Reif, Lindsey K.; Rivera, Vanessa; Bertrand, Rachel; Belizaire, Marie; Joseph, Bajo; Louis, Bianca; Joseph, Bernadette; Anglade, Benedict; Seo, Grace; Severe, Patrice; Rouzier, Vanessa; Pape, Jean W.; Fitzgerald, Daniel W.; McNairy, Margaret L.

No abstract available…

Venanzi Rullo E, Cannon L, Pinzone M, et al.

HIVNaïveMemoryreservoir…

Candice M. Chetty-Makkan, Jonathan M. Grund, Reuben Munyai, Vuyokazi Gadla, Violet Chihota, Mpho Maraisane, Salome Charalambous

by Candice M. Chetty-Makkan, Jonathan M. Grund, Reuben Munyai, Vuyokazi Gadla, Violet Chihota, Mpho Maraisane, Salome Charalambous Introduction Voluntary medical male circumcision (VMMC) reduces the risk of HIV infection in heterosexual men and has long-term indirect protection for women, yet VMMC uptake in South Africa remains low (49.8%) in men (25–49 years). We explored the attitude and willingness of women to start conversations on VMMC with their sexual partners in a South African peri-urban setting to increase VMMC uptake. Methods Thirty women with median age of 30 years (inter-quartile range 26–33 years) were interviewed in a language of their choice. Key questions included: types of approach to use, gender roles, benefits and barriers to introducing the topic of VMMC, and perceptions of VMMC. Interviews were digitally-recorded, transcribed, and translated. Through a standard iterative process, a codebook was developed (QSR NVIVO 10 software) and inductive thematic analysis applied. Results Most women were willing talk to their sexual partners about circumcision, but indicated that the decision to circumcise remained that of their sexual partner. Women felt that they should encourage their partners, show more interest in circumcision, be patient, speak in a caring and respectful tone, choose a correct time when their partner was relaxed and talk in a private space about VMMC. Using magazine/newspaper articles, pamphlets or advertisements were identified as tools that could aid their discussion. Substantial barriers to initiating conversations on VMMC included accusations by partner on infidelity, fear of gender-based violence, cultural restrictions and hesitation to speak to a mature partner about circumcision. Conclusions Women need to ensure that before talking to their partner about circumcision, the environment and approach that they use are conducive. Female social network forums could be used to educate women on conversation techniques, skills to use when talking to their partners and how to address communication challenges about circumcision. Involvement of women in VMMC awareness campaigns could encourage circumcision uptake among men.…

Pedro Cahn, Juan Sierra Madero, José Ramón Arribas, Andrea Antinori, Roberto Ortiz, Amanda E Clarke, Chien-Ching Hung, Jürgen K Rockstroh, Pierre-Marie Girard, Jörg Sievers, Choy Man, Alexander Currie, Mark Underwood, Allan R Tenorio, Keith Pappa, Brian Wynne, Anna Fettiplace, Martin Gartland, Michael Aboud, Kimberly Smith, GEMINI Study Team

The non-inferior efficacy and similar tolerability profile of dolutegravir plus lamivudine to a guideline-recommended three-drug regimen at 48 weeks in ART-naive adults supports its use as initial therapy for patients with HIV-1 infection.

Michael Aboud, Richard Kaplan, Johannes Lombaard, Fujie Zhang, José A Hidalgo, Elmira Mamedova, Marcelo H Losso, Ploenchan Chetchotisakd, Carlos Brites, Jörg Sievers, Dannae Brown, Judy Hopking, Mark Underwood, Maria Claudia Nascimento, Yogesh Punekar, Martin Gartland, Kimberly Smith

When administered with two NRTIs, dolutegravir was superior to ritonavir-boosted lopinavir at 48 weeks and can be considered a suitable option for second-line treatment.

Joris Hemelaar, Ramyiadarsini Elangovan, Jason Yun, Leslie Dickson-Tetteh, Isabella Fleminger, Shona Kirtley, Brian Williams, Eleanor Gouws-Williams, Peter D Ghys, WHO–UNAIDS Network for HIV Isolation Characterisation

Global and regional HIV diversity is complex and evolving, and is a major challenge to HIV vaccine development. Surveillance of the global molecular epidemiology of HIV-1 remains crucial for the design, testing, and implementation of HIV vaccines.

Jack Stone, Hannah Fraser, Aaron G Lim, Josephine G Walker, Zoe Ward, Louis MacGregor, Adam Trickey, Sam Abbott, Steffanie A Strathdee, Daniela Abramovitz, Lisa Maher, Jenny Iversen, Julie Bruneau, Geng Zang, Richard S Garfein, Yung-Fen Yen, Tasnim Azim, Shruti H Mehta, Michael-John Milloy, Margaret E Hellard, Rachel Sacks-Davis, Paul M Dietze, Campbell Aitken, Malvina Aladashvili, Tengiz Tsertsvadze, Viktor Mravčík, Michel Alary, Elise Roy, Pavlo Smyrnov, Yana Sazonova, April M Young, Jennifer R Havens, Vi

Incarceration is associated with substantial short-term increases in HIV and HCV acquisition risk among PWID and could be a significant driver of HCV and HIV transmission among PWID. These findings support the need for developing novel interventions to minimise the risk of HCV and HIV acquisition, including addressing structural risks associated with drug laws and excessive incarceration of PWID.

Rosanna Wai Wan Peeling, David Mabey

WHO recommends syndromic management of sexually transmitted infections in patients attending health-care facilities in resource-limited settings where laboratory services are limited. With a syndromic approach, care providers treat all the common causes of a presenting syndrome, and provide counselling, condom promotion, and contact tracing. Syndromic management has been successfully rolled out to primary health care in many countries, and has been shown to reduce the prevalence of sexually transmitted infections and HIV.

The Lancet

The February, 2019, Centers for Disease Control and Prevention (CDC) publication, Estimated HIV Incidence and Prevalence in the United States, 2010–2016, comes at a time when much positive noise is being made about effectively eliminating new HIV infections in the USA. In his recent State of the Union address, President Donald Trump unexpectedly announced a commitment to “eliminate the HIV epidemic in the United States within 10 years”, with a government report out the same day putting these goals at a 75% reduction in new cases within 5 years and a 90% reduction within 10 years.

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.

Seth C Inzaule, Raph L Hamers, Meg Doherty, Robert W Shafer, Silvia Bertagnolio, Tobias F Rinke de Wit

To improve virological suppression and address the emerging threat of HIV drug resistance, many low-income and middle-income countries are moving away from non-nucleoside reverse transcriptase inhibitors (NNRTI) and transitioning to dolutegravir as part of a more affordable and standardised antiretroviral therapy (ART). Although this transition could decrease the effect of rising NNRTI resistance and yield improved ART outcomes, it also presents new challenges. First, current safety concerns for dolutegravir use in women of childbearing potential require alternative solutions.

Richard Barnett

From 1817 onwards European governments, struggling in the aftermath of the Napoleonic Wars, watched with growing horror as a new and terrible disease left its historical heartland in south Asia and began to move west. Cholera, in the words of an editorial in the Quarterly Review, was “one of the most terrible pestilences which have ever devastated the earth”. Like malaria or HIV/AIDS, cholera has an inescapably global history: seven subsequent pandemics have provoked revolutions in public health, and an entirely new vision of global medicine in an age of interconnection.

