected reduction in prevalence. Stratified analysis by scenarios indicates that the likelihood of a male advantage with respect to the fractions of prevented infections varies from 6% to 49% among the scenarios. It is substantial only if the risk of systemic absorption and development of resistance to ARV-VMB is high and the HIV-positive women use VMB indefinitely without interruption. Therefore, the use of ARV-VMB, with successful control measures restricting usage by HIV-positive women, is still very much a female prevention tool.

Risk reduction counseling is associated with decreased HIV transmission-associated behaviors in high-risk Indian heterosexuals.

Objective: To estimate the incidence of HIV and study the impact of risk-reduction counseling (RRC) in a cohort of people with high-risk behavior for HIV transmission in Chennai, India. Design: Prospective cohort follow-up of 500 HIV-negative people (250 men and 250 women) at increased risk for HIV acquisition in Chennai, India for a maximum of 1 year was conducted. They received RRC at 0, 6, and 12 months. Generalized estimating equation methodology was used to determine the statistical significance of differences reported in behavior between baseline, 6 months, and 12 months. Results: The overall HIV incidence in this cohort was 0.44 per 100 person-years (95% confidence interval: 0.05-1.60). In the course of the study, both male and female participants reported statistically significant decreases in the number of different sexual partners, the number of new partners, and the proportion of sexual encounters with nonprimary partners. Participants who had more than 3 different partners at baseline and/or exchanged money for sex in the 6 months before enrollment demonstrated the greatest reductions in the number of different sexual partners. Conclusions: Individualized sexual RRC seems to be a useful intervention to reduce risk-taking behavior among at-risk heterosexuals in India.