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HIV Seropositivity: HELP
Articles from University of Washington
Based on 121 articles published since 2008
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These are the 121 published articles about HIV Seropositivity that originated from University of Washington during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Review CNS Persistence of HIV-1 in Children: the Untapped Reservoir. 2018

Chahroudi, Ann / Wagner, Thor A / Persaud, Deborah. ·Emory University School of Medicine, Atlanta, GA, USA. · Seattle Children's Hospital and University of Washington, Seattle, WA, USA. · Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Building 1170, Baltimore, MD, 21205, USA. dpers@jhmi.edu. ·Curr HIV/AIDS Rep · Pubmed #30159813.

ABSTRACT: PURPOSE OF REVIEW: The central nervous system (CNS) represents a potential HIV-1 reservoir that may need to be specifically targeted by remission strategies. Perinatally HIV-1-infected children and youth are exposed to HIV-1 at a critical period of brain development. This review summarizes the current literature regarding HIV-1 and the CNS in perinatal infection. RECENT FINDINGS: HIV-1-associated encephalopathy is prevalent with perinatal infection and neurocognitive impairment persists even following antiretroviral treatment (ART)-mediated suppression of viremia. Compartmentalization of HIV-1 between plasma and CSF of ART-naïve, perinatally infected children suggests the presence of a CNS reservoir; however, similar studies have not yet been conducted with ART suppression. CSF viral escape where CSF and plasma virus concentrations are discordant has been reported in this population, but larger studies with well-defined virologic and immunologic parameters are needed. A better understanding of HIV-1 persistence in the CNS with perinatal infection is essential for improving long-term neurocognitive outcomes and for designing strategies to induce HIV-1 remission in this population.

2 Review Prevalence of HIV-Seropositivity and Associated Impact on Mortality among Injured Patients from Low-and Middle-Income Countries: A Systematic Review and Meta-Analysis. 2017

Aluisio, Adam R / Rege, Soham / Stewart, Barclay T / Kinuthia, John / Levine, Adam C / Mello, Michael J / Farquhar, Carey. ·Department of Emergency Medicine, Alpert Medical School of Brown University, Providence, RI, USA. · Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States. · Department of Surgery, University of Washington, Seattle, USA. · Department of Interdisciplinary Health Sciences, Stellenbosch University, Cape Town, South Africa. · Department of Research & Programs, Kenyatta National Hospital, Nairobi, Kenya. · Department of Global Health, University of Washington, Seattle, USA. · Department of Epidemiology, University of Washington, Seattle, USA. · Department of hMedicine, University of Washington, Seattle, USA. ·Curr HIV Res · Pubmed #28933280.

ABSTRACT: BACKGROUND: Although HIV and injury contribute substantially to disease burdens in lowand middle-income countries (LMIC), their intersection is poorly characterized. OBJECTIVE: This systematic review assessed the prevalence and associated mortality impact of HIVseropositivity among injured patients in LMIC. METHODS: A systematic search of PubMed, EMBASE, Global Health, CINAHL, POPLINE and Cochrane databases through August 2016 was performed. Prospective and cross-sectional reports of injured patients from LMIC that evaluated HIV-serostatus were included. Two reviewers identified eligible records (kappa=0.83); quality was assessed using GRADE criteria. HIV-seroprevalence and mortality risks were summarized and pooled estimates were calculated using random-effects models with heterogeneity assessed. RESULTS: Of 472 retrieved records, sixteen met inclusion. All reports were of low or very low quality and derived from sub-Saharan Africa. HIV-serostatus was available for 3,994 patients. Individual report and pooled HIV-seroprevalence estimates were uniformly greater than temporally matched national statistics (range: 4.5-35.0%). Pooled reports from South Africa were three-fold greater than matched national prevalence (32.0%, 95% CI, 28.0-37.0%). Mortality data were available for 1,398 patients. Heterogeneity precluded pooled mortality analysis. Among individual reports, 66.7% demonstrated significantly increased relative risks (RR) of death; none found reduced risk of death among HIV-seropositive patients. Increased mortality risk among HIV-seropositive patients ranged from 1.86 (95% CI, 1.11-3.09) in Malawi to 10.7 (95% CI, 1.32-86.1) in South Africa. CONCLUSION: The available data indicate that HIV-seropositivity among the injured is high relative to national rates and may increase mortality, suggesting that integrated HIV-injury programming could be beneficial. Given the data limitations, further study of the HIV-injury intersection is crucially needed.

3 Review Guidelines for risk reduction when handling gametes from infectious patients seeking assisted reproductive technologies. 2016

Jindal, Sangita K / Rawlins, Richard G / Muller, Charles H / Drobnis, Erma Z. ·Department Obstetrics, Gynecology and Women's Health, Albert Einstein College of Medicine, Montefiore's Institute for Reproductive Medicine and Health, 1300 Morris Park Avenue, Bronx, NY 10461, USA. Electronic address: sangita.k.jindal@gmail.com. · Department Obstetrics and Gynecology, Rush University Medical Center, 1653 West Congress Parkway, Chicago, IL 60612. · Male Fertility Lab, Department Urology, University of Washington, 4245 Roosevelt Way NE, Seattle, WA 98105. · Reproductive Medicine and Fertility, Department Obstetrics, Gynecology and Women's Health, University of Missouri, 500 N. Keene St, Suite 203, Columbia, MO 65201. ·Reprod Biomed Online · Pubmed #27235103.

ABSTRACT: According to the Americans with Disabilities Act (1990), couples with blood-borne viruses that lead to infectious disease cannot be denied fertility treatment as long as the direct threat to the health and safety of others can be reduced or eliminated by a modification of policies or procedures. Three types of infectious patients are commonly discussed in the context of fertility treatment: those with human immunodeficiency virus (HIV), hepatitis C or hepatitis B. Seventy-five per cent of hepatitis C or HIV positive men and women are in their reproductive years, and these couples look to assisted reproductive techniques for risk reduction in conceiving a pregnancy. In many cases, only one partner is infected. Legal and ethical questions about treatment of infectious patients aside, the question most asked by clinical embryologists and andrologists is: "What are the laboratory protocols for working with gametes and embryos from patients with infectious disease?" The serostatus of each patient is the key that informs appropriate treatments. This guidance document describes protocols for handling gametes from seroconcordant and serodiscordant couples with infectious disease. With minor modifications, infectious patients with stable disease status and undetectable or low viral load can be accommodated in the IVF laboratory.

4 Review Vertical transmission of hepatitis C virus: systematic review and meta-analysis. 2014

Benova, Lenka / Mohamoud, Yousra A / Calvert, Clara / Abu-Raddad, Laith J. ·Infectious Disease Epidemiology Group, Weill Cornell Medical College-Qatar, Cornell University, Qatar Foundation-Education City, Doha, Qatar Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, United Kingdom. · Infectious Disease Epidemiology Group, Weill Cornell Medical College-Qatar, Cornell University, Qatar Foundation-Education City, Doha, Qatar. · Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, United Kingdom. · Infectious Disease Epidemiology Group, Weill Cornell Medical College-Qatar, Cornell University, Qatar Foundation-Education City, Doha, Qatar Department of Healthcare Policy and Research, Weill Cornell Medical College, Cornell University, New York, New York Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. ·Clin Infect Dis · Pubmed #24928290.

