The new role of antiretrovirals in combination HIV prevention: a mathematical modelling analysis.

BACKGROUND AND OBJECTIVES: Antiretroviral drugs can reduce HIV acquisition among uninfected individuals (as pre-exposure prophylaxis: PrEP) and reduce onward transmission among infected individuals (as antiretroviral treatment: ART). We estimate the potential impact and cost-effectiveness of antiretroviral-based HIV prevention strategies. DESIGN AND METHODS: We developed and analysed a mathematical model of a hyperendemic setting with relatively low levels of condom use. We estimated the prevention impact and cost of various PrEP interventions, assuming a fixed amount of spending on PrEP; investigated the optimal role of PrEP and earlier ART in terms of epidemiological impact and cost; and systematically explored the impact of earlier ART and PrEP, in combination with medical male circumcision services; on HIV transmission. RESULTS: A PrEP intervention is unlikely to generate a large reduction in HIV incidence, unless the cost is substantially reduced. In terms of infections averted and quality adjusted life years gained, at a population-level maximal cost-effectiveness is achieved by providing ART to more infected individuals earlier rather than providing PrEP to uninfected individuals. However, early ART alone cannot reduce HIV incidence to very low levels and PrEP can be used cost-effectively in addition to earlier ART to reduce incidence further. If implemented in combination and at ambitious coverage levels, medical male circumcision, earlier ART and PrEP could produce dramatic declines in HIV incidence, but not stop transmission completely. CONCLUSION: A combination prevention approach based on proven-efficacy interventions provides the best opportunity for achieving the much hoped for prevention advance and curbing the spread of HIV

Will circumcision provide even more protection from HIV to women and men? New estimates of the population impact of circumcision interventions.

BACKGROUND: Mathematical modelling has indicated that expansion of male circumcision services in high HIV prevalence settings can substantially reduce population-level HIV transmission. However, these projections need revision to incorporate new data on the effect of male circumcision on the risk of acquiring and transmitting HIV. METHODS: Recent data on the effect of male circumcision during wound healing and the risk of HIV transmission to women were synthesised based on four trials of circumcision among adults and new observational data of HIV transmission rates in stable partnerships from men circumcised at younger ages. New estimates were generated for the impact of circumcision interventions in two mathematical models, representing the HIV epidemics in Zimbabwe and Kisumu, Kenya. The models did not capture the interaction between circumcision, HIV and other sexually transmitted infections. RESULTS: An increase in the risk of HIV acquisition and transmission during wound healing is unlikely to have a major impact of circumcision interventions. However, it was estimated that circumcision confers a 46% reduction in the rate of male-to-female HIV transmission. If this reduction begins 2 years after the procedure, the impact of circumcision is substantially enhanced and accelerated compared with previous projections with no such effect-increasing by 40% the infections averted by the intervention overall and doubling the number of infections averted among women. CONCLUSIONS: Communities, and especially women, may benefit much more from circumcision interventions than had previously been predicted, and these results provide an even greater imperative to increase scale-up of safe male circumcision services

Quantitative assessment of the impact of partially protective anti-schistosomiasis vaccines

