Plasma Cotinine Cutoff for Distinguishing Smokers From Nonsmokers Among Persons Living With HIVRezahosseini, Omid;Knudsen, Andreas Dehlbæk;Gelpi, Marco;Ronit, Andreas;Ueland, Per Magne;Midttun, Øivind;Kirkegaard-Klitbo, Ditte Marie;Ullum, Henrik;Nielsen, Susanne Dam
doi: 10.1097/QAI.0000000000002189pmid: 31714432
aViro-immunology Research Unit, Department of Infectious Diseases 8632, Rigshospitalet, University of Copenhagen, Copenhagen bBevital AS, Bergen, Norway cDepartment of Infectious Diseases, Amager-Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark dDepartment of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark Research Foundation of Rigshospitalet, Danish Heart Foundation, Novo Nordisk Foundation, Lundbeck Foundation, Augustinus Foundation. O.R. received a grant from the Research Foundation of Rigshospitalet; A.D.K. received a grant from The Danish Heart Foundation and a travelling grant from Gilead; M.G. received a grant from Augustinus Foundation; A.R. received a grant from Augustinus Foundation; D.M.K.-K. received travel grants from Gilead; H.U. received unrestricted research grants from Novo Nordisk Foundation, the Research Foundation of Rigshospitalet, and The Danish Council for Independent Research and Novartis; S.D.N. received unrestricted research grants from Novo Nordisk Foundation, Lundbeck Foundation, Augustinus Foundation, and Gilead as well as traveling grants from Gilead. The remaining authors have no conflicts of interests to disclose. Received August 26, 2019 Accepted September 02, 2019
Brief Report: Incidence of HIV in a Nationwide Cohort Receiving Pre-exposure Prophylaxis for HIV PreventionVan Epps, Puja;Wilson, Brigid M.;Garner, Will;Beste, Lauren A.;Maier, Marissa M.;Ohl, Michael E.
doi: 10.1097/QAI.0000000000002186pmid: 31714421
Background: Cases of HIV, while infrequent, have been reported during tenofovir disoproxil fumarate/emtricitabine use as pre-exposure prophylaxis (PrEP). We describe the incidence of HIV and patterns of PrEP use within the Veterans Health Administration (VHA). Methods: We conducted a retrospective cohort study among persons initiating PrEP in the VHA between July 2012 and April 2016 using national VHA data. We defined time on PrEP and time at risk of HIV exposure as the total time from the first PrEP fill to exhaustion of supply of the final PrEP prescription. We identified incident cases of HIV infection after PrEP initiation based on laboratory data. Medication adherence measures and days without pills were calculated using pharmacy fill data. We used a chart review to determine patient-reported PrEP use around the time of diagnosis. Results: We identified 825 unique patients initiating PrEP; they were 97% men and 67% white, with a mean age of 41 years. Six HIV infections were observed during the study period, yielding an HIV incidence of 0.8 (Poisson exact 95% confidence interval: 0.3 to 1.8) cases per 100 person-years. Two cases occurred during active PrEP use by self-report and perfect adherence based on fill data. Both were infected with viruses containing the M184V mutation. Four additional cases were diagnosed after self-reported discontinuation. Conclusions: HIV infection was rare in a nationwide cohort of PrEP users. Although most of the infections occurred during inconsistent PrEP use, infections during periods of high measured adherence were also observed. These findings highlight the importance of PrEP persistence during periods of risk. aGeriatric Research Education and Clinical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, OH; bDivision of Infectious Diseases, Department of Medicine, Case Western School of Medicine, Cleveland, OH; cUniversity Hospitals Cleveland Medical Center, Cleveland, OH; dVA Puget Sound Health Care System, Seattle, WA; eDivision of General Internal Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA; fVA Portland Health Care System, Portland, OR; gDivision of Infectious Diseases, Oregon Health and Sciences University, Portland, OR; hCenter for Access and Delivery Research and Evaluation (CADRE), Iowa City, IA; and iDepartment of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA. Correspondence to: Puja Van Epps, MD, Louis Stokes Cleveland VA Medical Center, 10701 East Boulevard, Cleveland, OH 44106 (e-mail: [email protected]). Presented at the Conference on Retroviruses and Opportunistic Infections; March 4–7, 2019; Seattle, WA. P.V.E and B.M.W. receive support from the VA Geriatric Research Education and Clinical Center. M.M.M. and L.A.B. receive support from the VA Office of HIV, Hepatitis and Related Pathogens. M.E.O. receives support from VA Center for Access and Delivery Research and Evaluation. The remaining author has no conflicts of interest to disclose. Received April 19, 2019 Accepted September 09, 2019