ABSTRACT: BACKGROUND: We conducted a systematic review of estimates of hepatitis C virus (HCV) vertical transmission risk to update current estimates published more than a decade ago. METHODS: PubMed and Embase were searched and 109 articles were included. Pooled estimates of risk were generated for children born to HCV antibody-positive and viremic women, aged ≥18 months, separately by maternal human immunodeficiency virus (HIV) coinfection. RESULTS: Meta-analysis of the risk of vertical HCV infection to children of HCV antibody-positive and RNA-positive women was 5.8% (95% confidence interval [CI], 4.2%-7.8%) for children of HIV-negative women and 10.8% (95% CI, 7.6%-15.2%) for children of HIV-positive women. The adjusted meta-regression model explained 51% of the between-study variation in the 25 included risk estimates. Maternal HIV coinfection was the most important determinant of vertical transmission risk (adjusted odds ratio, 2.56 [95% CI, 1.50-4.43]). Additional methodological (follow-up rate and definition of infection in children) and risk factors independently predicted HCV infection and need to be captured and reported by future studies of vertical transmission. Studies assessing the contribution of nonvertical exposures in early childhood to HCV prevalence among children at risk of vertical transmission are needed. CONCLUSIONS: More than 1 in every 20 children delivered by HCV chronically infected women are infected, highlighting that vertical transmission likely constitutes the primary transmission route among children. These updated estimates are a basis for decision making in prioritization of research into risk-reducing measures, and inform case management in clinical settings, especially for HIV-positive women in reproductive age.

5 Review Recommendations for the follow-up of study participants with breakthrough HIV infections during HIV/AIDS biomedical prevention studies. 2013

Etter, Paige / Landovitz, Raphael / Sibeko, Sengeziwe / Sobieszczyk, Magdalena E / Riddler, Sharon A / Karg, Carissa / Tsibris, Athe / Schouten, Jeffrey. ·Office of HIV/AIDS Network Coordination, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. ·AIDS · Pubmed #23262497.

ABSTRACT: OBJECTIVE: To facilitate collection of cumulative data on longitudinal HIV disease outcomes during HIV prevention studies by developing recommendations for follow-up of the relatively few study participants with breakthrough infections. DESIGN: We formed a working group to compare and contrast the various approaches taken in recent HIV prevention trials, to summarize the advantages and disadvantages associated with each, and to explore the feasibility of developing protocols for the long-term follow-up of seroconverters. METHODS: We reviewed study designs, objectives, and assessments in 15 interventional studies that followed HIV seroconverters. Protocol team members joined discussions of the various approaches and developed recommendations. RESULTS: Most HIV prevention clinical trials share a core set of objectives, including the description/comparison of virological, immunological, and clinical course of HIV, and sometimes a comparison of preseroconversion and postseroconversion behavior. Long-term follow-up of seroconverters can be conducted in separate studies if the transition from parent protocol is effectively managed. CONCLUSION: We recommend the development of harmonized seroconverter protocols. Although specific research questions in the postseroconversion period may differ depending on prevention modality, harmonizing key evaluations would create an opportunity to ask overarching questions that inform the prevention field with respect to design and implementation of future combination prevention studies. Follow-up immediately postseroconversion should be conducted in the parent protocol before roll over into a follow-up protocol. Development of specimen repositories with ample volumes for future assays, standardized definitions of infection, diagnosis and seroconversion dates, and harmonization of study objectives and sample collections at key time points are important.

6 Review Systemic and topical drugs for the prevention of HIV infection: antiretroviral pre-exposure prophylaxis. 2013

Baeten, Jared / Celum, Connie. ·Department of Global Health, University of Washington, USA. jbaeten@uw.edu ·Annu Rev Med · Pubmed #23020883.

ABSTRACT: Pre-exposure prophylaxis (PrEP), in which HIV-uninfected persons use oral or topical antiretroviral medications to protect against HIV acquisition, is a promising new HIV prevention strategy. The biologic rationale for evaluation of PrEP for sexual HIV prevention included nonhuman primate models and the efficacy of antiretroviral prophylaxis for HIV-exposed infants. Proof-of-concept that PrEP protects against sexual HIV acquisition has been demonstrated in four clinical trials, which used the antiretroviral medication tenofovir, either as a vaginal gel or as daily oral tenofovir disoproxil fumarate, alone or coformulated with emtricitabine. Importantly, however, two trials failed to demonstrate HIV protection with PrEP; low adherence to daily use of PrEP is the leading hypothesis to account for the lack of efficacy. Next steps in the field include rigorous evaluation of uptake and adherence to PrEP in implementation settings and research into next-generation PrEP agents with longer half-life and less user dependence.

7 Review HIV-1 prevention for HIV-1 serodiscordant couples. 2012

Curran, Kathryn / Baeten, Jared M / Coates, Thomas J / Kurth, Ann / Mugo, Nelly R / Celum, Connie. ·International Clinical Research Center, Department of Global Health, University of Washington, Seattle, WA 98104, USA. kgcurran@uw.edu ·Curr HIV/AIDS Rep · Pubmed #22415473.

ABSTRACT: A substantial proportion of HIV-1 infected individuals in sub-Saharan Africa are in stable relationships with HIV-1 uninfected partners, and HIV-1 serodiscordant couples thus represent an important target population for HIV-1 prevention. Couple-based HIV-1 testing and counseling facilitates identification of HIV-1 serodiscordant couples, counseling about risk reduction, and referrals to HIV-1 treatment, reproductive health services, and support services. Maximizing HIV-1 prevention for HIV-1 serodiscordant couples requires a combination of strategies, including counseling about condoms, sexual risk, fertility, contraception, and the clinical and prevention benefits of antiretroviral therapy (ART) for the HIV-1-infected partner; provision of clinical care and ART for the HIV-1-infected partner; antenatal care and services to prevent mother-to-child transmission for HIV-1-infected pregnant women; male circumcision for HIV-1-uninfected men; and, pending guidelines and demonstration projects, oral pre-exposure prophylaxis (PrEP) for HIV-1-uninfected partners.

8 Review Use of the designation "shedder" in mucosal detection of herpes simplex virus DNA involving repeated sampling. 2009

Magaret, A S / Johnston, C / Wald, A. ·Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195, USA. amag@u.washington.edu ·Sex Transm Infect · Pubmed #19211593.

ABSTRACT: OBJECTIVES: We evaluated two methods to describe detection of herpes simplex virus (HSV) from the genital mucosa. METHODS: We assessed genital swabs from HSV-2 seropositive people participating in longitudinal studies of HSV DNA detection at the University of Washington Virology Research Clinic. We determined the length of observation period necessary to ensure some HSV detection for most individuals. We compared two measures to assess differences in shedding according to HIV status, the shedding rate ratio, defined as the proportion of total samples with detectable HSV in HIV-1 seropositive versus HIV-1 seronegative participant, and the ratio of "shedders", defined as the proportion of people with any shedding over the interval in HIV-1 seropositive versus HIV-1 seronegative people. RESULTS: While only 17% (51/308) of HSV-2 seropositive people shed on their first day on study, 77% (238/308) had some genital shedding over 30 days (any HSV DNA detected on genital swabs). Shedding rate ratios (SRR) for HIV-seropositive versus HIV-seronegative people varied from SRR = 1.42 using 10 samples to SRR = 1.35 using 50 samples. The ratio of "shedders" (RS) approached 1 as the observation period increased (RS = 1.13 using 10 samples to RS = 1.01 using 50 samples). In a hypothetical case, the ratio of "shedders" was shown to exceed 1 when shedding rates were equal. CONCLUSIONS: Most HSV-2 seropositive people shed HSV from the genital mucosa. Dichotomisation of people into "shedders" and "non-shedders" or "high" and "low" shedders yields inferences that depend upon sampling interval length. Overall shedding rates provide consistent measures regardless of the number of swabs collected.

