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Nicholas Musinguzi, Timothy Muwonge, Kenneth Ngure, Elly Katabira, Nelly Mugo, Bridget Frances O'Rourke Burns, Jared M Baeten, Renee Heffron, Jessica E Haberer
OBJECTIVE: SMS can collect adherence data on a frequent basis and is relatively anonymous, and therefore could potentially reduce recall and social desirability biases prevalent in other self-reported measures. METHODS: We compared SMS self-reported adherence to three self-reported adherence questions (rating of ability to adhere, frequency of doses taken, percentage of doses taken) and two objective adherence measures (electronic adherence monitoring [EAM] and plasma tenofovir levels) using data from HIV-uninfected members of serodiscordant couples enrolled in a pre-exposure prophylaxis demonstration project in Kenya and Uganda...
July 12, 2018: AIDS
Yuxin Liu, Morgan Blakely, Keith Sigel, Tin Htwe Thin, Pei Hui, Michael Donovan, Michael M Gaisa
OBJECTIVES: To determine whether biomarker P16 predicts progression risk for anal low-grade squamous intraepithelial lesions (LSIL). DESIGN: Retrospective study METHODS:: 109 HIV-infected and 18 HIV-uninfected patients with biopsy-proven anal LSIL at initial screening underwent surveillance high-resolution anoscopy and biopsy within two years of diagnosis. P16 immunohistochemistry (IHC) was performed on index lesions and evaluated using a semi-quantitative scoring system...
July 12, 2018: AIDS
Mads Harsløf, Andreas D Knudsen, Thomas Benfield, Børge G Nordestgaard, Ulla Feldt-Rasmussen, Susanne D Nielsen
OBJECTIVES: Possible effects of HIV on thyroid function in the modern combination antiretroviral therapy (cART) era are largely unknown. We aimed to investigate the prevalence and associated risk factors of thyroid dysfunction in well treated people living with HIV (PLWH) and matched uninfected controls and to examine whether HIV is independently associated with thyroid dysfunction. DESIGN AND METHODS: Thyroid stimulating hormone (TSH), free thyroxine, total thyroxine and free triiodothyronine were measured in 826 PLWH from the Copenhagen co-morbidity in HIV infection (COCOMO) Study and in 2,503 matched uninfected controls, and medical treatment for hypo- or hyperthyroidism was recorded...
July 12, 2018: AIDS
Paul R Gorry, Fahim Ahmad, Jon Mohl, Ghalib Alkhatib
OBJECTIVES: This study investigated whether Env-mediated fusion levels of R5X4 viruses are associated with long-term survival of an infected CCR5-/- patient. DESIGN: Four R5X4 Envs were cloned from each of two infected homosexual individuals (DR and C2) homozygous for the CCR5Δ32 allele. DR is a long-term survivor chronically infected with HIV-1 and his Envs were cloned 12 years after testing HIV+, while C2 Envs were isolated 1 year after primary infection. METHODS: The current study sequenced the gp41 subunits and created hybrid Envs that contained exchanged gp41 subunits or V3 loops...
July 12, 2018: AIDS
Helen Kelly, Admire Chikandiwa, Rhian Warman, Michel Segondy, Bernard Sawadogo, Natasa Vasiljevic, Marie-Noelle Didelot, Nicolas Meda, Helen A Weiss, Sinead Delany-Moretlwe, Philippe Mayaud, Attila Lorincz
OBJECTIVES: To evaluate associations of DNA methylation of the human tumour suppressor gene EPB41L3 with high-grade cervical intraepithelial neoplasia (CIN2+) and HIV-related factors among women living with HIV-1 (WLHIV) in Burkina Faso (BF) and South Africa (SA). DESIGN: Case-control study of WLHIV aged 25-50 with histology-determined CIN2+ (cases, N = 152) and ≤CIN1 (controls, N = 210). METHODS: EPB41L3 methylation was measured by pyrosequencing of bisulfite converted DNA from exfoliated cervical specimens at baseline and 16 months later...
