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1. Changes in HIV-1 Subtypes B and C Genital Tract RNA in Women and Men After Initiation of Antiretroviral Therapy

Author

Robert W. Coombs, Susan Cu-Uvin, Susan H. Eshleman, Irving F. Hoffman, Jonathan Uy, Donna Mildvan, David W. Haas, Thomas B. Campbell, Kelly Burke, David D. Celentano, Edith Swann, Ronald T. Mitsuyasu, Ann C. Collier, Beatriz Grinsztejn, Newton Kumwenda, Laurie Frarey, Breno Santos, Apsara Nair, Ann Walawander, David Chilongozi, Bartolo Santos, Taha E. Taha, Chiedza Maponga, Sima Berendes, S. Poongulali, M. P. Revuelta, Charles van der Horst, Robert C. Bollinger, Suniti Solomon, Jorge Sanchez, Francis Martinson, N. Kumarasamy, Joan Dragavon, James Hakim, Rosa Infante, Richard B. Pendame, Farida Amod, Roy M. Gulick, Jody Lawrence, P. Jan Geiseler, Joan Gormley, Judith S. Currier, Cynthia Firnhaber, Laura Moran, Larisa Zifchak, Myron S. Cohen, Keith A. Pappa, Beverly Putnam, Charles Flexner, David H. Haas, Sandra W. Cardoso, Karin L. Klingman, Ruben Lopez, Joel E. Gallant, James F. Rooney, Jabin Sharma, Edde Loeliger, Pablo Tebas, Beverly E. Sha, Barbara Brizz, Wendy Snowden, Scott M. Hammer, Johnstone Kumwenda, Javier R. Lama, Karin Nielsen, Christine Wanke, Steve Tabet, Alberto La Rosa, Wadzanai Samaneka, Joseph J. Eron, Michael K. Klebert, Renard S. Descallar, Bharat Ramratnam, Kenneth H. Mayer, Cheryl Marcus, Yvonne J. Bryson, Nikki Gettinger, Vicki L. Bailey, Adriana Andrade, David Shugarts, Robert T. Schooley, Ken Braun, David Currin, Eric S. Daar, Michael Hughes, Laura M. Smeaton, Vladimir Berthaud, Sharlaa Badal-Faesen, Victor De Gruttola, Cecelia Kanyama, Timothy P. Flanigan, Mark A. Winters, Yvette Delph, Smanga Ntshele, Peter N. Kazembe, Deise Lucia Faria, Mina C. Hosseinipour, Steven A. Safren, Ronald L. Barnett, Ana Martinez, Abel Tilahun Eshete, Beth D. Mullan, Henry H. Balfour, Ge-Youl Kim, Anthony Chisada, Yajing Bao, Ian Sanne, Virginia Kayoyo, Susan A. Fiscus, Janice M. Fritsche, and Nancy Webb

Subjects
Adult, Male, Microbiology (medical), Cart, medicine.medical_specialty, Sexual transmission, viruses, HIV Infections, Genitalia, Male, Gastroenterology, law.invention, Plasma, Randomized controlled trial, law, Internal medicine, Blood plasma, Humans, Medicine, business.industry, virus diseases, RNA, Genitalia, Female, Viral Load, Antiretroviral therapy, Infectious Diseases, Anti-Retroviral Agents, Genital tract, Immunology, HIV-1, HIV/AIDS, RNA, Viral, Female, business, Viral load
Abstract

