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.

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.

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.

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.…

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.

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.…

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.

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 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.…

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.…

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.…

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.…

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

Abstract Background Despite substantial advances in antiretroviral therapy (ART) for human immunodeficiency virus (HIV) in the last decades, non-adherence (NA) continues to be a major challenge in the real-life treatment. To meet this challenge, adherence-promoting interventions with a tailored approach towards patient-specific adherence barriers that are identified using a reliable and practicable questionnaire are needed. The aim of this investigation was to develop and validate a respective questionnaire (Adherence Barriers Questionnaire for HIV: ABQ-HIV), based on an earlier version of the ABQ. Methods The existing ABQ was discussed by an expert panel and revised according to the specifications of ART therapy for HIV patients. Initially, the ABQ-HIV consisted of 17 items formulated as statements (4-point-Likert-scale ranging from “strongly agree” to “strongly disagree”). A higher score indicates a higher influence of a certain barrier on patient’s perceptions. The ABQ-HIV was applied in a cross-sectional survey of German HIV patients. Evaluation of the questionnaire included an assessment of internal consistency as well as factor analysis. Convergent validity was assessed by comparing the ABQ-HIV score with the degree of self-reported adherence measured by the 8-item Morisky Medication Adherence Scale (MMAS-8©). Results Three hundred seventy patients were able to be included in all validation analyses. The included patients had a mean age of 51.2 years, and 15.7% were female. The mean HIV infection time was 11.7 years, and the mean duration of treatment since first starting ART was 8.7 years. Twenty-five patients – excluded from all further analyses - were not able/willing to answer all ABQ-HIV questions. The results of the reliability analysis showed a Cronbach’s α of 0.708 for the initial 17-items in the ABQ-HIV draft. Two items were eliminated from the initial questionnaire, resulting in a Cronbach’s α of 0.720 and a split-half reliability of 0.724 (Spearman–Brown coefficient). Based on the reduced 15-item scale, the factor analysis resulted in three different components of the questionnaire. Component 1, with seven items, represents the unintentional adherence barriers. The second component, which contains five items, can be labelled as a subscale describing barriers associated with disease/treatment knowledge. Finally, three items, which can be summarized as intentional adherence barriers, show maximum loading in the third component. The score of the reduced 15-item ABQ-HIV scale, as well as the scores of the three subscales, correlated significantly with the MMAS score. All correlation coefficients were negative, indicating that higher burdens of adherence barriers measured by ABQ-HIV or its subscales were associated with a lower MMAS score and thus, with a lower adherence level. The ROC analysis using the MMAS low adherence classification as its state variable provided a cut-off for the ABQ-HIV scale of > 28 (sensitivity: 61.5%, specificity: 83.3%). In our sample, 85 patients (23.0%) reached a score of > 28 and appeared to face a high non-adherence risk. Conclusions The ABQ-HIV is a practical, reliable, and valid instrument for identifying patient-specific barriers to adherence in the HIV treatment. It is also useful in identifying HIV patient subgroups, according to adherence barriers specific to these patients.…

Norihiko Inoue, Kiyohide Fushimi

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.…

Prat, Laura Iogna; Roccarina, Davide; Lever, Robert; Lombardi, Rosa; Rodger, Alison; Hall, Andrew; Luong, Tu Vinh; Bhagani, Sanjay; Tsochatzis, Emmanuel

