Preventing Sexual Transmission of HIV With Anti-HIV Drugs

Initiation of antiretroviral therapy (ART) in the HIV infected population has been shown to
dramatically reduce the morbidity and mortality of HIV infection through sustained reduction
in HIV viral replication. However, such therapy does not cure HIV infection or prevent the
spread of the virus. ART may, however, make HIV infected people less contagious by lowering
plasma HIV-1 RNA levels, compared with people not on ART. This study seeks to determine
whether initiating ART in ART-naive, HIV infected people can prevent the sexual transmission
of HIV among HIV-discordant couples, as well as to demonstrate whether quality of life
changes with the initiation of ART. Both opposite and same sex couples will be recruited at
study sites in Brazil, India, Malawi, Thailand, the United States, and Zimbabwe for this
study.

Participating couples will be enrolled for approximately 78 months (6.5 years). Couples will
be randomly assigned to one of two arms. HIV infected partners in Arm 1 will begin ART in
addition to receiving HIV primary care. HIV infected partners in Arm 2 will receive HIV
primary care. When the CD4 count in these participants reaches 200 to 250 cells/mm3, drops
below 200 cells/mm3, or develops an AIDS-defining illness, they will initiate ART. All
couples will receive HIV counseling and have their urine and blood collected at screening
and enrollment, and at selected monthly, quarterly, and yearly intervals. They will be asked
to periodically report information about their adherence to the ART regimen.

Note: Per LoA#5, on the Data and Safety and Monitoring Board (DSMB) recommendation, as of
May 10, 2011, all HIV-infected participants in Arm 2 who have not already initiated ART will
be offered ART as soon as possible.

Inclusion Criteria for HIV Infected Partner:

- Positive HIV test within 60 days of study entry

- CD4 count between 350 and 550 cells/mm3 within 30 days of study entry

- If pregnant or breastfeeding, willing to be randomized to either arm of the study

Inclusion Criteria for HIV Uninfected Partner:

- Negative HIV test within 14 days of study entry

Inclusion Criteria for Both Partners:

- Plans to maintain sexual relationship with partner

- Reports having sex (vaginal or anal) with partner at least three times in the last 3
months

- Willing to disclose HIV test results to partner

- Plans to stay in the area and does not have a job or other obligations that may
require long absences during the duration of the study

Exclusion Criteria for HIV Infected Partner:

- Current or previous use of any ART. Participants who previously took a short-term
course of ART for prevention of mother-to-child transmission of HIV are not excluded.

- Documented or suspected acute hepatitis within 30 days of study entry, if the
infected partner's starting regimen in the study contains nevirapine or atazanavir

- Current or previous AIDS-defining illness or opportunistic infection

- Documented or suspected acute hepatitis within 30 days prior to study entry

- Acute therapy of serious medical illnesses within 14 days prior to study entry

- Radiation therapy or systemic chemotherapy within 45 days prior to study entry

- Immunomodulatory or investigational therapy within 30 days prior to study entry

- Active drug or alcohol dependence that, in the opinion of the investigator, would
interfere with the study

- Vomiting or inability to swallow medications

- Require certain medications

- Allergy or sensitivity to any of the study drugs

Exclusion Criteria for Both Partners:

- History of injection drug use within 5 years of study entry

- Previous and/or current participation in an HIV vaccine study

- Currently detained in jail or for treatment of a psychiatric or physical illness

- Any condition that, in the opinion of the study staff, would make participation in
the study unsafe, complicate interpretation of study outcome data, or otherwise
interfere with achieving the study objectives

- Certain abnormal laboratory values