Angela M Bengtson, Alan M Sanfilippo, Brenna L Hughes, David A Savitz

HIV-exposed but uninfected (HEU) infants are at an increased risk of many infectious diseases that can contribute to the high mortality seen among HEU children. Maternal immunisation could be a promising strategy to reduce infections in HEU infants. However, very little research has explored the effect of HIV on the immunogenicity and effectiveness of vaccines given during pregnancy. We review the available evidence on maternal immunisation among women living with HIV (WLWH) for all vaccines recommended, considered, or being investigated for routine or risk-based use during pregnancy.

Julian S Peters, Jason R Andrews, Mark Hatherill, Sabine Hermans, Leonardo Martinez, Erwin Schurr, Yuri van der Heijden, Robin Wood, Roxana Rustomjee, Bavesh D Kana

Tuberculosis claims more human lives than any other infectious disease. This alarming epidemic has fuelled the development of novel antimicrobials and diagnostics. However, public health interventions that interrupt transmission have been slow to emerge, particularly in HIV-endemic settings. Transmission of tuberculosis is complex, involving various environmental, bacteriological, and host factors, among which concomitant HIV infection is important. Preventing person-to-person spread is central to halting the epidemic and, consequently, tuberculosis transmission is now being studied with renewed interest.

Patrick G T Cudahy, Jason R Andrews, Alyssa Bilinski, David W Dowdy, Barun Mathema, Nicolas A Menzies, Joshua A Salomon, Sourya Shrestha, Ted Cohen

As the leading infectious cause of death worldwide and the primary proximal cause of death in individuals living with HIV, tuberculosis remains a global concern. Existing tuberculosis control strategies that rely on passive case-finding appear insufficient to achieve targets for reductions in tuberculosis incidence and mortality. Active case-finding strategies aim to detect infectious individuals earlier in their infectious period to reduce onward transmission and improve treatment outcomes. Empirical studies of active case-finding have produced mixed results and determining how to direct active screening to those most at risk remains a topic of intense research.

Palwasha Y Khan, Tom A Yates, Muhammad Osman, Robin M Warren, Yuri van der Heijden, Nesri Padayatchi, Edward A Nardell, David Moore, Barun Mathema, Neel Gandhi, Vegard Eldholm, Keertan Dheda, Anneke C Hesseling, Valerie Mizrahi, Roxana Rustomjee, Alexander Pym

The emergence and expansion of the multidrug-resistant tuberculosis epidemic is a threat to the global control of tuberculosis. Multidrug-resistant tuberculosis is the result of the selection of resistance-conferring mutations during inadequate antituberculosis treatment. However, HIV has a profound effect on the natural history of tuberculosis, manifesting in an increased rate of disease progression, leading to increased transmission and amplification of multidrug-resistant tuberculosis. Interventions specific to HIV-endemic areas are urgently needed to block tuberculosis transmission.

Xun Yuan

Officials now say that there is no detectable HIV antibody in the suspect plasma batch, but no explanation has been offered to explain original test results. Xun Yuan reports.

Tony Kirby

Twelve years on from the so-called Berlin patient, a second patient in London, UK, appears to be in remission from HIV infection. Tony Kirby reports.

Susan Jaffe

The unexpected announcement in the State of the Union address could set the start of a realistic agenda to end HIV/AIDS in the USA, provided funds are secured. Susan Jaffe reports.

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.

Bassirou Diarra, Mahamadou Kone, Antieme Combo Georges Togo, Yeya dit Sadio Sarro, Aissata Boubakar Cisse, Amadou Somboro, Boureima Degoga, Mohamed Tolofoudie, Bourahima Kone, Moumine Sanogo, Bocar Baya, Ousmane Kodio, Mamoudou Maiga, Michael Belson, Susan Orsega, Meryam Krit, Sounkalo Dao, Ibrahim Izétiegouma Maiga, Robert L. Murphy, Leen Rigouts, Seydou Doumbia, Souleymane Diallo, Bouke Catherine de Jong

by Bassirou Diarra, Mahamadou Kone, Antieme Combo Georges Togo, Yeya dit Sadio Sarro, Aissata Boubakar Cisse, Amadou Somboro, Boureima Degoga, Mohamed Tolofoudie, Bourahima Kone, Moumine Sanogo, Bocar Baya, Ousmane Kodio, Mamoudou Maiga, Michael Belson, Susan Orsega, Meryam Krit, Sounkalo Dao, Ibrahim Izétiegouma Maiga, Robert L. Murphy, Leen Rigouts, Seydou Doumbia, Souleymane Diallo, Bouke Catherine de Jong Objective Ancestral M. tuberculosis complex lineages such as M. africanum are underrepresented among retreatment patients and those with drug resistance. To test the hypothesis that they respond faster to TB treatment, we determined the rate of smear conversion of new pulmonary tuberculosis patients in Bamako, Mali by the main MTBc lineages. Methods Between 2015 and 2017, we conducted a prospective cohort study of new smear positive pulmonary tuberculosis patients in Bamako. Confirmed MTBc isolates underwent genotyping by spoligotyping for lineage classification. Patients were followed at 1 month (M), 2M and 5M to measure smear conversion in auramine (AR) and Fluorescein DiAcetate (FDA) vital stain microscopy. Result All the first six human MTBc lineages were represented in the population, plus M. bovis in 0.8% of the patients. The most widely represented lineage was the modern Euro-American lineage (L) 4, 57%, predominantly the T family, followed by L6 (M. africanum type 2) in 22.9%. Ancestral lineages 1, 5, 6 and M. bovis combined amounted to 28.8%. Excluding 25 patients with rifampicin resistance, smear conversion, both by AR and FDA, occurred later in L6 compared to L4 (HR 0.80 (95% CI 0.66–0.97) for AR, and HR 0.81 (95%CI 0.68–0.97) for FDA). In addition we found that HIV negative status, higher BMI at day 0, and patients with smear grade at baseline ≤ 1+ were associated with earlier smear conversion. Conclusion The six major human lineages of the MTBc all circulate in Bamako. Counter to our hypothesis, we found that patients diseased with modern M. tuberculosis complex L4 respond faster to TB treatment than those with M. africanum L6.…