Background. Combination antiretroviral therapy (cART) reduces genital tract human immunodeficiency virus type 1 (HIV-1) load and reduces the risk of sexual transmission, but little is known about the efficacy of cART for decreasing genital tract viral load (GTVL) and differences in sex or HIV-1 subtype. Methods. HIV-1 RNA from blood plasma, seminal plasma, or cervical wicks was quantified at baseline and at weeks 48 and 96 after entry in a randomized clinical trial of 3 cART regimens. Results. One hundred fifty-eight men and 170 women from 7 countries were studied (men: 55% subtype B and 45% subtype C; women: 24% subtype B and 76% subtype C). Despite similar baseline CD4+ cell counts and blood plasma viral loads, women with subtype C had the highest GTVL (median, 5.1 log10 copies/mL) compared to women with subtype B and men with subtype C or B (4.0, 4.0, and 3.8 log10 copies/mL, respectively; P < .001). The proportion of participants with a GTVL below the lower limit of quantification (LLQ) at week 48 (90%) and week 96 (90%) was increased compared to baseline (16%; P < .001 at both times). Women were significantly less likely to have GTVL below the LLQ compared to men (84% vs 94% at week 48, P = .006; 84% vs 97% at week 96, P = .002), despite a more sensitive assay for seminal plasma than for cervical wicks. No difference in GTVL response across the 3 cART regimens was detected. Conclusions. The female genital tract may serve as a reservoir of persistent HIV-1 replication during cART and affect the use of cART to prevent sexual and perinatal transmission of HIV-1.

Published
2013

2. Central venous catheter-related bacteremia due to Tsukamurella species in the immunocompromised host: a case series and review of the literature

Author

LaDonna C. Carlson, Ann C. Collier, Carolyn K. Wallis, M. A. Schwartz, Steve Tabet, M. M. Kattar, Marie B. Coyle, and T. T. Nguyen

Subjects
Microbiology (medical), Tsukamurella, Adult, Male, Bacilli, Catheterization, Central Venous, Prosthesis-Related Infections, Adolescent, medicine.medical_treatment, Corynebacterium, Bacteremia, medicine.disease_cause, Microbiology, Immunocompromised Host, Actinomycetales, medicine, Humans, Child, Aged, Tsukamurella pulmonis, biology, business.industry, Infant, Middle Aged, Antimicrobial, 16S ribosomal RNA, biology.organism_classification, medicine.disease, Infectious Diseases, Child, Preschool, Female, business, Central venous catheter
Abstract

We report 6 cases of bacteremia due to Tsukamurella species, all of which were in immunosuppressed patients with indwelling central venous catheters (CVCs). Fewer than 20 cases of serious illness due to these gram-positive bacilli have been reported in the medical literature; these cases have mostly been ascribed to the species Tsukamurella paurometabola. Tsukamurella species are frequently misidentified as Rhodococcus or Corynebacterium species. We used high-performance liquid chromatography to identify these organisms to the genus level and 16S ribosomal RNA gene sequencing and DNA-DNA dot blots for species identification. Three of our isolates were identified as Tsukamurella pulmonis, 1 was identified as Tsukamurella tyrosinosolvans, and 1 was identified as a unique species. One isolate was not maintained long enough for species identification. All patients were successfully treated with antimicrobial therapy and CVC removal. Infection with this organism should be considered in the immunosuppressed patient with an indwelling CVC and gram-positive bacilli in the blood.