July 12, 2018: AIDS
Horacio A Duarte, Ingrid A Beck, Molly Levine, Catherine Kiptinness, James M Kingoo, Bhavna Chohan, Samah R Sakr, Michael H Chung, Lisa M Frenkel
OBJECTIVES: An increasing prevalence of HIV pre-treatment drug resistance (PDR) has been observed in Sub-Saharan Africa, which could decrease the effectiveness of antiretroviral therapy (ART) programs. We describe our experiences, the costs and challenges of implementing an oligonucleotide ligation assay (OLA) for management of PDR in Nairobi, Kenya. DESIGN: An observational report of the implementation of OLA in a Kenyan laboratory for a randomized clinical trial evaluating whether onsite use of OLA in individuals initiating ART would decrease rates of virologic failure...
July 12, 2018: AIDS
Catherine A Koss, Albert Y Liu, Jose Castillo-Mancilla, Peter Bacchetti, Cricket Mchugh, Karen Kuncze, Mary Morrow, Alexander Louie, Sharon Seifert, Hideaki Okochi, Samantha Mawhinney, Monica Gandhi, Peter L Anderson
OBJECTIVES: Women likely require higher adherence than men to pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) for similar efficacy. Pharmacologic metrics of adherence predict efficacy better than self-report, but expected drug levels (adherence benchmarks) must be established using directly-observed therapy. We sought to evaluate whether tenofovir hair concentrations differ between women and men receiving directly-observed TDF/FTC. METHODS: We assessed tenofovir hair concentrations in HIV-uninfected volunteers randomized to receive 100%, 67%, or 33% of daily dosing of TDF/FTC for 12 weeks (DOT-DBS, NCT02022657)...
July 12, 2018: AIDS
Hana Lee, Xiaotian K Wu, Becky L Genberg, Michael J Mugavero, Stephen R Cole, Bryan Lau, Joseph W Hogan
OBJECTIVES: Studies examining engagement in HIV care often capture cross-sectional patient status to estimate retention and identify predictors of attrition, which ignore longitudinal patient care-seeking behaviors. We describe the cyclical nature of (dis)engagement and re-entry into HIV care using the state transition framework. DESIGN: We represent the dynamic patterns of patient care-retention using five states: Engaged in care, missed 1, 2, 3 or more expected visits, and deceased...
July 12, 2018: AIDS
Christina C Chang, Vivek Naranbhai, Jared Stern, Michael Roche, Ashanti Dantanarayana, Ruian Ke, Surekha Tennakoon, Ajantha Solomon, Rebecca Hoh, Wendy Hartogensis, Frederick M Hecht, Ken Sikaris, David J Price, Julian H Elliott, Steven G Deeks, Melissa Churchill, Paul U Cameron, Nicolas Hengartner, Alan S Perelson, Sharon R Lewin
OBJECTIVE(S): To determine whether variation in cell associated (CA) unspliced (US) HIV RNA in HIV-infected individuals on antiretroviral therapy (ART) has a circadian basis. METHODS: Prospective observational study of HIV-infected individuals on ART. Blood was collected on three occasions and CA-US HIV RNA and mRNA of the Circadian-locomotor-output-cycles-kaput (CLOCK)-associated genes quantified by real time PCR. CLOCK-associated proteins were over expressed in a cell line stably transfected with an HIV long terminal repeat (LTR) luciferase reporter...
July 12, 2018: AIDS
Paula Andrea Serna Ortega, Irma Saulle, Vincenzo Mercurio, Salomè Valentina Ibba, Elisa Maria Lori, Claudio Fenizia, Michela Masetti, Daria Trabattoni, Sergio Lo Caputo, Francesca Vichi, Francesco Mazzotta, Mario Clerici, Mara Biasin
BACKGROUND: Interleukin-21 (IL-21) modulates HIV-1 infection through the elicitation of different antiviral mechanisms, including Th17 lineage commitment and induction of microRNA (miR)-29, a miRNA endowed with anti-HIV activity. As miR-29 expression is significantly increased in HIV-1-exposed seronegative individuals (HESN), we investigated the role of miR-29/IL21 axis in the natural control of HIV-1 infection. METHODS: PBMCs isolated from 15 Italian sexually-exposed HESN and 15 HIV-unexposed healthy controls (HC) were in vitro infected with an R5-tropic HIV-1Ba-L strain...