Background: Spectrum of liver injury among HIV positive people is wide; in particular prevalence of non-alcoholic fatty liver disease (NAFLD) seems to be higher compared to HIV-negative people. Methods: We retrospectively evaluated all liver biopsies performed at Royal Free Hospital from 2000 to 2017 in HIV mono-infected patients with abnormal transaminases, in order to assess the underlying cause of liver disease and to characterize the extent of fibrosis. We furthermore evaluated the diagnostic accuracy of FIB4 and Fibroscan™ as non-invasive tools for fibrosis assessment. Results: 97 patients were included. Most common histological findings were NAFLD (28%), non-specific changes (26%) and normal histology (13%). 20% patients had significant fibrosis, 11% had advanced fibrosis. FIB4, at a cut-off of 1.3, had a specificity of 82% and NPV of 95% for exclusion of advanced fibrosis. Fibroscan was available in 28% patients and 33% had a liver stiffness ≥7.5 kPa. Fibroscan showed a specificity of 77% and NPV of 94% for exclusion of significant fibrosis. Among patients with NAFLD (n=27), 18% had advanced fibrosis while the majority (56%) did not have any fibrosis. The NPV of FIB4 for advanced fibrosis in these patients was 93%. Conclusions: Among HIV positive patients with elevated transaminases, a surprisingly high number of patients had non-significant changes or even normal histological findings. The prevalence of NAFLD was lower than reported in other series. Use of non-invasive tools with a high NPV for significant fibrosis can help reduce the number of required biopsies. Correspondence to: Dr Emmanuel A. Tsochatzis e.tsochatzis@ucl.ac.uk Sheila Sherlock Liver Unit and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK, NW3 2QG Tel.: +44 2077 94500, Fax: +44 2074 726226 Conflicts of Interest and Source of Funding: none Meetings where parts of the data were presented: International Liver Congress 11-15 April 2018 Paris Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Mwinnyaa, George; Gray, Ronald H.; Grabowski, Mary K.; Ssekasanvu, Joseph; Ndyanabo, Anthony; Ssekubugu, Robert; Kagaayi, Joseph; Kigozi, Godfrey; Nakigozi, Gertrude; Serwadda, David M.; Laeyendecker, Oliver

Background: Age-disparate relationships are associated with increased HIV prevalence. We determined whether the frequency of age-disparate relationships in never married women changed over time and whether they are associated with HIV prevalence in Rakai, Uganda. Methods: 10,061 never married women, aged 15-49 in the Rakai Community Cohort Study provided information on the age of their male sexual partners from 1997 to 2013. Logistic regression was used to assess trends in age-disparate relationships (≥5 years) between never married women and their male partners. Log-binomial regression was used to estimate adjusted prevalence ratios (adjPR) of HIV prevalence associated with age-disparate relationships. Results: 2,992 women (30%) had a male partner ≥5 years older which remained stable over time. The prevalence of HIV among women in age-disparate relationships was 14%, 10% for women in relationships with men 0-4 years older (adjPR 1.36, 95% CI 1.22, 1.53) not controlling women’s age, however after age adjustment the impact of age-disparate relationships on HIV prevalence was attenuated. Age-disparate relationships were associated with increased HIV prevalence among women aged 15-17 (adjPR 1.83, 95% CI 1.10, 3.19), but not in other age groups. Conclusions: The frequency of age-disparate relationships among never married women were unchanged over a 15-year period in Rakai, Uganda. Age-disparate relationships were associated with increased HIV prevalence among adolescents 15-17, but not older women. Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government. Corresponding Author: Oliver Laeyendecker 855 North Wolfe St. Rangos Building Room 538A Baltimore MD, 21205 email: olaeyen1@jhmi.edu The authors report no conflicts of interest related to this work. The study was presented at the Conference on Retroviruses and Opportunistic Infections (CROI), Boston, March 3-7, 2018. Supported by the National Institute of Mental Health (R01MH107275), the National Institute of Allergy and Infectious Diseases (R01AI110324, U01AI100031, U01AI075115, R01AI110324, R01AI102939, K01AI125086-01), the National Institute of Child Health and Development (RO1HD070769, R01HD050180), and Division of Intramural Research of the National Institute for Allergy and Infectious Diseases, the World Bank, the Doris Duke Charitable Foundation, the Bill & Melinda Gates Foundation (#08113, 22006.02), and the Johns Hopkins University Center for AIDS Research (P30AI094189). The findings and conclusions in this report are those of the authors and do not represent the official position of the funding agencies. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Albrecht, Sascha; Franzeck, Fabian C.; Mapesi, Herry; Hatz, Christoph; Kalinjuma, Aneth V.; Glass, Tracy R.; Mnzava, Dorcas; Letang, Emili; Paris, Daniel H.; Battegay, Manuel; Weisser, Maja; on behalf of the KIULARCO Study Group

