Stephen S Morse

Memories of plagues remain with us. The 1918 influenza pandemic, one of the greatest natural disasters in history, the devastating effects of Ebola virus disease in 2014, the toll of the HIV/AIDS pandemic, and resonances of the medieval Black Death are among the reminders that infectious diseases still evoke powerful images and fear. As I write, an Ebola virus disease outbreak in Democratic Republic of the Congo is just winding down, and Nipah virus has appeared again in India, causing 17 deaths.

Douglas G. Widman, Savanna Gornisiewicz, Sharon Shacham, Sharon Tamir

by Douglas G. Widman, Savanna Gornisiewicz, Sharon Shacham, Sharon Tamir Infection of immunocompromised individuals with normally benign opportunistic viruses is a major health burden globally. Infections with viruses such as Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), Kaposi’s sarcoma virus (KSHV), adenoviruses (AdV), BK virus (BKPyV), John Cunningham virus (JCPyV), and human papillomavirus (HPV) are significant concerns for the immunocompromised, including when these viruses exist as a co-infection with human immunodeficiency virus (HIV). These viral infections are more complicated in patients with a weakened immune system, and often manifest as malignancies resulting in significant morbidity and mortality. Vaccination is not an attractive option for these immune compromised individuals due to defects in their adaptive immune response. Verdinexor is part of a novel class of small molecules known as SINE (Selective Inhibitor of Nuclear Export) compounds. These small molecules demonstrate specificity for the nuclear export protein XPO1, to which they bind and block function, resulting in sequestration of XPO1-dependent proteins in the nucleus of the cell. In antiviral screening, verdinexor demonstrated varying levels of efficacy against all of the aforementioned viruses including previously with HIV. Studies by other labs have discussed likely mechanisms of action for verdinexor (ie. XPO1-dependence) against each virus. GLP toxicology studies suggest that anti-viral activity can be achieved at a tolerable dose range, based on the safety profile of a previous phase 1 clinical trial of verdinexor in healthy human volunteers. Taken together, these results indicate verdinexor has the potential to be a broad spectrum antiviral for immunocompromised subjects for which vaccination is a poor option.

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

Ranmini S. Kularatne, Ronelle Niit, Jane Rowley, Tendesayi Kufa-Chakezha, Remco P. H. Peters, Melanie M. Taylor, Leigh F. Johnson, Eline L. Korenromp

by Ranmini S. Kularatne, Ronelle Niit, Jane Rowley, Tendesayi Kufa-Chakezha, Remco P. H. Peters, Melanie M. Taylor, Leigh F. Johnson, Eline L. Korenromp Objectives To estimate trends in prevalence and incidence of syphilis, gonorrhea and chlamydia in adult men and women in South Africa. Methods The Spectrum-STI tool estimated trends in prevalence and incidence of active syphilis, gonorrhea and chlamydia, fitting South African prevalence data. Results were used, alongside programmatic surveillance data, to estimate trends in incident gonorrhea cases resistant to first-line treatment, and the reporting gap of symptomatic male gonorrhea and chlamydia cases treated but not reported as cases of urethritis syndrome. Results In 2017 adult (15–49 years) the estimated female and male prevalences for syphilis were 0.50% (95% CI: 0.32–0.80%) and 0.97% (0.19–2.28%), for gonorrhea 6.6% (3.8–10.8%) and 3.5% (1.7–6.1%), and for chlamydia 14.7% (9.9–21%) and 6.0% (3.8–10.4%), respectively. Between 1990 and 2017 the estimated prevalence of syphilis declined steadily in women and men, probably in part reflecting improved treatment coverage. For gonorrhea and chlamydia, estimated prevalence and incidence showed no consistent time trend in either women or men. Despite growing annual numbers of gonorrhea cases − reflecting population growth − the estimated number of first line treatment-resistant gonorrhea cases did not increase between 2008 and 2017, owing to changes in first-line antimicrobial treatment regimens for gonorrhea in 2008 and 2014/5. Case reporting completeness among treated male urethritis syndrome episodes was estimated at 10–28% in 2017. Conclusion South Africa continues to suffer a high STI burden. Improvements in access and quality of maternal, STI and HIV health care services likely contributed to the decline in syphilis prevalence. The lack of any decline in gonorrhea and chlamydia prevalence highlights the need to enhance STI services beyond clinic-based syndromic case management, to reinvigorate primary STI and HIV prevention and, especially for women, to screen for asymptomatic infections.