July 12, 2018: AIDS
Marion Noret, Stéphanie Balavoine, Marion Noret, Claire Pintado, Martin Siguier, Alexandre Brun, Rebecca Bauer, Bénédicte Loze, Anne Leplatois, Alexandre Aslan, Khafil Moudachirou, Constance Delaugerre, Willy Rozenbaum, Jean-Michel Molina
BACKGROUND: On Demand oral TDF/FTC has been approved for pre-exposure prophylaxis (PrEP) in men who have sex with men (MSM) in France following the results of clinical studies but data are limited on real-world experience. DESIGN: A single center, open-label, prospective cohort study that recruited people at high risk of HIV infection in Paris. METHODS: Subjects were enrolled in a single hospital-based outpatient clinic and were proposed to start PrEP with daily or on demand TDF/FTC...
July 12, 2018: AIDS
William Worodria, Victor Ssempijja, Coleen Hanrahan, Richard Ssegonja, Abdallah Muhofwa, Doreen Mazapkwe, Harriet Mayanja-Kizza, Steven J Reynolds, Robert Colebunders, Yukari C Manabe
INTRODUCTION: HIV-tuberculosis (TB) co-infection remains an important cause of mortality in sub-Saharan Africa. Clinical trials have reported early (within 2 weeks of TB therapy) antiretroviral therapy (ART) reduces mortality among HIV-TB co-infected research participants with low CD4 counts, but this has not been consistently observed. We aimed to evaluate the current WHO recommendations for ART in HIV-TB co-infected patients on mortality in routine clinical settings. METHODS: We compared two cohorts before (2008-2010) and after (2012-2013) policy change on ART timing after TB and examined the effectiveness of early versus delayed ART on mortality in HIV-TB co-infected participants with CD4 100 cells/μl or less...
July 12, 2018: AIDS
Malango T Msukwa, Janne Estill, Andreas D Haas, Joep J van Oosterhout, Lyson Tenthani, Mary-Ann Davies, Kali Tal, Nozgechi Phiri, Adrian Spoerri, Bryan C Mthiko, Frank Chimbwandira, Olivia Keiser
OBJECTIVE: To compare birth weight and weight gain in HIV-exposed, uninfected infants up to 24 months old, who enrolled in the Malawian national HIV care clinic (HCC) programme either before or after Option B+ (OB+) was implemented. DESIGN, SETTING AND PARTICIPANTS: HIV-exposed infants enrol in the HCC programme as soon as possible after birth and are followed up to at least 24 months old. This analysis includes HIV-exposed, uninfected (HEU) infants with recorded birth weight, date of birth, gender and at least one follow-up weight measurement from 21 health facilities in central and southern Malawi (January 2010 - December 2014)...
July 12, 2018: AIDS
Madeleine D Hunter, Adele Shenoy, Andrew Dwork, Mitchell S V Elkind, Randolph Marshall, Jay P Mohr, Susan Morgello, Jose Gutierrez
OBJECTIVE: To test whether HIV is associated with brain large artery vulnerable intima. DESIGN: Cross-sectional study of autopsied HIV+ cases sex and age-matched to HIV- controls. METHODS: Brain large arteries from 302 autopsied cases (50% HIV+) were evaluated morphometrically for the presence of atherosclerosis, size of necrotic core, and fibrous cap thickness. Intima vulnerability was measured as intima elastolytic score [0-5, based on intimal metalloproteinases (MMP)-2, MMP-3, and MMP-9, and tissue inhibitor for MMP-1 and MMP-2 staining], intima inflammatory score (0-3, based on intimal presence of CD3 and CD68 cells and TNF-α staining), neoangiogenesis (factor VIII staining), and apoptosis (caspase 3 staining)...
July 12, 2018: AIDS
Cecile D Lahiri, Nakita L Brown, Kevin J Ryan, Edward P Acosta, Anandi N Sheth, Cyra C Mehta, Jessica Ingersoll, Ighovwerha Ofotokun
OBJECTIVES: Despite plasma virologic suppression with antiretroviral therapy (ART), HIV persists in gut tissue. The objectives of this study were to compare plasma and rectal tissue (RT) HIV RNA dynamics and to assess relationships with dolutegravir (DTG) plasma and tissue concentrations. DESIGN: A longitudinal cohort study of HIV-infected treatment-naïve individuals initiating DTG-based ART was conducted over 12 weeks with plasma and RT sampling (Clinicaltrials...