Ji Soo Choi, Sang Hoon Lee, Ah Young Leem, Joo Han Song, Song Yee Kim, Kyung Soo Chung, Ji Ye Jung, Young Ae Kang, Young Sam Kim, Joon Chang, Moo Suk Park

by Ji Soo Choi, Sang Hoon Lee, Ah Young Leem, Joo Han Song, Song Yee Kim, Kyung Soo Chung, Ji Ye Jung, Young Ae Kang, Young Sam Kim, Joon Chang, Moo Suk Park Background Pneumocystis jirovecii pneumonia (PCP) is often fatal in human immunodeficiency (HIV)-negative patients and typically presents with respiratory insufficiency. Predicting treatment failure is challenging. This study aimed to identify prognostic factors and examine PCP polymerase chain reaction (PCR)-negative conversion in non-HIV PCP patients with respiratory failure. Method We retrospectively enrolled 81 non-HIV patients diagnosed with and treated for PCP with respiratory failure in the intensive care unit at a tertiary hospital over a 3-year period. PCP was diagnosed via nested PCR-mediated detection of Pneumocystis jirovecii in induced sputum samples, endotracheal aspirates, and bronchoalveolar lavage fluids. PCP PCR was performed weekly to check for negative conversion. Results The overall survival rate was 35.8%. Seventy-four patients (91.3%) required mechanical ventilation, and 6 (7.4%) required high-flow nasal oxygen treatment. The PCP PCR-negative conversion rate was 70.5% (survivors, 97%; non-survivors, 63.5%); the median time to conversion was 10 (7.0–14.0) days. On univariate analysis, the APACHE II score (p < 0.001), renal failure requiring renal replacement therapy (p = 0.04), PCP PCR-negative conversion (p = 0.003), and the PaO2/FiO2 ratio (first 24 hours) (p < 0.001) significantly correlated with mortality. On multivariate analysis, PCP PCR-negative conversion (hazard ratio, 0.433; 95% confidence interval, 0.203–0.928; p = 0.031) and the PaO2/FiO2 ratio (first 24 hours) (hazard ratio, 0.988; 95% confidence interval, 0.983–0.993; p < 0.001) independently predicted prognosis. Conclusions Determination of PCP PCR-negative conversion and PaO2/FiO2 ratios may help physicians predict treatment failure and mortality in non-HIV PCP patients with respiratory failure.…

Jao, Jennifer; Jacobson, Denise L.; Yu, Wendy; Borkowsky, William; Geffner, Mitchell E.; McFarland, Elizabeth J.; Patel, Kunjal; Williams, Paige L.; Miller, Tracie; for the Pediatric HIV/AIDS Cohort Study

Background: Metabolic perturbations in HIV-exposed uninfected (HEU) obese youth may differ from those in the general obese pediatric population. Methods: Metabolic parameters of obese (Body Mass Index Z-score >95th percentile) HEU youth in the Pediatric HIV/AIDS Cohort Study (PHACS) Surveillance Monitoring of ART Toxicities (SMARTT) study were compared with a matched sample of obese youth from the U.S. National Health and Nutrition Examination Survey (NHANES). We evaluated systolic and diastolic hypertension [blood pressure (BP) >90th percentile for age, sex, and height], total cholesterol (TC) >200 mg/dL, high-density lipoprotein cholesterol (HDL) 130 mg/dL, triglycerides (TG) >150 mg/dL, and Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) >4.0. Modified Poisson regression models were fit to quantify the prevalence ratio (PR) of each outcome comparing the two cohorts, adjusting for confounders. Results: The BP outcome analytic subgroup included 1096 participants (n=304 HEU), the TC and HDL subgroup 1301 participants (n=385 HEU), and the LDL, TG, and HOMA-IR subgroup 271 (n=83 HEU). After adjustment, obese HEU youth had a higher prevalence of systolic and diastolic hypertension [PR=3.34, 95% Confidence Interval (CI): 2.48-4.50; PR=2.04, 95% CI: 1.18-3.52, respectively], but lower prevalence of insulin resistance (PR=0.67, 95% CI: 0.54-0.85) and hypercholesterolemia (PR=0.67, 95% CI: 0.44-1.01) compared to obese NHANES youth. Conclusions: In the U.S., obese HEU youth appear to have increased risk for hypertension, but lower risk for insulin resistance and hypercholesterolemia, compared to a general obese pediatric population. Monitoring for cardiovascular morbidity in adulthood may be warranted in HEU children. Corresponding author: Jennifer Jao, MD, MPH, Northwestern University, Feinberg School of Medicine, 225 E. Chicago Ave, Box 20, Chicago, IL 60611, jennifer.jao@northwestern.edu, 312.227.4080 (office), 312.227.9709 (fax) Note: The conclusions and opinions expressed in this article are those of the authors and do not necessarily reflect those of the National Institutes of Health or U.S. Department of Health and Human Services. JJ was supported by NICHD K23HD070760 during the part of the preparation of this manuscript. MG serves as a consultant for AbbVie, BioBridge, Daiichi Sankyo, Diurnal, Endo, Nutritional Growth Solutions, Novo Nordisk, Pfizer, and Sandoz; is a member of data safety monitoring boards for Ascendis and Tolmar; receives royalties from McGraw-Hill and UpToDate. EJM receives institutional support for conducting clinical trials investigating pediatric antiretrovirals sponsored by Gilead, Inc. For the remaining authors, no other funding sources or conflicts of interests were declared. Conflicts of Interests and Funding Sources: The Pediatric HIV/AIDS Cohort Study (PHACS) was supported by the Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD) with co-funding from the National Institute Of Dental & Craniofacial Research (NIDCR), the National Institute Of Allergy And Infectious Diseases (NIAID), the National Institute Of Neurological Disorders And Stroke (NINDS), the National Institute On Deafness And Other Communication Disorders (NIDCD), Office of AIDS Research (OAR), the National Institute Of Mental Health (NIMH), the National Institute On Drug Abuse (NIDA), and the National Institute On Alcohol Abuse And Alcoholism (NIAAA), through cooperative agreements with the Harvard T.H. Chan School of Public Health (HD052102) and the Tulane University School of Medicine (HD052104). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Kristal Duncan, Edina Sinanovic

by Kristal Duncan, Edina Sinanovic Background In South Africa, 600–700 new cases of paediatric cancers have been reported every year for the past 25 years, and in the year 2000, HIV/AIDS was responsible for 42,479 deaths in children under five. These children need intermediate care but research in the field is lacking, with the few costing studies conducted in South Africa reporting a range of inpatient day costs. Methods A retrospective cost analysis for the period April 2014-March 2015 was undertaken from the provider perspective in the public sector, using a step down costing approach. Costs of paediatric intermediate care were estimated for an intermediate care facility (ICF) and a tertiary hospital in Cape Town. Costs were inflated to 2016 prices and reported in US dollars. Results Cost per inpatient day was $713.09 at the hospital and $695.17 at the ICF for any child requiring care at these institutions. The cost for a paediatric patient who is HIV/TB co-infected was $7 130.94 and $6 951.67 at the hospital and ICF respectively, assuming an average length of stay of 10 days. For a patient with terminal brain carcinoma the cost was $19 966.63 and $19 464.69 at the hospital and ICF respectively, assuming an average length of stay of 28 days. Personnel costs accounted for 60% and 17% of the total cost at the hospital and ICF respectively. Overhead costs accounted for 12.33% at the ICF and 4.48% at the hospital. Conclusions The drivers of cost are not uniform across settings. Providing intermediate care at an ICF could be less costly than providing this care at a hospital, however more in-depth analysis is needed. The costs presented in this study were considerably higher than those found in other studies, however, the paucity of cost data available in this area makes comparisons difficult.…

Abstract Background The roll out of antiretroviral therapy (ART) in Sub-Saharan Africa led to a decrease in mortality. Few studies have documented the causes of deaths among patients on long term antiretroviral therapy in Sub-Saharan Africa. Our objective was to describe the causes of death among patients on long term ART in Sub-Saharan Africa. Methods We used data from a prospective cohort of ART naïve patients receiving care and treatment at the Infectious Diseases Institute in Kampala, Uganda. Patients were followed up for 10 years. All deaths were recorded and possible causes established using verbal autopsy. Deaths were grouped as HIV-related (ART toxicities, any opportunistic infections (OIs) and HIV-related malignancies) and non-HIV related deaths while some remained unknown. We used Kaplan Meier survival methods to estimate cumulative incidence and rates of mortality for all causes of death. Results Of the 559, (386, 69%) were female, median age 36 years (IQR: 21–44), 89% had WHO clinical stages 3 and 4, and median CD4 count at ART initiation was 98 cells/μL (IQR: 21–163). A total of 127 (22.7%) deaths occurred in 10 years. The HIV related causes of death (n = 70) included the following; Tuberculosis 17 (24.3%), Cryptococcal meningitis 10 (15.7%), Kaposi’s Sarcoma 7(10%), HIV related toxicity 6 (8.6%), HIV related anemia 5(7.1%), Pneumocystis carinii Pneumonia (PCP) 5 (7.1%), HIV related chronic diarrhea 4 (5.7%), Non-Hodgkin Lymphoma 3 (4.3%), Herpes Zoster 2 (2.8%), other 10 (14.3%). The non-HIV related causes of death (n = 20) included non-communicable diseases (diabetes, hypertension, stroke) 6 (30%), malaria 3 (15%), pregnancy-related death 2 (10%), cervical cancer 2 (10%), trauma 1(5%) and others 6 (30%). Conclusion Despite the higher rates of deaths from OIs in the early years of ART initiation, we observed an emergence of non-HIV related causes of morbidity and mortality. It is recommended that HIV programs in resource-limited settings start planning for screening and treatment of non-communicable diseases.…

Kapoor, Nitin; Audsley, Jennifer; Rupali, Priscilla; Sasadeusz, Joe; Paul, Thomas V.; Thomas, Nihal; Lewin, Sharon R.

Despite the decreasing total incidence of liver-related deaths, liver disease remains one of the major non-AIDS causes of morbidity and mortality amongst people living with HIV, and a significant proportion of liver disease in these individuals can be attributed to nonalcoholic fatty liver disease (NAFLD). NAFLD in HIV infection is a growing problem in view of increasing life expectancy associated with the use of effective antiretroviral therapy (ART), wider uptake of ART and increasing rates of obesity in many Asian as well as western countries. The problem may be more pronounced in developing countries where there are limited resources available for mass screening and diagnosis of NAFLD. There is a small but growing body of literature examining NAFLD in the setting of HIV, with data from low and middle-income countries (LMICs) particularly lacking. Here, we review the cohort data on NAFLD in HIV, and discuss the risk factors, pathogenesis of hepatic steatosis, NAFLD and nonalcoholic steatohepatitis (NASH), diagnostic approaches and therapeutic options available for NAFLD in the setting of HIV, and the specific challenges of NAFLD in HIV for LMICs. Correspondence to Jennifer Audsley, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, VIC, Australia. E-mail: jennifer.audsley@unimelb.edu.au Received 24 October, 2018 Revised 10 January, 2019 Accepted 10 January, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

Leung J, Peacock A, Colledge S, et al.

AbstractBackgroundWomen-specific factors exist that increases vulnerability to drug-related harms from injecting drug use including bloodborne viruses (BBV), but gender differences in BBV prevalence have not been systematically examined.MethodsWe conducted meta-analyses to estimate country, regional, and global prevalence of serologically-confirmed HIV, hepatitis C (anti-HCV) and hepatitis B (HBsAg) prevalence in people who inject drugs (PWID) by gender. Gender differences in BBV (relative risks, RR in women vs men) were regressed on country-level prevalence and inequality measures. ResultsGender differences varied by countries and regions. HIV prevalence was higher among women than men in Sub-Saharan Africa (RR=2.8, 95%CI 1.8-4.4) and South Asia (RR=1.7, 1.1-2.7); anti-HCV was lower among women in the Middle East and North Africa (RR=0.6, 0.5-0.7) and East and Southeast Asia (RR=0.8, 0.7-0.9). Gender differences varied with country-levels of BBV in the general population, human development, and income distribution. ConclusionHIV infection was more prevalent in women who inject drugs compared to their male counterparts in some countries, but there is between and within regional variation. In countries where women are at higher risks, there is a need to develop gender-sensitive harm reduction services for the particularly marginalized population of women who inject drugs.

Ross, Jeremy L; Teeraananchai, Sirinya; Lumbiganon, Pagakrong; Hansudewechakul, Rawiwan; Chokephaibulkit, Kulkanya; Khanh, Truong Huu; Van Nguyen, Lam; Jamal Mohamed, Thahira A; Nik Yusoff, Nik Khairulddin; Fong, Moy Siew; Prasitsuebsai, Wasana; Sohn, Annette H; Kerr, Stephen J

Background: Adolescents living with HIV (ALHIV) have poorer adherence and clinical outcomes than adults. We conducted a study to assess behavioral risks and antiretroviral therapy (ART) outcomes among ALHIV in Asia. Methods: A prospective cohort study among ALHIV and matched HIV-uninfected controls aged 12 to 18 years was conducted at nine sites in Malaysia, Thailand and Vietnam from July 2013-March 2017. Participants completed an audio computer-assisted self-interview at weeks 0, 48, 96 and 144. Virologic failure (VF) was defined as >1 viral load (VL) measurement >1000 copies/mL. Generalized estimating equations were used to identify predictors for VF. Results: Of 250 ALHIV and 59 HIV-uninfected controls, 58% were Thai and 51% female. Median age was 14 years at enrollment; 93% of ALHIV were perinatally infected. At week 144, 66% of ALHIV were orphans vs. 28% of controls (p 1 sexual partner, and living with non-parent relatives, a partner or alone, were associated with VF at any time. Conclusions: The subset of ALHIV with poorer adherence and VF require comprehensive interventions that address sexual risk, substance use, and HIV-status disclosure. Corresponding Author: Jeremy L Ross, MBBS, MSc TREAT Asia/amfAR – The Foundation for AIDS Research 388 Sukhumvit Road, Suite 2104, Klongtoey, Bangkok 10110, Thailand Phone: +662 663 7561 Fax: +662 663 7562 E-mail: jeremy.ross@treatasia.org. Conflicts of Interest and Source of Funding: The authors declare no conflicts of interest related to this study. Funding support was provided through a grant to amfAR, The Foundation for AIDS Research from the U.S. National Institutes of Health’s National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Cancer Institute, National Institute of Mental Health, and National Institute on Drug Abuse as part of the International Epidemiology Databases to Evaluate AIDS (IeDEA; U01AI069907), and additional support from LIFE+, Austria. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of any of the institutions mentioned above. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Abstract Background The new HIV treatment guidelines in China recommend antiretroviral therapy (ART) for all people living with HIV, but significant gaps in implementation still exist. Pre-exposure prophylaxis (PrEP) can effectively reduce the risk of HIV transmission among men who have sex with men (MSM). This study assessed the epidemiological impact and cost effectiveness of PrEP, enhanced biomedical interventions and their combination among MSM in China. Methods A deterministic mathematical model was developed and projected over 20 years to assess the impact of the PrEP, biomedical interventions and their combinations. Incidence and prevalence of HIV were measured, and cost-effectiveness was assessed using incremental cost (international dollars, Int.$) per quality-adjusted life year (QALY) gained. Results A total of 0.78 million new HIV infections were estimated to occur over the next 20 years if no additional interventions are implemented among MSM. The PrEP-only strategy covering 25–75% of HIV-negative high-risk MSM can prevent 0.09–0.20 million (12.1–25.7%) new infections, at a cost of 17,277–18,452 Int.$/QALY. The optimal cost-effectiveness path is from test-and-treat to the combination strategy of test-and-treat and PrEP. Some strategies could almost eliminate new HIV infections over the next 20 years. Conclusions PrEP, test-and-treat, and their combinations among MSM are effective and cost-effective relative to current policy. PrEP is an important and cost-effective addition to current policy in China.…

Perumal R, Padayatchi N, Yende-Zuma N, et al.

