Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking.

Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter.

Progressive immune dysfunction and the acquired immunodeficiency syndrome (AIDS) develop in most persons with untreated infection with human immunodeficiency virus type 1 (HIV-1) but in only approximately 20 to 30% of persons infected with HIV type 2 (HIV-2); among persons infected with both types, the natural history of disease progression is poorly understood.

Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations.

The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain.

There is considerable genetic diversity among viruses of different subtypes (designated A to J) in the major group of human immunodeficiency virus type 1 (HIV-1), the form of HIV that is dominant in the global epidemic. If available, HIV-1 sequences pre-dating the recognition of AIDS could be crucial in defining the time of origin and the subsequent evolution of these viruses in humans. The oldest known case of HIV-1 infection was reported to be that of a sailor from Manchester who died of an AIDS-like illness in 1959; however, the authenticity of this case has not been confirmed. Genetic analysis of sequences from clinical materials obtained from 1971 to 1976 from members of a Norwegian family infected earlier than 1971 showed that they carried viruses of the HIV-1 outlier group, a variant form that is mainly restricted to West Africa. Here we report the amplification and characterization of viral sequences from a 1959 African plasma sample that was previously found to be HIV-1 seropositive. Multiple phylogenetic analyses not only authenticate this case as the oldest known HIV-1 infection, but also place its viral sequence near the ancestral node of subtypes B and D in the major group, indicating that these HIV-1 subtypes, and perhaps all major-group viruses, may have evolved from a single introduction into the African population not long before 1959.

Yusnelkis Milanés-Guisado, Alicia Gutiérrez-Valencia, María Trujillo-Rodríguez, Nuria Espinosa, Pompeyo Viciana, Luis Fernando López-Cortés

by Yusnelkis Milanés-Guisado, Alicia Gutiérrez-Valencia, María Trujillo-Rodríguez, Nuria Espinosa, Pompeyo Viciana, Luis Fernando López-Cortés Objectives To analyse the correlation and concordance between aCD4, CD4%, CD4/CD8, their intra-patient variability, and to compare the immune recovery (IR) rates based on the three parameters in HIV-infected patients after starting antiretroviral therapy. Methods From a prospectively followed cohort, patients who maintained HIV-RNA suppression in ≥95% of the determinations throughout the follow-up were selected. IR was defined as aCD4 >650/μl, CD4% ≥38% or CD4/CD8 ≥1. Results A total of 1164 patients with a median follow-up of 5 years were analysed. The increases in aCD4, CD4% and CD4/CD8 were highest during the first year and considerably lower thereafter regardless of baseline aCD4. The annual increases in aCD4 showed poor correlations with those of CD4% (r = 0.143–0.250) and CD4/CD8 (r = 0.101–0.192) but were high between CD4% and CD4/CD8 (r = 0.765–0.844; p650/μl, CD4% ≥38%, and CD4/CD8 ≥1, respectively, while only 31% achieved both aCD4 and CD4/CD8 target values. Conclusions The increases in aCD4 poorly correlate with those of CD4% and CD4/CD8. IR rates based on aCD4 significantly overstate those obtained by CD4% and CD4/CD8. CD4% and CD4/CD8 are more stable markers than aCD4 and should be taken into account to monitor the IR after treatment initiation.

Ingo Bulla, Ian H. Spickanll, Dmitry Gromov, Ethan Obie Romero-Severson

by Ingo Bulla, Ian H. Spickanll, Dmitry Gromov, Ethan Obie Romero-Severson Predicting the population-level effects of an infectious disease intervention that incorporate multiple modes of intervention is complicated by the joint non-linear dynamics of both infection transmission and the intervention itself. In this paper, we consider the sensitivity of Dynamic Optimal Control Profiles (DOCPs) for the optimal joint investment in both a contagiousness and susceptibility-based control of HIV to bio-behavioral, economic, and programmatic assumptions. The DOCP is calculated using recently developed numerical algorithms that allow controls to be represented by a set of piecewise constant functions that maintain a constant yearly budget. Our transmission model assumes multiple stages of HIV infection corresponding to acute and chronic infection and both within- and between-individual behavioral heterogeneity. We parameterize a baseline scenario from a longitudinal study of sexual behavior in MSM and consider sensitivity of the DOCPs to deviations from that baseline scenario. In the baseline scenario, the primary determinant of the dominant control were programmatic factors, regardless of budget. In sensitivity analyses, the qualitative aspects of the optimal control policy were often robust to significant deviation in assumptions regarding transmission dynamics. In addition, we found several conditions in which long-term joint investment in both interventions was optimal. Our results suggest that modeling in the service of decision support for intervention design can improve population-level effects of a limited set of economic resources. We found that economic and programmatic factors were as important as the inherent transmission dynamics in determining population-level intervention effects. Given our finding that the DOCPs were robust to alternative biological and behavioral assumptions it may be possible to identify DOCPs even when the data are not sufficient to identify a transmission model.