9 Review The epidemiology of Molluscum contagiosum in HIV-seropositive patients: a unique entity or insignificant finding? 2008

Gur, I. ·Department of Family Medicine, University of Washington, Seattle, WA 98195-6390, USA. gur08@u.washington.edu ·Int J STD AIDS · Pubmed #18663032.

ABSTRACT: Molluscum contagiosum (MC) is common in human immunodeficiency virus (HIV) seropositive and immunocompromised patients. This study evaluates the current literature concerning the clinical features of MC in this population, the utility of MC as a predictor of immunocompromised state and the natural history of MC and HIV in patients with these co-morbidities. PubMed database search for English-written original studies found 10 of them, all enrolled for HIV patients. There was no unique feature of MC in adult HIV patients; nevertheless, the appearance of MC lesions in adult men should require evaluation for immunocompromised state. In HIV-positive patients, MC tends to occur during the advanced phase of the disease. MC in children is rarely associated with immunodeficiency and usually no further evaluation is needed. In patients with known HIV infection, the presence of MC may signify advancing immunosuppression.

10 Clinical Trial Efficacy of oral pre-exposure prophylaxis (PrEP) for HIV among women with abnormal vaginal microbiota: a post-hoc analysis of the randomised, placebo-controlled Partners PrEP Study. 2017

Heffron, Renee / McClelland, R Scott / Balkus, Jennifer E / Celum, Connie / Cohen, Craig R / Mugo, Nelly / Bukusi, Elizabeth / Donnell, Deborah / Lingappa, Jairam / Kiarie, James / Fiedler, Tina / Munch, Matthew / Fredricks, David N / Baeten, Jared M / Anonymous5530913. ·Department of Global Health, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA. Electronic address: rheffron@uw.edu. · Department of Global Health, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA. · Department of Epidemiology, University of Washington, Seattle, WA, USA; Vaccine and Infectious Disease Division, Fred Hutch, Seattle, WA, USA. · Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA. · Department of Global Health, University of Washington, Seattle, WA, USA; Centre for Clinical Research, Nairobi, Kenya; Kenya Medical Research Institute, Nairobi, Kenya. · Department of Global Health, University of Washington, Seattle, WA, USA; Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA; Centre for Microbiology Research, Nairobi, Kenya. · Department of Global Health, University of Washington, Seattle, WA, USA; Vaccine and Infectious Disease Division, Fred Hutch, Seattle, WA, USA. · Department of Global Health, University of Washington, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA. · Human Reproduction Programme, WHO, Geneva, Switzerland. · Vaccine and Infectious Disease Division, Fred Hutch, Seattle, WA, USA. ·Lancet HIV · Pubmed #28732773.

ABSTRACT: BACKGROUND: Daily oral tenofovir-based pre-exposure prophylaxis (PrEP) is high efficacious for HIV prevention among women with high adherence. However, the effect of abnormal vaginal microbiota on PrEP efficacy is of concern. We investigated whether bacterial vaginosis modified the efficacy of oral PrEP. METHODS: We used prospectively collected data from women in the Partners PrEP Study, a placebo-controlled trial of daily oral PrEP (either tenofovir monotherapy or a combination of tenofovir and emtricitabine) in HIV serodiscordant couples aged 18 years or older in Kenya and Uganda that showed high efficacy in women. We used Cox proportional hazards regression to assess PrEP efficacy among subgroups of women defined by bacterial vaginosis status based on yearly microscopy and Nugent scoring (0-3 indicated healthy microbiota, 4-6 intermediate, and 7-10 bacterial vaginosis). In separate efficacy analyses, we also investigated individual components of the score (ie, detection of Gardnerella vaginalis or Bacteroides spp and non-detection of Lactobacillus spp) as markers of abnormal microbiota. FINDINGS: Of 1470 women (median age 33 years), 357 (24%) had bacterial vaginosis at enrolment. 45 women seroconverted to HIV. The HIV prevention efficacy of PrEP did not differ significantly among women with healthy microbiota (incidence 0·6 per 100 person years in PrEP group and 2·5 per 100 person-years in the placebo group; efficacy 76·55% [95% CI 43·09 to 90·37]), intermediate microbiota (HIV incidence 1·8 per 100 person-years in the PrEP group and 3·5 per 100 person-years in the placebo group; efficacy 62·72% [95% CI -66·59 to 91·66]), or bacterial vaginosis (HIV incidence 0·9 per 100 person-years in the PrEP group and 3·5 per 100 person-years in the placebo group; efficacy 72·50% [95% CI 5·98 to 91·95]; p INTERPRETATION: Among African women with a high prevalence of bacterial vaginosis and high adherence to PrEP, the efficacy of daily oral PrEP for HIV prevention did not differ significantly among women with abnormal versus healthy vaginal microbiota as defined by Nugent score. These data are reassuring that oral PrEP delivery to women can continue without the need for concurrent testing for bacterial vaginosis or vaginal dysbiosis. FUNDING: Bill & Melinda Gates Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Institute of Allergy and Infectious Diseases.

11 Clinical Trial Brief Report: Impact of Early Antiretroviral Therapy on the Performance of HIV Rapid Tests and HIV Incidence Assays. 2017

Fogel, Jessica M / Piwowar-Manning, Estelle / Debevec, Barbara / Walsky, Tamara / Schlusser, Katherine / Laeyendecker, Oliver / Wilson, Ethan A / McCauley, Marybeth / Gamble, Theresa / Tegha, Gerald / Soko, Dean / Kumwenda, Johnstone / Hosseinipour, Mina C / Chen, Ying Q / Cohen, Myron S / Eshleman, Susan H. ·Departments of *Pathology; and †Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD; ‡Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Baltimore, MD; §Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; ‖Science Facilitation Department, FHI 360, Washington, DC; ¶Science Facilitation Department, FHI 360, Durham, NC; #UNC Project Laboratory, Tidziwe Centre, Kamuzu Central Hospital, Lilongwe, Malawi; **College of Medicine-Johns Hopkins Project, Blantyre, Malawi; ††Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC; ‡‡UNC Project-Malawi, Institute for Global Health and Infectious Diseases, Lilongwe, Malawi; §§Vaccine and Infectious Disease Division and Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and ‖‖Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC. ·J Acquir Immune Defic Syndr · Pubmed #28471839.

