A Key Link for Transmission Prevention

The HIV epidemic in sub-Saharan Africa is severe and continues to grow. In urban areas of Malawi, 19% of pregnant women seeking antenatal care and 15.6% of Malawians aged 15-49 years were infected with HIV in 2007. Prevention interventions that prevent onward transmission of HIV are urgently needed.

Persons with acute HIV infection (AHI) may be responsible for a substantial proportion of onward transmission of HIV infection. AHI is characterized by unfettered replication of HIV in a "ramp up viremia". The high concentration of HIV in blood and genital secretions remains elevated for up to 10-12 weeks before it declines to the levels observed in established infection. These high levels of HIV shedding in the genital tract are likely to produce very efficient sexual transmission and the proportion of virions that are infectious may be substantially higher during acute compared to chronic infection. Consequently, the probability of transmission during unprotected intercourse for those with AHI is very high. Identifying persons with AHI and intervening to reduce onward transmission represents a tantalizing, but unproven, opportunity for HIV prevention.

To have maximal impact, a prevention program targeting AHI must identify a substantial number of acutely infected persons and intervene quickly to minimize onward transmission. An effective immediate intervention would require behavioral modification to limit sexual partners and unprotected sex acts, and a biological intervention to reduce infectious viral burden in genital secretions. This is the first study to pilot a combined behavioral and biomedical intervention in individuals with AHI to reduce onward transmission of HIV.

Inclusion criteria

Primary participants:

• Acute HIV-1 infection
• Men and women age greater than/= 18 years.
• Intention to remain in the Lilongwe area for the duration of the study.
• Ability and willingness of participant to provide informed consent.
• Willingness to provide contact/locator information, be contacted, and asked to return for AHI results.

Partner Participants:

• Referred by a primary participant and present with a referral card.
• Had vaginal or anal sex with a primary participant within 12 weeks prior to that primary participant's enrolling
• Men and women age greater than/=18 years.
• remain in the Lilongwe area for the duration of the study.
• Ability and willingness of participant to provide informed consent.

Exclusion criteria

Primary Participants:

• HIV infection based on two positive HIV antibody rapid tests at the time of screening.
• HIV-negative based on one or more antibody rapid test and an HIV RNA PCR test.
• Serious illness, including tuberculosis or opportunistic infection, requiring systemic treatment and/or hospitalization.
• Active drug or alcohol use or dependence.
• Current imprisonment or involuntary incarceration.
• Any other condition that in the opinion of the study investigator would compromise the safety of the study participant or study staff, or would prevent proper conduct of the study.

Partner Participants:

• Active drug or alcohol use or dependence.
• Current imprisonment or involuntary incarceration in a medical facility for psychiatric or physical illness.

Exclusion for Receipt of Antiretroviral Drugs in the BIA Arm

Note:A key component of this pilot study is to estimate the potential effect of ARVs during acute infection when applied on a large population scale.In effect, this pilot study should be viewed as a pilot for an effectiveness trial. Consequently, we will randomize all eligible participants to one of the three arms. If, however, persons should not receive ARVs for a variety of medically-related reasons, these persons will remain in the BIA arm, but will not receive ARVs. Women who are of reproductive potential but who refuse to use at least one form of contraception (see below), will remain in the BIA arm but will not receive ARVs. Similarly, persons randomized to the BI arm who do not attend all sessions will remain in the BI arm.

Persons randomized to BIA with any of the following conditions will be excluded from receiving ARVs, but will remain in the BIA group for purposes of analysis.

• Laboratory values obtained at Day 0 prior to initiating ARVs at a subsequent visit
• Absolute neutrophil count <300/mm3
• Hemoglobin <8.0 g/dL
• Platelet count <40,000/mm3
• Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase > 5 x upper limit of normal (ULN)
• Total bilirubin >2.5 x ULN
• Creatinine Clearance (CrCl) <60 mL/min
• Hepatitis B surface antigen positivity
• Positive serum or urine pregnancy test at Day 0.
• Breastfeeding
• Refusal to use at least one method of contraception, if a woman is of reproductive potential.

Acceptable forms of contraception include: condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, intrauterine device (IUD), or a hormonal-based contraceptive.

Women not meeting the reproductive potential criteria above may receive the study drugs without using contraception.

• Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation.
• Requirement for any current medications that are prohibited with any study drugs.