Simulation predicts PrEP may be effective in high-risk gay/bisexual US men, but cost-effectiveness uncertain

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According to a computer simulation, tenofovir/emtricitabine pre-exposure prophylaxis (PrEP) could reduce lifetime HIV infection risk from 44% to 25% among high-risk men who have sex with men in the US, if it is 50% effective at preventing new HIV infections. However, the predicted overall increase in life expectancy was very small, and the average lifetime cost of PrEP provision was estimated at USD $151,600 per person. The study was published in the February 4 edition of Clinical Infectious Diseases.

The study of PrEP – the use of antiretroviral medications before exposure to HIV in the hope of reducing infection risk – has so far been limited to animal studies, preliminary findings of one human trial in at-risk women (previously reported at the Sixteenth International AIDS Conference and now published), and several analyses using computer models, by Desai and others.

This study also used a computer model which simulated both population characteristics – such as risk behaviour, the effects of prevention efforts, and the resulting incidence of new infections – and disease characteristics such as the progression of HIV disease, resulting complications, life expectancy and cost of care. The simulation was based on the following assumptions:

Glossary

cost-effective

Cost-effectiveness analyses compare the financial cost of providing health interventions with their health benefit in order to assess whether interventions provide value for money. As well as the cost of providing medical care now, analyses may take into account savings on future health spending (because a person’s health has improved) and the economic contribution a healthy person could make to society.

quality adjusted life year (QALY)

Used in studies dealing with cost-effectiveness and life expectancy, this gives a higher value to a year lived with good health than a year lived with poor health, pain or disability. 

risky behaviour

In HIV, refers to any behaviour or action that increases an individual’s probability of acquiring or transmitting HIV, such as having unprotected sex, having multiple partners or sharing drug injection equipment.

phase II

The second stage in the clinical evaluation of a new drug or intervention, in which preliminary data on effectiveness and additional information about safety is collected among a few hundred people with the disease or condition.

matched

In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. 

  • PrEP consisted of full-dose tenofovir/emtricitabine (Truvada), at the current average wholesale price of USD $724 per month. An additional monthly cost of USD $28 was added to allow for quarterly laboratory monitoring.
  • PrEP was used in an American population of high-risk men who have sex with men (MSM), with a mean age of 34 years and an annual HIV incidence of 1.6%. These characteristics matched those of men in the HIV Network for Prevention Trials (HIVNET) Vaccine Preparedness Study conducted in the US.
  • PrEP was estimated to be 50% effective at preventing infection overall – the same estimate used in the Desai analysis, comparable to results from animal trials, and less than the 65% (non-statistically significant) estimate from the Peterson trial in women. This estimate was also meant to account for behavioural effects such as possible increases in risky sex due to PrEP use.

In this high-risk group, current practices of prevention and care led to a 44% lifetime risk of HIV infection and a mean survival of 40 years, at a cost of USD $81,100 per person. Use of tenofovir/emtricitabine PrEP, as modeled in this analysis, reduced lifetime infection risk to 25%, but increased cost to USD $232,700 per person, and only increased mean survival time to 40.7 years. When translated into "quality-adjusted years of life" (QALY), the increase was even more meagre – from 21.7 to 22.2 QALYs, for a cost of USD $298,000 per QALY gained.

This "unattractive" estimate of cost-effectiveness raises many questions. First of all, it was much more pessimistic than the Desai analysis, which estimated a cost of USD $31,970 per QALY saved. However the Desai study also accounted for the benefits of secondary infections prevented – i.e. infections that were prevented in men not accessing PrEP directly themselves, but due to reduced HIV prevalence in the community. The current study did not look at this effect.

Any computer-modeled simulations are, of course, speculative – how PrEP would actually play out in the real world would depend on many factors such as how effective it actually is, the characteristics (including risk level) of the people who use it, and the number of people who receive it. The study team found that, according to their model, PrEP would be more cost-effective if it were used in higher-risk populations with higher HIV incidence, and – naturally – if it were more than 50% effective or was made available at a lower cost.

Despite the poor cost-effectiveness findings of this particular simulation, the researchers suggested that PrEP could "substantially reduce the lifetime risk of HIV infection in persons at high risk in the United States," – especially with improvements in efficacy, targeting, or pricing – and that "this finding alone justifies continued study of PrEP-based approaches". They also noted that prevention and treatment efforts are interdependent, and that "the costs and benefits of one can only be evaluated in the context of the other".

References:

Paltiel AD HIV pre-exposure prophylaxis in the United States: impact on lifetime infection risk, clinical outcomes, and cost-effectiveness. Clin Infect Dis 48; 806-815, 2009.

Garcia-Lerma JG et al. Prevention of rectal SHIV transmission on macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. PloS Medicine 5(2):291-299, 2008. (Read the study here.)

Peterson L et al. Tenofovir disoproxil fumarate for prevention of HIV infection in women: a phase 2, double-blind, randomized, placebo-controlled trial. PLoS Clin Trials 2:e27. 2007. (Read the study here.)