ABSTRACT: BACKGROUND: Antiretroviral therapy (ART) can downregulate antibody responses to HIV infection. We evaluated the impact of early vs. delayed ART on the performance of HIV diagnostic and incidence assays. METHODS: Samples were obtained from 207 participants in the HPTN 052 trial, who were stably suppressed on ART for ≥4 years [Malawi sites; pre-ART CD4 cell count 350-550 cells/mm (early ART arm, N = 180) or <250 cells/mm or an AIDS-defining illness (delayed ART arm, N = 27)]. Samples were tested with 2 HIV rapid tests and 2 HIV incidence assays; selected samples were also tested with two fourth-generation immunoassays and a Western blot (WB) assay. A pre-ART sample was analyzed if the follow-up sample had a false-negative or weakly-reactive rapid test result, or had an incidence assay result indicative of recent infection (false-recent result). RESULTS: Ten (4.8%) samples had a nonreactive or weakly-reactive rapid test result (7/180 early ART arm, 3/27 delayed ART arm, P = 0.13); one sample had nonreactive fourth-generation assay results and 3 had indeterminate WBs. Forty (18.9%) samples had a false-recent incidence assay result; 16 (7.8%) had false-recent results with both incidence assays. Baseline samples had stronger rapid test and WB bands, higher fourth-generation assay signal-to-cutoff values, and fewer HIV incidence assay results indicative of recent infection. CONCLUSIONS: False-negative/weakly-reactive HIV rapid tests and false-recent HIV incidence assay results were observed in virally-suppressed individuals, regardless of pre-ART CD4 cell count. Downregulation of the antibody response to HIV infection in the setting of ART may impact population-level surveys of HIV prevalence and incidence.

12 Clinical Trial Brief Report: Medication Sharing Is Rare Among African HIV-1 Serodiscordant Couples Enrolled in an Efficacy Trial of Oral Pre-exposure Prophylaxis (PrEP) for HIV-1 Prevention. 2017

Thomson, Kerry A / Haberer, Jessica E / Marzinke, Mark A / Mujugira, Andrew / Hendrix, Craig W / Celum, Connie / Ndase, Patrick / Ronald, Allan / Bangsberg, David R / Baeten, Jared M / Anonymous4680899. ·*Department of Epidemiology, University of Washington, Seattle, WA; †Center for Global Health and Department of Medicine, Massachusetts General Hospital, Boston, MA; ‡Departments of Pathology and Medicine, Johns Hopkins University, Baltimore, MD; §Department of Epidemiology and Biostatistics, Makerere University, Kampala, Uganda; ‖Division of Clinical Pharmacology and Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; ¶Departments of Global Health, Medicine, and Epidemiology, University of Washington, Seattle, WA; #Department of Global Health, University of Washington, Seattle, WA; **Department of Medicine, University of Manitoba, Winnipeg, Canada; ††Oregon Health and Sciences University and Portland State University School of Public Health, Portland, OR; and ‡‡Departments of Global Health, Medicine, and Epidemiology, University of Washington, Seattle, WA. ·J Acquir Immune Defic Syndr · Pubmed #28291050.

ABSTRACT: Sharing of pre-exposure prophylaxis (PrEP) medications is a concern for PrEP implementation. For HIV-1 serodiscordant couples, sharing may undermine the HIV-1 prevention benefit and also cause antiretroviral resistance if taken by HIV-1 infected partners. Within a PrEP efficacy trial among HIV-1 serodiscordant couples, we assessed the occurrence of PrEP sharing by self-report and plasma tenofovir concentrations in HIV-1 infected partners. PrEP sharing was self-reported at <0.01% of visits, and 0%-1.6% of randomly selected and 0% of purposively selected specimens from HIV-1 infected participants had detectable tenofovir concentrations (median: 66.5 ng/mL, range: 1.3-292 ng/mL). PrEP sharing within HIV-1 serodiscordant couples was extremely rare.

13 Clinical Trial Feasibility of interim positron emission tomography (PET)-adapted therapy in HIV-positive patients with advanced Hodgkin lymphoma (HL): a sub-analysis of SWOG S0816 Phase 2 trial. 2017

Danilov, Alexey V / Li, Hongli / Press, Oliver W / Shapira, Ilan / Swinnen, Lode J / Noy, Ariela / Reid, Erin / Smith, Sonali M / Friedberg, Jonathan W. ·a Oregon Health & Science University , Portland , OR , USA. · b SWOG Statistical Center , Seattle , WA , USA. · c Fred Hutchinson Cancer Research Center , Seattle , WA , USA. · d Mount Sinai Beth Israel Medical Center , New York , NY , USA. · e Johns Hopkins Cancer Center , Baltimore , MD , USA. · f Memorial Sloan Kettering Cancer Center and Weill-Cornell Medical College , New York , NY , USA. · g University of California at San Diego Moores Cancer Center , La Jolla , CA , USA. · h University of Chicago , Chicago , IL , USA. · i University of Rochester , Rochester , NY , USA. ·Leuk Lymphoma · Pubmed #27386786.

ABSTRACT: -- No abstract --

14 Clinical Trial Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants. 2016

Churchyard, Gavin / Mlisana, Koleka / Karuna, Shelly / Williamson, Anna-Lise / Williamson, Carolyn / Morris, Lynn / Tomaras, Georgia D / De Rosa, Stephen C / Gilbert, Peter B / Gu, Niya / Yu, Chenchen / Mkhize, Nonhlanhla N / Hermanus, Tandile / Allen, Mary / Pensiero, Michael / Barnett, Susan W / Gray, Glenda / Bekker, Linda-Gail / Montefiori, David C / Kublin, James / Corey, Lawrence. ·Aurum Institute for Health Research, Klerksdorp, South Africa. · School of Public Health, University of Witwatersrand, Johannesburg, South Africa. · Advancing Care and Treatment for TB and HIV, Medical Research Council Collaborating Centre, Klerksdorp, South Africa. · University of Kwa-Zulu Natal, Durban, South Africa. · Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America. · Institute of Infectious Disease and Molecular Medicine, Division of Medical Virology, University of Cape Town, Cape Town, South Africa; National Health Laboratory Services, Observatory, Cape Town, South Africa. · National Institute for Communicable Diseases, National Health Laboratory Services, Sandringham, Johannesburg, South Africa. · Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States of America. · Department of Laboratory Medicine, University of Washington, Seattle, WA, United States of America. · Vaccine Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America. · Novartis Vaccines and Diagnostics, Cambridge, MA, United States of America. · South African Medical Research Council, Cape Town, South Africa. · Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Braamfontein, Johannesburg, South Africa. · Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. · Laboratory for AIDS Vaccine Research and Development, Duke University Medical Center, Durham, NC, United States of America. ·PLoS One · Pubmed #27583368.

