OBJECTIVE: To measure in-vitro antiviral drug susceptibilities of human immunodeficiency virus type 1 (HIV-1) isolates recovered from patients treated with alpha-interferon or zidovudine and patients not treated with these drugs and to examine the relation of these susceptibility measurements to duration of therapy, disease stage, and response to alpha-interferon therapy. DESIGN: Cross-sectional study. SETTING: Outpatient HIV clinic. PATIENTS: Twenty-six ambulatory HIV-1-infected patients: Fifteen of these patients were receiving alpha-interferon therapy, and 11 had never received such therapy. Nine patients were participating in a clinical trial of combination therapy with zidovudine and alpha-interferon. MEASUREMENTS: The 50% inhibitory concentration (IC50) of zidovudine and alpha-interferon was determined for HIV-1 isolates recovered from each patient. Plasma concentrations of HIV-1 p24 antigen in the nine patients in the clinical trial were measured monthly after alpha-interferon was added to zidovudine monotherapy. RESULTS: Zidovudine IC50 (range, 0.01 to 4.87 microM) increased steadily with duration of zidovudine therapy (r = 0.57, P = 0.003). In contrast, alpha-interferon IC50 (range, 0.8 to 415 units/mL) was not related to duration of alpha-interferon treatment; in fact, high IC50s were found in isolates from patients who had never received exogenous alpha-interferon therapy. Resistance to alpha-interferon was greater in isolates from the 15 patients with the acquired immunodeficiency syndrome (AIDS) (median, 104 units/mL) than in those from the 10 patients without AIDS (median, 50 units/mL). Interferson activity was detected in plasma samples from 23 of 24 patients and was also at higher levels in patients with AIDS than in HIV-infected patients without AIDS. Reductions in plasma concentrations of HIV-1 p24 antigen in nine patients after beginning alpha-interferon therapy were greater in those with more susceptible isolates (r = -0.72, P = 0.03). CONCLUSIONS: Interferon resistance, possibly due to endogenous interferon, is not related to duration of interferon therapy but may limit the effectiveness of interferon therapy. Determinations of interferon susceptibility may identify patients most likely to benefit from this agent.
OBJECTIVE: To measure in-vitro antiviral drug susceptibilities of human immunodeficiency virus type 1 (HIV-1) isolates recovered from patients treated with alpha-interferon or zidovudine and patients not treated with these drugs and to examine the relation of these susceptibility measurements to duration of therapy, disease stage, and response to alpha-interferon therapy. DESIGN: Cross-sectional study. SETTING:Outpatient HIV clinic. PATIENTS: Twenty-six ambulatory HIV-1-infectedpatients: Fifteen of these patients were receiving alpha-interferon therapy, and 11 had never received such therapy. Nine patients were participating in a clinical trial of combination therapy with zidovudine and alpha-interferon. MEASUREMENTS: The 50% inhibitory concentration (IC50) of zidovudine and alpha-interferon was determined for HIV-1 isolates recovered from each patient. Plasma concentrations of HIV-1p24 antigen in the nine patients in the clinical trial were measured monthly after alpha-interferon was added to zidovudine monotherapy. RESULTS:Zidovudine IC50 (range, 0.01 to 4.87 microM) increased steadily with duration of zidovudine therapy (r = 0.57, P = 0.003). In contrast, alpha-interferon IC50 (range, 0.8 to 415 units/mL) was not related to duration of alpha-interferon treatment; in fact, high IC50s were found in isolates from patients who had never received exogenous alpha-interferon therapy. Resistance to alpha-interferon was greater in isolates from the 15 patients with the acquired immunodeficiency syndrome (AIDS) (median, 104 units/mL) than in those from the 10 patients without AIDS (median, 50 units/mL). Interferson activity was detected in plasma samples from 23 of 24 patients and was also at higher levels in patients with AIDS than in HIV-infectedpatients without AIDS. Reductions in plasma concentrations of HIV-1p24 antigen in nine patients after beginning alpha-interferon therapy were greater in those with more susceptible isolates (r = -0.72, P = 0.03). CONCLUSIONS: Interferon resistance, possibly due to endogenous interferon, is not related to duration of interferon therapy but may limit the effectiveness of interferon therapy. Determinations of interferon susceptibility may identify patients most likely to benefit from this agent.
Authors: C Rinaldo; X L Huang; Z F Fan; M Ding; L Beltz; A Logar; D Panicali; G Mazzara; J Liebmann; M Cottrill Journal: J Virol Date: 1995-09 Impact factor: 5.103
Authors: Shilpa S Iyer; Frederic Bibollet-Ruche; Scott Sherrill-Mix; Gerald H Learn; Lindsey Plenderleith; Andrew G Smith; Hannah J Barbian; Ronnie M Russell; Marcos V P Gondim; Catherine Y Bahari; Christiana M Shaw; Yingying Li; Timothy Decker; Barton F Haynes; George M Shaw; Paul M Sharp; Persephone Borrow; Beatrice H Hahn Journal: Proc Natl Acad Sci U S A Date: 2017-01-09 Impact factor: 11.205
Authors: Marcos V P Gondim; Scott Sherrill-Mix; Frederic Bibollet-Ruche; Ronnie M Russell; Stephanie Trimboli; Andrew G Smith; Yingying Li; Weimin Liu; Alexa N Avitto; Julia C DeVoto; Jesse Connell; Angharad E Fenton-May; Pierre Pellegrino; Ian Williams; Emmanouil Papasavvas; Julio C C Lorenzi; D Brenda Salantes; Felicity Mampe; M Alexandra Monroy; Yehuda Z Cohen; Sonya Heath; Michael S Saag; Luis J Montaner; Ronald G Collman; Janet M Siliciano; Robert F Siliciano; Lindsey J Plenderleith; Paul M Sharp; Marina Caskey; Michel C Nussenzweig; George M Shaw; Persephone Borrow; Katharine J Bar; Beatrice H Hahn Journal: Sci Transl Med Date: 2021-01-13 Impact factor: 17.956
Authors: Martin J Deymier; Zachary Ende; Angharad E Fenton-May; Dario A Dilernia; William Kilembe; Susan A Allen; Persephone Borrow; Eric Hunter Journal: PLoS Pathog Date: 2015-09-17 Impact factor: 6.823
Authors: Angharad E Fenton-May; Oliver Dibben; Tanja Emmerich; Haitao Ding; Katja Pfafferott; Marlen M Aasa-Chapman; Pierre Pellegrino; Ian Williams; Myron S Cohen; Feng Gao; George M Shaw; Beatrice H Hahn; Christina Ochsenbauer; John C Kappes; Persephone Borrow Journal: Retrovirology Date: 2013-12-03 Impact factor: 4.602