Laure Stella Ghoma Linguissi, Violaine Lucaccioni, Matthew Bates, Alimuddin Zumla, Francine Ntoumi

Iacopo Franconi, Olga Theou, Lindsay Wallace, Andrea Malagoli, Cristina Mussini, Kenneth Rockwood, Giovanni Guaraldi

by Iacopo Franconi, Olga Theou, Lindsay Wallace, Andrea Malagoli, Cristina Mussini, Kenneth Rockwood, Giovanni Guaraldi Background Standard care for HIV clinical practice has started focusing on age-related problems, but despite this recent change physicians involved in HIV care do not often screen HIV patients for frailty. Our aim was to construct three indexes from an HIV clinical database (i.e. Frailty Index, (FI), HIV Index, (HIVI), and Protective Index (PI)) and to assess levels of frailty, HIV severity and demographic and protective lifestyle factors among HIV patients. Methods and findings We included data from 1612 patients who attended an Italian HIV clinic between September 2016 and December2017 (mean±SD age: 53.1±8 years, 73.9% men).We used 92 routine variables collected by physicians and other health care professionals to construct three indexes: a 72-item FI (biometric, psychiatric, blood test, daily life activities, geriatric syndromes and nutrition data), a 10-item HIVI (immunological, viral and therapeutics) and a 10-item PI (income, education, social engagement, and lifestyle habits data)(the lower the FI and HIVI scores, and the higher the PI scores, the lower the risk for participants).The FI, HIVI and PI scores were 0.19±0.08, 0.48±0.17 and 0.62±0.13, respectively. Men had higher FI (0.19±0.08 vs 0.18±0.08; p = 0.010) and lower HIVI (0.47±0.18 vs 0.50±0.15; p = 0.038) scores than women. FI and HIVI scores both increased 1.9% per year of age (p < 0.001), whereas the PI decreased 0.2% per year (p…

Mazhnaya, Alyona; Marcus, Ruthanne; Bojko, Martha J.; Zelenev, Alexei; Makarenko, Iuliia; Pykalo, Iryna; Filippovych, Sergii; Dvoriak, Sergey; Altice, Frederick L.

Background: The HIV treatment cascade is a crucial tool to guide HIV prevention and treatment strategies. The extent to which opioid agonist treatments (OAT) like methadone and buprenorphine influence this cascade was examined in a nationwide study of people who inject drugs (PWID) in Ukraine. Setting: Cross-sectional stratified survey of PWID followed by HIV and HCV testing in five Ukrainian cities. Methods: Opioid dependent PWID (N=1,613) were sampled from January 2014 to March 2015. Analysis was confined to 520 participants with HIV, with 184 (35.4%) prescribed OAT. Weighted logistic regression models were used to assess independent factors associated with the five steps in the HIV treatment cascade. Results: Compared to PWID not on OAT (N=336), participants prescribed OAT (N=184) were significantly more likely to be diagnosed (91% vs. 71%), linked (81% vs. 52%) and retained (69% vs. 35%) in HIV care, and prescribed (56% vs. 31%) and optimally (>95% of doses) adherent to antiretroviral therapy (41% vs. 22%). Receiving OAT contributed most as an independent factor with every step of the cascade. Other steps in the HIV treatment cascade were influenced by age, depression and geographical variability. Conclusions: OAT remains an essential and effective strategy to not only treat patients with opioid use disorder, but also a crucial strategy to engage PWID in care to meet UNAIDS 90-90-90 targets. Geographical differences suggest local structural impediments. With low OAT coverage prescribed for 2.9% of the estimated 347,000 PWID in Ukraine, OAT expansion requires strategic interventions that target the individual, clinical care settings, policies and funding. Corresponding author: Alyona Mazhnaya, MS, MPH 5 Dilova St., build 10A, 9th floor, 03680 Kyiv, Ukraine Cell: +1(518) 530-8727 e-mail: hmazhnaya@gmail.com, amazhna1@jhmi.edu Conflicts of Interest and Source of Funding: No conflicts of interest related to this research were declared. The authors would like to acknowledge the National Institute on Drug Abuse for funding for research (R01 DA029910, R01 DA043125 and R01 DA033679) and career development (K24 DA017072, K01DA037826 ) and the Global Health Equity Scholars Program funded by the Fogarty International Center and the National Institute of Allergy and Infectious Diseases (Research Training Grant R25 TW009338) as well as New York State International Training and Research Program through an in-country training grant funded by the Fogarty International Center (D43TW000233). Preliminary data presented at the 21st International AIDS Conference (Durban, South Africa, July 18-22, 2016) Declaration of interests: Authors do not have any financial or personal relationships with other people or organizations that could inappropriately influence this manuscript. Authors’ Contributions: AM was responsible for study design, survey construction, data analysis, conceptualizing and conducting the analysis, data interpretation, writing the first draft and reviewing the manuscript. RM, MJB, IM, IP were involved with study design, survey construction, and reviewing the manuscript. AZ was involved in data analysis and interpretation and reviewing the manuscript. SD was involved in study design and reviewing the manuscript. SF was the site co-investigator and was involved in the study design and reviewing the manuscript. FLA was the Principal Investigator and was involved in the funding, study design, survey construction, data analysis, conceptualizing the analysis, data interpretation, and final review of the manuscript. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Milam, Joel; Jain, Sonia; Dubé, Michael P.; Daar, Eric S.; Sun, Xiaoying; Corado, Katya; Ellorin, Eric; Blumenthal, Jill; Haubrich, Richard; Moore, David J.; Morris, Sheldon R.; the CCTG Team

Background: A public health concern regarding HIV pre-exposure prophylaxis (PrEP) is sexual risk compensation (i.e., increased unsafe sex among PrEP users that may undermine prevention efforts). Methods: This demonstration study (NCT#01761643; initiated in 2013) included 398 men who have sex with men (MSM) who initiated PrEP and were followed over 48 weeks at 4 sites in Southern California. Wilcoxon signed-rank tests compared prior 30-day number of sex partners and condomless insertive and receptive anal sex acts (CIAS and CRAS, respectively) at weeks 4, 12, 24, 36 and 48 to baseline. At 2 sites, PrEP users were also compared to a lagged, comparison group of 99 MSM who did not receive PrEP over 24 weeks using linear regression models, adjusting for age, race/ethnicity, education, and respective baseline scores. Logistic regression compared week 24 sexually transmitted infection (STI) rates. Results: Over 48 weeks in the PrEP group, there were significant decreases in the number of unknown HIV status sex partners and increases in CRAS at all study visits; there was no consistent change in number of HIV+ sex partners or CIAS. Among participants at two sites, there were no significant differences between PrEP and non-PrEP users in change in number of partners, CIAS, CRAS, or STI rates at week 24. Conclusions: Among early adopters of PrEP, there is some evidence for sexual risk compensation. Results support current guidelines of regular STI screening and behavioral risk reduction and adherence counseling with the provision of PrEP. Corresponding Author: Joel Milam, Department of Preventive Medicine, University of Southern California, 2001 Soto Building, MC9239, Los Angeles, CA 90032 Conflict of Interest and Sources of Funding: Dr. Haubrich is Professor Emeritus at UCSD and a current employee of Gilead Sciences. Dr. Daar receives research support from Gilead, Merck, and ViiV and has been a consultant for Gilead, Merck and Theratechnologies. For the remaining authors none were declared. This work was supported by National Institute of Mental Health (R21MH100979) and the California HIV Research Program (CHRP: MC08-SD-700 and EI-11-SD-005). Additional funding includes NIAID grants: AI 064086 (K24 to RH); AI 36214 (CFAR Clinical Investigation Core and Biostatistics and Modeling Core). Study drug was provided by Gilead Sciences. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Streed, Carl G Jr; Goldstein, Zil; Poteat, Tonia; Mukherjee, Monica; Radix, Asa

No abstract available…

K. T. Bruner et al.

Brumme, Zabrina; Sudderuddin, Hanwei; Ziemniak, Carrie; Luzuriaga, Katherine; Jones, Bradley R.; Joy, Jeffrey B.; Cunningham, Coleen K.; Greenough, Thomas; Persaud, Deborah

Objective: Timely initiation of combination antiretroviral therapy (ART) limits latent HIV reservoir size and should also limit reservoir genetic complexity. However, the relationship between these two factors remains unclear, particularly among HIV-infected youth. Design: Retrospective analysis of replication-competent latent HIV clones serially isolated by limiting-dilution culture from resting CD4+ T-cell reservoirs from ART-suppressed, young adult participants of a historic phase I therapeutic vaccine trial (PACTG/IMPAACT-P1059). Methods: Replication-competent latent HIV clones isolated from resting CD4+ T-cells of 4 perinatally- and 10 non-perinatally-infected young adults (average 22 versus 6 years uncontrolled infection, respectively) were sequenced in Pol and Nef. Within-host HIV sequence datasets were characterized with respect to their genetic diversity and inferred immune escape mutation burden. Results: While participants were comparable in terms of sociodemographic and HIV sampling characteristics (e.g. on average, a mean 17 Pol sequences were recovered at 5 timepoints over up to 70 weeks) and the length of ART suppression at study entry (average 3 years), replication-competent HIV reservoir size, genetic diversity, immune escape mutation burden and variant complexity were significantly higher among the perinatally-infected participants who experienced longer durations of uncontrolled viremia. Nevertheless, viral sequences inferred to retain susceptibility to host cellular immune responses were detected in all participants, irrespective of uncontrolled viremia duration. Conclusions: HIV elimination in late-suppressed youth may be doubly challenged by larger and more genetically complex reservoirs. Strategies that integrate host and viral genetic complexity to achieve HIV remission or cure may merit consideration in such cases. Correspondence to Zabrina Brumme, PhD, Associate Professor, Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada. Tel: 1 778 782 8872; fax: 1 778 782 5927; e-mail: zbrumme@sfu.ca; Deborah Persaud, MD, Professor of Pediatrics, Johns Hopkins University School of Medicine and Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 200 North Wolfe Street, Baltimore, MD, 21205, USA. Tel: 1 443 287 3733; e-mail: dpers@jhmi.edu Received 17 July, 2018 Accepted 13 September, 2018 Copyright © 2018 Wolters Kluwer Health, Inc.

Gossez, Morgane; Martin, Genevieve Elizabeth; Pace, Matthew; Ramjee, Gita; Premraj, Anamika; Kaleebu, Pontiano; Rees, Helen; Inshaw, Jamie; Stöhr, Wolfgang; Meyerowitz, Jodi; Hopkins, Emily; Jones, Mathew; Hurst, Jacob; Porter, Kholoud; Babiker, Abdel; Fidler, Sarah; Frater, John; on behalf of the SPARTAC Trial Investigators

Introduction: There are few data on the frequency of virological remission in African individuals after treatment with antiretroviral therapy (ART) in primary HIV infection (PHI). Methods: We studied participants (n = 82) from South Africa and Uganda in SPARTAC, the first trial of treatment interruption (TI) in African individuals with PHI randomized to deferred ART or 48 weeks of immediate ART. All were female and infected with non-B HIV subtypes, mainly C. We measured HIV DNA in CD4 T cells, CD4 count, plasma viral load (pVL), cell-associated HIV RNA and T cell activation and exhaustion. We explored associations with clinical progression and time to pVL rebound after TI (n = 22). Data were compared with non-African SPARTAC participants. Results: Pre-therapy pVL and integrated HIV DNA were lower in Africans compared with non-Africans (median 4.16 vs 4.72 log10 copies/ml and 3.07 vs 3.61 log10 copies/million CD4 T-cells respectively; p …

Vieira, Vinicius A.; Zuidewind, Peter; Muenchhoff, Maximilian; Roider, Julia; millar, Jane; Clapson, Margaret; Van Zyl, Anriette; Shingadia, Delane; Adland, Emily; Athavale, Rohin; Grayson, Nicholas; Ansari, M. Azim; Brander, Christian; Guash, Claudia Fortuny; Naver, Lars; Puthanakit, Thanyawee; Songtaweesin, Wipaporn Natalie; Ananworanich, Jintanat; Peluso, Denise; Thomé, Beatriz; Pinto, Jorge; Jooste, Pieter; Tudor-Williams, Gareth; Cotton, Mark F.; Goulder, Philip