ABSTRACT: BACKGROUND: The safety and immunogenicity of SAAVI DNA-C2 (4 mg IM), SAAVI MVA-C (2.9 x 109 pfu IM) and Novartis V2-deleted subtype C gp140 (100 mcg) with MF59 adjuvant in various vaccination regimens was evaluated in HIV-uninfected adults in South Africa. METHODS: Participants at three South African sites were randomized (1:1:1:1) to one of four vaccine regimens: MVA prime, sequential gp140 protein boost (M/M/P/P); concurrent MVA/gp140 (MP/MP); DNA prime, sequential MVA boost (D/D/M/M); DNA prime, concurrent MVA/gp140 boost (D/D/MP/MP) or placebo. Peak HIV specific humoral and cellular responses were measured. RESULTS: 184 participants were enrolled: 52% were female, all were Black/African, median age was 23 years (range, 18-42 years) and 79% completed all vaccinations. 159 participants reported at least one adverse event, 92.5% were mild or moderate. Five, unrelated, serious adverse events were reported. The M/M/P/P and D/D/MP/MP regimens induced the strongest peak neutralizing and binding antibody responses and the greatest CD4+ T-cell responses to Env. All peak neutralizing and binding antibody responses decayed with time. The MVA, but not DNA, prime contributed to the humoral and cellular immune responses. The D/D/M/M regimen was poorly immunogenic overall but did induce modest CD4+ T-cell responses to Gag and Pol. CD8+ T-cell responses to any antigen were low for all regimens. CONCLUSIONS: The SAAVI DNA-C2, SAAVI MVA-C and Novartis gp140 with MF59 adjuvant in various combinations were safe and induced neutralizing and binding antibodies and cellular immune responses. Sequential immunization with gp140 boosted immune responses primed by MVA or DNA. The best overall immune responses were seen with the M/M/P/P regimen. TRIAL REGISTRATION: ClinicalTrials.gov NCT01418235.

15 Clinical Trial Intimate Partner Violence and Adherence to HIV Pre-exposure Prophylaxis (PrEP) in African Women in HIV Serodiscordant Relationships: A Prospective Cohort Study. 2016

Roberts, Sarah T / Haberer, Jessica / Celum, Connie / Mugo, Nelly / Ware, Norma C / Cohen, Craig R / Tappero, Jordan W / Kiarie, James / Ronald, Allan / Mujugira, Andrew / Tumwesigye, Elioda / Were, Edwin / Irungu, Elizabeth / Baeten, Jared M / Anonymous18030869. ·*Department of Epidemiology, University of Washington, Seattle, WA; †Department of Medicine and Center for Global Health, Massachusetts General Hospital, Boston, MA; ‡Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA; Departments of §Global Health; ‖Medicine, University of Washington, Seattle, WA; ¶Kenya Medical Research Institute, Nairobi, Kenya; #Division of Global Health Equity, Department of Medicine, Brigham and Women's Hospital, Boston, MA; **Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA; ††Centers for Disease Control and Prevention, Atlanta, GA; ‡‡Department of Obstetrics and Gynaecology, University of Nairobi, Nairobi, Kenya; §§Department of Medicine, University of Manitoba, Winnipeg, Canada; ‖‖Kabwohe Clinical Research Center, Kabwohe, Uganda; ¶¶Department of Reproductive Health, Moi University, Eldoret, Kenya; and ##Kenyatta National Hospital, Nairobi, Kenya. ·J Acquir Immune Defic Syndr · Pubmed #27243900.

ABSTRACT: BACKGROUND: Intimate partner violence (IPV) is associated with higher HIV incidence, reduced condom use, and poor adherence to antiretroviral therapy and other medications. IPV may also affect adherence to pre-exposure prophylaxis (PrEP). METHODS: We analyzed data from 1785 HIV-uninfected women enrolled in a clinical trial of PrEP among African HIV serodiscordant couples. Experience of verbal, physical, or economic IPV was assessed at monthly visits by face-to-face interviews. Low PrEP adherence was defined as clinic-based pill count coverage <80% or plasma tenofovir levels <40 ng/mL. The association between IPV and low adherence was analyzed using generalized estimating equations, adjusting for potential confounders. In-depth interview transcripts were examined to explain how IPV could impact adherence. RESULTS: Sixteen percent of women reported IPV during a median of 34.8 months of follow-up (interquartile range 27.0-35.0). Overall, 7% of visits had pill count coverage <80%, and 32% had plasma tenofovir <40 ng/mL. Women reporting IPV in the past 3 months had increased risk of low adherence by pill count (adjusted risk ratio 1.49, 95% confidence interval: 1.17 to 1.89) and by plasma tenofovir (adjusted risk ratio 1.51, 95% confidence interval: 1.06 to 2.15). Verbal, economic, and physical IPV were all associated with low adherence. However, the impact of IPV diminished and was not statistically significant 3 months after the reported exposure. In qualitative interviews, women identified several ways in which IPV affected adherence, including stress and forgetting, leaving home without pills, and partners throwing pills away. CONCLUSIONS: Women who reported recent IPV in the Partners PrEP Study were at increased risk of low PrEP adherence. Strategies to mitigate PrEP nonadherence in the context of IPV should be evaluated.

16 Clinical Trial Risk of drug resistance among persons acquiring HIV within a randomized clinical trial of single- or dual-agent preexposure prophylaxis. 2015

Lehman, Dara A / Baeten, Jared M / McCoy, Connor O / Weis, Julie F / Peterson, Dylan / Mbara, Gerald / Donnell, Deborah / Thomas, Katherine K / Hendrix, Craig W / Marzinke, Mark A / Frenkel, Lisa / Ndase, Patrick / Mugo, Nelly R / Celum, Connie / Overbaugh, Julie / Matsen, Frederick A / Anonymous5070817. ·Division of Human Biology Department of Global Health. · Department of Global Health Department of Medicine Department of Epidemiology, University of Washington. · Division of Public Health Sciences. · Division of Human Biology. · Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center Department of Global Health. · Department of Global Health. · Department of Medicine Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. · Seattle Children's Research Institute, Seattle, Washington. · Department of Global Health Kenyatta National Hospital, University of Nairobi, Kenya. · Division of Human Biology Division of Public Health Sciences. ·J Infect Dis · Pubmed #25587020.

ABSTRACT: BACKGROUND: Preexposure prophylaxis (PrEP) with emtricitabine plus tenofovir disoproxil fumarate (FTC/TDF) or TDF alone reduces the risk of human immunodeficiency virus (HIV) acquisition. Understanding the risk of antiretroviral resistance selected by PrEP during breakthrough infections is important because of the risk of treatment failure during subsequent antiretroviral use. METHODS: Within the largest randomized trial of FTC/TDF versus TDF as PrEP, plasma samples were tested for HIV with resistance mutations associated with FTC (K65R and M184IV) and TDF (K65R and K70E), using 454 sequencing. RESULTS: Of 121 HIV seroconverters, 25 received FTC/TDF, 38 received TDF, and 58 received placebo. Plasma drug levels in 26 individuals indicated PrEP use during or after HIV acquisition, of which 5 had virus with resistance mutations associated with their PrEP regimen. Among those with PrEP drug detected during infection, resistance was more frequent in the FTC/TDF arm (4 of 7 [57%]), compared with the TDF arm (1 of 19 [5.3%]; P = .01), owing to the FTC-associated mutation M184IV. Of these cases, 3 had unrecognized acute infection at PrEP randomization, and 2 were HIV negative at enrollment. CONCLUSIONS: These results suggest that resistance selected by PrEP is rare but can occur both with PrEP initiation during acute seronegative HIV infection and in PrEP breakthrough infections and that FTC is associated with a greater frequency of resistance mutations than TDF.