AbstractBackgroundThe substitution of moxifloxacin for ethambutol produced promising results for improved tuberculosis (TB) treatment outcomes. MethodWe conducted an open-label randomized trial to test whether a moxifloxacin-containing treatment regimen was superior to the standard regimen for the treatment of recurrent TB. The primary and secondary outcomes were sputum culture conversion rate at the end of 8 weeks and the proportion of participants with a favourable outcome, respectively.ResultsWe enrolled 196 participants; 69.9% were male and 70.4% were co-infected with HIV. There was no significant difference between the study groups in the proportion of patients achieving culture conversion at the end of 8 weeks [83.0% (Moxifloxacin) vs 78.5% (Control), p=0.463], however the median time to culture conversion was significantly shorter (6.0 weeks, IQR 4.0 – 8.3) in the moxifloxacin group than the control group (7.9 weeks, IQR 4.0– 11.4) (p=0.018). A favourable end-of-treatment outcome was reported in 86 participants (87.8%) in the moxifloxacin group and 93 participants (94.9%) in the control group, for an adjusted absolute risk difference of -5.5 (95% CI -13.8 to 2.8, p=0.193) percentage points. There was a significantly higher proportion of participants with grade 3 or 4 adverse events [43.9% (43/98) vs 25.5% (25/98), p=0.011] and serious adverse events [27.6% (27/98) vs 12.2% (12/98), p=0.012] in the moxifloxacin group. ConclusionReplacement of ethambutol with moxifloxacin did not significantly improve culture conversion rates at the end of 8 weeks or treatment success, and was associated with a higher incidence of adverse events.

Marr K, Sun Y, Spec A, et al.

AbstractBackgroundCryptococcosis is increasingly recognized in people without HIV.MethodsA multicenter, prospective cohort study was performed in 25 U.S. centers. Consenting patients were prospectively followed for up to 2 years. Neurologic morbidities were assessed with longitudinal event depiction and functional scores (Montreal Cognitive Assessment, MoCA). Risks for death were analyzed using Cox regression.Results145 subjects were enrolled. Most were male (95, 65.5%) and had immunosuppression (120, 82.8%), including solid organ transplant (SOT, 33.8%), autoimmunity (15.9%), and hematologic malignancies (11.7%). Disease involved the central nervous system (CNS) in 71 subjects (49%). Fever was uncommon, documented in 40 (27.8%) subjects, and absence was associated with diagnostic delay (mean 48.2 vs. 16.5 days, p=0.007). Abnormal MoCA scores (60 years) was associated with higher risks for death (HR 2.14, 95% CI 1.05–4.38, p=0.036), and lower risks were noted with underlying hematologic malignancy (HR 0.29, 95% CI 0.09–0.98, p=0.05) and prior SOT (HR 0.153, 95% CI 0.05–0.44, p=0.001).ConclusionDespite aggressive antifungal therapies, outcomes of CNS cryptococcosis in people who don’t have HIV is characterized by substantial long-term neurologic sequelae. Studies are needed to understand mechanism(s) of cognitive decline and to enable better treatment algorithms.

Curtis, Kelly A.; Campbell, Ellsworth M.; Hanson, Debra L.; Rudolph, Donna L.; Duwve, Joan; Blosser, Sara; Gentry, Jessica; Lovchik, Judy; Peters, Philip J.; Owen, S. Michele; Switzer, William M.

Background: Laboratory assays for determining recent HIV-1 infection are an important public health tool for aiding in the estimation of HIV incidence. Some incidence assay analytes are remarkably predictive of time since seroconversion and may be useful for additional applications, such as predicting recent transmission events during HIV outbreaks and informing prevention strategies. Methods: Plasma samples (n= 154) from a recent HIV-1 outbreak in a rural community in Indiana were tested with the customized HIV-1 Multiplex assay, based on the Bio-Rad Bio-Plex platform, which measures antibody response to HIV envelope antigens, gp120, gp160, and gp41. Assay cutoffs for each analyte were established to determine whether an individual seroconverted within 30, 60, or 90 days of the sample collection date. Additionally, a novel bioinformatics method was implemented to infer infection dates of persons newly diagnosed with HIV during the outbreak. Results: Sensitivity/specificity of the HIV-1 Multiplex assay for predicting seroconversion within 30, 60, 90 days, based on a training data set, was 90.5%/95.4%, 94.1%/90%, 89.4%/82.9%, respectively. Of 154 new diagnoses in Indiana between December 2014 and August 2016, the majority (71%) of recent infections (≤3 months since seroconversion) were identified between February and May 2016. The epidemiologic curve derived from the bioinformatics analysis indicated HIV transmission began as early as 2010, grew exponentially in 2014, and leveled off in April 2015. Conclusion: The HIV-1 Multiplex assay has the potential to identify and monitor trends in recent infection during an epidemic to assess the efficacy of programmatic or treatment interventions. Corresponding author: Kelly A. Curtis Centers for Disease Control and Prevention 1600 Clifton Rd. NE, MS-D10 Atlanta, GA 30329 (404) 639-1002 czv2@cdc.gov Conflicts of Interest and Sources of Funding: No conflicts of interest were declared. This work was supported through intramural CDC funding. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Abstract Background The detection of submicroscopic infections in low prevalence settings has become an increasingly important challenge for malaria elimination strategies. The current field rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria are inadequate to detect low-density infections. Therefore, there is a need to develop more sensitive field diagnostic tools. In parallel, a highly sensitive laboratory reference assay will be essential to evaluate new diagnostic tools. Recently, the highly sensitive Alere™ Malaria Ag P.f ELISA (HS ELISA) was developed to detect P. falciparum histidine-rich protein 2 (HRP2) in clinical whole blood specimens. In this study, the analytical and clinical performance of the HS ELISA was determined using recombinant P. falciparum HRP2, P. falciparum native culture parasites, and archived highly pedigreed clinical whole blood specimens from Karen village, Myanmar and Nagongera, Uganda. Results The HS ELISA has an analytical sensitivity of less than 25 pg/mL and shows strong specificity for P. falciparum HRP2 when tested against P. falciparum native culture strains with pfhrp2 and pfhrp3 gene deletions. Additionally, the Z′-factor statistic of 0.862 indicates the HS ELISA as an excellent, reproducible assay, and the coefficients of variation for inter- and intra-plate testing, 11.76% and 2.51%, were acceptable. Against clinical whole blood specimens with concordant microscopic and PCR results, the HS ELISA showed 100% (95% CI 96.4–100) diagnostic sensitivity and 97.9% (95% CI 94.8–99.4) diagnostic specificity. For P. falciparum positive specimens with HRP2 concentrations below 400 pg/mL, the sensitivity and specificity were 100% (95% CI 88.4–100) and 88.9% (95% CI 70.8–97.6), respectively. The overall sensitivity and specificity for all 352 samples were 100% (CI 95% 96–100%) and 97.3% (CI 95% 94–99%). Conclusions The HS ELISA is a robust and reproducible assay. The findings suggest that the HS ELISA may be a useful tool as an affordable reference assay for new ultra-sensitive HRP2-based RDTs.…

