As highly active antiretroviral therapy (HAART) becomes increasingly available for the treatment of HIVdisease, drug resistant strains of HIV-1 are emerging that necessitate the use of newer, more expensive drugs, and often result in treatment failure. Sexually transmitted infections (STIs) have been associated with elevated HIV-1 levels in semen, presumably due to promotion of HIV-1 replication in the genital tract by inflammatory cytokines which are upregulated by STIs, or by direct effects on HIV-1 gene expression by the pathogens themselves. A highly prevalent STI, genital Herpes Simplex Virus 2 (HSV-2) infection, has been associated with increased levels of HIV-1 in genital secretions and an increased rate of HIV-1 sexual transmission. Clinical trials are currently underway to determine whether suppression of HSV-2 infection with acyclovir impacts HIV-1 acquisition and transmission rates. To date, studies on HSV-2/HIV interactions have focused on ART-naive populations. The primary objective of this study is to determine whether Herpes Simplex Virus 2 (HSV-2) co-infection in HIV-1 infected men on HAART promotes HIV replication in the genital tract and the evolution of sexually-transmissible drug-resistant HIV-1. Clinically stable HIV-1 infected men on HAART will be tested for HSV-2 antibodies and enrolled into a cross-sectional study to compare levels of HIV-1 RNA and DNA in semen and blood of HSV-2 co-infected vs. HSV-2 uninfected men (n=125 men/group). A longitudinal study will be conducted in the HSV-2/HIV-1 co-infected group to determine whether anogenital HSV-2 reactivation (clinical symptoms and/or genital HSV shedding) is associated with increased genital shedding of HIV-1. The frequency of RTI and PI drug resistance mutations in HIV-1 RNA from genital and paired blood samples will be determined by TRUGENE. We will also investigate whether seminal HSV-2 DNA and HIV-1 RNA levels are correlated with concentrations of seminal inflammatory and immunological factors (cytokines, antibodies, leukocytes and other mediators of innate immunity). This study will provide valuable information concerning potential interactions between genital HSV-2 and HIV-1 infections in HAART patients, and could have important implications for public health policy regarding provision of antiretroviral therapy to HIV-infected persons in populations with a high prevalence of concomitant STIs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
High Priority, Short Term Project Award (R56)
Project #
1R56AI071909-01A2
Application #
7426241
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Mckaig, Rosemary G
Project Start
2007-06-15
Project End
2010-05-31
Budget Start
2007-06-15
Budget End
2010-05-31
Support Year
1
Fiscal Year
2007
Total Cost
$647,202
Indirect Cost
Name
Boston University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Politch, Joseph A; Mayer, Kenneth H; Anderson, Deborah J (2016) HIV-1 is undetectable in preejaculatory secretions from HIV-1-infected men on suppressive HAART. AIDS 30:1899-903
Politch, Joseph A; Mayer, Kenneth H; Welles, Seth L et al. (2012) Highly active antiretroviral therapy does not completely suppress HIV in semen of sexually active HIV-infected men who have sex with men. AIDS 26:1535-43
Pudney, Jeffrey; Anderson, Deborah (2011) Innate and acquired immunity in the human penile urethra. J Reprod Immunol 88:219-27
Anderson, Deborah; Politch, Joseph A; Pudney, Jeffrey (2011) HIV infection and immune defense of the penis. Am J Reprod Immunol 65:220-9
Anderson, Deborah J (2010) Finally, a macaque model for cell-associated SIV/HIV vaginal transmission. J Infect Dis 202:333-6
Anderson, Deborah J; Politch, Joseph A; Nadolski, Adam M et al. (2010) Targeting Trojan Horse leukocytes for HIV prevention. AIDS 24:163-87
Politch, Joseph A; Mayer, Kenneth H; Anderson, Deborah J (2009) Depletion of CD4+ T cells in semen during HIV infection and their restoration following antiretroviral therapy. J Acquir Immune Defic Syndr 50:283-9