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.

Suthar A, Coggin W, Raizes E.

To the Editor—Wallis et al recently reviewed key determinants of human immunodeficiency virus (HIV) drug resistance in low- and middle-income countries (LMICs) [1]. In addition to the determinants that were reviewed, we believe the quality of antiretrovirals (ARVs) available in antiretroviral therapy regimens also merits attention.

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.

Carlos Iniesta, Débora Álvarez-del Arco, Luis Miguel García-Sousa, Belén Alejos, Asunción Díaz, Nieves Sanz, Jorge Garrido, Michael Meulbroek, Ferran Pujol, Santiago Moreno, María José Fuster-Ruiz de Apocada, Pep Coll, Antonio Antela, Jorge del Romero, Oskar Ayerdi, Melchor Riera, Juanse Hernández, Julia del Amo

by Carlos Iniesta, Débora Álvarez-del Arco, Luis Miguel García-Sousa, Belén Alejos, Asunción Díaz, Nieves Sanz, Jorge Garrido, Michael Meulbroek, Ferran Pujol, Santiago Moreno, María José Fuster-Ruiz de Apocada, Pep Coll, Antonio Antela, Jorge del Romero, Oskar Ayerdi, Melchor Riera, Juanse Hernández, Julia del Amo Objective To assess the awareness, knowledge, use, and willingness to use and need of PrEP among men who have sex with men (MSM) and transgender women (TW) who attended World Gay Pride (WGP) 2017 in Madrid. Design and methods Online survey. Participants were recruited through gay-oriented dating apps and HIV Non-Governmental Organizations´ social media. Inclusion criteria included being MSM or TW, age 18 years old or above, and having attended WGP in Madrid. Information regarding the participant’s awareness and knowledge, use or willingness to use, and need for PrEP was collected, as well as sociodemographic characteristics. Participants were considered to be in need of PrEP if they met one of the following indication criteria: having practiced unprotected anal intercourse with more than 2 partners, having practiced chemsex, or having engaged in commercial sex—all in the preceding 6 months. Descriptive and multivariable analyses with logistic regression were conducted. Results 472 participants met the inclusion criteria and completed the questionnaire. The mean age was 38, 97.7% were MSM, 77% had a university education, and 85% were living in Spain, mostly in big cities. Overall, 64% of participants were aware of PrEP, but only 33% knew correctly what PrEP was. 67% of HIV-negative participants were willing to take PrEP, although only 5% were taking it during WGP, mostly due to lack of access. 43% of HIV-negative respondents met at least one PrEP indication criteria. For HIV-negative men living in Spain, university education and living in big cities was associated with PrEP awareness. Lower education level and meeting PrEP criteria was associated with willingness to use PrEP. Conclusions Our study shows that among MSM attending WGP 2017 in Madrid, there was limited PrEP awareness, low accuracy of PrEP knowledge, and a high need and willingness to use PrEP. Health authorities should strengthen existing preventive strategies and implement PrEP.

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 …

Habib Hasan Farooqui, Sakthivel Selvaraj, Aashna Mehta, David L. Heymann

by Habib Hasan Farooqui, Sakthivel Selvaraj, Aashna Mehta, David L. Heymann India was the largest consumer of antibiotics in 2010 in the world. Evidence suggests that countries with high per-capita antibiotic consumption have higher rates of antibiotic resistance. To control antibiotic resistance, not only reduction in antibiotic consumption is required, socio-economic factors like access to clean water and sanitation, regulation of private healthcare sector and better governance are equally important. The key objective of this research was to investigate the five year trends in consumption of major antibiotic classes in India and compare them with European Surveillance of Antimicrobial Consumption Network (ESAC-Net) countries. We used Intercontinental Marketing Statistics (IMS) Health (now IQVIA) medicine sales audit data of antibiotic sales in the retail private sector (excluding the hospitals sector) in India. We then standardized dosage trends and assigned defined daily dose (DDD) to all formulations based on the ATC/DDD index. We expressed our data in standardized matrices of DDD per 1000 inhabitants’ per day (DID) to compare antibiotic use in India with ESAC-Net countries. The antibiotic use was plotted and reported by year and antibiotic class. Our main findings are—per capita antibiotic consumption in the retail sector in India has increased from 13.1 DID in 2008 to 16.0 DID in 2012—an increase of ~22%; use of newer class of antibiotics like carbapenems (J01DH), lincosamides (J01FF), glycopeptides (J01XA), 3rd generation cephalosporins (J01DD) and penicillin’s with beta-lactamase inhibitors has risen; and antibiotic consumption rates in India are still low as compared to ESAC-Net countries (16.0 DID vs. 21.54 DID). To conclude our study has provided the first reliable estimates of antibiotic use in the retail sector in India vis-à-vis ESAC-Net countries. In addition, our study could provide a reference point to measure the impact of interventions directed towards reducing antibiotic use.

Deborah Nyirenda, Kate Gooding, Wezzie Lora, Moses Kumwenda, Meredith McMorrow, Dean Everett, Nicola Desmond

by Deborah Nyirenda, Kate Gooding, Wezzie Lora, Moses Kumwenda, Meredith McMorrow, Dean Everett, Nicola Desmond Background Community engagement on research design is widely highlighted as an important approach for ethical research. This article reports the experience of consulting with communities on the logo used for an influenza study in Malawi. The logo was designed for use on badges worn by study researchers, participant information sheets and other project documents, and could affect perceptions of the study and consequent engagement in the research. Methods Four focus group discussions were conducted with populations targeted by the influenza study: pregnant women, people with HIV, mothers and community members. The focus groups incorporated a participatory matrix exercise focusing on key themes emerging from the discussions such as: attractiveness, comprehension, acceptability and suggestions for improvement. Findings from the focus groups were analyzed according to these key themes. Results The consultation highlighted important benefits of discussion with communities on research design, including providing new perspectives and helping to avoid harm. For example, people living with HIV felt that one of the possible logos could increase stigma within communities. The experience also indicated potential challenges of consultation. In particular, there were contrasting perspectives among the groups, such that the consultation did not provide a clear answer about which logo should be selected. Conclusions Our experience adds to current evidence on community engagement by reporting on an area where there is less discussion of community consultation for design of a study logo. The consultation exercise reaffirmed the value of community engagement, but also the difficulty of relying on a brief consultation for decision-making in research design. Further ethical guidance is required on how to negotiate contradictory views during consultations.

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…

Naomi Lince-Deroche, Craig van Rensburg, Jaqueline Roseleur, Busola Sanusi, Jane Phiri, Pam Michelow, Jennifer S. Smith, Cindy Firnhaber

by Naomi Lince-Deroche, Craig van Rensburg, Jaqueline Roseleur, Busola Sanusi, Jane Phiri, Pam Michelow, Jennifer S. Smith, Cindy Firnhaber Background Cervical cancer incidence is significant in countries, such as South Africa, with high burdens of both HIV and human papillomavirus (HPV). Cervical cancer is largely preventable if dysplasia is diagnosed and treated early, but there is debate regarding the best approaches for screening and treatment, especially for low-resource settings. Currently South Africa provides Pap smears followed by colposcopic biopsy and LEEP if needed in its public health facilities. We estimated the costs and cost-effectiveness of two approaches for treating cervical intraepithelial neoplasia grade 2 or higher (CIN2+) among HIV-infected women, most of whom were taking antiretroviral treatment, at a public HIV treatment facility in Johannesburg, South Africa. Methods Method effectiveness was derived from an intention-to-treat analysis of data gathered in a clinical trial completed previously at the study facility. In the trial, women who were diagnosed with CIN2+ and eligible for cryotherapy were randomized to cryotherapy or LEEP. If women were CIN2+ at six months as determined via Pap smear and colposcopic biopsy, all women—regardless of their original treatment assignment—received LEEP. “Cure” was then defined as the absence of disease at 12 months based on Pap smear and colposcopic biopsy. Health service costs were estimated using micro-costing between June 2013 and April 2014. Capital costs were annualized using a discount rate of 3%. Two different service volume scenarios were considered, and results from an as-treated analysis were considered in sensitivity analysis. Results In total, 166 women with CIN2+ were enrolled (86 had LEEP; 80 had cryotherapy). At 12 months, cumulative loss to follow-up was 12.8% (11/86) for the LEEP group and 13.8% (11/80) for cryotherapy. Based on the unadjusted intention-to-treat analysis conducted for this economic evaluation, there was no significant difference in efficacy. At 12 months, 83.8% (95% CI 73.8–91.1) of women with CIN2+ at baseline and randomized to cryotherapy were free of CIN2+ disease. In contrast, 76.7% (95% CI 66.4–85.2) of women assigned to LEEP were free from disease. On average, women initially treated with cryotherapy were less costly per patient randomized at US$ 118.00 (113.91–122.10), and per case “cured” at US$ 140.90 (136.01–145.79). Women in the LEEP group cost US$ 162.56 (157.90–167.22) per patient randomized and US$ 205.59 (199.70–211.49) per case cured. In the as-treated analysis, which was based on trial data, LEEP was more efficacious than cryotherapy; however, the difference was not significant. Cryotherapy remained more cost-effective than LEEP in all sensitivity and scenario analyses. Conclusions For this cost-effectiveness analysis, using an intention-to-treat approach and taking into consideration uncertainty in the clinical and cost outcomes, a strategy involving cryotherapy plus LEEP if needed at six months was dominant to LEEP plus LEEP again at six months if needed for retreatment. However, compared to other studies comparing LEEP and cryotherapy, the efficacy results were low in both treatment groups–possibly due to the HIV-positivity of the participants. Further research is needed, but at present choosing the “right” treatment option may be less important than ensuring access to treatment and providing careful monitoring of treatment outcomes.

K. T. Bruner et al.

Lesko, Catherine R.; Lau, Bryan; Chander, Geetanjali; Moore, Richard D.

Objective: Describe all-cause mortality associated with history of injection drug use (IDU) after a validated diagnosis of four non-communicable disease (NCD) diagnoses: 1) end-stage liver disease (ESLD); 2) end-stage renal disease (ESRD); 3) cancer; or 4) myocardial infarction (MI) or stroke. Design: We followed 4 cohorts of persons in continuity HIV care in the Johns Hopkins HIV Clinic with a validated diagnosis of ESLD (n = 67), ESRD (n = 187), cancer (n = 424), and MI or stroke (n = 213) from 1996 through approximately 2014. Methods: Crude and adjusted Cox proportional hazards models to estimate hazard ratios [HR] for death after a validated diagnosis of one of four NCD diagnoses associated with history of IDU as an HIV acquisition risk factor. Results: History of IDU was not associated with death after ESRD (standardized HR = 0.98, 95% Confidence Interval [CI]: 0.57, 1.68). Associations between history of IDU and death after ESLD and MI or stroke were weak, imprecise and not statistically significant (HR = 1.17, 95% CI: 0.63, 2.19; HR = 1.21, 95% CI: 0.80, 1.83). History of IDU was not associated with death after cancer in the first 6 months, but subsequently, the adjusted HR was 2.03 (95% CI: 1.26, 3.27). Conclusion: PWID and non-IDU had strikingly similar risk and hazard of mortality after several major NCD diagnoses. Mortality after cancer diagnosis in this cohort was higher for persons with a history of IDU than those without; this may be due to being diagnosed with a different mix of specific sites and stages of cancers. Correspondence to Catherine R. Lesko, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, E7139, Baltimore, MD 21205. Tel: 410 614 6517; Fax: 410 955 0863; e-mail: clesko2@jhu.edu Received 15 May, 2018 Accepted 21 September, 2018 Copyright © 2018 Wolters Kluwer Health, Inc.

Abstract Background Viral hepatitis is an important public health issue in sub-Saharan Africa. Due to rising mortality from cirrhosis and hepatocellular carcinoma and limited implementation of screening and treatment programmes, it has been characterised as a neglected tropical disease. Synthesis of the existing evidence on the epidemiology of viral hepatitis B, C and D in Malawi is required to inform policy and identify research gaps. Methods We searched Pubmed, EMBASE and Scopus for studies reporting the epidemiology of viral hepatitis B, C and D in Malawi from 1990 to 2018. Articles reporting prevalence estimates were included provided they described details of participant selection, inclusion criteria and laboratory methods (detection of HBsAg, anti-HCV or anti-HDV antibody, HCV antigen or HCV RNA or HDV RNA). We assessed study quality using a prevalence assessment tool. Where appropriate, a pooled prevalence was calculated using a DerSimonian Laird random effects model. Results Searches identified 199 studies, 95 full text articles were reviewed and 19 articles were included. Hepatitis B surface antigen (HBsAg) seroprevalence was assessed in 14 general population cohorts. The pooled prevalence among adults was 8.1% (95% CI 6.1, 10.3). In 3 studies where HBsAg was stratified by HIV status, no effect of HIV on HBsAg prevalence was observed (OR 1.2 (95% CI: 0.8, 1.6, p = 0.80)). In a single study of HIV/HBV infected individuals, anti-hepatitis D antibody (anti-HDV) prevalence was low (1.5%). HCV antibody prevalence (anti-HCV) ranged from 0.7 to 18.0% among 12 cohorts in general populations. Among three studies which used PCR to confirm current infection, the pooled rate of HCV RNA confirmation among anti-HCV positive individuals was only 7.3% (95% CI: 0.0, 24.3). Conclusions Hepatitis B is highly prevalent in Malawi. There is a paucity of epidemiological data from rural areas where 85% of the population reside, and the Northern region. Priority research needs include large-scale representative community studies of HBV, HDV and HCV seroprevalence, assessment of children following introduction of the HBV vaccine in 2002, prevalence estimates of viral hepatitis among individuals with cirrhosis and HCC and data on HCV prevalence using PCR confirmation, to support a viral hepatitis strategy for Malawi.

Eyasu Ejeta, Getenet Beyene, Getu Balay, Zegeye Bonsa, Gemeda Abebe

by Eyasu Ejeta, Getenet Beyene, Getu Balay, Zegeye Bonsa, Gemeda Abebe Background Tuberculosis (TB) is a leading cause of public health challenges among immigrant refugees and their surrounding communities in developing countries. Evaluating the treatment outcome of TB patients is one of the key indicators to understand the performance of TB control program. Hence, this study aims to assess profile, treatment outcome and factors associated with unsuccessful outcome of TB patients treated under the TB control program among refugees and their surrounding communities (SCs) in Gambella Regional State, Ethiopia. Methodology Retrospective study was conducted in the health facilities of refugee and their SCs in Gambella Regional State from March 1 to May 30, 2017. Demographic and related data of all TB patients registered in TB Control Program between September, 2008 and October, 2017 in health facilities of refugee and the SCs was extracted using data extraction format. Eight years trend of TB, treatment outcome and factors associated with unsuccessful outcome among refugees and the SCs were computed using SPSS version 20.0 software. Result A total of 886 refugees and 3284 SCs TB patients, registered for anti TB treatment in the last eight years, were evaluated in the study. The trend of all forms of TB is progressively increasing among refugees contrary to the SCs in the course of the study period (X2 trend = 207.7; p

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.

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.

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…

Abstract Background Cryptococcal meningitis remains the leading cause of adult meningitis in Sub-Saharan Africa. Immune Reconstitution Inflammatory Syndrome (IRIS) following anti-retroviral therapy (ART) initiation is an important complication. Here we report the first documented case of a IRIS reaction presenting as an ischemic stroke. Case presentation A 38 year old newly diagnosed HIV-infected, ART naive Malawian male presented to a tertiary referral hospital in Blantyre, Malawi with a 2 week history of headache. A diagnosis of cryptococcal meningitis was made and the patient was started on 1200 mg fluconazole once daily and flucytosine 25 mg/kg four times daily as part of the Advancing Cryptococcal Treatment for Africa (ACTA) clinical trial. There was an initial clinical and microbiological response to anti-fungal treatment and anti-retroviral therapy was started at week 4. The patient re-presented 16 days later with recurrence of headache, fever, and a sudden onset of left sided weakness in the context of rapid immune reconstitution; peripheral CD4 count had increased from a baseline of 29 cells/μl to 198 cells/μl. Recurrence of cryptococcal meningitis was excluded through CSF examination and fungal culture. Magnetic Resonance Imaging (MRI) of the brain demonstrated multi-focal DWI (diffusion weighted imaging) positive lesions consistent with an ischemic stroke. Given the temporal relationship to ART initiation, these MRI findings in the context of sterile CSF with raised CSF protein and a rapid immune reconstitution, following an earlier favorable response to treatment is most consistent with a paradoxical Immune Reconstitution Inflammatory Syndrome. Conclusions Stroke is an increasing cause of morbidity and mortality amongst HIV infected persons. Ischemic stroke is a recognized complication of cryptococcal meningitis in the acute phase and is thought to be mediated by an infectious vasculitis. This is the first time an ischemic stroke has been described as part of a paradoxical IRIS reaction. This report adds to the spectrum of clinical IRIS presentations recognized and highlights to clinicians the potential complications encountered at ART initiation in severely immunocompromised patients.

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 …

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…

M. Verdecchia, K. Keus, S. Blankley, D. Vambe, C. Ssonko, T. Piening, E. C. Casas

by M. Verdecchia, K. Keus, S. Blankley, D. Vambe, C. Ssonko, T. Piening, E. C. Casas Introduction Since 2011 Médecins sans Frontières together with the eSwatini Ministry of Health have been managing patients with multi-drug resistant tuberculosis (MDR-TB) at Matsapha and Mankayane in Manzini region. This analysis describes the model of care and outcomes of patients receiving a 20 months MDR-TB treatment regimen between 2011 and 2013. Method We conducted a retrospective observational cohort study of MDR-TB patients enrolled for treatment between May 2011 and December 2013. An extensive package of psychological care and socio-economic incentives were provided including psychological support, paid treatment supporters, transport fees and a monthly food package. Baseline demographic details and treatment outcomes were recorded and for HIV positive patient’s univariate analysis as well as a cox regression hazard model were undertaken to assess risk factors for unfavorable outcomes. Results From the 174 patients enrolled, 156 (89.7%) were HIV co-infected, 102 (58.6%) were female, median age 33 years old (IQR: 28–42), 55 (31.6%) had a BMI less than 18 and 86 (49.4%) had not been previously treated for any form of TB. Overall cohort outcomes revealed a 75.3% treatment success rate, 21.3% mortality rate, 0.6% failure and 0.6% lost to follow-up rate. In the adjusted multivariate analysis, low BMI and low CD4 count at treatment initiation were associated with an increased risk of unfavorable outcome. Conclusions A model of care that included psychosocial support and patient’s enablers led to a high level of treatment success with a very low lost to follow up rate. Limiting the overall treatment success was a high mortality rate which was associated with advanced HIV and a low BMI at presentation. These factors will need to be addressed in order to improve upon the overall treatment success rate in future.

The European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) Study Group

Objectives: to investigate whether specific nucleoside reverse transcriptase inhibitor (NRTI) backbones are associated with risk of adverse pregnancy outcomes among pregnant women starting antiretroviral therapy (ART) Design: Seven observational studies across eight European countries of pregnancies in HIV-positive women Methods: Individual-level data were pooled on singleton pregnancies conceived off-ART in which a single combination ART regimen was initiated ≥2 weeks before delivery, and ending in a live birth in 2008-2014. Preterm delivery (PTD) was defined as…

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.

Albert Magohe, Todd Mackenzie, Josephine Kimario, Zohra Lukmanji, Kristy Hendricks, John Koethe, Nyasule Majura Neke, Susan Tvaroha, Ruth Connor, Richard Waddell, Isaac Maro, Mecky Matee, Kisali Pallangyo, Muhammad Bakari, C. Fordham von Reyn, DarDar-2 Study Team

by Albert Magohe, Todd Mackenzie, Josephine Kimario, Zohra Lukmanji, Kristy Hendricks, John Koethe, Nyasule Majura Neke, Susan Tvaroha, Ruth Connor, Richard Waddell, Isaac Maro, Mecky Matee, Kisali Pallangyo, Muhammad Bakari, C. Fordham von Reyn, DarDar-2 Study Team Objective To determine if a protein-calorie supplement (PCS) plus a micronutrient supplement (MNS) improves outcomes for HIV-infected lactating women and their infants. Design Randomized, controlled trial. Setting Dar es Salaam, Tanzania Subjects, participants Pregnant HIV-infected women enrolled in PMTCT programs who intended to breastfeed for 6 months. Intervention Randomization 1:1 to administration of a PCS plus MNS versus MNS alone among 96 eligible women beginning in the third trimester and continuing for 6 months of breast-feeding. Main outcome measure(s) Primary: infant weight at 3 months. Secondary: maternal BMI at 6 months. Results PCS resulted in significant increases in daily energy intake compared to MNS at all time points (range of differences: +388–719 Kcal); and increases in daily protein intake (range of differences: +22–33 gm). Infant birth weight (excluding twins) was higher in the PCS than MNS groups: 3.30 kg vs 3.04 kg (p = 0.04). Infant weight at 3 months did not differ between PCS and MNS groups: 5.63 kg vs 5.99 kg (p = 0.07). Maternal BMI at 6 months did not differ between PCS and MNS groups: 24.3 vs 23.8 kg/m2 (p = 0.68). HIV transmission occurred in 0 infants in the PCS group vs 4 in the MNS group (p = 0.03). Conclusions In comparison to MNS the PCS + MNS intervention was well tolerated, increased maternal energy and protein intake, and increased infant birth weight, but not weight at 3 months or maternal BMI at 6 months. Reduced infant HIV transmission in the PCS + MNS group was observed. Trial registration Clinical Trials.Gov NCT01461863.

Liza Coyer, Ward van Bilsen, Janneke Bil, Udi Davidovich, Elske Hoornenborg, Maria Prins, Amy Matser

by Liza Coyer, Ward van Bilsen, Janneke Bil, Udi Davidovich, Elske Hoornenborg, Maria Prins, Amy Matser Objective Currently, HIV pre-exposure prophylaxis (PrEP) is not covered by health insurance in the Netherlands. We examined time trends in use of PrEP, characteristics of PrEP users, PrEP eligibility and intention to use PrEP among HIV-negative men who have sex with men (MSM) participating in the Amsterdam Cohort Studies (ACS). Design Prospective cohort study. Methods We used data from four 6-monthly questionnaire waves, collected between 2015–2017. PrEP use over time was examined in logistic regression models using generalized estimating equations. Using descriptive statistics, we compared PrEP users before first-time initiation to non-PrEP-users. We used national guidelines to assess PrEP eligibility. Results We included 687 MSM. Median age was 40 (IQR 33–47) years in 2015. Recent PrEP use was reported by 57/687 (8%) MSM. PrEP use increased over calendar time (P…

Rodríguez-Gallego E, Tarancón-Diez L, García F, et al.

AbstractBackgroundElite Controllers (EC) spontaneously control plasma HIV-1-RNA without antiretroviral therapy. However, 25% lose virological control over time. The aim of this work was to study the proteomic profile that preceded this loss of virological control to identify potential biomarkers.MethodsPlasma samples from EC who spontaneously lost virological control (Transient Controllers, TC), at two and one year before the loss of control, were compared with a control group of EC who persistently maintained virological control during the same follow-up period (Persistent Controllers, PC). Comparative plasma shotgun proteomics was performed with TMT isobaric tag labeling and nanoflow liquid chromatography coupled to Orbitrap mass spectrometry.ResultsEighteen proteins exhibited differences comparing PC and pre-loss TC time points. These proteins were involved in proinflammatory mechanisms and some of them play a role in HIV-1 replication and pathogenesis and interact with structural viral proteins. Coagulation factor XI, Alpha-1-antichymotrypsin, Ficolin-2, 14-3-3 protein and Galectin-3-binding protein were considered potential biomarkers.ConclusionThe proteomic signature associated with the spontaneous loss of virological control was characterized by higher levels of inflammation, transendothelial migration and coagulation. Galectin-3-binding protein could be considered as potential biomarker for the prediction of virological progression and as therapeutic target in EC.

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 =  …

Wallis C, Godfrey C, Fitzgibbon J, et al.

To the Editor—We agree with Suthar and colleagues that substandard and falsified antiretrovirals (ARV) could affect the efficacy of antiretroviral therapy (ART) and promote the emergence and spread of human immunodeficiency virus-1 (HIV-1) drug resistance. Rigorous quality control of the ARV supply will ensure appropriate ARV exposure to both maintain viral suppression and minimize ARV-related toxicities. A key unanswered question is the range of ARV exposures across large populations of individuals that maintain both efficacy and safety. A recent study of cumulative ARV exposure, measured by their levels in hair samples, showed that a broad range of ARV exposures are compatible with sustained suppression of HIV-1 [1].

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

No abstract available…

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.

Zuckerman, Neta S.; Mor, Zohar; Bucris, Efrat; Wax, Marina; Mendelson, Ella; Mor, Orna

Objectives: Men who have sex with men (MSM) comprise ∼30% of new HIV infections in Israel, a country with mixed Jewish and Arab populations. We molecularly characterized HIV-1 in the Arab and Jewish MSM (AMSM, JMSM) populations to reveal possible inter-ethnical connections. Design: Cross-sectional study Methods: All Israeli-born, HIV-1-infected MSM diagnosed between 2005 and 2016 (n = 1143) were cross-matched with the National Civil Registry to identify religion (Jews/Muslim/Christian). Transmitted drug-resistance mutations (TDRM) and HIV-1 subtypes were determined on the first partial protease (PR) and reverse transcriptase (RT) sequences from treatment-naive patients and phylogenetic trees were constructed. Results: Among MSM, 6.4% (73/1,143) were Arabs and 93.6% (1,070/1,143) were Jews. Interestingly, a higher proportion of Arabs was identified among non-MSM (19%, 46/247 versus 6.4%, 73/1,143, p …

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.

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.

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.

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 …