Background: Reports of posttreatment control following antiretroviral therapy (ART) have prompted the question of how common immune control of HIV infection is in the absence of ART. In contrast to adult infection, where elite controllers have been very well characterized and constitute approximately 0.5% of infections, very few data exist to address this question in paediatric infection. Methods: We describe 11 ART-naïve elite controllers from 10 cohorts of HIV-infected children being followed in South Africa, Brazil, Thailand, and Europe. Results: All but one elite controllers (91%) are girls. The median age at which control of viraemia was achieved was 6.5 years. Five of these 11 (46%) children lost control of viraemia at a median age 12.9 years. Children who maintained control of viraemia had significantly higher absolute CD4+ counts in the period of elite control than those who lost viraemic control. On the basis of data available from these cohorts, the prevalence of elite controllers in paediatric infection is estimated to be 5–10-fold lower than in adults. Conclusion: Although conclusions are limited by the study design, these data suggest that, whilst paediatric elite control can be achieved, compared with adult elite controllers, this occurs rarely, and takes some years after infection to achieve. Also, loss of immune control arises in a high proportion of children and often relatively rapidly. These findings are consistent with the more potent antiviral immune responses observed in adults and in females. Correspondence to Philip Goulder, MD, MSc, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK. E-mail: philip.goulder@paediatrics.ox.ac.uk Received 3 July, 2018 Accepted 11 September, 2018 Copyright © 2018 Wolters Kluwer Health, Inc.

Nichols, Madeleine J.; Gates, Thomas M.; Soares, James R.; Moffat, Kirsten J.; Rae, Caroline D.; Brew, Bruce J.; Cysique, Lucette A.

Objective: There is a lack of evidence for the neurobiological underpinning of Asymptomatic Neurocognitive Impairment (ANI) and Mild Neurocognitive disorders (MND) in virally-suppressed HIV + persons. We hypothesized that such mild impairment would be associated with focal brain atrophy. Design: Cross-sectional observational study. Methods: 85 virally-suppressed HIV + and 44 geographically, demographically, and lifestyle comparable HIV- men underwent anatomical MRI, neuropsychological evaluation, and HIV laboratory tests. Volumes of interest (VOI) from MR images were extracted using FreeSurfer to yield grey (GM) and white matter (WM) volumes in regions associated with HIV-related brain injury. HAND (ANI = 38%, MND = 13%, HIV-associated dementia (HAD) = 3% vs. neuropsychologically (NP)-normal) was classified using Global Deficit Score (GDS≥0.5) and functional decline. Effects of HIV status on VOI were assessed with multivariate analyses controlling for family-wise error. HAND categories and HIV biomarker effects on VOI were assessed with multiple regression. Results: Relative to the HIV- group, the HIV + group demonstrated subcortical grey (d = 0.50–0.60) and WM (d = 0.43–0.69) atrophy, with relative cortical sparing (d = 0.23). ANI showed reduced medial-orbitofrontal WM compared to NP-normal cases (p = .04). MND showed enlarged lateral ventricles (p = .02) and reduced caudal-middle-frontal WM (p = .04), caudal-anterior-cingulate WM (p = .006), and inferior-parietal WM (p = .04) compared to NP-normal. Across the HIV + group, lower CD4/CD8 ratio was the strongest predictor of atrophy in subcortical regions. Across HAND categories, HIV disease duration uniquely predicted greater medial-orbitofrontal WM atrophy only in ANI (p = .002). Conclusions: ANI shows specific frontal WM atrophy to which HIV disease duration is a unique contributor. MND is characterised by more widespread subcortical atrophy. Correspondence to Lucette A. Cysique, NeuroHIV and Quantitative Neuropsychology Research Group, Neuroscience Research Australia, PO Box 1165, Randwick NSW 2031, Australia. e-mail: lcysique@unsw.edu.au Received 30 July, 2018 Accepted 11 September, 2018 Copyright © 2018 Wolters Kluwer Health, Inc.

Cheru, Lediya T.; Fitch, Kathleen V.; Saylor, Charles F.; Lu, Michael; Hoffmann, Udo; Lo, Janet; Grinspoon, Steven K.

