Glynn, J.R.

Population-level effect of potential HSV2 prophylactic vaccines on HIV incidence in sub-Saharan Africa (Article)

2009-02-05T00:00:00Z

Herpes simplex virus type-2 (HSV2) infection increases HIV transmission. We explore the impact of a potential prophylactic HSV2 vaccination on HIV incidence in Africa using STDSIM an individual-based model. A campaign that achieved 70% coverage over 5 years with a vaccine that reduced susceptibility to HSV2 acquisition and HSV2 reactivation by 75% for 10 years, reduced HIV incidence by 30-40% after 20 years (range 4-66%). Over 20 years, in most scenarios fewer than 100 vaccinations were required to avert one HIV infection. HSV2 vaccines could have a substantial impact on HIV incidence. Intensified efforts are needed to develop an effective HSV2 vaccine.

Population-level effect of HSV-2 therapy on the incidence of HIV in sub-Saharan Africa (Article)

2008-10-01T00:00:00Z

Background: Herpes simplex virus type 2 (HSV-2) infection increases acquisition and transmission of HIV, but the results of trials measuring the impact of HSV-2 therapy on HIV genital shedding and HIV acquisition are mixed, and the potential impact of HSV-2 therapy on the incidence of HIV at the population level is unknown. Methods: The effects of episodic and suppressive HSV-2 therapy were simulated using the individual-level model STDSIM fitted to data from Cotonou, Benin (relatively low HIV prevalence) and Kisumu, Kenya (high HIV prevalence). Clinician- and patient-initiated episodic therapy, started when symptomatic, were assumed to reduce ulcer duration. Suppressive therapy, given regardless of symptoms, was also assumed to reduce ulcer frequency and HSV-2 infectiousness. Results: Clinician-initiated episodic therapy in the general population had almost no effect on the incidence of HIV. The impact of patient-initiated therapy was higher because of earlier treatment initiation, but still low (<5%) unless symptom recognition and treatment-seeking behaviour were very high. Suppressive therapy given to female sex workers (FSW) in Kisumu had little effect on population HIV incidence. In Cotonou, suppressive therapy in FSW with high coverage and long duration reduced population HIV incidence by >20% in the long term. Impact was increased in both cities by also treating a proportion of their clients. Long-term suppressive therapy with high coverage in the general population could reduce HIV incidence by more than 30%. Conclusions: These results show that HSV-2 therapy could potentially have a population-level impact on the incidence of HIV, especially in more concentrated epidemics. However, a substantial impact requires high coverage and long duration therapy, or very high symptom recognition and treatment-seeking behaviour.

Male circumcision for HIV prevention in sub-Saharan Africa: Who, what and when? (Article)

2008-09-12T00:00:00Z

BACKGROUND AND OBJECTIVE: Male circumcision (circumcision) reduces HIV incidence in men by 50-60%. The United Nations Joint Programme on HIV/AIDS (UNAIDS) recommends the provision of safe circumcision services in countries with high HIV and low circumcision prevalence, prioritizing 12-30 years old HIV-uninfected men. We explore how the population-level impact of circumcision varies by target age group, coverage, time-to-scale-up, level of risk compensation and circumcision of HIV-infected men. DESIGN AND METHODS: An individual-based model was fitted to the characteristics of a typical high-HIV-prevalence population in sub-Saharan Africa and three scenarios of individual-level impact corresponding to the central and the 95% confidence level estimates from the Kenyan circumcision trial. The simulated intervention increased the prevalence of circumcision from 25 to 75% over 5 years in targeted age groups. The impact and cost-effectiveness of the intervention were calculated over 2-50 years. Future costs and effects were discounted and compared with the present value of lifetime HIV treatment costs (US$ 4043). RESULTS: Initially, targeting men older than the United Nations Joint Programme on HIV/AIDS recommended age group may be the most cost-effective strategy, but targeting any adult age group will be cost-saving. Substantial risk compensation could negate impact, particularly if already circumcised men compensate. If circumcision prevalence in HIV-uninfected men increases less because HIV-infected men are also circumcised, this will reduce impact in men but would have little effect on population-level impact in women. CONCLUSION: Circumcision is a cost-saving intervention in a wide range of scenarios of HIV and initial circumcision prevalence but the United Nations Joint Programme on HIV/AIDS/WHO recommended target age group should be widened to include older HIV-uninfected men and counselling should be targeted at both newly and already circumcised men to minimize risk compensation. To maximize infections-averted, circumcision must be scaled up rapidly while maintaining quality.

