A Key Link for Transmission Prevention (MP3)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by University of North Carolina, Chapel Hill
Sponsor:
Information provided by (Responsible Party):
William (Bill) C. Miller, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT01450189
First received: September 18, 2011
Last updated: March 27, 2014
Last verified: March 2014

September 18, 2011
March 27, 2014
October 2011
August 2014   (final data collection date for primary outcome measure)
  • Number of participants who screen and enroll into the study with acute HIV-infection (AHI). [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Proportion of participants in Arm BI who complete the behavioral sessions within 3 weeks of enrollment. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Proportion of participants completing full course of ARVs in Arm BIA and the number and type of adverse events/social harms. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Proportion of participants in Arm BIA who complete the behavioral sessions within 3 weeks of enrollment. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01450189 on ClinicalTrials.gov Archive Site
  • Unprotected sexual acts assessed at weeks 12, 26, and 52. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • The number of partners reporting for HIV testing. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Time to suppression of HIV RNA. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Cumulative incidence of incident gonorrhea, chlamydial infection, trichomoniasis, and herpes simplex virus type 2 at 26 and 52 weeks. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Blood and genital HIV RNA concentration with area under the curve. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Antiretroviral therapy (ART) resistance. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Proportion of partners reporting for HIV testing. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
A Key Link for Transmission Prevention
Acute HIV Infection - A Key Link for Transmission Prevention: A Randomized Pilot Study

This study will assess the potential public health benefit of behavioral and antiretroviral interventions during acute HIV infection.

Hypothesis The investigators hypothesize that delivering behavioral and antiretroviral interventions to acutely infected persons will reduce onward transmission.

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.

Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
HIV
  • Behavioral: Standard HIV prevention messages
    The standard counseling (SC) arm consists of a single session of standard HIV prevention messages during HIV post-test counseling. The counseling will be comparable to that given to persons with established HIV infection with supplemental information regarding the acute stage of their infection.
  • Behavioral: 5 counselor-delivered sessions
    The behavioral intervention (BI) arm consists of five counselor-delivered sessions based on the Information-Motivation-Behavioral Skills (IMB) Model. The sessions are designed to provide participants with the information, motivation, and skills needed to abstain or practice protected sex during the brief acute HIV period, as well as plan for long-term behavioral risk reduction.
  • Drug: ARVs with raltegravir and emtricitabine/tenofovir disoproxil fumarate
    The behavioral intervention and antiretroviral (BIA) arm consists of the same behavioral intervention plus antiretroviral drugs (ARV) with raltegravir (400mg twice daily) and fixed dose combination (FDC) emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) (200/300mg daily) orally for 12 weeks.
  • Active Comparator: Standard Counseling Arm
    The SC arm consists of a single session of standard HIV prevention messages during HIV post-test counseling. The counseling will be comparable to that given to persons with established HIV infection with supplemental information regarding the acute stage of their infection.
    Intervention: Behavioral: Standard HIV prevention messages
  • Active Comparator: Behavioral Intervention Arm
    The BI arm consists of five counselor-delivered sessions based on the Information-Motivation-Behavioral Skills (IMB) Model. The sessions are designed to provide participants with the information, motivation, and skills needed to abstain or practice protected sex during the brief acute HIV period, as well as plan for long-term behavioral risk reduction.
    Intervention: Behavioral: 5 counselor-delivered sessions
  • Active Comparator: Behavioral Intervention plus antiretrovirals (BIA)
    The BIA arm consists of the same behavioral intervention plus antiretroviral drugs (ARVs) with raltegravir (400 mg twice daily) and fixed dose combination (FDC) emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) (200/300 mg daily) orally for 12 weeks.
    Intervention: Drug: ARVs with raltegravir and emtricitabine/tenofovir disoproxil fumarate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
115
November 2015
August 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years to 65 Years
No
Contact: William C Miller, MD, PhD, MPH 919-966-9407 bill_miller@unc.edu
Contact: Audrey Pettifor, PhD, MPH 919-966-7439 apettif@email.unc.edu
Malawi
 
NCT01450189
IRB 11-0815, CID 1002
Yes
William (Bill) C. Miller, MD, University of North Carolina, Chapel Hill
William (Bill) C. Miller, MD
Not Provided
Study Chair: William C Miller, MD, PhD, MPH University of North Carolina, Chapel Hill
Study Chair: Audrey Pettifor, PhD, MPH University of North Carolina, Chapel Hill
Principal Investigator: Sam Phiri, PhD, MSc Kamuzu Central Hospital, Lilongwe, Malawi
University of North Carolina, Chapel Hill
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP