Behavioral, Clinical and Basic Science Studies of Non-occupational Post-exposure Prophylaxis ("PEP-2") (PEP-2)

This is a randomized trial to compare the effect of standard versus enhanced risk reduction counseling on risk behavior incidence in individuals receiving PEP medications. The study seeks to 1) determine if there are equivalent changes in the incidence of self-reported risk behaviors, STD incidence, and adherence to medications in individuals who receive enhanced risk reduction and adherence counseling and those who received standard risk reduction and adherence counseling; 2) evaluate viral and host biological factors involved in sexual transmission that may either influence PEP efficacy, or themselves be negatively or positively affected by the administration of PEP medications; and 3) contribute to the CDC registry in an attempt to provide crucial data for a case control analysis to establish the efficacy of PEP for sexual and injection drug use exposures. The principal outcome will be the change in participants' number of unprotected sexual acts following administration of PEP. This is defined as the number of prior 3-month acts of high risk unprotected sex, assessed at 12 months following a course of PEP, minus the number of unprotected acts the participant reported in the 3 and 6 months prior to beginning PEP (assessed at baseline). Methods to be used consist of interview data collection, questionnaires, risk reduction and adherence counseling and source recruitment counseling (index subject).

A. SPECIFIC AIMS Our group (including behavioral, epidemiological, basic, and clinical scientists from UCSF, San Francisco General Hospital, The San Francisco Department of Public Health, and the UCSF-affiliated Gladstone Institute of Virology and Immunology) conducted a feasibility study of Post Exposure Prevention (PEP) in which we successfully recruited, retained, and assessed over 400 individuals recently and substantially exposed to HIV-1 (index cases), as well as a significant number of the persons (source cases) who exposed the index cases to HIV-1.

We are frequently asked by physicians and public health professionals for help in establishing similar programs in various communities. PEP has two promising possibilities: (a) it may prevent HIV infection and (b) it may be a viable way to attract high risk uninfected individuals into counseling. But tremendous uncertainty remains about how to integrate PEP into existing clinical and prevention programs. Because we felt that risk reduction counseling was essential to prevent disinhibition, we provided intensive (5 session) prevention counseling in our feasibility study. Adherence counseling was also essential as incomplete adherence could reduce the effectiveness of the medications or increase the chance of infection with a resistant isolate. However, multi-session counseling is very resource intensive.

The most urgent question to be addressed about PEP is whether PEP medications must be offered with an enhanced counseling program, or if standard HIV pre- and post-test counseling and routine adherence counseling will result in equivalent risk behavior following PEP and adherence with antiretroviral medications.

Thus, we propose the following primary aim:

1. To conduct a randomized trial to determine whether enhanced (multi-session) risk reduction and adherence counseling is equivalent to standard (2 session) risk reduction and adherence counseling in terms of self-reported risk behaviors and documented STDs and adherence to PEP medications.

   In addition, because we are recruiting a cohort of HIV-infected individuals who are engaging in behavior potentially capable of transmitting HIV, as well as HIV uninfected individuals who have recently exposed themselves to HIV, we have the unique opportunity to address the following important aims:

2. Source (HIV infected person potentially transmitting) virologic characteristics: To describe and compare the (a) HIV-1 RNA level and (b) antiretroviral resistance mutation prevalence in the plasma and genital secretions of source subjects.

3. Index (exposed HIV uninfected) subject CD8+ T-cell antiviral factor activity responses:

   1. To determine whether PEP medications blunt CD8+ T-cell antiviral factor (CAF) activity by comparing the changes in CAF following HIV exposure in persons receiving PEP medications to individuals matched for exposure who do not receive medications;
   2. To determine whether there is a correlation between source plasma and genital secretion HIV-1 RNA levels and index CAF activity.)
4. To evaluate the safety of adding 2 doses of nevirapine to the existing medication regimens that are based on two nucleoside analogue reverse transcriptase inhibitors ¬+ a protease inhibitor.