Thursday, May 15, 2014

CDC Guidelines Codify HIV Prophylaxis

health, CDC Guidelines Codify HIV Prophylaxis For people at high risk of acquiring HIV, doctors should consider prescribing antiretroviral drugs as a preventive measure, the CDC said.

Action Points
A clinical practice guideline provides comprehensive information for the use of daily oral antiretroviral pre- exposure prophylaxis to reduce the risk of acquiring HIV infection in adults. The medication currently approved by FDA for PrEP in healthy adults at risk of acquiring HIV infection is the fixed-dose combination of tenofovir disoproxil fumarate and emtricitabine in a single daily dose, Truvada. Note that HIV infection should be assessed at least every 3 months while patients are taking prophylaxis so that those with incident infection do not continue taking it as it is inadequate therapy for established HIV infection, and its use may engender resistance to either or both drugs.

In clinical practice guidelines, the agency says evidence supports what has been dubbed pre- exposure prophylaxis, or PrEP, in several groups at high risk.

The 67-page guideline document combines advice dispensed piecemeal over the past few years as evidence became available, according to Dawn Smith, MD, of the agency's division of HIV/AIDS prevention and who led guideline development.

And it adds detailed guidance for physicians on how identify patients at risk as well as how to prescribe and monitor PrEP, Smith told MedPage Today.

The idea of PrEP is that HIV- negative people with a small amount of anti-HIV drug in their systems would be protected against the virus if they were exposed.

The medication approved for PrEP is the single-pill combination of 300 milligrams of tenofovir co- formulated with 200 milligrams of emtricitabine (Truvada).

Clinical trials have demonstrated that the approach is safe and effective in men who have sex with men, injection drug users, and people whose regular sexual partner has the infection, Smith said:

"What we're telling doctors is that there is now solid evidence that PrEP works, if people take the medication," she said, "and it's safe for people who don't have HIV to take this particular medication."

Estimates are that about 500,000 people in the U.S. are at high enough risk "that PrEP might make sense for them," Smith said. "We would like (doctors) to offer those patients PrEP."

The CDC hopes that PrEP can be an important tool in cutting the annual toll of new HIV cases in the U.S., she added. The HIV epidemic has been "stalled" at about 50,000 new infections a year for several years, Smith noted.

PrEP Challenges

The idea of PrEP has been controversial, with critics fearing increases in risky sexual behavior, adverse effects of the drugs, and the possibility of drug resistance.

Those fears are justified but can be addressed by careful counseling and monitoring of patients on PrEP, Smith said, and the guidelines suggest ways doctors can mitigate the risks.

PrEP has also been criticized as a diversion from other ways of slowing or halting the HIV/AIDS pandemic.

Julio Montaner, MD, of the B.C. Centre for Excellence in HIV/AIDS in Vancouver has said it will only have value as a "very targeted" approach to prevention in small groups of people.

Montaner -- a former president of the International AIDS Society -- has consistently argued that simply increasing the number of HIV-positive people on full-scale three-drug treatment would be a more effective prevention strategy.

Studies have shown that full- scale therapy for HIV-positive people renders them almost completely noninfectious, as well as treating the disease itself.

In that context, using HIV drugs for PrEP looks like a wasteful diversion of resources, Montaner has said:

"From the CDC perspective, we would like both things to happen," Smith said, adding: "we don't think treatment-as- prevention is going to solve the entire problem."

Among other things, she noted that, for various reasons, only about one U.S. HIV patient in three actually is on treatment and has suppressed the virus to the point of being noninfectious.

The guidelines say there is top- level evidence that PrEP is appropriate as "one prevention option" for sexually-active adult men who have sex with men, adult heterosexually active men and women, and adult injection drug users if they are at "substantial risk" of HIV.

Identifying the Population

Exactly how to determine who is eligible for PrEP has been difficult; the guideline document provides a box that, for each group, defines:

What would constitute "substantial risk" Who is clinically eligible What the prescription should be What follow-up services are needed.

Doctors should discuss PrEP with heterosexually-active women and men whose partners are HIV-positive as one of several options to protect the uninfected partner during conception and pregnancy, the guidelines say.

On the other hand, data are insufficient on the efficacy and safety of PrEP for adolescents, so the risks and benefits should be "weighed carefully," taking into account local laws about medical autonomy for minors.

For all the risk groups, the guidelines offer a series of sample questions that can be used to help doctors determine the degree of risk faced by an HIV-negative patient.

The questions cover such things as number of sex partners, type of sexual activity, and use of condoms. Doctors should also take into account any history of bacterial sexually transmitted diseases, alcohol abuse, or the use of noninjection drugs of abuse, such as amyl nitrate.

The local epidemiological picture is also important, since acts that are risky when local HIV prevalence is high might be less dangerous if prevalence is low. Taking a single HIV drug while infected leads universally to drug resistance, the guidelines note.

So a key first step before PrEP is prescribed is to exclude pre-existing HIV infection, the guidelines note. Doctors should take a symptom history and order HIV blood tests. For the same reason, patients should have an HIV test every 3 months while on PrEP, the guidelines say.

The tenofovir/emtricitabine combination is the only FDA-approved PrEP medication, and the guidelines urge that -- with one exception -- others should not be used.

The exception is that -- in trials among injection drug users and heterosexually active adults -- tenofovir showed efficacy by itself and therefore "can be considered" as an alternative.

But it has not been studied in men who have sex with men and shouldn't be used in that group. The guidelines also warn that PrEP needs to be used continuously, rather than being timed for periods of sexual activity.

Tenofovir can have renal adverse effects, so kidney function should be assessed when starting PrEP and every 6 months afterward.

Specifically, a serum creatinine test should be done, and creatinine clearance estimated with the Cockcroft-Gault formula; a clearance rate of less than 60 milliliter per minute should rule out PrEP.

As well, the guidelines note that active hepatitis B is a safety issue when taking tenofovir/ emtricitabine, so tests for the virus are needed before prescribing PrEP.

The guidelines also urge doctors, when PrEP is prescribed, to provide access to risk-reduction services and to encourage patients to use other prevention methods as well.

Smith said it's hard to know how widely PrEP is currently being used.

The Time Is Right

Many physicians, she said, have been reluctant to start patients on PrEP in the absence of comprehensive guidelines and others may not be aware of the approach.

"In the past year, we have become aware of a lot more providers who are interested in PrEP," she said, but in 2013 it's likely that fewer then 10,000 people in the U.S. were on PrEP.

"We need to ramp up the numbers of providers who are aware of PrEP and are comfortable with it," she said, "and we need more awareness on the part of patients."

Full-scale anti-HIV therapy is expensive and cost can be a barrier to treatment, but Smith noted that many public and private insurers are paying for PrEP.

She said the CDC is not aware of many cases in which lack of insurance coverage has prevented people from getting PrEP.

The guideline development was supported by the CDC. Smith is an employee of the agency.

(Source by:
By Michael Smith, North American Correspondent, MedPage Today Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania.
Michael Smith, North American Correspondent, MedPage Today Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania.

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