Oral "hot topic" presentation at the 4th AIDS Impact Conference in July 1999, in Ottawa, Ontario

The Cost of Providing Non-Occupational Post-Exposure Prophylaxis

Steve Martindale, Sophie Low-Beer, Amy E. Weber, Keith Chan, Robert S. Hogg: BC Centre for Excellence in HIV/AIDS.

ISSUE TO BE DISCUSSED: When should short-term antiretroviral therapy be administered to prevent HIV infection? Current guidelines include accidental and occupational exposure and sexual assault, but exclude consensual sexual exposure. What would be the cost of providing post-exposure prophylaxis to gay and bisexual men who engage in high-risk sexual behaviour?

CONTENT: The cost of non-occupation post-exposure prophylaxis was estimated by multiplying the cost of antiretroviral prophylaxis per course by the number of gay and bisexual men at non-occupation risk and by the average number of non-occupational incidents per person per year. Non-occupational risk was based on the percentage of Vanguard participants who had at least one episode of unprotected anal sex with a casual male partner in the previous year, or who reported having unprotected anal sex with someone they knew at the time was HIV positive. The cost of post-exposure prophylaxis was taken from the HIV/AIDS Drug Treatment Program. The proportion of the West End male population 20 years and over estimated to be gay or bisexual was derived from a random telephone survey conducted by Simon Fraser University. Monte Carlo trials were used to simulate the confidence limits around our cost estimate.

The gay and bisexual male population in the West End was estimated to be 5,100. Based on Vanguard data we estimated that 1391 individuals (27.3%) in this population would be at non-occupation risk for HIV. The average number of incidents per year was three. The average cost for antiretroviral prophylaxis therapy was $560 with the range being $530 for double and $903 for triple therapy. The potential annual non-occupational post-exposure prophylaxis to all those at risk in the West End was estimated to be $2,400,000 (95% CI: $800,000 - $4,100,000).

Our results indicate that providing post-exposure prophylaxis for those at high sexual risk of contracting HIV would cost a minimum of $800,000 per year. While this figure is approximately equal to the province's current budget for accidental and occupational post-exposure prophylaxis, it represents only a fraction of the what it would cost to provide antiretroviral therapy.to the individuals who might otherwise become HIV-positive.

Notes:

• Partially based on Sophie's talk at CAHR '99 in Victoria.
• She has submitted a letter to AIDS.
• Sophie focused mainly on the economic issues.
• I'll present a condensed version of her findings as a springboard to discuss the broader issues.

Four weeks of:

• Double therapy:
  • Stavudine (d4T)
  • Lamivudine (3TC)
• Triple therapy (in cases of higher risk):
  • add Nelfinavir

Must be started within 72 hours of exposure

Notes:

• Define PEP
• Duration
• Drugs used:
  • commonly AZT & 3TC (in the US)
  • in BC it's 3TC and d4T
  • with a protease inhibitor such as nelfinavir for higher-risk exposures
• Must be started within 72 hours, preferably within 2 hours

• Occupational Exposure
  • e.g. needlestick injuries
• "Community" Exposure
  • accidental exposure
  • sexual assault

Notes:

• Current treatment guidelines in BC (established by the CfE).
• Free in BC for those who qualify.
• PEP currently costs about $800,000/year for the drugs alone.
• People who don't qualify can pay: $500 to $1000 per month.
  • not covered by provincial health coverage or most extended health plans.
  • user-pay makes PEP inaccessible for those who may need it most (Globe & Mail editorial called this "two-tiered medicine of the most pernicious sort."
• Anecdotal reports of people lying about circumstances of exposure in order to meet the current guidelines.

• Receptive vaginal intercourse: 0.1 - 0.2%
• Needlestick (percutaneous): 0.4%
• Intravenous needle/syringe: 0.4 - 3.0%
• Receptive anal intercourse: 0.5 - 3.0%

Notes:

Considering the risk of HIV transmission associated with unprotected anal intercourse...

And that PEP is believed to be effective enough to prescribe in cases of occupational exposure and sexual assault...

...should therapeutic guidelines include the use of post-exposure prophylaxis for high-risk sexual exposures?

How effective is PEP?

• may reduce likelihood of infection after occupational exposure by 80%
• reliability of this figure

Other factors play a role:

• quantity of blood exchanged
• viral load of source
• immune system of recipient

• Avoidability
• Frequency of exposure
• Likelihood of determining HIV status of source
• Elapsed time between incident and intervention
• Evidence of effectiveness of PEP exists only for occupational exposure

Notes:

Effectiveness of PEP proven only for occupational exposure

• its effectiveness for sexual exposure is speculative
• data may never be available (i.e. placebo-controlled clinical trial not feasible)
• but it's being prescribed for sexual assault, so why not consensual sex?

PEP Guidelines

• Which risk behaviours would qualify?
• Would anyone be excluded?
• How often is too often?
• How to publicize it?

Notes:

What would we do with people who are chronically at risk?

How to publicize availability of PEP without sending the message that prevention is no longer important?

"An analagous situation is emergency 'morning-after' contraception. Although opponents feared that it would encourage sexual risk taking, there is no evidence that non-emergency contraceptive use rates declined after morning-after contraceptives were approved.

-- Dr. Peter Lurie et al, JAMA Nov. '98.

