HIV prophylaxis

Associate Editors-in-Chief: Ujjwal Rastogi, MBBS [mailto:urastogi@perfuse.org]

Overview
Prophylaxis refers to measures taken to prevent diseases, (or injuries) rather than curing them or treating their symptoms.

Pre-exposure prophylaxis
Pre-exposure prophylaxis (PrEP) is a process, when HIV negative people who are at high risk, take antiretroviral medication daily to try to lower their chances of becoming infected with HIV if they are exposed to it.

Indications
PrEP has been shown to be effective in the following:
 * Men who have sex with men (MSM).
 * Heterosexual men and women.

Landmark Studies

 * In November 2010, the National Institutes of Health (NIH) announced the results of the iPrEx clinical trial, a large, multi-country research study examining PrEP. The study found that daily oral use of tenofovir plus emtricitabine (TDF/FTC) provided an average of 44% additional protection to men who have sex with men (MSM) who also received a comprehensive package of prevention services that included the following:
 * Monthly HIV testing.
 * Condom provision.
 * Management of other sexually transmitted infections.


 * In July 2011, a new CDC study called the TDF2 study, along with a separate trial by the University of Washington, provided evidence that a daily oral dose of antiretroviral drugs used to treat HIV infection can reduce HIV acquisition among uninfected individuals exposed to the virus through heterosexual sex:
 * The TDF2 study, conducted in partnership with the Botswana Ministry of Health, found that once-daily TDF/FTC reduced the risk of acquiring HIV infection by roughly 63 percent overall in the study population of uninfected heterosexual men and women. CDC researchers also conducted a separate analysis to better understand the level of effectiveness among trial participants believed to be taking their study medications. This analysis excludes any HIV infections that occurred more than 30 days after a participant's last reported drug dose, because those individuals could not have been taking study pills at the time of infection. These results indicate that TDF/FTC reduced the risk of HIV infection by 78 percent.
 * The University of Washington study, called Partners PrEP, found that two separate antiretroviral regimens – tenofovir and TDF/FTC – significantly reduced HIV transmission among serodiscordant couples, in which one partner is infected with HIV and the other is not (by 62 percent and 73 percent, respectively). CDC co-managed two of the nine sites for this study.

Guidelines for pre-exposure prophlaxis in MSM

 * Before initiating PrEP
 * Determine eligibility
 * Document negative HIV antibody test(s) immediately before starting PrEP medication.
 * Test for acute HIV infection if patient has symptoms consistent with acute HIV infection.
 * Confirm that patient is at substantial, ongoing, high risk for acquiring HIV infection.
 * Confirm that calculated creatinine clearance is ≥60 mL per minute (via Cockcroft-Gault formula).
 * Other recommended actions
 * Screen for hepatitis B infection; vaccinate against hepatitis B if susceptible, or treat if active infection exists, regardless of decision about prescribing PrEP.
 * Screen and treat as needed for STIs.
 * Beginning PrEP medication regimen
 * Prescribe 1 tablet of Truvada* (TDF [300 mg] plus FTC [200 mg]) daily.
 * In general, prescribe no more than a 90-day supply, renewable only after HIV testing confirms that patient remains HIV-uninfected.
 * If active hepatitis B infection is diagnosed, consider using TDF/FTC for both treatment of active hepatitis B infection and HIV prevention.
 * Provide risk-reduction and PrEP medication adherence counseling and condoms.
 * Follow-up while PrEP medication is being taken
 * Every 2--3 months, perform an HIV antibody test; document negative result.
 * Evaluate and support PrEP medication adherence at each follow-up visit, more often if inconsistent adherence is identified.
 * Every 2--3 months, assess risk behaviors and provide risk-reduction counseling and condoms. Assess STI symptoms and, if present, test and treat for STI as needed.
 * Every 6 months, test for STI even if patient is asymptomatic, and treat as needed.
 * 3 months after initiation, then yearly while on PrEP medication, check blood urea nitrogen and serum creatinine.


 * On discontinuing PrEP (at patient request, for safety concerns, or if HIV infection is acquired)
 * Perform HIV test(s) to confirm whether HIV infection has occurred.
 * If HIV positive, order and document results of resistance testing and establish linkage to HIV care.
 * If HIV negative, establish linkage to risk-reduction support services as indicated.
 * If active hepatitis B is diagnosed at initiation of PrEP, consider appropriate medication for continued treatment of hepatitis B.

Post-exposure prophylaxis
Post-exposure prophylaxis (PEP) is short-term antiretroviral treatment to reduce the likelihood of HIV infection after potential exposure, either occupationally or through sexual intercourse.

Indications

 * Within the health sector, PEP should be provided as part of a comprehensive universal precautions package that reduces staff exposure to infectious hazards at work.
 * PEP is recommended for exposure from a documented HIV source but considered optional when HIV status of the source is unknown.

Importance

 * The risk of transmission of HIV from an infected patient through a needlestick where the skin is punctured by a sharp is less than 1%. The risk for transmission from exposure to infected fluids or tissues is believed to be lower than for exposure to infected blood.
 * The risk of exposure from needlesticks and other means exists in many settings where protective supplies are limited and the rates of HIV infection in the patient population are high. The availability of PEP may reduce the occurrence of occupationally acquired HIV infection in health care workers. It is believed that the availability of PEP for health workers will serve to increase staff motivation to work with people infected with HIV, and may help to retain staff concerned about the risk of exposure to HIV in the workplace.
 * There is significant debate on the need to use PEP after sexual exposure. The United Nations offers PEP to its staff in cases of rape when the likelihood of HIV exposure is considered high.

Prevention
Prevention of exposure remains the most effective measure to reduce the risk of HIV transmission to health workers. The priority must be to train health workers in prevention methods (universal precautions) and to provide them with the necessary materials and protective equipment. Staff should as well be knowledgeable about risks of acquiring HIV sexually, and be easily able to access condoms and confidential STI treatment services.

Managing occupational exposure to HIV

 * First AID should be given immediately after the injury: wounds and skin sites exposed to blood or body fluids should be washed with soap and water, and mucous membranes flushed with water.
 * The risk for HIV infection should be evaluated based on the following:
 * Exposure type: percutaneous vs mucous membrane vs intact skin.
 * Severity of exposure: small vs large volume, superficial vs deep injury.
 * Potential to transmit HIV infection (based on body substance and severity of exposure).
 * Source status: Known or unknown HIV status.
 * The exposure source should be evaluated for HIV infection. Testing of source persons should only occur after obtaining informed consent, and should include appropriate counselling and care referral. Confidentiality must be maintained.
 * Clinical evaluation and baseline testing of the exposed health care worker should proceed only after informed consent.
 * Exposure risk reduction education should occur with counsellors reviewing the sequence of events that preceded the exposure in a sensitive and non-judgmental way.

Regimen

 * For low-risk exposures (Eg: mucus membrane) : Basic (2 drug) regimen is recommended.
 * For high-risk exposure (Eg: percutaneous needle stick) : Expanded (3 drug) regimen is recommended.
 * Preferred Basic regimen:
 * Zidovudine plus lamivudine.
 * Zidovudine plus emtricitabine.
 * Tenofovir plus lamivudine.
 * Tenofovir plus emtricitabine.
 * Preferred Expanded regimen:
 * Basic plus lopinavir/ritonavir.
 * Duration of therapy
 * Ideally therapy should be started within hours of exposure and continued for 28 days.

Related Chapters

 * Antiretroviral therapy