Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-4 (of 4 Records) |
Query Trace: Farshy C[original query] |
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Combination emtricitabine and tenofovir disoproxil fumarate prevents vaginal SHIV infection in macaques harboring C. trachomatis and T. vaginalis
Radzio J , Henning T , Jenkins L , Ellis S , Farshy C , Phillips C , Holder A , Kuklenyik S , Dinh C , Hanson D , McNicholl J , Heneine W , Papp J , Kersh EN , Garcia-Lerma JG . J Infect Dis 2016 213 (10) 1541-5 Genital inflammation associated with STIs increases susceptibility to HIV but it is unclear if the increased risk can reduce the efficacy of pre-exposure prophylaxis (PrEP). We investigated if co-infection of macaques with Chlamydia trachomatis and Trichomonas vaginalis decreases the prophylactic efficacy of oral FTC/TDF. Macaques were exposed to SHIV vaginally each week for up to 16 weeks and received placebo or FTC/TDF peri-coitally. All placebos were infected with SHIV while 4/6 PrEP-treated animals remained uninfected (p=0.03). Oral FTC/TDF maintains efficacy in a macaque model of STI coinfection, although the infection of 2 macaques signals a modest loss of PrEP activity. |
Increased susceptibility to vaginal SHIV transmission in pigtail macaques coinfected with Chlamydia trachomatis and Trichomonas vaginalis
Henning T , Butler K , Hanson D , Sturdevant G , Ellis S , Sweeney EM , Mitchell J , Deyounks F , Phillips C , Farshy C , Fakile Y , Papp J , Secor WE , Caldwell H , Patton D , McNicholl J , Kersh E . J Infect Dis 2014 210 (8) 1239-47 BACKGROUND: Sexually transmitted infections (STIs) are associated with increased HIV infection risk, but their biological effect on HIV susceptibility is not fully understood. METHODS: Female pigtail macaques, inoculated with C. trachomatis and T. vaginalis (n=9) or media (controls, n=7), were repeatedly intravaginally challenged with SHIVSF162p3. Virus levels were evaluated by real-time PCR, plasma and genital cytokine levels by Luminex assays, and STI clinical signs by colposcopy. RESULTS: SHIV susceptibility was enhanced in STI-positive macaques (p=0.04, log rank; 2.5-times as high relative risk of infection, 95% CI 1.1, 5.6). All STI-positive macaques were SHIV-infected, while n=3 (43%) of controls remained uninfected. Moreover, relative to non-STI, infections occurred earlier in the menstrual cycle in STI-positive macaques (p=0.01, Wilcoxon). Inflammatory cytokines were higher in STI-positive macaques during STI inoculation (IFN-gamma, IL-6, and G-CSF) and SHIV exposure periods (G-CSF) (p≤0.05, Wilcoxon). CONCLUSIONS: C. trachomatis and T. vaginalis increase susceptibility to SHIV, likely due to prolonged genital tract inflammation. These novel data demonstrate a biological link between these non-ulcerative STIs and (S)HIV risk, supporting epidemiological observations. This study establishes a macaque model for high-risk HIV transmission and prevention studies. |
Development of a rectal sexually transmitted infection - HIV coinfection model utilizing Chlamydia trachomatis and SHIV
Henning T , Butler K , Mitchell J , Ellis S , Deyounks F , Farshy C , Phillips C , Papp J , Patton D , Caldwell H , Sturdevant G , McNicholl J , Kersh E . J Med Primatol 2014 43 (3) 135-43 BACKGROUND: Rectal sexually transmitted infections (STIs) may increase HIV susceptibility in men who have sex with men (MSM), and Chlamydia trachomatis is prevalent among HIV-positive MSM. To study STIs and HIV infection in MSM, we first evaluated whether cynomolgus macaques can sustain both C. trachomatis and SHIVSF162p3 infections. METHODS: Four SHIVSF162p3 -positive male cynomolgus macaques were used (n = 3 rectally inoculated with 106 IFU; n = 1 control). Systemic and rectal SHIV RNA levels and cytokines were measured by real-time PCR and Luminex assays, respectively. RESULTS: Macaques were successfully Chlamydia infected. Rectal SHIV shedding (P = 0.02 chi2 ) and levels of G-CSF, IL-1ra, IL-6, IL-8, IFN-gamma, and TNF-alpha (P ≤ 0.01, Mann-Whitney) in rectal secretions increased following infection. CONCLUSIONS: These pilot data successfully demonstrate rectal C. trachomatis-SHIV coinfection in cynomolgus macaques and suggest the feasibility of a rectal C. trachomatis model for SHIV susceptibility and biomedical prevention studies in the context of rectal STIs. |
HIV-1 RNA rectal shedding is reduced in men with low plasma HIV-1 RNA viral loads and is not enhanced by sexually transmitted bacterial infections of the rectum
Kelley CF , Haaland RE , Patel P , Evans-Strickfaden T , Farshy C , Hanson D , Mayer K , Lennox JL , Brooks JT , Hart CE . J Infect Dis 2011 204 (5) 761-7 BACKGROUND: Among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) taking combination antiretroviral therapy (cART), the impact of rectal sexually transmitted infections (STIs) on rectal HIV-1 shedding is unknown. METHODS: Human immunodeficiency virus type 1 (HIV-1) RNA was quantified from rectal swabs collected for Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) screening of HIV-1-infected MSM. Correlations of STIs with rectal viral load were explored using multinomial regression modeling. HIV-1 coreceptor tropism was predicted from sequencing in a subset of men. RESULTS: Thirty-one (39%) of 80 men (59 prescribed combination antiretroviral therapy [cART]) had HIV detected in 38 (42%) of 91 rectal swabs. Rectal HIV detection was associated with plasma virus loads above 3.15 log(10) copies/mL (95% confidence limit [CL] 2.73, 3.55) and paired rectal viral loads and plasma viral loads were correlated (Kendall's tau [tau] 0.68, Spearman rho [P] = .77). Rectal STIs and abnormal anal cytology were not associated with rectal viral load. HIV coreceptor distribution was very similar between the plasma and rectum in 3 of 4 men. CONCLUSIONS: Plasma and rectal viral load were correlated, and rectal STIs did not increase the likelihood of detecting HIV in the rectal secretions in MSM, including those with low or undetectable plasma viral load. Suppressing plasma viral load is likely to reduce risk of HIV transmission to insertive partners. |
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