Brief Report: Low Sensitivity of the Fracture Risk Assessment Tool in Young HIV-Infected Patients: Time to Revise Our Screening Strategyvan Welzen, Berend J.;Yesilay, Sultan;Arends, Joop E.;Hoepelman, Andy I. M.;Mudrikova, Tania
doi: 10.1097/QAI.0000000000002177pmid: 31714423
Objectives: The burden of reduced bone mineral density (BMD) is high among HIV-infected patients. As a screening strategy, current guidelines recommend calculating a Fracture Risk Assessment Tool (FRAX) score in patients aged 40–49 years. Patients with a 10-year risk of a major osteoporotic fracture ≥10% should undergo dual-energy x-ray absorptiometry (DXA) to assess BMD. The aim of this study was to establish the sensitivity of this threshold to identify patients with risk of osteoporosis in this age category—as a surrogate marker for high fracture risk. Methods: The study group consisted of patients aged 50–59 years and living with HIV for at least 10 years who recently underwent dual-energy x-ray absorptiometry (DXA). A clinical risk factor–based FRAX score was calculated using patient characteristics from 10 years earlier. In this way, we assessed which patients would have undergone DXA while they were 40–49 year old. Results: The cohort consisted of 126 patients; 23 patients (18.3%) had osteoporosis. Ten years before the DXA, none of them met the guideline threshold of a 10-year major osteoporotic fracture probability of ≥10%, resulting in a sensitivity of 0% in this cohort. There was no difference between the median FRAX score between patients who developed osteoporosis and those who did not (3.3% vs. 3.4%. P = 0.55). Conclusions: FRAX lacks sensitivity to determine which HIV-infected patients aged 40–49 years should undergo BMD testing to identify reduced BMD. Its role should be limited to treatment decisions. Department of Internal Medicine and Infectious Diseases, University Medical Centre Utrecht, Utrecht, the Netherlands. Correspondence to: Berend J. van Welzen, MD, Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Huispostnummer F.02.126, PO Box 85500, 3508 GA, Utrecht (e-mail: [email protected]). J.E.A. reports institutional fees from Gilead Sciences, ViiV Healthcare, MSD & Janssen. T.M. reports institutional fees from Gilead Sciences and congress grant from MSD. The remaining authors have no conflicts of interest to disclose. Received June 28, 2019 Accepted August 19, 2019
Definition of Immunological Nonresponse to Antiretroviral Therapy: A Systematic ReviewRb-Silva, Rita;Goios, Ana;Kelly, Christine;Teixeira, Pedro;João, Cristina;Horta, Ana;Correia-Neves, Margarida
doi: 10.1097/QAI.0000000000002157pmid: 31592836
Background: Terms and criteria to classify people living with HIV on antiretroviral therapy who fail to achieve satisfactory CD4+ T-cell counts are heterogeneous, and need revision and summarization. Methods: We performed a systematic review of PubMed original research articles containing a set of predefined terms, published in English between January 2009 and September 2018. The search retrieved initially 1360 studies, of which 103 were eligible. The representative terminology and criteria were extracted and analyzed. Results: Twenty-two terms and 73 criteria to define the condition were identified. The most frequent term was “immunological nonresponders” and the most frequent criterion was “CD4+ T-cell count <350 cells/µL after ≥24 months of virologic suppression.” Most criteria use CD4+ T-cell counts as a surrogate, either as an absolute value before antiretroviral therapy initiation or as a change after a defined period of time. Distinct values and time points were used. Only 9 of the 73 criteria were used by more than one independent research team. Herein we propose 2 criteria that could help to reach a consensus. Conclusions: The high