At least 25,000 people in the US may now be using PrEP

As many as 30,000 people in the US may now be taking pre-exposure prophylaxis to prevent HIV, the fourth IAPAC Controlling the HIV Epidemic with Antiretrovirals summit in Paris heard last week.

Meanwhile, as the summit also heard, European and other countries face frustrating delays in securing access.

Dr Bob Grant, Principal Investigator of the iPrEx study, told meeting attendees that a survey of US pharmacies that dispense PrEP found 8512 individuals who had had Truvada (tenofovir/emtricitabine) prescribed to them as PrEP from the beginning of 2012. The last time aidsmap.com reported on this study a year ago, the figure was 3253, so prescriptions have more than doubled in a year.

The true number of people on PrEP, however, is considerably higher. The proportion of US pharmacies participating in the PrEP survey has also declined during the year, from 55% to 39%, so the increase has probably been even greater and could be nearly 22,000, if non-reporting pharmacies prescribed PrEP at the same rate as reporting ones.

In addition to pharmacy-prescribed PrEP, an estimated 8,000 people are receiving PrEP in demonstration studies, through the US Medicaid system, or via the patient assistance programme operated by Truvada manufacturers Gilead. This adds up to nearly 30,000 people.

The true figure is likely to be somewhat lower, as non-reporting pharmacies may be prescribing less PrEP and also because some people may have already stopped PrEP. Dr Ken Mayer, principal investigator of the ADAPT study, said that at his own clinic, the Fenway Center in Boston, 14.5% of those who had started PrEP had already stopped (another 30% stopped PrEP but subsequently restarted). However the total of PrEP users in the US is now unlikely to be below 25,000.

The Fenway’s PrEP project started in 2012, but 80% of its 663 participants started last year, reflecting a general recent expansion in PrEP use. This experience is echoed by that of other clinics. For instance, in New York’s large Callen/Lorde Community Health Center, although PrEP has been on offer since March 2012, only 30 people had come forward for it up to January 2014. At this point demand started to increase and is still increasing: the cumulative number of PrEP prescriptions is now 982.

Dr Mayer said that this figure only represented one-twentieth of the people in the US who might benefit from PrEP. It is estimated that there are approximately 275,000 gay men and 140,000 heterosexuals in the US – 415,000 in total – who are at the kind of risk of HIV that would justify taking PrEP.

Bob Grant added that it still seemed to be the case that those who were at the highest risk were the most likely to ask for PrEP: three separate surveys in San Francisco have found that 4 to 10% of gay men with one sexual partner in the last year were now taking, or had ever taken, PrEP, 11 to 17% of those with two partners, and 25 to 33% of those with three or more. “PrEP is essentially a demand-driven measure,” he added.

Mayer said that PrEP prescribing was still skewed to those who could afford it with over 80% having it paid through private insurance and 80% of recipients being white gay men. The two biggest barriers to PrEP use were still lack of demand and lack of insurance coverage: however a survey of healthcare practitioners found that the third most common reason was that practitioners felt untrained to prescribe PrEP.

The global cost of PrEP

A number of speakers looked at PrEP prescribing outside the US. Meg Doherty of the World Health Organization (WHO) went through the meta-analysis of PrEP studies that the WHO conducted to reach its most recent recommendations on PrEP (see this report). She said that the WHO considered PrEP urgently necessary for key affected populations such as men who have sex with men, who were at 19 times the risk of HIV than the general population globally, and transgender women, who were at 49 times the risk. As for cisgender women, in Nigeria 20% of female sex workers had HIV, in Zimbabwe 50%, and in South Africa 17% of young women in the general population had HIV.

Despite the fact that some PrEP studies such as Fem-PrEP and VOICE had not found that PrEP was effective, the meta-analysis found that over all the studies, PrEP was 51% effective, preventing half of the infections that would otherwise have occurred, and that in people with over 70% adherence it was 70% effective. Its effectiveness was higher in men (62%) versus women (43%) and the same gap was observed if this was analysed as anal versus vaginal sex. There was no difference between the effectiveness of Truvada (51%) or solo tenofovir (49%) – a fact that may guide future prescribing policy. The meta-analysis found that, with only the Ipergay study so far releasing results, there were not enough data on intermittent PrEP regimens to decide on their relative effectiveness. It did confirm that PrEP seemed to be considerably less effective in young people, almost certainly owing to low adherence: it only prevented 29% of HIV infections that would otherwise have occurred in people under 25.