Published
2001

3. Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

Author

David Chilongozi, Sharla Faesen, Breno Santos, Mamta K. Jain, Pablo Tebas, Apsara Nair, Cynthia Riviere, Beatriz Grinsztejn, Sima Berendes, Steve Tabet, Joan Gormley, M. Graham Ray, Johnstone Kumwenda, Judith Feinberg, Todd Stroberg, Kenneth H. Mayer, Nikki Gettinger, Vicki L. Bailey, James Hakim, Selvamuthu Poongulali, Sandra W. Cardoso, Marineide Gonçalves de Melo, Karin L. Klingman, Rosie Mngqibisa, Thomas B. Campbell, Amneris E. Luque, Beverly Putnam, Thira Sirisanthana, Janice M. Fritsche, Ann Walawander, Ge Youl Kim, Roberto Corales, Richard B. Pollard, Ronald T. Mitsuyasu, Martha Silberman, Rita Alves Lira, Janet Forcht, Norbert Bischofberger, Ana Martinez, Barbara Brizz, Laura M. Smeaton, Asmita Gaikwad, Farida Amod, Srikanth Tripathy, Babafemi Taiwo, Anthony Chisada, Chiedza Maponga, Charles van der Horst, Michael Wulfsohn, Javier R. Lama, Taha E. Taha, Manuel Revuelta, Christine Hurley, David Currin, Wendy Snowden, Keith A. Pappa, Rosa Infante, T. Petersen, Donna V. McGregor, Susan Cu-Uvin, Susan A. Fiscus, Eric S. Daar, Jody Lawrence, P. Jan Geiseler, Irving F. Hoffman, Luis Lopez-Detres, Karen T. Tashima, Larisa Zifchak, Victor De Gruttola, Timothy P. Flanigan, Laura Moran, Farideh Said, Alberto La Rosa, Raman R. Gangakhedkar, Maria Palmer, Michael F. Para, Joel E. Gallant, Nancy Webb, Cecilia Kanyama, Wadzanai Samaneka, Jabin Sharma, Yvonne J. Bryson, Mark A. Winters, Ian Sanne, David Shugarts, Yun Chen, Sampada Dhayarkar, Peter N. Kazembe, Scott M. Hammer, Adriana Andrade, Robert T. Schooley, Beth D. Mullan, Henry H. Balfour, Patrice Severe, Beverly E. Sha, Madeline Torres, Cathi Basler, Andrew K. Cheng, Jolene Noel-Connor, Vladimir Berthaud, Jonathan Uy, Michael K. Klebert, Virginia Kayoyo, Donna Mildvan, David W. Haas, Joseph J. Eron, Cheryl Mogridge, David D. Celentano, Ruben Lopez, Ronald L. Barnett, Karin Nielsen, Helen Patterson, Renard S. Descallar, Jenifer Baer, Deise Lucia Faria, Cheryl Marcus, Khuanchai Supparatpinyo, Mina C. Hosseinipour, Newton Kumwenda, Yvette Delph, Smanga Ntshele, Edith Swann, Steven A. Safren, David M. Asmuth, Kelly Burke, Laurie Frarey, Joseph Steele, Gary M. Cox, Umesh G. Lalloo, Richard B. Pendame, Mary Adams, Bharat Ramratnam, Christine Wanke, James F. Rooney, Francis Martinson, Edde Loeliger, Anjali A. Joglekar, John Martin, Myron S. Cohen, Sheela Godbole, Robert C. Bollinger, Roy M. Gulick, Cynthia Firnhaber, Charles Flexner, William A. O'Brien, Suniti Solomon, Jorge Sanchez, Yue Chen, Susan H. Eshleman, Kathy J. Watson, N. Kumarasamy, David H. Haas, Ann C. Collier, Bartolo Santos, Suwat Chariyalertsak, Michelle S. Cespedes, Howard Jaffe, Judith S. Currier, and Deeks, Steven G

Subjects
Male, Comparative Effectiveness Research, Time Factors, Internationality, HIV Infections, Medical and Health Sciences, law.invention, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, Pregnancy, law, 030212 general & internal medicine, 0303 health sciences, education.field_of_study, Coinfection, Hazard ratio, virus diseases, General Medicine, 3. Good health, Infectious Diseases, Treatment Outcome, 6.1 Pharmaceuticals, Combination, HIV/AIDS, Medicine, Female, Patient Safety, Infection, medicine.drug, medicine.medical_specialty, Efavirenz, Anti-HIV Agents, Clinical Trials and Supportive Activities, Population, Antiretroviral Therapy, Emtricitabine, 03 medical and health sciences, Drug Therapy, Clinical Research, General & Internal Medicine, Internal medicine, PEARLS study team of the ACTG, medicine, Humans, Highly Active, Dosing, education, 030306 microbiology, business.industry, Evaluation of treatments and therapeutic interventions, Mycobacterium tuberculosis, Surgery, Atazanavir, Regimen, Withholding Treatment, chemistry, HIV-1, business, Follow-Up Studies
Abstract

BackgroundAntiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and findings1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; pConclusionEFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.Trial registrationwww.ClinicalTrials.gov NCT00084136. Please see later in the article for the Editors' Summary.

Published
2012

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