disparity in terms and criteria here reported precludes data aggregation and progression of the knowledge on this condition, because it renders impossible to compare data from different studies. This review will foster the discussion of terms and criteria to achieve a consensual definition. aLife and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal; bICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal; cDepartment of Onco-Hematology, Portuguese Institute of Oncology of Porto, Porto, Portugal; dHIV Molecular Research Group, University College Dublin, Dublin, Ireland; eNOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal; fChampalimaud Centre for the Unknown, Fundação Champalimaud, Lisboa, Portugal; gDepartment of Infectious Diseases, Centro Hospitalar do Porto, Porto, Portugal; and hDivision of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. Correspondence to: Margarida Correia-Neves, PhD, Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal (e-mail: [email protected]). Supported by: FEDER, through the Competitiveness Factors Operational Program (COMPETE); by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038 and NORTE-01-0145-FEDER-000013; and by Programa Gilead GÉNESE (PGG/018/2017). R.R.-S. was supported by an FCT grant, in the context of PhDOC—Doctoral Program in Ageing and Chronic Diseases (PD/BD/106047/2015). A.H. is consultant for Abbvie LDA, Bristol-Myers Squibb, Gilead Sciences, Janssen-Cilag, Merck Sharp and Dohme and ViiV Healthcare. C.J. serves as adviser for Celgene, Janssen-Cilag and Takeda. R.R.-S., A.G., C.K., P.T., and M.C.-N. have nothing to disclose. R.R.-S. and A.G. conceived and designed the review, performed the search and analyzed the data. M.C.-N. coordinated all the steps of the review. R.R.-S., A.G., C.K., P.T., C.J., A.H., and M.C.-N. contributed to the writing and revision of the manuscript. All authors discussed the results and contributed to the final manuscript. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jaids.com). Received June 19, 2019 Accepted August 12, 2019
Association of HIV Infection and Antiretroviral Therapy With Sudden Cardiac DeathYen, Yung-Feng;Lai, Yun-Ju;Chen, Yu-Yen;Lai, Hsin-Hao;Chuang, Pei-Hung;Chen, Chu-Chieh;Deng, Chung-Yeh
doi: 10.1097/QAI.0000000000002161pmid: 31714425
Background: HIV infection potentially increases coronary artery disease and heart failure risks. However, the association between HIV infection and sudden cardiac death (SCD) has not been extensively studied. This nationwide cohort study aimed to determine SCD risks in Taiwanese patients with and without HIV infection. Methods: Adult people living with HIV/AIDS (PLWHA) since January 1, 2003, were identified from the Taiwan Centers for Disease Control HIV surveillance system. HIV-infected individuals were defined as positive HIV-1 Western blot. A control cohort without HIV infection, matched for age and sex, was selected for comparison from the Taiwan National Health Insurance Research Database. All patients were followed up until SCD, mortality for another cause, or till December 31, 2014. A time-dependent Cox proportional hazards model was used to determine the association of HIV and antiretroviral therapy (ART) with SCD. Results: During a mean 5.86-year follow-up, 5342 (4.40%) of 121,530 patients (24,306 PLWHA and 97,224 matched controls) died; among them, 150 (0.12%) died of SCD. Among 150 SCD events, 97 (64.7%) and 53 (33.3%) occurred in PLWHA and controls, respectively, which corresponded to incidences of 68.31 in PLWHA and 9.31 per 100,000 person-years in controls (P < 0.001). After adjusting for age, sex, and comorbidities, HIV infection was an independent risk factor for SCD (adjusted hazard ratio, 8.15; 95% confidence interval: 5.58 to 11.90). SCD incidence was significantly lower in PLWHA receiving ART (adjusted hazard ratio 0.53; 95% confidence interval: 0.32 to 0.87). Conclusions: HIV infection is an independent risk factor for SCD. SCD rates are low in PLWHA receiving ART. aSection of Infectious Diseases, Taipei City Hospital, Taipei, Taiwan; bDepartment of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan; cInstitute of Public Health, National Yang-Ming University, Taipei, Taiwan; dSchool of Medicine, National Yang-Ming University, Taipei, Taiwan; eDivision of