Objective: To investigate the association of mild renal impairment and coronary plaque in people living with HIV (PLHIV). Methods: PLHIV and non-HIV controls with serum creatinine…

Aldersley, Jordan; Lorenz, David R.; Misra, Vikas; Uno, Hajime; Gabuzda, Dana

Objective(s): HIV-positive individuals have elevated rates of anal squamous cell carcinoma (SCC), and sexually transmitted infections with its causative agent, high-risk human papillomavirus, and other oncoviruses including hepatitis B virus (HBV). HBV infection can cause liver cancer, and has been associated with increased risk of some extra-hepatic cancers including biliary tract cancer, pancreatic cancer, and non-Hodgkin lymphoma. Whether HBV is associated with anal SCC risk is unknown. Design: Prospective study of anal SCC risk in HIV-positive and -negative men who have sex with men (MSM) in the Multicenter AIDS Cohort Study from 1984–2014. Methods: Poisson regression models were used to examine the association between past or current HBV infection (positive tests for HBV core antibodies, surface antigen, and/or DNA) and anal SCC risk. Results: We observed 53 cases of anal SCC among 5,298 participants with 79,334 person-years follow-up. Among HIV-positive men, past or current HBV infection was associated with anal SCC risk in models adjusted for age, CD4+ cell counts, HAART use, and other risk factors (incidence rate ratio [IRR], 95% confidence interval [CI] 3.15, 1.27–7.82). Additional risk factors included immunological parameters one and six years prior to diagnosis (IRR, 95% CI 2.45, 1.31–4.58 and 2.44, 1.3–4.59 for CD4+ counts…

Srinivasa, Suman; Fitch, Kathleen V.; Torriani, Martin; Zanni, Markella V.; Defilippi, Christopher; Christenson, Robert; Maehler, Patrick; Looby, Sara E.; Lo, Janet; Grinspoon, Steven K.

Objective: Persons living with HIV (PLWH) well-treated on antiretroviral therapies remain at risk for ensuing arterial disease. We investigated the relationship between adipose depots and biomarkers of arterial injury and inflammation to gain insight into the link between body composition and CVD risk. Designs/Methods: 155 HIV-infected and 70 non-HIV-infected individuals were well-phenotyped for body composition. Adipose depots were assessed via single-slice abdominal CT. Circulating markers of arterial disease and generalized inflammation [lipoprotein-associated phospholipase A2 (LpPLA2), oxidized LDL (oxLDL), high sensitivity cardiac troponin T (hs-cTnT), high sensitivity C reactive protein (hsCRP)] were evaluated. Results: Despite similar BMI and visceral adipose tissue (VAT), HIV-infected individuals had significantly lower subcutaneous adipose tissue (SAT, 199[126,288] vs. 239[148,358]cm2, P = .04) compared to non-HIV-infected individuals. Among HIV-infected individuals, reduced SAT inversely correlated with LpPLA2 (ρ = -0.19, P = .02) and hs-cTnT (ρ = -0.24, P = .004), whereas increased VAT significantly and positively related to LpPLA2 (ρ = 0.25, P = .003), oxLDL (ρ = 0.28, P = .0005), hs-cTnT (ρ = 0.28, P = .0007), and hsCRP (ρ = 0.32, P =  …

Lucar, Olivier; Sadjo Diallo, Mariama; Bayard, Charles; Samri, Assia; Tarantino, Nadine; Debré, Patrice; Thiébaut, Rodolphe; Brun-Vézinet, Françoise; Matheron, Sophie; Cheynier, Rémi; Vieillard, Vincent; for the ANRS CO5 IMMUNOVIR-2 Study group

Objective: HIV-1 and HIV-2 differ notably in their epidemiology, with worldwide HIV-1 spread and HIV-2 mainly confined to West Africa. Natural killer (NK) cells are critical antiviral effectors of the immune system; however, limited information is available about these innate effector cells during HIV-2 infection. Method: In this study, 24 untreated HIV-2-infected patients were analyzed and compared with 21 long-term nonprogressor and 10 controller HIV-1+ patients, and healthy donors. Extensive phenotype and functional NK-cell characteristics, as well as ligands of activating NK receptors involved in NK lysis were determined by flow cytometry. Results: We report in HIV-2+ patients a very significant reduced expression of the activating NKp30 receptor (P …

Merchante, Nicolás; Figueruela, Blanca; Rodríguez-Fernández, Miguel; Rodríguez-Arrondo, Francisco; Revollo, Boris; Ibarra, Sofía; Galindo, María J.; Merino, Esperanza; Montero, Marta; Téllez, Francisco; García-Deltoro, Miguel; Rivero-Juárez, Antonio; Delgado-Fernández, Marcial; Ríos-Villegas, María J.; Aguirrebengoa, Koldo; García, María A.; Portu, Joseba; Vera-Méndez, Francisco J.; Villalobos, Marina; Mínguez, Carlos; Santos, Ignacio De Los; López-Ruz, Miguel A.; Omar, Mohamed; Galera, Carlos; Macías, Juan