Ayieko, James; Petersen, Maya L.; Charlebois, Edwin D.; Brown, Lillian B.; Clark, Tamara D.; Kwarisiima, Dalsone; Kamya, Moses R.; Cohen, Craig R.; Bukusi, Elizabeth A.; Havlir, Diane V.; Van Rie, Annelies

Introduction: As countries move towards universal HIV treatment, many individuals fail to link to care following diagnosis of HIV. Efficient and effective linkage strategies are needed. Methods: We implemented a patient-centered, multi-component linkage strategy in the SEARCH “test-and-treat” trial (NCT 01864603) in Kenya and Uganda. Following population-based, community-wide HIV testing, eligible participants were (1) introduced to clinic staff after testing, (2) provided a telephone “hot-line” for enquiries, (3) provided an appointment reminder phone call, (4) given transport reimbursement upon linkage, and (5) tracked if linkage appointment was missed. We estimated the proportion linked to care within one year and evaluated factors associated with linkage at 7, 30 and 365 days after diagnosis. Results: Among 71,308 adults tested, 6,811(9.6%) were HIV-infected; of these, 4,760(69.9%) were already in HIV care, 30.1% were not. Among 2,051 not in care, 58% were female, median age was 32(IQR 26-40)years, and median CD4 count was 493(IQR 331-683)cells/µL. Half (49.7%) linked within one week, and 73.4% within one year. Individuals who were younger (15-34 vs.>35 years, aRR 0.83,95%CI:0.74-0.94), tested at home vs. community campaign (aRR=0.87,95%CI:0.81-0.94),had a high-HIV-risk vs. low-risk occupation(aRR=0.81,95% CI:0.75-0.88) and were wealthier(aRR 0.90,95% CI:0.83-0.97)were less likely to link. Linkage did not differ by marital status, stable residence, level of education or having a phone contact. Conclusion: Using a multi-component linkage strategy, high proportions of people living with HIV but not in care linked rapidly following HIV testing. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Corresponding author: James Ayieko, P.O. Box 614-40100 Kisumu, Kenya, Telephone: +254-720-925-262 e-mail: jimayieko@gmail.com Conflict of interest and source of funding: DVH reports grants from National Institutes of Health,grants from Gates Foundation and non-financial support from Gilead Sciences, during the conduct of the study; outside the submitted work.EDC reports grants from National Institutes of Health, during the conduct of the study. For the remaining authors none were declared. The study was funded bythe Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health under award number U01AI099959, and in part by the President’s Emergency Plan for AIDS Relief. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Carlos A.M. Silva, Barbara Graham Andre, Kristofor Webb, Laura Vari Ashton, Marisa Harton, Annie Luetkemeyer, Samantha Bokatzian, Reem Almubarak, Sebabrata Mahapatra, Laura Hovind, Michelle A. Kendall, Diane Havlir, John T. Belisle, Mary Ann De Groote

The human immunodeficiency virus (HIV) causes functional disruption of the immune response and impairs host ability to control infection by Mycobacterium tuberculosis (Walker et al., 2013) - the etiological agent of tuberculosis (TB). In 2014, there were 9.6 million cases of TB, of which 1.2 million (12.5%) were co-infected with HIV (WHO, 2016). The World Health Organization recommends that all persons with HIV and active TB be promptly treated with antiretroviral therapy (ART) in order to reduce morbidity and mortality (WHO, 2017).

Meikle, V., Mossberg, A.-K., Mitra, A., Hakansson, A. P., Niederweis, M.

Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis (TB), has surpassed HIV/AIDS as the leading cause of death from a single infectious agent. The increasing occurrence of drug resistant strains has become a major challenge for health care systems and, in some cases, rendered TB untreatable. However, developing new TB drugs has been plagued with high failure rates and costs. Alternative strategies to increase the efficacy of current TB treatment regimens include host-directed therapies or agents that make Mtb more susceptible to existing TB drugs. In this study, we show that HAMLET, an alpha-lactalbumin - oleic acid complex derived from human milk, has bactericidal activity against Mtb. HAMLET consists of a micellar oleic acid core surrounded by a shell of partially denatured alpha-lactalbumin molecules and unloads oleic acid into cells upon contact with lipid membranes. At sub-lethal concentrations, HAMLET potentiated a remarkably broad array of TB drugs and antibiotics against Mtb. For example, the minimal inhibitory concentrations of rifampicin, bedaquiline, delamanid and clarithromycin were decreased by 8- to 16-fold. HAMLET also killed Mtb and enhanced the efficacy of TB drugs inside macrophages, a natural habitat of Mtb. Previous studies showed that HAMLET is stable after oral delivery in mice and non-toxic in humans and that it is possible to package hydrophobic compounds in the oleic acid core of HAMLET to increase their solubility and metabolic stability. The potential of HAMLET and other liprotides as drug delivery and sensitization agents in TB chemotherapy is discussed.…

Yin, Michael T; RoyChoudhury, Arindam; Bucovsky, Mariana; Colon, Ivelisse; Ferris, David C; Olender, Susan; Agarwal, Sanchita; Sharma, Anjali; Zeana, Cosmina; Zingman, Barry; Shane, Elizabeth

Background: Prevalence of osteoporosis and fracture is increased among older people with HIV. We compared the effects of Low (1000 IU) vs Moderate (3000 IU) Vitamin D3 (VItD) supplementation on areal and volumetric bone mineral density (aBMD and vBMD) in African American and Hispanic postmenopausal women with HIV on antiretroviral therapy. Methods: We performed a 12-month prospective, randomized, double-blind, placebo-controlled study with primary outcomes of change in aBMD by dual-energy X-ray absorptiometry (DXA) and secondary outcomes of change in vBMD by quantitative computed tomography and bone turnover markers. An intent to treat analysis was performed on 85 randomized subjects (43 Low and 42 Moderate) for primary DXA outcomes, and complete case analysis performed for secondary outcomes. Results: Mean age was 56+5 years, median CD4 count 722 cells/mm3 and 74% had HIV RNA…

Abstract Background High retention (follow-up) rates improve the validity and statistical power of outcomes in longitudinal studies and the effectiveness of programs with prolonged administration of interventions. We assessed participant retention in a potential HIV vaccine trials population of fishing communities along Lake Victoria, Uganda. Methods In a community-based individual randomized trial, 662 participants aged 15–49 years were randomized to either mobile phone or physical contact tracing reminders and followed up at months 1, 2, 3, 6, 12 and 18 post-enrolment. The visit schedules aimed at mimicking a vaccine efficacy trial representing an early interval (months 1–6) where most vaccinations would be administered and a later period of post-vaccination follow-up. The primary outcome was retention measured as the proportion of post-baseline follow up visits completed by a participant. Retention was estimated in early and later follow-up intervals, and overall for all the six follow-up visits. Adjusted differences in retention between the study arms were determined by multivariable logistic regression using Stata® 14. One participant was later dropped from the analysis because of age ineligibility discovered after enrolment. Results Of the expected total follow up visits of 3966 among 661 participants, 84.1% (3334) were attained; 82.1% (1626/1980) in the phone arm and 86% (1708/1986) in the physical tracing arm (p = 0.001). No statistically significant differences in retention were observed between the study arms in the first 6 months but thereafter, retention was significantly higher for physical contact reminders than mobile phones; 91.5% versus 82.1% (p 

Dubé M, Chan E, Lake J, et al.