Endocrinology and Metabolism, Department of Internal Medicine, Puli Branch of Taichung Veterans General Hospital, Nantou, Taiwan; fDepartment of Exercise Health Science, National Taiwan University of Sport, Taichung, Taiwan; gDepartment of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan; hTaipei Association of Health and Welfare Data Science, Taipei, Taiwan; and iInstitute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan. Correspondence to: Chung-Yeh Deng, MD, ScD, Institute of Hospital and Health Care Administration, National Yang-Ming University, 155, Section 2, Ni-Long Street, Taipei 11221, Taiwan (e-mail: [email protected]). The authors have no conflicts of interest to disclose. C.-Y. Deng and Y.-J. Lai contributed equally to this article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jaids.com). Received April 27, 2019 Accepted June 17, 2019
Benzodiazepine Use Is Associated With an Increased Risk of Neurocognitive Impairment in People Living With HIVSaloner, Rowan;Grelotti, David J.;Tyree, Griffin;Sundermann, Erin E.;Ma, Qing;Letendre, Scott;Heaton, Robert K.;Cherner, Mariana
doi: 10.1097/QAI.0000000000002183pmid: 31714426
Objective: Despite potential for dependence and adverse neurological effects, long-term benzodiazepine (BZD) use is common among people living with HIV (PLWH). As PLWH are at risk for central nervous system dysfunction, we retrospectively examined the association between BZD use and HIV-associated neurocognitive impairment (NCI). Methods: Three hundred six PLWH underwent comprehensive neurobehavioral evaluations. Current BZD use (BZD+) was determined through self-report. Using propensity scores, 153 BZD− individuals were matched to 153 BZD+ participants on demographics and medical comorbidities. Multiple regression models examined NCI and demographically adjusted neurocognitive T-scores as a function of BZD status, adjusting for estimated premorbid ability, current affective symptoms, and nadir CD4 count. Secondary analyses explored neurocognitive correlates of positive BZD urine toxicology screens (TOX+) and specific BZD agents. Results: Median duration of BZD use was 24 months. Current BZD use related to higher likelihood of NCI (odds ratio = 2.13, P = 0.003) and poorer global (d = −0.28, P = 0.020), processing speed (d = −0.23, P = 0.047), and motor T-scores (d = −0.32, P = 0.008). Compared with BZD−/TOX−, BZD+/TOX+ exhibited additional decrements in executive function (d = −0.48, P = 0.013), working memory (d = −0.49, P = 0.011), and delayed recall (d = −0.41, P = 0.032). For individual agents, diazepam, lorazepam, and alprazolam were most strongly associated with NCI (odds ratios >2.31). Discussion: BZD use may elevate risk for NCI in PLWH, potentially through diffuse neurocognitive slowing and acute compromise of recall and higher-order capacities. These effects are robust to psychosocial and HIV-specific factors and occur in comparison with a tightly matched BZD− group. Prospective and interventional studies should evaluate causal associations between NCI and BZD use and explore treatment alternatives to BZDs in PLWH. aDepartment of Psychiatry, University of California, San Diego, CA; bSan Diego State University/University of California, San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA; and cDepartment of Pharmacy Practice, University at Buffalo, Buffalo, NY. Correspondence to: Rowan Saloner, BS, SDSU/UC San Diego Joint Doctoral Program in Clinical Psychology, University of California, San Diego, HIV Neurobehavioral Research Program, 220 Dickinson Street, Suite B, Mail Code 8231, San Diego, CA 92103-8231 (e-mail: [email protected]). Supported by the Translational Methamphetamine AIDS Research Center (TMARC) award P50DA026306, the HIV Neurobehavioral Research Center (HNRC) award P30MH062512, the California NeuroAIDS Tissue Network (CNTN) awards U01MH083506, R24MH59745, and U24MH100928, and the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study awards N01MH22005, HHSN271201000036C, and HHSN271201000030C. R.S. is supported by NIAAA award T32AA013525. Poster to be presented at the National Academy of Neuropsychology (NAN) Annual Conference; November 14, 2019; San Diego, CA. The authors have no conflicts of interest to disclose. Received June 12, 2019 Accepted September 02, 2019