17 Clinical Trial HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention. 2014

Donnell, Deborah / Baeten, Jared M / Bumpus, Namandjé N / Brantley, Justin / Bangsberg, David R / Haberer, Jessica E / Mujugira, Andrew / Mugo, Nelly / Ndase, Patrick / Hendrix, Craig / Celum, Connie. ·*Department of Global Health University of Washington and Vaccine and Infectious Disease Institute Fred Hutchinson Cancer Research Center, Seattle, WA; Departments of †Global Health; ‡Medicine; §Epidemiology, University of Washington, Seattle, WA; Departments of ‖Pharmacology and Molecular Sciences; ¶Medicine, Johns Hopkins University, Baltimore, MD; #Center for Global Health, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA; **Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda; ††Department of Obstetrics and Gynecology, University of Nairobi and Kenyatta National Hospital, Nairobi; and ‡‡Department of Epidemiology, Johns Hopkins University, Baltimore, MD. ·J Acquir Immune Defic Syndr · Pubmed #24784763.

ABSTRACT: BACKGROUND: Antiretroviral pre-exposure prophylaxis (PrEP) is a novel HIV prevention strategy for which adherence is a known determinant of efficacy. Blood concentrations of PrEP medications are one objective marker of adherence. METHODS: In a placebo-controlled PrEP efficacy trial of tenofovir disoproxil fumarate (TDF) and TDF with emtricitabine (FTC/TDF) among 4747 African women and men with an HIV-infected partner, we measured plasma tenofovir concentrations from participants in the active PrEP arms: 29 HIV seroconverters (cases) and 196 randomly selected controls who remained uninfected. RESULTS: Among controls, 71% of visits had tenofovir concentrations >40 ng/mL, consistent with steady-state daily dosing, compared with 21% of cases at the visit HIV was first detected. Pill count data indicated that 96% of controls and 66% of cases had >80% adherence for these same visits. The estimated protective effect of PrEP against HIV, based on concentrations >40 ng/mL, was 88% (95% confidence interval: 60 to 96, P < 0.001) for individuals receiving TDF and 91% (95% confidence interval: 47 to 98, P = 0.008) for individuals receiving FTC/TDF. Controls had consistent patterns of PrEP concentrations during follow-up; among the 81% with concentrations >40 ng/mL at month 1, 75% maintained this concentration at month 12. Only 5 of 29 seroconverters seemed to be consistently adherent to PrEP. Tenofovir concentrations >40 ng/mL were associated with older age and shorter time on study; concentrations ≤40 ng/mL occurred more commonly when participants reported no sex with their HIV-infected partner. CONCLUSIONS: Plasma concentrations of tenofovir consistent with daily dosing were highly predictive of protection from HIV acquisition. Most of those who took PrEP seemed to have high and consistent adherence.

18 Clinical Trial Maternal valacyclovir and infant cytomegalovirus acquisition: a randomized controlled trial among HIV-infected women. 2014

Roxby, Alison C / Atkinson, Claire / Asbjörnsdóttir, Kristjana / Farquhar, Carey / Kiarie, James N / Drake, Alison L / Wald, Anna / Boeckh, Michael / Richardson, Barbra / Emery, Vincent / John-Stewart, Grace / Slyker, Jennifer A. ·Department of Medicine, University of Washington, Seattle, Washington, United States of America. · Centre for Virology, Department of Infection, School of Biomedical and Life Sciences, University College London, London, United Kingdom. · Department of Epidemiology, University of Washington, Seattle, Washington, United States of America. · Department of Medicine, University of Washington, Seattle, Washington, United States of America ; Department of Epidemiology, University of Washington, Seattle, Washington, United States of America ; Department of Global Health, University of Washington, Seattle, Washington, United States of America. · Department of Obstetrics and Gynaecology, University of Nairobi, Nairobi, Kenya. · Department of Global Health, University of Washington, Seattle, Washington, United States of America. · Department of Medicine, University of Washington, Seattle, Washington, United States of America ; Department of Epidemiology, University of Washington, Seattle, Washington, United States of America ; Department of Laboratory Medicine, University of Washington, Seattle, Washington, United States of America ; Division of Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America. · Department of Medicine, University of Washington, Seattle, Washington, United States of America ; Division of Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America ; Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America. · Department of Global Health, University of Washington, Seattle, Washington, United States of America ; Department of Biostatistics, University of Washington, Seattle, Washington, United States of America ; Division of Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America. · Department of Microbial and Cellular Science, University of Surrey, Guildford, United Kingdom. · Department of Medicine, University of Washington, Seattle, Washington, United States of America ; Department of Epidemiology, University of Washington, Seattle, Washington, United States of America ; Department of Global Health, University of Washington, Seattle, Washington, United States of America ; Department of Pediatrics, University of Washington, Seattle, Washington, United States of America. ·PLoS One · Pubmed #24504006.

ABSTRACT: BACKGROUND: Studies in HIV-1-infected infants and HIV-1-exposed, uninfected infants link early cytomegalovirus (CMV) acquisition with growth delay and cognitive impairment. We investigated maternal valacyclovir to delay infant acquisition of CMV. METHODS: Pregnant women with HIV-1, HSV-2 and CD4 count >250 cells/µl were randomized at 34 weeks gestation to 500 mg twice-daily valacyclovir or placebo for 12 months. Maternal CMV DNA was measured in plasma at 34 weeks gestation, in cervical secretions at 34 and 38 weeks gestation, and in breast milk at 7 postpartum timepoints; infant CMV DNA was measured in dried blood spots at 8 timepoints including birth. RESULTS: Among 148 women, 141 infants were compared in intent-to-treat analyses. Maternal and infant characteristics were similar between study arms. Infant CMV acquisition did not differ between study arms, with 46/70 infants (66%) in placebo arm and 47/71 infants (66%) in the valacyclovir arm acquiring CMV; median time to CMV detection did not differ. CMV DNA was detected in 92% of 542 breast milk specimens with no difference in CMV level between study arms. Change in cervical shedding of CMV DNA between baseline and 38 weeks was 0.40-log greater in the placebo arm than the valacyclovir arm (p = 0.05). CONCLUSIONS: In this cohort of HIV-1-seropositive mothers, two-thirds of infants acquired CMV by one year. Maternal valacyclovir had no effect on timing of infant CMV acquisition or breast milk CMV viral loads, although it modestly reduced cervical CMV shedding. Maternal prophylaxis to reduce infant CMV acquisition warrants further evaluation in trials with antiviral agents. TRIALS REGISTRATION: ClinicalTrials.gov NCT00530777.

19 Clinical Trial Use of principal components analysis and protein microarray to explore the association of HIV-1-specific IgG responses with disease progression. 2014

Gerns Storey, Helen L / Richardson, Barbra A / Singa, Benson / Naulikha, Jackie / Prindle, Vivian C / Diaz-Ochoa, Vladimir E / Felgner, Phil L / Camerini, David / Horton, Helen / John-Stewart, Grace / Walson, Judd L. ·1 University of Washington , Seattle, Washington. ·AIDS Res Hum Retroviruses · Pubmed #24134221.