Objective: Causes of morbidity and mortality of people living with HIV are changing with access to antiretroviral therapy and increased life expectancy. Age-related data on comorbidities and their impact on mortality in sub-Saharan Africa are scarce. Design: This prospective analysis evaluated comorbidities, assessed by means of International Classification of Diseases and Related Health problems 10th revision codes and clinical variables, derived from data collected from the Kilombero & Ulanga antiretroviral cohort of people living with HIV in rural Tanzania. Methods: We calculated prevalences and incidences of comorbidities in patients enrolled from 2013 to 2017 and evaluated their association with a combined endpoint of death and loss to follow-up (LTFU) in various age groups (15–29, 30–49 and ≥50 years) using Cox regression analysis. Results: Of 1622 patients [65% females, median age 38 years (interquartile range 31–46)], 11% were at least 50 years. During a median follow-up of 22.1 months (interquartile range 10.6–37.3), 48 (2.9%) patients died and 306 (18.9%) were LTFU. Anaemia was the most prevalent comorbidity (66.3%) irrespective of age and was associated with increased mortality/LTFU [hazard ratios 2.02 (95% confidence interval (CI) 1.57–2.60); P …

Dupnik K, Lee M, Mishra P, et al.

AbstractBackgroundSchistosomiasis increases the risk of HIV acquisition in women, by mechanisms that are incompletely defined. Our objective was to determine how the cervical environment is impacted by Schistosoma haematobium or S. mansoni infection using mucosal gene expression and cervicovaginal lavage cytokine levels.MethodsWe recruited women with/without S. haematobium and with/without S. mansoni infections from separate villages in rural Tanzania, as determined by urine and stool microscopy and serum circulating anodic antigen. RNA was extracted from cervical cytobrush samples for transcriptome analysis. Cytokine levels were measured by magnetic bead immunoassay.ResultsIn the S. haematobium village, 110 genes were differentially expressed in the cervical mucosa of women with (n=18) versus without (n=39) S. haematobium. Among the 27 cytokines analyzed in cervicovaginal lavage fluids, interleukin 15 (IL-15) was lower in women with S. haematobium (62.8 versus 102.9 pg/mL, adjusted p=0.0013). Differences were not observed in the S. mansoni setting between women with (n=11) or without (n=29) S. mansoni.ConclusionsWe demonstrate altered cervical mucosal gene expression and lower IL-15 levels in women with S. haematobium but not S. mansoni, which may impact HIV acquisition and cancer risks. Studies to determine effects of anti-schistosome treatment on these mucosal alterations are needed.

Nasi M, Pecorini S, De Biasi S, et al.

AbstractThe expression and activity of main inflammasome components in monocytes from successfully treated HIV+ patients are poorly studied. Thus, we enrolled 18 patients with low and 17 with normal CD4/CD8 ratio compared to 11 healthy donors. Our results show that patients with low ratio have a decreased CCR2 expression among classical and intermediate monocytes and an increased CCR5 expression among classical, compared to whose with normal ratio. They also showed higher NAIP and PYCARD mRNA levels after LPS-stimulation suggesting an altered ability to control immune activation that could affect their immune reconstitution.

Adam S. Dingens, Dana Arenz, Haidyn Weight, Julie Overbaugh, Jesse D. Bloom

Dingens et al. mapped all possible single amino acid viral-escape mutations for a panel of HIV-1 broadly neutralizing antibodies that target major sites of vulnerability of HIV Env. This mutation-level antigenic atlas provides a comprehensive dataset for understanding viral immune escape and refining antibody-based immunotherapies and vaccines.

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.