AbstractBackgroundDipeptidyl peptidase-4 (DPP-4) inhibitors have pleotropic anti-inflammatory and immune regulatory effects in addition to their glucoregulatory actions. We evaluated inflammation and immune markers in suppressed HIV infection during treatment with the DPP-4 inhibitor sitagliptin.MethodsVirologically suppressed adults with HIV without diabetes mellitus on stable ART with ≥100/mm 3 CD4 cells were randomized to 16 weeks of sitagliptin 100 mg/d vs. placebo in a multicenter trial. The primary endpoint was the change in plasma soluble CD14 (sCD14) from baseline to week 15/16. Additional soluble biomarkers, and lymphocyte and monocyte activation were assessed.ResultsNinety participants were randomized, and 42 from each arm were included in per-protocol analyses. Evaluable participants were 45% non-Hispanic white, 38% non-Hispanic black, 15% Hispanic, median age of 51 years, 83% male, with median CD4 count 602 cells/mm 3. At week 15/16, there was no difference in sCD14 change between the two arms (p=0.69). Relative to placebo, the sitagliptin arm had 47% greater decline in CXCL10 (95% CI:-57,-35) at week 15 (p

Abstract Background Hepatitis B virus (HBV) infection is the major public health problem worldwide. In clinical practice, serological and molecular assays are the most commonly used diagnostic methods to detect HBV infection in clinical practices. Methods Here we present a rapid and sensitive recombinase aided amplification assay (RAA) to detect HBV at 39.0 °C for 30 min without DNA extraction from serum samples. The analytical sensitivity of RAA assay was 100 copies per reaction and showed no cross reaction with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). The universality of RAA assay was validated by testing of 41 archived serum samples with predefined HBV genotypes (B, C and D). Results A total of 130 archived suspected HBV infected serum samples were detected by commercial qPCR with DNA extraction and RAA assay without DNA extraction (heat-treatment). Compared with qPCR assay as a reference, the RAA assay obtained 95.7% sensitivity and 100% specificity and a kappa value of 0.818. Conclusions We developed a rapid, convenient, highly sensitive and specific method to detect HBV without DNA extraction in clinical samples. This RAA method of HBV detection is very suitable for clinical testing.…

Abstract Background Geographic differences in HIV, syphilis and condomless sex among men who have sex with men in China remained unknown. We aimed to elucidate these spatiotemporal changing patterns in China. Methods We conducted a spatiotemporal meta-analysis. We searched four databases for studies conducted between 2001 and 2015. We included studies that reported original data of HIV/syphilis prevalence in China, the study’s area/province, and period of data collection. We grouped studies into six regions and four time periods. We examined the changing patterns of national and regional prevalence of HIV, syphilis and condomless sex. Results Search results yielded 2119 papers, and 272 were included in the meta-analysis. The sample sizes of the studies ranged from 19 to 47,231. National HIV prevalence increased from 3.8% (95% CI 3.0–4.8) in 2001–07 to 6.6% (5.6–7.7) in 2013–15. In most regions, the rise occurred before 2010 and the HIV prevalence remained relatively stable afterwards, except for the Northwest which showed a considerable increase since 2008. National syphilis prevalence decreased from 12.3% (10.2–14.9) in 2001–07 to 7.1% (5.6–8.9) in 2013–15. Conclusions The trends of HIV and syphilis infections have been effectively curbed in MSM in most regions of China. Continuous efforts, particularly promotion of condom use, are needed to further reduce these infections.…

Samet, Jeffrey H.; Blokhina, Elena; Cheng, Debbie M.; Walley, Alexander Y.; Lioznov, Dmitry; Gnatienko, Natalia; Quinn, Emily K.; Bridden, Carly; Chaisson, Christine E.; Toussova, Olga; Gifford, Allen L.; Raj, Anita; Krupitsky, Evgeny

Objective: To determine whether the LINC strengths-based case management intervention was more effective than usual care for linking people who inject drugs (PWID) to HIV care and improving HIV outcomes. Design: Two-armed randomized controlled trial. Setting: Participants recruited from a narcology hospital in St. Petersburg, Russia. Participants: 349 HIV-positive PWID not on antiretroviral therapy (ART). Intervention: Strengths-based case management over 6 months. Main outcome measures: Primary outcomes were linkage to HIV care and improved CD4 count. We performed adjusted logistic and linear regression analyses controlling for past HIV care using the intention-to-treat approach. Results: Participants (N=349) had the following baseline characteristics: 73% male, 12% any past ART use, and median values of 34.0 years of age and CD4 count 311. Within 6 months of enrollment 51% of the intervention group and 31% of controls linked to HIV care (AOR 2.34; 95% CI: 1.49–3.67; p …

Abstract Background CD4 cell count has been identified to be an essential component in monitoring HIV treatment outcome. However, CD4 cell count monitoring sometimes fails to predict virological failure resulting in unnecessary switch of treatment lines which causes drug resistance and limitations of treatment options. This study assesses the use of both viral load (HIV RNA) and CD4 cell count in the monitoring of HIV/AIDS progression. Methods Time-homogeneous Markov models were fitted, one on CD4 cell count monitoring and the other on HIV RNA monitoring. Effects of covariates; gender, age, CD4 baseline, HIV RNA baseline and adherence to treatment were assessed for each of the fitted models. Assessment of the fitted models was done using prevalence plots and the likelihood ratio tests. The analysis was done using the “msm” package in R. Results Results from the analysis show that viral load monitoring predicts deaths of HIV/AIDS patients better than CD4 cell count monitoring. Assessment of the fitted models shows that viral load monitoring is a better predictor of HIV/AIDS progression than CD4 cell count. Conclusion From this study one can conclude that although patients take more time to achieve a normal CD4 cell count and less time to achieve an undetectable viral load, once the CD4 cell count is normal, mortality risks are reduced. Therefore, both viral load monitoring and CD4 count monitoring can be used to provide useful information which can be used to improve life expectance of patients living with HIV. However, viral load monitoring is a better predictor of HIV/AIDS progression than CD4 cell count and hence viral load is deemed superior.…

Kusejko K, Bachmann N, Chaudron S, et al.

AbstractTo systematically test whether coinfections spread along the HIV-1 transmission network and whether similarities of HIV-1 genomes predict AIDS-defining illnesses and comorbidities, we analyzed the distribution of these variables on the HIV-phylogeny of the densely sampled Swiss HIV Cohort Study. By combining different statistical methods, we could detect, quantify and explain the clustering of diseases: Infectious conditions such as hepatitis C, but also Kaposi’s sarcoma, clustered significantly, suggesting transmission of these infections along the HIV-1 transmission network. The clustering of patients with neurocognitive complaints, however, could not be completely explained by the clustering of patients with similar demographic risk factors, which suggests a potential impact of viral genetics. In summary, the consistent and robust signal for infectious conditions highlights the strong interaction of HIV-1 and other infections and shows the potential of combining phylogenetic methods to identify disease traits that are likely to be related to virus genetic factors.

