A mathematical modelling study based on the HIV epidemic in the Netherlands has found that daily pre-exposure prophylaxis (PrEP) would be cost-effective even at current drug prices if it was targeted at gay men at high risk of HIV infection.
In a base case where PrEP was 80% effective, 10% of higher-risk gay men took it, current drug prices were used, and PrEP was taken every day, then PrEP’s cost per quality-adjusted life year (QALY) gained would be €11,000. This would fall to only €2000 if PrEP was used on demand and only half as much drug was used. The model regards a cost of under €20,000 as cost-effective.
Daily PrEP would actually be cost-saving (it would save more in terms of infections prevented than its provision would cost) if drug prices fell 70% or more. If PrEP was taken on demand, then prices would only have to fall by 30 to 40% for PrEP to save money. Applying generic rather than on-patent prices turned PrEP in most scenarios from cost-effective to cost-saving.
The model calculates these savings over a 40-year time span. However, the researchers add that most of the savings achieved would actually take place in the first ten years, because that is when the majority of HIV infections would be prevented.
There are several reasons why this model, unlike some previous ones, finds that PrEP will be cost-effective under most scenarios. Firstly, it assumes a general effectiveness of PrEP of 80%, higher than many previous models that used more conservative figures derived from studies like iPrEx. Ths model uses the effectiveness seen in the PROUD and Ipergay studies.
Secondly, it assumes that PrEP is taken by only 10% of the gay men in the two highest risk groups in the Netherlands (men with 5-18 sexual partners in a year, and men with more than 18). “The actual uptake of PrEP is likely to be only a small percentage of those at high risk,” the authors assert.
In terms of figures, this implies 4500 gay men taking PrEP in any one year, and the authors assume that the average gay man will stay on PrEP for five years.
However, even if 80% of men in the two highest risk groups were taking PrEP – implying 36,000 men on PrEP in any one year – this would only increase the cost per year of providing PrEP versus not providing it by 40%, and it would remain cost-saving under many scenarios.
Thirdly, its base case assumes that the costs of antiretroviral therapy (ART) for HIV do not fall to the same degree as PrEP. Even if the price of ART did fall to the same degree as the price of PrEP, however, PrEP would still remain cost-effective. The cost per QALY gained of on-demand PrEP would rise from €2000 to €4000 if both ART and PrEP prices fell by 70%. The authors say they consider this unlikely, as ART is more likely to continue to feature new, patented and costlier drugs due to factors like resistance and long-term drug toxicity in an ageing HIV-positive population.
Fourthly, and unlike many cost-effectiveness studies, this one also takes account of preventing secondary infections – the HIV transmissions that would otherwise be passed on by men who acquire HIV if they do not take PrEP. However, even if these are not taken into account, PrEP remains cost-effective; at current prices and if PrEP is taken daily, ignoring secondary infections would only increase the cost per QALY gained from €11,000 to €13,100, and if it was taken on-demand from €1980 to €2300.
Similarly, even if the average duration of PrEP is doubled from five years to ten years, the cost per QALY gained increases only from €10,800 to €11,400 for daily PrEP and from €1900 to €2100 for on-demand PrEP.
Other base-case assumptions in the model include that the full current price of PrEP is €7400 per year and that the cost of ART and monitoring is €13,000 per year. It assumes ART and monitoring costs €2500 more than this in the first year after diagnosis. It adds in STI (sexually transmitted infection) clinic or GP visit costs of €124 for four visits per year and €572 for HIV clinic visits. (These figures are the actual current costs for drugs, monitoring and clinic visits in the Netherlands.) It assumes that all HIV-positive people start treatment on diagnosis and that the reduction in infectiousness caused by ART is 80 to 96%. It does assume that people in early infection are more infectious, but also assumes that the period of raised infectiousness is quite short.
The cost of HIV treatment and care in the Netherlands over the next 40 years is estimated at €8.3 billion. Providing a programme of daily PrEP, at current drug prices and at 10% takeup, would add €423 million or 4.3% to this 40-year cost, or €93 million (0.5%) if it was taken on-demand. If the price of PrEP was reduced by 70% relative to the price of ART then daily PrEP would actually save €25 million and on-demand PrEP would save €101 million.
The most important determinants of PrEP cost-effectiveness in this model were, for daily PrEP, its future fall in costs relative to ART and, for on-demand PrEP, its absolute future fall in costs.
The degree to which gay men were ‘targeted’ was also important; if more took PrEP then the number of new HIV cases prevented per year would rise (i.e. incidence would fall) relative to the 10% base case, but the cost per infection prevented would also rise, because as time went by there would be fewer new cases to prevent.
However, while in other studies, “targeting” is the most important determinant of cost-effectiveness, it runs second to drug price in this one. This is partly because the higher effectiveness assumed by this study means that it becomes less crucial only to direct PrEP at the very highest-risk gay men, who would even benefit as a population from moderately-effective PrEP. However, the model does not go into the cost implications of providing PrEP to the more numerous lower-risk gay men with fewer than five sexual partners a year.
“Although the short-term costs of PrEP provision might be high,” the authors comment, “PrEP could save HIV-related healthcare costs in the long run, especially when the price of PrEP is reduced.”
Nichols BE et al. Cost-effectiveness analysis of pre-exposure prophylaxis for HIV-1 prevention in the Netherlands: a mathematical modelling study. The Lancet, early online publication, 22 September 2016. See http://dx.doi.org/10.1016/S1473-3099(16)30311-5