ABSTRACT: The role of HIV-1-specific antibody responses in HIV disease progression is complex and would benefit from analysis techniques that examine clusterings of responses. Protein microarray platforms facilitate the simultaneous evaluation of numerous protein-specific antibody responses, though excessive data are cumbersome in analyses. Principal components analysis (PCA) reduces data dimensionality by generating fewer composite variables that maximally account for variance in a dataset. To identify clusters of antibody responses involved in disease control, we investigated the association of HIV-1-specific antibody responses by protein microarray, and assessed their association with disease progression using PCA in a nested cohort design. Associations observed among collections of antibody responses paralleled protein-specific responses. At baseline, greater antibody responses to the transmembrane glycoprotein (TM) and reverse transcriptase (RT) were associated with higher viral loads, while responses to the surface glycoprotein (SU), capsid (CA), matrix (MA), and integrase (IN) proteins were associated with lower viral loads. Over 12 months greater antibody responses were associated with smaller decreases in CD4 count (CA, MA, IN), and reduced likelihood of disease progression (CA, IN). PCA and protein microarray analyses highlighted a collection of HIV-specific antibody responses that together were associated with reduced disease progression, and may not have been identified by examining individual antibody responses. This technique may be useful to explore multifaceted host-disease interactions, such as HIV coinfections.

20 Clinical Trial Statistical considerations for the HPTN 052 Study to evaluate the effectiveness of early versus delayed antiretroviral strategies to prevent the sexual transmission of HIV-1 in serodiscordant couples. 2012

Chen, Ying Qing / Masse, Benoit / Wang, Lei / Ou, San-San / Li, Xin / Donnell, Deborah / McCauley, Marybeth / Gamble, Theresa / Ribauldo, Heather J / Cohen, Myron S / Fleming, Thomas R. ·Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. yqchen@fhcrc.org ·Contemp Clin Trials · Pubmed #22813645.

ABSTRACT: The HIV Prevention Trial Network (HPTN) 052 Study is a Phase III, two-arm, controlled, open-labeled, randomized clinical trial designed to determine whether early antiretroviral therapy (ART) can prevent the sexual transmission of human immunodeficiency virus type 1 (HIV-1). A total of 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative were enrolled in four continents, nine countries and thirteen study sites. The HIV-1-positive partner was randomly assigned to either of the two arms: "immediate" (early) therapy with ART initiated upon enrollment plus HIV primary care, or "delayed" therapy with HIV primary care but ART initiated when the index case would have two consecutive measurements of a CD4+ cell count within or below the range of 200-250 cells/mm(3), or develop an AIDS-defining illness. In this paper, we describe several key statistical considerations for the design of this landmark study. Despite that the observed event rates were lower than expected, which might have compromised the study power, an early release of the trial results in May 2011 showed an overwhelming 96% risk reduction for the immediate therapy in the prevention of genetically linked HIV-1 incident transmissions. Nevertheless, the durability of its long-term effectiveness is yet to be assessed. The HPTN 052 Study is still ongoing and will not complete till 2015.

21 Clinical Trial Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. 2012

Baeten, Jared M / Donnell, Deborah / Ndase, Patrick / Mugo, Nelly R / Campbell, James D / Wangisi, Jonathan / Tappero, Jordan W / Bukusi, Elizabeth A / Cohen, Craig R / Katabira, Elly / Ronald, Allan / Tumwesigye, Elioda / Were, Edwin / Fife, Kenneth H / Kiarie, James / Farquhar, Carey / John-Stewart, Grace / Kakia, Aloysious / Odoyo, Josephine / Mucunguzi, Akasiima / Nakku-Joloba, Edith / Twesigye, Rogers / Ngure, Kenneth / Apaka, Cosmas / Tamooh, Harrison / Gabona, Fridah / Mujugira, Andrew / Panteleeff, Dana / Thomas, Katherine K / Kidoguchi, Lara / Krows, Meighan / Revall, Jennifer / Morrison, Susan / Haugen, Harald / Emmanuel-Ogier, Mira / Ondrejcek, Lisa / Coombs, Robert W / Frenkel, Lisa / Hendrix, Craig / Bumpus, Namandjé N / Bangsberg, David / Haberer, Jessica E / Stevens, Wendy S / Lingappa, Jairam R / Celum, Connie / Anonymous2030731. ·Department of Global Health, University of Washington, Seattle, WA 98104, USA. jbaeten@uw.edu ·N Engl J Med · Pubmed #22784037.

ABSTRACT: BACKGROUND: Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations. METHODS: We conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1-serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1-seronegative partner in each couple was randomly assigned to one of three study regimens--once-daily tenofovir (TDF), combination tenofovir-emtricitabine (TDF-FTC), or matching placebo--and followed monthly for up to 36 months. At enrollment, the HIV-1-seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services. RESULTS: We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF-FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1-seronegative partner was male. Among HIV-1-seropositive participants, the median CD4 count was 495 cells per cubic millimeter (interquartile range, 375 to 662). A total of 82 HIV-1 infections occurred in seronegative participants during the study, 17 in the TDF group (incidence, 0.65 per 100 person-years), 13 in the TDF-FTC group (incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 per 100 person-years), indicating a relative reduction of 67% in the incidence of HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P<0.001) and of 75% with TDF-FTC (95% CI, 55 to 87; P<0.001). Protective effects of TDF-FTC and TDF alone against HIV-1 were not significantly different (P=0.23), and both study medications significantly reduced the HIV-1 incidence among both men and women. The rate of serious adverse events was similar across the study groups. Eight participants receiving active treatment were found to have been infected with HIV-1 at baseline, and among these eight, antiretroviral resistance developed in two during the study. CONCLUSIONS: Oral TDF and TDF-FTC both protect against HIV-1 infection in heterosexual men and women. (Funded by the Bill and Melinda Gates Foundation; Partners PrEP ClinicalTrials.gov number, NCT00557245.).

22 Clinical Trial Highly active antiretroviral therapy versus zidovudine/nevirapine effects on early breast milk HIV type-1 Rna: a phase II randomized clinical trial. 2008

Chung, Michael H / Kiarie, James N / Richardson, Barbra A / Lehman, Dara A / Overbaugh, Julie / Kinuthia, John / Njiri, Francis / John-Stewart, Grace C. ·Department of Medicine, University of Washington, Seattle, WA, USA. mhchung@u.washington.edu ·Antivir Ther · Pubmed #18839781.

ABSTRACT: BACKGROUND: Defining the effect of antiretroviral regimens on breast milk HIV type-1 (HIV-1) levels is useful to inform the rational design of strategies to decrease perinatal HIV-1 transmission. METHODS: Pregnant HIV-1 seropositive women (CD4+ T-cell count >250 and <500 cells/mm3) electing to breastfeed in Nairobi, Kenya were randomized to highly active antiretroviral therapy (HAART; zidovudine [ZDV], lamivudine and nevirapine [NVP]) during pregnancy and 6 months post-partum or to short-course ZDV plus single-dose NVP (ZDV/NVP). Breast milk samples were collected two to three times per week in the first month post-partum. RESULTS: Between November 2003 and April 2006, 444 breast milk samples were collected from 58 randomized women during the first month after delivery. Between 3 and 14 days post-partum, women in the HAART and ZDV/NVP arms had a similar prevalence of undetectable breast milk HIV-1 RNA. From 15 to 28 days post-partum, women in the HAART arm had significantly lower levels of breast milk HIV-1 RNA than women randomized to ZDV/NVP (1.7 log10 copies/ml [limit of detection] versus >2.10 log10 copies/ml, P<0.001). In contrast to breast milk HIV-1 RNA, suppression of plasma HIV-1 RNA during the neonatal period was consistently several log10 greater in the HAART arm compared with the ZDV/NVP arm. CONCLUSIONS: HAART resulted in lower breast milk HIV-1 RNA than ZDV/NVP; however, ZDV/NVP yielded comparable breast milk HIV-1 RNA levels in the first 2 weeks post-partum. Breast milk HIV-1 RNA remained suppressed in the ZDV/NVP arm despite increased plasma HIV-1 levels, which might reflect local drug effects or compartmentalization.