As the WHO guidelines say, PrEP is probably economically affordable in people whose risk of HIV exceeds 3% a year, but that heterogeneity of risk in populations may make it hard to identify these people. David Burns of the US CDC said that a couple of sexual-risk algorithms had been developed in the US that accurately predicted someone’s risk of HIV infection over the last year. The San Diego Early Test (SDET) and EXPLORE algorithms both gave ‘points’ for condomless receptive anal sex with HIV-positive partners and with multiple partners (three points each in the SDET score), and for any kind of sex with more than ten partners or diagnosis of a bacterial STI (two points). EXPLORE also added in ’chemsex’ drug use.

In a validation of the SDET score, two-thirds of people diagnosed with early or acute HIV infection (compared with a matched control group who were not infected) had an SDET score of five or more for the previous year while virtually none with an SDET score of eight or more were not infected. (At the same time, 25% with early infection had an SDET score of zero, showing that not all risk is captured.)

He added that for PrEP to be more available, prices would have to fall: the inequity between the $78 a year that generic Truvada costs, and the $10,200 it costs at full price in the USA, had to be ended.

Katie Callahan of the Clinton HIV/AIDS Initiative also said that making sure that only those at high risk of HIV receive PrEP was key to its economic use. In Kenya, the use of HIV drugs as treatment costs $8375 for every HIV infection averted due to their prevention effect. In a cohort of female sex workers with 3% annual HIV incidence PrEP would cost $5593 per infection averted and thus be a net cost-saving measure compared with treating those otherwise infected. If given to the general population however, with an incidence of 0.1% a year, it would cost $128,205 per infection averted, not merely because fewer people would be infected without PrEP but because in a lower-incidence population, testing and linking to care is inherently less efficient.

However, she pointed out, PrEP was not alone in needing to be targeted, it had just been subject to more rigorous cost analyses. In the case of home-based HIV testing, for instance, which have been widely promoted and found to be popular and effective in several African countries, background HIV incidence makes a huge difference to the affordability of programmes. In a population with an HIV prevalence of 8%, the cost per test of a home-based test programme is $6, the cost per HIV-positive person identified is $50, and the cost of linking each diagnosed person to care is $57. If HIV prevalence is 1%, then those figures become $15, $955 and $1698 respectively. Callahan wanted, however, that while PrEP costs less per person per year among a high incidence cohort as a prevention measure, it is difficult to compare the two interventions head-to-head. The cost of treatment is not only just a preventative intervention, it is also saving an HIV-positive person’s life at the same time.

She said that although both antiretroviral-related and non-antiretroviral-related costs in HIV programmes continued to fall, the UNAIDS target of 73% of all people with HIV on treatment and virally suppressed by 2020 would actually be more achievable if programmes targeted those at most risk of HIV, rather than if programmes attempted universal testing and treatment.

Slow progress in Europe

It was notable that Europe-based speakers at the IAPAC summit expressed frustration with the rate of progress towards achieving access to PrEP there. Jean-Michel Molina, principal investigator of the Ipergay study, said that the French Ministry of Health had now asked an expert panel and the French National AIDS Council to give recommendations for PrEP provision “…but not too soon.”

He said this posed a possibly dangerous situation, with more and more people asking for PrEP and, as a survey by AIDES recently documented (link in French), rising rates of informal usage of PrEP and requests for post-exposure prophylaxis (PEP) as a way of getting PrEP.

Sheena McCormack of the PROUD Study said that she thought that the fears of European PrEP providers of an unaffordably high demand for PrEP were misplaced: “I think that we will struggle to get all those who need PrEP to recognise or accept they are at sufficient risk to need it,” she commented.

She added that intermittent PrEP use on the Ipergay model could solve some of the problems of targeting: “In both Ipergay and PROUD we had some participants at low risk. In PROUD, 25% only had one condomless anal intercourse partner in the last 3 months. In an intermittent PrEP regimen, the lower the risk, the lower the use of drug.”

Dominique Costagliola of ANRS, the French HIV research agency, said that despite the fact that 94% of those diagnosed in France are receiving ART and that 60% of patients with CD4 counts over 500 cells/mm³ received ART from 2013 onwards compared with just 15% from 2010-2012, HIV prevalence in men who have sex with men was now 17% and annual incidence was 1.04% - six times the rate in people who inject drugs and 13 times the rate in women who were not French nationals, the next two highest-risk groups.

“There is a critical situation of MSM in Europe,” she said, “which is unlikely to be controlled by more HIV testing and the offer of ART at diagnosis.”