Abstract Introduction Oral pre-exposure prophylaxis (PrEP) is an effective strategy to reduce the risk of HIV transmission in high risk individuals. However, the effectiveness of oral pre-exposure prophylaxis is highly dependent on user adherence, which some previous trials have struggled to optimise particularly in low and middle income settings. This systematic review aims to ascertain the reasons for non-adherence to pre-exposure prophylaxis to guide future implementation. Methods We performed structured literature searches of online databases and conference archives between August 8, 2016 and September 16, 2017. In total, 18 prospective randomized control trials and implementation studies investigating oral pre-exposure prophylaxis were reviewed. A structured form was used for data extraction and findings summarized regarding efficacy, effectiveness, adherence and possible reasons for non-adherence. Results Adherence varied between differing populations both geographically and socioeconomically. Common reasons for non-adherence reported over multiple studies were; social factors such as stigma, low risk perception, low decision making power, an unacceptable dosing regimen, side effects, and the logistics of daily life. Oral pre-exposure prophylaxis with included antiviral regimens was not associated with a high risk of antiviral resistance development in the reviewed studies. Conclusion Our findings indicate that oral pre-exposure prophylaxis should be delivered within a holistic intervention, acknowledging the other needs of the targeted demographic in order to maximise acceptability. Socioeconomic factors and poor governmental policy remain major barriers to widespread implementation of pre-exposure prophylaxis.…

Abstract Background Repressive legal environments and widespread human rights violations act as structural impediments to efforts to engage key populations at risk of HIV infection in HIV prevention, care, and treatment efforts. The identification and scale-up of human rights programs and rights-based interventions that enable coverage of and retention in evidence-based HIV prevention and treatment approaches is crucial for halting the epidemic. Methods We conducted a systematic review of studies that assessed the effectiveness of human rights interventions on improving HIV-related outcomes between 1/1/2003–28/3/2015 per PRISMA guidelines. Studies of any design that sought to evaluate an intervention falling into one of the following UNAIDS’ key human rights program areas were included: HIV-related legal services; monitoring and reforming laws, policies, and regulations; legal literacy programs; sensitization of lawmakers and law enforcement agents; and training for health care providers on human rights and medical ethics related to HIV. Results Of 31,861 peer-reviewed articles and reports identified, 23 were included in our review representing 15 different populations across 11 countries. Most studies (83%) reported a positive influence of human rights interventions on HIV-related outcomes. The majority incorporated two or more principles of the human rights-based approach, typically non-discrimination and accountability, and sought to influence two or more elements of the right to health, namely availability and acceptability. Outcome measures varied considerably, making comparisons between studies difficult. Conclusion Our review revealed encouraging evidence of human rights interventions enabling a comprehensive HIV response, yet critical gaps remain. The development of a research framework with standardized indicators is needed to advance the field. Promising interventions should be implemented on a larger scale and rigorously evaluated. Funding for methodologically sound evaluations of human rights interventions should match the demand for human rights-based and structural approaches to protect those most vulnerable from HIV infection.…

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.…

Pintye, Jillian; Drake, Alison L.; Begnel, Emily; Kinuthia, John; Abuna, Felix; Lagat, Harison; Dettinger, Julia; Wagner, Anjuli D.; Thirumurthy, Harsha; Mugwanya, Kenneth; Baeten, Jared M.; John-Stewart, Grace

Background: Providing HIV self-tests to women for distribution to male partners may provide a unique opportunity to increase male partner and couples testing among women in HIV high-burden settings. Methods: Between November 2017 and June 2018, we offered self-tests for at-home couples or partner HIV-testing to HIV-uninfected women seeking routine maternal child health (MCH) and family planning (FP) services at 8 facilities in Kisumu, Kenya. Women accepting self-tests were offered ≥2 self-tests (OraQuick) to take to their partner(s) with instructions on use. HIV self-testing (HIVST) outcomes were evaluated using available programmatic data. Results: Overall, 3620 women were offered self-tests for at-home male partner HIV testing. The median age was 24 years (IQR 21–28) and 81% were in monogamous marriages. Overall, 1422 (39%) women reported having a partner of unknown HIV status, of whom 755 (53%) accepted self-tests. Among women with partners of unknown HIV status who declined self-tests (n=667), 49% reported needing to consult their partner. Pregnant women were more likely to accept HIVST than non-pregnant women (prevalence ratio = 1.2, 95%CI 1.0–1.4, p = 0.013). Self-testing outcomes were ascertained for 389 (44%) women who accepted self-tests. Among these women, 93% offered HIVSTs to their male partner; of these, 95% reported their male partners used the self-test and 99% used a self-test with their partner. Conclusions: Among women attending routine MCH and FP services who had male partners of unknown HIV status, over half accepted self-tests for partner testing. Most women with outcomes ascertained reported that male partners accepted and used self-tests and that couples testing occurred. Correspondence to Jillian Pintye, PhD, University of Washington, Department of Global Health, 325 Ninth Ave., Box 359909, Seattle, WA 98104. Tel: +1 206 543 4278; fax: +1 206 543 4818; e-mail: jpintye@uw.edu Received 3 December, 2018 Revised 16 February, 2019 Accepted 22 February, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

Abstract Background Plasmodium falciparum infected erythrocytes sequestering in placental tissue release Plasmodium lactate dehydrogenase (pLDH) and histidine-rich protein-II (HRP-II). These proteins can be detected in peripheral blood using monoclonal antibody-based rapid diagnostic tests (RDTs). Nevertheless, studies to evaluate the reliability of RDTs in detecting placental malaria compared with microscopy of placental tissue impression smear (PTIS) as the gold standard are scarce. Methods Between August 2013 and January 2015, Giemsa-stained blood smears for peripheral blood smear (Pbs), placental intervillous space (IVS) blood smear and placental tissue impression smear (PTIS)] were prepared from HIV-negative women during delivery at the Marie Reine Medical Health Centre in Yaoundé, Cameroon. RDTs with monoclonal antibodies specific to HRP-II (P.f) or pLDH (Pan) antigens were used to screen maternal peripheral blood samples. Results The prevalence of malaria was 16%, 7.5%, 11.5%, 8% and 13% for One Step malaria HRP-II and pLDH RDTs, peripheral blood smear, IVS blood and placental tissue impression smears, respectively. The proportion of women positive by One Step malaria pLDH RDT and Pbs increased with parasite density in PTIS, while One Step malaria HRP-II RDT detected high proportion of infected women even with low parasite density. Although the prevalence of malaria infection by both microscopy and RDTs decreased significantly with mother age (0.0008 ≤ p ≤ 0.025), parity seemed to have very little influence. The sensitivity of One Step malaria HRP-II and pLDH RDTs were 96.15% and 61.53%, respectively, compared to 80.76% for Pbs (p = 0.014 and 0.0029, respectively). The specificity of these RDTs was 96.49% and 100%, respectively, compared to 100% for Pbs (p ≥ 0.12). In addition, the positive predictive values were 80.64% and 100% for HRP-II and pLDH-based RDTs, respectively, compared to 100% for Pbs (p 

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