July 12, 2018: AIDS
Theresa E Matson, Kathleen A Mcginnis, Anna D Rubinsky, Madeline C Frost, Maggie Czarnogorski, Kendall J Bryant, E Jennifer Edelman, Derek D Satre, Sheryl L Catz, Kara M Bensley, David A Fiellin, Amy C Justice, Emily C Williams
OBJECTIVES: To investigate whether gender is associated with three recommended stages of the HIV care continuum and whether gender modifies known associations between level of alcohol use and HIV care among US veterans. DESIGN: Retrospective cohort. METHODS: Veterans Aging Cohort Study data were used to identify Veterans Health Administration (VA) patients with HIV and AUDIT-C alcohol screening 2/1/2008-9/30/2014. Modified Poisson regression models estimated the relative risk and predicted prevalences of engagement in HIV care (documented CD4 cells/μl or viral load copies/mL lab values), ART treatment (≥1 prescription), and viral suppression (HIV RNA <500 copies/mL) in the year following AUDIT-C (1) for women compared to men, and (2) for each level of alcohol use compared to nondrinking among women and among men...
July 12, 2018: AIDS
Gary M Clifford, Laurent Siproudhis, Lionel Piroth, Isabelle Poizot-Martin, Sylvie Radenne, Jacques Reynes, Anne Lesage, Isabelle Heard, Sebastien Henno, Jean-Francois Flejou, Lucie Marchand, Jean-Damien Combes, Isabelle Etienney
OBJECTIVE: To assess determinants for histologically proven high-grade anal intraepithelial lesions (hHSIL) in HIV-positive MSM, a population at high-risk of HPV-related anal cancer. DESIGN: APACHES is a prospective study of anal HPV and related-lesions in 513 HIV-positive MSM aged ≥35 in six centres across France. METHODS: At baseline, participants underwent high-resolution anoscopy (HRA) with biopsy of suspicious lesions, preceded by anal swabs for liquid-based cytology, p16/Ki67 immunostaining, and HPV DNA...
July 12, 2018: AIDS
Jonathan L Golob, Joshua Stern, Sarah Holte, Mari M Kitahata, Heidi M Crane, Robert W Coombs, Erin Goecker, Ann E Woolfrey, Robert D Harrington
We examined specimens from 111 HIV-infected participants virally suppressed on ART for a minimum of 5 years who had donated serial peripheral blood mononuclear cell (PBMC) specimens to the University of Washington / Fred Hutch Center for AIDS Research (CFAR) Specimen Repository. We determined the HIV proviral copy number per million PBMCs, corrected for CD4 count, in 477 specimens collected after a minimum of 5-years of follow up and up to 15.5 years of clinical viral suppression. Generalized estimating equation regression was used to examine the association between the reservoir size and time, age at study entry, antiretroviral (ARV) regimen, and risk factors for HIV acquisition...
July 12, 2018: AIDS
Gustaf Ulfhammer, Arvid Edén, Åsa Mellgren, Dietmar Fuchs, Henrik Zetterberg, Lars Hagberg, Staffan Nilsson, Aylin Yilmaz, Magnus Gisslén
OBJECTIVE: Low-grade immune activation is common in people living with HIV (PLHIV), despite long-term viral suppression by antiretroviral therapy (ART). The clinical significance of this activation remains unclear. The aim of this study was to examine residual intrathecal immune activation in relation to signs of neuronal injury and neurocognitive impairment in PLHIV who had been virally suppressed on ART > 10 years. DESIGN/METHODS: Twenty neuroasymptomatic PLHIV on suppressive ART for a median of 13...
July 12, 2018: AIDS
Alexei A Adzhubei, Anastasia A Anashkina, Yaroslav V Tkachev, Yury V Kravatsky, Tatiana Pushkarsky, Amol Kulkarni, Alexander A Makarov, Michael I Bukrinsky
BACKGROUND: HIV-associated atherosclerosis is a major co-morbidity due in part to systemic effects of the virus on cholesterol metabolism. HIV protein Nef plays important role in this pathology by impairing maturation of the main cellular cholesterol transporter, ABCA1. ABCA1 maturation critically depends on calnexin, an integral endoplasmic reticulum membrane chaperone, and Nef binds to the cytoplasmic domain of calnexin and impairs interaction of calnexin with ABCA1. Overarching goal of the present study was to model Nef-calnexin interaction interface, and identify small molecule compounds potentially inhibiting this interaction...
July 12, 2018: AIDS
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