Treating curable sexually transmitted infections to prevent HIV in Africa: Still an effective control strategy? (Article)

2008-03-01T00:00:00Z

BACKGROUND: Evidence regarding the effectiveness of sexually transmitted infection (STI) treatment for HIV prevention in Africa is equivocal, leading some policy makers to question whether it should continue to be promoted for HIV control. We explore whether treating curable STIs remains a cost-effective HIV control strategy in Africa. METHODS: The model STDSIM was fitted to the characteristics of 4 populations in East and West Africa. Over the simulated HIV epidemics, the population-attributable fractions (PAFs) of incident HIV attributable to STIs, the impact of syndromic STI management on HIV incidence, and the cost per HIV infection averted were evaluated and compared with an estimate of lifetime HIV treatment costs (US $3500). RESULTS: Throughout the HIV epidemics in all cities, the total PAF for all STIs remained high, with ≥50% of HIV transmission attributed to STIs. The PAF for herpes simplex virus type 2 increased during the epidemics, whereas the PAF for curable STIs and the relative impact of syndromic management decreased. The models showed that the absolute impact of syndromic management remains high in generalized epidemics, and it remained cost-saving in 3 of the 4 populations in which the cost per HIV infection averted ranged between US $321 and $1665. CONCLUSION: Curable STI interventions may remain cost-saving in populations with generalized HIV epidemics, particularly in populations with high-risk behaviors or low male circumcision rates.

Proportion of new HIV infections attributable to herpes simplex 2 increases over time: Simulations of the changing role of sexually transmitted infections in sub-Saharan African HIV epidemics (Article)

2007-08-01T00:00:00Z

Objective: To understand the changing impact of herpes simplex 2 (HSV-2) and other sexually transmitted infections (STIs) on HIV incidence over time in four sub-Saharan African cities, using simulation models. Methods: An individual-based stochastic model was fitted to demographic, behavioural and epidemiological data from cross-sectional population-based surveys in four African cities (Kisumu, Kenya; Ndola, Zambia; Yaoundé, Cameroon; and Cotonou, Benin) in 1997. To estimate the proportion of new HIV infections attributable to HSV-2 and other STIs over time, HIV incidence in the fitted model was compared with that in model scenarios in which the cofactor effect of the STIs on HIV susceptibility and infectivity were removed 5, 10, 15, 20 and 25 years into the simulated HIV epidemics. Results: The proportion of incident HIV attributable to HSV-2 infection (the model estimated population attributable fraction (PAFM)) increased with maturity of the HIV epidemic. In the different cities, the PAFMwas 8-31% 5 years into the epidemic, but rose to 35-48% 15 years after the introduction of HIV. In contrast, the proportion of incident HIV attributable to chancroid decreased over time with strongest effects five years after HIV introduction, falling to no effect 15 years after. Sensitivity analyses showed that, in the model, recurrent HSV-2 ulcers had more of an impact on HIV incidence than did primary HSV-2 ulcers, and that the effect of HSV-2 on HIV infectivity may be more important for HIV spread than the effect on HIV susceptibility, assuming that HSV-2 has similar cofactor effects on HIV susceptibility and infectivity. The overall impact of other curable STIs on HIV spread (syphilis, gonorrhoea and chlamydia) remained relatively constant over time. Conclusions: Although HSV-2 appears to have a limited impact on HIV incidence in the early stages of sub-Saharan African HIV epidemics when the epidemic is concentrated in core groups, it has an increasingly large impact as the epidemic progresses. In generalised HIV epidemics where control programmes for curable STIs are already in place, interventions against HSV-2 may have a key role in HIV prevention.

Risk factors for developing clinical infection with methicillin-resistant Staphylococcus aureus (MRSA) amongst hospital patients initially only colonized with MRSA. (Article)

1997-09-01T00:00:00Z

In hospital outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) many patients are initially colonized without infection. The reasons why some progress to infection while others do not are not known. A cohort of 479 hospital patients, initially only colonized with MRSA, was followed prospectively for the development of MRSA infection. Risk factors for progression to infection were assessed using Cox proportional hazards survival analysis. Fifty-three patients (11.1%) developed 68 MRSA infections. Intensive care setting, administration of three or more antibiotics, ulcers, surgical wounds, nasogastric or endotracheal tubes, drains, and urinary or intravenous catheterization were all associated with increased rates of MRSA infection. Multivariate analysis showed that intensive care patients, compared with medical patients, had a higher rate of developing MRSA infection within the first four days of admission, with a hazard ratio of 26.9 (95% CI 5.7-126). Surgical wounds, pressure ulcers and intravenous catheterization were also independent risk factors, with hazard ratios (and 95% CI) of 2.9 (1.3-6.3); 3.0 (1.6-5.7) and 4.7 (1.4-15.6), respectively. These findings suggest that, during an MRSA outbreak, clinical infection would be reduced if surgical and intensive care patients received priority for the prevention of initial colonization with MRSA. Prevention of pressure ulcers, and strict aseptic care of intravenous catheters and surgical wounds would also reduce the development of MRSA infection. Since early treatment with vancomycin is known to reduce the mortality, patients colonized with MRSA who also have one or more of these risk factors may warrant empirical vancomycin therapy at the earliest suggestion of infection.