Objective: To assess the performance of ultrasound (US) surveillance for the diagnosis of hepatocellular carcinoma (HCC) in HIV-infected patients. Methods: The GEHEP-002 cohort recruits HCC cases diagnosed in HIV-infected patients from 32 centers across Spain. The proportion of ‘US lack of detection’, defined as HCC diagnosed within the first 3 months after a normal surveillance US, and the proportion of ‘surveillance failure’, defined as cases in which surveillance failed to detect HCC at early stage, were assessed. To assess the impact of HIV, a control population of 104 HCC cases diagnosed in HCV-monoinfected patients during the study period was used. Results: 186 (54%) out of 346 HCC cases in HIV-infected patients were diagnosed within a US surveillance program. US lack of detection occurred in 16 (8.6%) of them. US surveillance failure occurred in 107 (57%) out of 186 cases diagnosed by screening whereas this occurred in 18 (29%) out of 62 diagnosed in the control group (p …

Tugume L, Rhein J, Hullsiek K, et al.

AbstractBackgroundCryptococcal meningitis can occur in persons with less apparent immunosuppression. We evaluated clinical characteristics and outcomes of persons with HIV-related Cryptococcus presenting with higher CD4 counts.MethodsWe enrolled 736 participants from two prospective cohorts in Uganda and South Africa from November 2010 to May 2017. We compared participants with CD4 =100 cells/mcL. Participants with CD4 >=100 cells/mcL presented more often with altered mental status (52% vs 39%; P=.03) despite a 10-fold lower initial median CSF fungal burden of 7,850 (IQR 860–65,500) vs 79,000 (IQR 7,400–380,000) CFU/mL; P=100 cells/mcL had higher median CSF levels of interferon-gamma,interleukin (IL)-6, IL-8, and IL-13; and lower monocyte chemokine, CCL2 (P=100 cells/mcL presented more frequently with altered mental status despite having 10-fold lower fungal burden and with greater Th2 (IL-13) immune response. Higher CD4 count was protective despite an increased propensity for immune-mediated damage, consistent with damage-response framework.

Solomon Sisay, Ayehu Mekonen, Adugna Abera, Yifru Berhan, Tadele Kebede, Abebe Ferede

Globally, Human Immunodeficiency Virus (HIV) and Tuberculosis (TB) are one of the leading causes of death if they occurred as co-morbidity in affected individuals. Therefore, we aimed to evaluate the collaboration of TB and HIV control activities by determining the co-morbidity rate between 2009 and 2015 in Oromia Region, Ethiopia.

Abstract Background Incomplete virologic suppression results in mutations associated with resistance and is a major obstacle to disease control. We analyzed the genotypic profiles of HIV-1 patients at the time of the first virologic failure and the response to a salvage regimen after 48 weeks. Methods This work was a cross-sectional, retrospective, analytical study based on data collected from medical records and genotyping tests between 2006 and 2016. The sample consisted of data on individuals living with HIV (PLWH) from three major reference centers. Results A total of 184 patients were included in the data analysis. Viral subtype B was the most common (81.3%) as well as M184 V/I (85.3%) and K103 codon mutations (65.8%). Forty-eight weeks after switching to a salvage regimen, 67.3% of patients achieved an undetectable viral load. Discussion The number of mutations associated with nucleos(t)ide reverse transcriptase inhibitors (NRTI(t)s) did not affect virologic suppression (9.3% for zero NRTI(t)-associated mutations vs 48.6% for 1–2 NRTI(t)-associated mutations vs 42.1% for ≥3 NRTI(t)-associated mutations, p = 0.179). An ARV time (the beginning of the first ARV regimen up to genotyping) of > 36 months was a protective factor for detectable viral load (PR = 0.60, 95% CI = 0.39–0.92, p = 0.020) and a risk factor for developing ≥3 NRTI(t)-associated mutations (PR = 2.43, 95% CI 1.38–4.28, p = 0.002). Conclusions We found that extensive resistance to NRTI(t)s at the time of the first virologic failure did not impact virologic suppression at 48 weeks after switching to a second-line therapy based on NRTI(t)s plus protease inhibitors.