Stephen Solis-Reyes, Mariano Avino, Art Poon, Lila Kari

by Stephen Solis-Reyes, Mariano Avino, Art Poon, Lila Kari For many disease-causing virus species, global diversity is clustered into a taxonomy of subtypes with clinical significance. In particular, the classification of infections among the subtypes of human immunodeficiency virus type 1 (HIV-1) is a routine component of clinical management, and there are now many classification algorithms available for this purpose. Although several of these algorithms are similar in accuracy and speed, the majority are proprietary and require laboratories to transmit HIV-1 sequence data over the network to remote servers. This potentially exposes sensitive patient data to unauthorized access, and makes it impossible to determine how classifications are made and to maintain the data provenance of clinical bioinformatic workflows. We propose an open-source supervised and alignment-free subtyping method (Kameris) that operates on k-mer frequencies in HIV-1 sequences. We performed a detailed study of the accuracy and performance of subtype classification in comparison to four state-of-the-art programs. Based on our testing data set of manually curated real-world HIV-1 sequences (n = 2, 784), Kameris obtained an overall accuracy of 97%, which matches or exceeds all other tested software, with a processing rate of over 1,500 sequences per second. Furthermore, our fully standalone general-purpose software provides key advantages in terms of data security and privacy, transparency and reproducibility. Finally, we show that our method is readily adaptable to subtype classification of other viruses including dengue, influenza A, and hepatitis B and C virus.

Yu-Ching Huang, Yen-Fang Huang, Min-Hau Lin, Jyh-Yuan Yang, Yu-Hsin Liao, Hsiu-Yun Lo, Carl Latkin, Kenrad E. Nelson

by Yu-Ching Huang, Yen-Fang Huang, Min-Hau Lin, Jyh-Yuan Yang, Yu-Hsin Liao, Hsiu-Yun Lo, Carl Latkin, Kenrad E. Nelson Introduction The aim of this study was to report an HIV outbreak related to propofol-injection and the impact of regulating propofol on the HIV epidemic among people who inject drugs (PWID). Methods A retrospective cohort study of 252 PWID who were diagnosed with an HIV infection between 2014 and 2017 in Taiwan. The propofol information was collected by routine epidemic surveillance and interviews. We linked several national databases to collect other related factors, including methadone maintenance treatment (MMT) attendance and incarceration. The serums were tested for recent infection by the LAg‐avidity EIA assay and relationship of the trains by the Phylogenetic tree analysis. Analyses were conducted using the R Surveillance package for retrospective modeling for outbreak detection. A multiple logistic regression was used to evaluate the association between propofol-injection and other related factors. Results There were 28 cases reported with propofol-injection, all of which were reported in Central Taiwan. A total of 11 (50%) cases among 22 propofol-injectors with serums were recent infections, which were higher than that 33 (23.4%) of non-propofol group. The phylogenetic tree indicated that 6 propofol-injectors were grouped together with the same cluster in circular. The HIV epidemic curve among PWID revealed an outbreak of 82 in 2015, which then decreased to 43 in 2016 after propofol began to be regulated as a Schedule 4 controlled drug in August 2015. In a multiple logistic regression, attendance at methadone clinics was associated with a significantly higher risk for propofol-injection (adjusted OR = 2.43, 95% CI = 0.98–5.98), and HIV reported in the year 2015 was associated with an increased risk of propofol-injection (adjusted OR = 4, 95% CI = 1.08–14.86). Conclusions Our data indicate that the government regulation of propofol as a controlled drug strategy was associated with significant reduction in the spread of HIV among PWID.…

Avi J. Hakim, Kelsey Coy, Padmaja Patnaik, Nouhoum Telly, Tako Ballo, Bouyagui Traore, Seydou Doumbia, Maria Lahuerta