• It could prevent infections
• Could be cost-effective
• Side-effects may be deterrent
• Intervention for people at high risk

Notes:

• How many prevented infections makes it worth doing?
• Can you place a dollar value on prevented infections?
• Cost/benefit analysis: How many infections would you have to prevent per year for it to be cost effective?
• Once may be enough: The side effects may be enough to discourage people from putting themselves at risk in the future.
• It could get people at high risk in the door for counselling and referrals:

"The behavioural component is the most important thing. This is another way to get high-risk engagers to come in and get the skills to avoid infection. The medication is the bait."

-- Dr. Joshua Bamberger, quoted in The Advocate.

• Side-effects & health impact
• Poor adherence
• Possibility of resistant strains developing
• Impact on risk behaviour
• Cost

Notes:

• Side-effects: What is the health impact of repeated or prolonged PEP on HIV-negative individuals?
• Adherence is poor because of the side effects and because PEP is often discontinued if the source tests negative.
• Resistance: Although less likely with combination therapy, still a concern.
• Would people begin to rely on it instead of prevention? (Is all good news about AIDS counter-productive?)
• Globe & Mail editorial:"Nobody wants to encourage risky behaviour, but it is not our place to judge who is entitled to treatment."
• Cost: Would that money be better spent elsewhere? (e.g. prevention education, vaccine research)

To estimate the annual cost of providing non-occupational post-exposure prophylaxis to gay and bisexual men in the West End of Vancouver.

Notes:

PEP is currently free in BC, so if the guidelines are to be expanded, the government will need to know what it will cost.

High Non-Occupational Risk:

• at least one episode of unprotected anal sex with a CASUAL male partner in the previous year

OR

• at least one episode of unprotected anal sex with an HIV-positive male (either regular or casual) in the previous year

Notes:

• We didn't include unprotected oral sex.
• We didn't include unprotected anal sex with regular partners (unless partner is known to be HIV+)

• SLIDE 11
  What would it cost?
  ESTIMATED VARIABLES
• MSM population in West End: 5,057
• % at high risk in previous year: 26.6%
• Average # of risk incidents per year: 3 (range: 0-6)
• Average cost of 1 month of PEP: $560.00 (range = $532 - $903)

Notes:

• Sophie's calculations.
• Sources.
• Limitations.

The potential cost of providing post-exposure prophylaxis for all those at non-occupational risk in the West End was estimated at : $2,259,780

Notes:

• Likely an underestimate of potential cost.
• Note: low figure equal to current cost of PEP for whole province
• Other researchers have found PEP to be cost-effective for high-risk cases (e.g.. anal sex) but not for low-risk exposures.
• May be an underestimate of actual cost, as not everyone at risk would access PEP, and many would do so only once.

• Three-year pilot project began Oct. '97
• Free PEP from two health clinics
• Funded by National Institutes of Health and SF Department of Health
• Drugs donated by manufacturers
• Includes 10 counselling sessions/year
• Not an efficacy trial

Notes:

• To explore the feasibility of providing PEP for non-occupational exposures.
• Two clinics offered free PEP.
• Publicized in gay community.
• Much north-south travel within the gay communities of Vancouver, Seattle, San Francisco and L.A.
  • gay men in Vancouver are aware of PEP as it's available for their friends in SF
• Anecdotal reports of "PREP" (pre-exposure prophylaxis).

• Approx. 200 patients in first year
• Mostly male (85%); mostly 20 to 50 years old
• Exposure almost entirely sexual (only 1% IDU)
• Risk activity mostly anal receptive (some anal insertive; only 1% oral sex)
• Half known HIV+ source; nearly half established risk factors of source
• 96% took PEP (94% of those took double therapy)

Notes:

• They weren't overwhelmed with the demand.
• Two clinics, 200 people in 10 months.
• Clients were mostly ideal candidates for PEP.
• Note: double therapy, not triple.

"...practitioners have an ethical obligation to act in the best interests of the patient and to address the patient's clinical needs, regardless of the cause of the patient's clinical problems."

-- Dr. Peter Lurie et al, JAMA Nov. '98.

Notes:

Is it ethical to withhold PEP from people who need it?

"Ethically, respect for the autonomy of the exposed patient requires the disclosure of an unproven but plausible use of available drugs to prevent a potentially fatal infection."

-- Dr. Peter Lurie et al, JAMA Nov. '98.

Are we being puritan or judgmental about it?

"...some HCWs may be reluctant to provide PEP to individuals whose sexual activities or drug use they deem irresponsible or self-destructive. However deep these feelings... (SEE QUOTE ON SLIDE)"

-- Dr. Peter Lurie et al, JAMA Nov. '98.

• PEP should be seen as one component of a range of prevention options
• PEP guidelines should be expanded to include non-occupational exposure
• Must be accompanied by an education campaign stressing:
  • Side effects
  • Effectiveness unknown
  • Continued need for prevention

Notes:

• This is not a policy statement of the BC Centre for Excellence in HIV/AIDS; these conclusions are my personal opinion.
• We have a treatment that we can assume is effective.
• We should provide it to those who need it.
• Must be accompanied by an education campaign stressing that:
  • PEP has side-effects.
  • it may not work.
• PEP should be viewed as one component of a range of prevention options, as is the case with the morning after pill and other forms of contraception.