<div><p>Background</p><p>Mass drug administration (MDA) of praziquantel has been the intervention of choice against schistosomiasis but with limited success in interrupting the transmission. The development of anti-<i>Schistosoma</i> vaccines is underway. Our objective is to quantify the population-level impact of anti-<i>Schistosoma</i> vaccines when administered alone and in combination with mass drug administration (MDA) and determine factors in vaccine design and public health implementation that optimize vaccination role in schistosomiasis control and elimination.</p><p>Methods and findings</p><p>We developed a deterministic compartmental model simulation of schistosomiasis transmission in a high-risk Kenyan community, including stratification by age, parasite burden, and vaccination status. The modeled schistosomiasis vaccines differed in terms of vaccine duration of protection (durability) and three biological efficacies. These are vaccine susceptibility effect (SE) of reducing person’s susceptibility to <i>Schistosoma</i> acquisition, vaccine mortality effect (ME) of reducing established worm burden and vaccine fecundity effect (FE) of reducing egg release by mature worms. We quantified the population-level impact of vaccination over two decades under diverse vaccination schemes (childhood vs. mass campaigns), with different age-targeting scenarios, different risk settings, and with combined intervention with MDA. We also assessed the sensitivity of our predictions to uncertainties in model parameters. Over two decades, our base case vaccine with 80% SE, FE, and ME efficacies, 10 years’ durability, provided by mass vaccination every 10 years, reduced host prevalence, mean intensity, incidence, and patent snail prevalence to 31%, 20 eggs/10-ml sample/person, 0.87 worm/person-year, and 0.74%, from endemic-state values of 71%, 152, 3.3, and 0.98%, respectively. Lower impact was found when coverage did not encompass all potential contaminators, and childhood-only vaccination schemes showed delayed and lower impact. In lower prevalence settings, the base case vaccine generated a proportionately smaller impact. A substantially larger vaccine program effect was generated when MDA + mass vaccination was provided every 5 years, which could be achieved by an MDA-only program only if drug was offered annually. Vaccine impact on schistosomiasis transmission was sensitive to a number of parameters including vaccine efficacies, human contact rates with water, human density, patent snails’ rate of patency and lifespan, and force of infection to snails.</p><p>Conclusions</p><p>To be successful a vaccine-based control strategy will need a moderately to highly effective formulation combined with early vaccination of potential contaminators and aggressive coverage in repeated rounds of mass vaccination. Compared to MDA-only program, vaccination combined with MDA accelerates and prolongs the impact by reducing the acquisition of new worms and reducing egg release from residual worms.</p></div

Vaccine biological effects.

<p>Vaccine biological effects.</p

The effect of higher vaccination frequency using the Base Case Vaccine (BCV) on four outcomes.

<p>The base case vaccine with a mean duration of protection of ten years (<i>D</i> = 10) is given according to different mass vaccination frequencies every ten, five and one years with universal coverage in each round. The panels indicate the impact of vaccination on (A) human host prevalence, (B) patent snail prevalence, (C) mean intensity of human infection (eggs/10-ml sample/person or e/s/p) and (D) incidence measured as the number of new worms acquired per person-year (w/p-y).</p

The impact of vaccination in terms of four outcomes in the short-term (year 2) and the long-term (year 22) at different assumptions of vaccine efficacies.

<p>The vaccine durability and the frequency of mass vaccination are both assumed to be 10 years assuming universal coverage in each round of vaccination. The unit (e/s/p) stands for the number of eggs per 10ml sample per person and (w/p-y) stands for the number of new worms acquired per person-year.</p

The effect of coverage level attained in mass vaccination rounds on the population-level impact of Base Case Vaccine (BCV).

<p>The impact at different coverage levels is shown on (A) human host prevalence, (B) patent snail prevalence, (C) the number of eggs/10-ml sample/person (mean intensity) and (D) the number of new worms acquired per person per year (incidence). The vaccine’s efficacies are SE = FE = ME = 80%, with a mean duration of protection (<i>D</i>) of ten years. Rounds of mass vaccination campaigns are assumed every 10 years at coverage levels of 20%, 60%, 80% and universal coverage. The percentage vaccinated is assumed to be randomly assigned.</p

The effect of shorter duration of vaccine effect on four outcomes.

<p>The vaccine is assumed to have different durations of effect, either 10, 5, or 2 years, with the mass vaccination administered at frequency intervals set equal to vaccine durability (adaptive vaccination frequency) with universal coverage in each round. The panels indicate the impact of vaccination on (A) human host prevalence, (B) patent snail prevalence, (C) mean intensity of human infection (eggs/10-ml sample/person or e/s/p) and (D) incidence measured as the number of new worms acquired per person-year (w/p-y).</p

Population-level impact of Base Case Vaccine (BCV) administered in the simulated Kenyan community.

<p>The impact is shown on (A) human host prevalence, (B) patent snail prevalence, (C) the number of eggs/10-ml sample/person (mean intensity) and (D) the number of new worms acquired per person per year (incidence). The vaccine’s efficacies are SE = FE = ME = 80%, with a mean duration of protection (<i>D</i>) of ten years. Two schedules with universal coverage are shown: mass vaccination every 10 years for three rounds of vaccination (Mass BCV every 10 years) and vaccination of newborns (BCV in childhood). Pre-control endemic values were 71% prevalence, 1% snail patency, 152 eggs/10-ml sample/person mean intensity, and 3.3 worms/person/year incidence.</p