by Avi J. Hakim, Kelsey Coy, Padmaja Patnaik, Nouhoum Telly, Tako Ballo, Bouyagui Traore, Seydou Doumbia, Maria Lahuerta Despite the high HIV prevalence among men who have sex with men (MSM) and transgender women (TGW), there are limited data on progress on their respective HIV antiretroviral treatment (ART) cascades to identify progress and gaps in meeting UNAIDS 90-90-90 targets. We conducted a respondent-driven sampling survey of MSM and TGW in Bamako, Mali from October 2014 to February 2015. We describe the HIV treatment cascade for MSM and TGW, identify correlates of being unaware of HIV-infected status and having unsuppressed viral load levels, and estimate proportion of recent infections. We enrolled 387 MSM and 165 TGW. HIV prevalence was 13.7%. Of those living with HIV, 10.4% were aware of their serostatus, 61.2% of them self-reported being on treatment, and of them, 100% were virally suppressed. In multivariate analysis, factors associated with being unaware of HIV infection included not using free condoms in the last six months (aOR: 5.7, 95% CI: 1.1–29.5) and not having comprehensive knowledge of HIV (aOR: 6.5, 95% CI: 1.4–29.9). Having unsuppressed viral load was associated with identifying as a transgender woman (aOR: 4.8, 95% CI: 1.1–20.7) and not having comprehensive knowledge of HIV (aOR: 6.5, 95% CI: 1.0–40.9). Of the 79 HIV-positive participants, 5.1% had recent infections. While the proportion aware of their HIV status was low despite adjusting for viral load biomarkers, all MSM and TGW on treatment were virally suppressed. Improved testing strategies are urgently needed to achieve the first 90 of the HIV cascade among MSM and TGW in Bamako.

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.

Davis, Nicole L; Corbett, Amanda; Kaullen, Josh; Nelson, Julie A. E.; Chasela, Charles S; Sichali, Dorothy; Hudgens, Michael G; Miller, William C; Jamieson, Denise J; Kourtis, Athena P

Background: Concentration of antiretroviral (ARV) drug found in plasma, and amounts of drug excreted into breastmilk, may affect HIV viral load and potentially perinatal HIV transmission. Methods: In this cohort study with two-phase sampling, we included mothers randomized to postpartum maternal ARVs or daily infant nevirapine during 28 weeks of breastfeeding in the Breastfeeding, Antiretrovirals and Nutrition (BAN) study. Among these, we included all mothers who transmitted HIV to their infants between 2-28 weeks and 15% of mothers who did not (n=27 and 227, respectively). Spearman correlation coefficients (r2) were used to assess correlation between maternal plasma and breastmilk ARV concentration. Associations between the median effective drug concentration (EC50) and detectable maternal viral load (plasma: >40 copies/ml, breastmilk: >56 copies/ml) were assessed using mixed effects models. Cox models were used to estimate the association between maternal or infant plasma drug concentration and breastmilk HIV transmission from 2-28 weeks. Results: All ARV compounds exhibited substantial correlations between maternal plasma and breastmilk concentrations (r2: 0.85-0.98, p-value…

Rijnders B, Rokx C.

Abstract Purpose The aim of the study was to assess guideline adherence to combined antiretroviral therapy (ART) in the German ClinSurv HIV Cohort and the real-life impact of the Strategic Timing of Antiretroviral Therapy (START) study, to identify patients not treated as recommended by new guidelines. Methods We used data from the multicenter ClinSurv cohort of the Robert-Koch-Institute (RKI) between 1999 and 2016. Inclusion criteria were people living with HIV/AIDS, ≥ 18 years of age and cART naïve at the first visit (FV). Adherence was defined as starting cART within 6 months of crossing the CD4+ T cell threshold as suggested by the German-Austrian treatment guidelines. Logistic regression was used to identify factors associated with non-adherence. Results 11,817 patients met the inclusion criteria. We observed an overall adherence rate of 60%, in patients with treatment indication who started cART timely between 2002 and 2015. Adherence rate increased constantly, demonstrating a potential increase in patients, with treatment indication, starting cART within 6 months of presentation from 55% in 2008 to 94% in 2015. Patients reporting injection drug use (OR 2.18, 95% CI 1.70–2.95) and patients between 18 years and 39 years of age at the time of their first visit (OR 2.89, 95% CI 1.35–6.18) were identified as risk groups associated with non-adherence. Conclusion The majority of patients below the CD4+ T cell count threshold of applicable guidelines initiated treatment within 6 months. We observed a slowly diminishing proportion of patients not starting cART timely. Delayed treatment was more frequent in patients reporting injection drug use.…

Gisslén M, Hunt P.