23 Article Changes in Sexual Behavior and STI Diagnoses Among MSM Initiating PrEP in a Clinic Setting. 2019

Montaño, Michalina A / Dombrowski, Julia C / Dasgupta, Sayan / Golden, Matthew R / Duerr, Ann / Manhart, Lisa E / Barbee, Lindley A / Khosropour, Christine M. ·Department of Epidemiology, University of Washington, 1959 NE Pacific Street, Box 357236, Seattle, WA, 98195, USA. micham@uw.edu. · Department of Medicine, University of Washington, Seattle, WA, USA. · Public Health - Seattle and King County HIV/STD Program, Seattle, WA, USA. · Fred Hutchinson Cancer Research Center, Seattle, WA, USA. · Department of Epidemiology, University of Washington, 1959 NE Pacific Street, Box 357236, Seattle, WA, 98195, USA. · Department of Global Health, University of Washington, Seattle, WA, USA. ·AIDS Behav · Pubmed #30117076.

ABSTRACT: We examined changes in sexual behavior and sexually transmitted infection (STI) prevalence among 183 men who have sex with men (MSM) initiating pre-exposure prophylaxis (PrEP) at an STD Clinic in Seattle, WA. We used generalized estimating equations to measure changes in sexual behavior during PrEP use, and linked PrEP patient data with STI surveillance data to compare the prevalence of chlamydia, gonorrhea, and early syphilis in the periods prior to and during PrEP use. Reporting never using condoms in the prior 30 days increased (adjusted relative risk = 1.46; 95% confidence interval 1.13, 1.88) at 12 months after PrEP initiation compared to the initial PrEP visit. Reporting unknown status partners in the prior 30 days decreased at 12 months compared to the initial PrEP visit, but there was no change in number of sexual partners or reporting HIV-positive or HIV-negative partners. The percentage of patients diagnosed with any STI while using PrEP (49.2%) was higher than the percentage diagnosed in the 12 months prior to PrEP use (35.0%), likely driven in part by increased STI screening during PrEP use. Among MSM on PrEP, we observed decreases in condom use, and a higher prevalence of STIs during PrEP use compared to prior to PrEP initiation.

24 Article Higher prevalence of viral control in HIV-1-infected women in serodiscordant relationships. 2018

Peebles, Kathryn / McClelland, R Scott / Overbaugh, Julie / Richardson, Barbra A / Bosire, Rose / Kiarie, James N / Farquhar, Carey / Guthrie, Brandon L. ·Department of Epidemiology, University of Washington, Seattle, Washington, United States of America. · Department of Medicine, University of Washington, Seattle, Washington, United States of America. · Department of Global Health, University of Washington, Seattle, Washington, United States of America. · Department of Microbiology, University of Washington, Seattle, Washington, United States of America. · Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America. · Department of Biostatistics, University of Washington, Seattle, Washington, United States of America. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. · Centre for Public Health Research, Kenya Medical Research Institute, Nairobi, Kenya. · Department of Obstetrics and Gynecology, University of Nairobi, Nairobi, Kenya. · Department of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, United States of America. ·PLoS One · Pubmed #30517204.

ABSTRACT: BACKGROUND: HIV-1-discordant couples that remain discordant despite repeated exposure may differ from the general population in their distribution of transmission risk factors, including low plasma viral load (PVL) in the infected partner even in the absence of antiretroviral therapy (ART). METHODS: We followed two cohorts of HIV-1-infected Kenyan women: females in discordant couples (FDC) and female sex workers (FSW). We compared the distribution of undetectable (<150 copies/mL) and low PVL (<1,000 copies/mL) between the cohorts using bootstrap methods and exact Poisson regression. RESULTS: We evaluated 296 FDC and 220 FSW. At baseline, FDC were more likely to have undetectable (RR = 6.94, bootstrap 95% CI: 3.47, 20.81) and low PVL (RR = 3.53, bootstrap 95% CI: 2.57, 5.65) than FSW. Similarly, both repeat undetectable PVL (RR = 9.36, bootstrap 95% CI: 6.04, 10.97) and repeat low (RR = 4.99, bootstrap 95% CI: 2.33, 14.04) PVL were more likely among FDC than FSW during follow-up. DISCUSSION: We observed higher prevalence of viral control in FDC compared to FSW in the absence of ART, suggesting potentially higher prevalence of biological HIV resistance factors among discordant couples.

25 Article HIV-1 envelope glycan modifications that permit neutralization by germline-reverted VRC01-class broadly neutralizing antibodies. 2018

LaBranche, Celia C / McGuire, Andrew T / Gray, Matthew D / Behrens, Shay / Kwong, Peter D / Chen, Xuejun / Zhou, Tongqing / Sattentau, Quentin J / Peacock, James / Eaton, Amanda / Greene, Kelli / Gao, Hongmei / Tang, Haili / Perez, Lautaro G / Chen, Xuejun / Saunders, Kevin O / Kwong, Peter D / Mascola, John R / Haynes, Barton F / Stamatatos, Leonidas / Montefiori, David C. ·Department of Surgery, Duke University Medical Center, Durham, NC, United States of America. · Fred Hutchinson Cancer Research Center, Department of Global Health, Seattle, WA, United States of America. · Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America. · The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, United Kingdom. · Duke University School of Medicine, Departments of Medicine and Immunology, Duke Human Vaccine Institute, Durham, NC, United States of America. · University of Washington, Department of Global Health, Seattle, Washington, United States of America. ·PLoS Pathog · Pubmed #30395637.

ABSTRACT: Broadly neutralizing antibody (bnAb) induction is a high priority for effective HIV-1 vaccination. VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models. Glycans bordering the CD4bs impede the binding of germline-reverted forms of VRC01-class bnAbs and therefore constitute a barrier to early events in initiating the correct antibody lineages. Deleting a subset of these glycans permits Env antigen binding but not virus neutralization, suggesting that additional barriers impede germline-reverted VRC01-class antibody binding to functional Env trimers. We investigated the requirements for functional Env trimer engagement of VRC01-class naïve B cell receptors by using virus neutralization and germline-reverted antibodies as surrogates for the interaction. Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs. Neither glycan modification alone rendered the virus susceptible to neutralization. The potency of neutralization in some cases rivaled the potency of mature VRC01 against wildtype viruses. Neutralization by the germline-reverted antibodies was abrogated by the known VRC01 resistance mutation, D279K. These findings improve our understanding of the restrictions imposed by glycans in eliciting VRC01-class bnAbs and enable a neutralization-based strategy to monitor vaccine-elicited early precursors of this class of bnAbs.

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