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.

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.

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 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.…

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.…

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 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.…

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.

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.

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.

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.…

Peterson, Tess E.; Baker, Jason V.

Purpose of review This article describes the use of biomarkers in expanding our understanding of chronic non-AIDS comorbidities among persons living with HIV (PLWH) receiving antiretroviral therapy (ART). Recent findings We review current evidence that biomarkers of chronic immune activation and inflammation associate with a broad spectrum of end-organ diseases in PLWH. We discuss how ART may impact inflammation associated with HIV infection and the degree to which inflammation persists despite effective suppression of viral replication in plasma. We then discuss the limitations of the current literature, which lacks evidence of causality and disproportionately involves a few protein biomarkers that are unable to disentangle complex and overlapping biological pathways. Summary Premature end-organ disease among PLWH has been repeatedly associated with higher levels of blood biomarkers reflecting inflammation and immune activation, which, despite viral suppression and CD4+ T-cell increases after ART treatment, remain elevated relative to uninfected persons. There remain important unanswered questions with implications for the development of anti-inflammatory treatment strategies aimed at mitigating excess risk for end-organ comorbidities among PLWH. Correspondence to Tess E. Peterson, MPH, Division of Epidemiology and Community Health, University of Minnesota, Hennepin County Medical Center, 914 South 8th Street, S2.305, Minneapolis, MN 55415, USA. Tel: +1 612 807 6786; fax: +1 612 904 4299; e-mail: pete9123@umn.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Abstract Background Men who have sex with men (MSM) are at high risk of HIV infection. However, there are only few data on HIV prevalence in MSM in Japan. The objective of this study was to explore the HIV prevalence in MSM at Shinjuku 2-chome, a well known gay quarter in Tokyo. Methods MSM directly collected the dried blood spot (DBS) self-collection HIV test kit from a drop-in center in Shinjuku 2-chome between August 2015 and December 2016. The participants collected their own blood by finger-prick and anonymously posted the kit to the laboratory. The participants accessed the study website and checked the results of their tests using unique ID and password. DBS was soaked in phosphate buffered saline overnight and the eluted sample was examined by the fourth generation HIV Ag/Ab test of LUMIPULSE (FUJIREBIO INC.), and followed by HISCL (Sysmex Corp.) when the first assay was positive. The result was defined provisionally positive if both were positive. Results A total of 1702 HIV test kits were distributed and 1403 DBS were returned (return rate: 82.4%). Since 20.2% of participants collected the test kit more than once, the estimated number of actual test kit users was 1120. Based on the results of the test kit, 34 cases were provisionally diagnosed with HIV. The estimated prevalence was 3.04% (95% confidence interval: 2.03–4.04). Of these 34, 24 (70.6%) were later confirmed to be HIV-positive in the hospital, while the remaining 10 were lost to follow-up. Among the participants, 34.5% received HIV test for the first time. Especially in those aged 20–29, 46.0% were first time HIV testers. Conclusions The prevalence of HIV infection in the study population was 3.04%. The high collection suggested a demand for this type of testing in MSM. The test should be expanded further to difficult-to-reach or hidden populations. Trial registration This study was registered with the University Hospital Medical Information Network Clinical Trial Registry in August 20th, 2015 (Registry number: UMIN000018699).…

Bernal, Enrique; Torres, Marcos; Alcaraz, Antonia; Alcaraz, Maria Jose; Rosa, Vicente de la; Valero, Salvador; Muñoz, Angeles; Onteniente, María; Vicente, Tomas; Cano, Alfredo

Background: Erectile dysfunction (ED) is frecuent in HIV infected patients and it can be associated with atherosclerosis and cardiovascular events. So, the objetive was to evaluate whether the presence of moderate-severe ED erectile dysfunction (ED) was a marker of subclinical atherosclerosis (SCA) in HIV-infected patients. Methods: A cross-sectional study was carried out in a cohort of HIV-infected patients. The presence of ED was assessed using the IIEF-5 (International Index Erectile Function) questionnaire. The presence of SCA was determined by calculating the mean carotid intima-media thickness (cIMT) with Doppler ultrasound. A logistic regression analysis was performed to check the variables associated with SCA. Results: 139 men of 45 (10) years of age were included, of which 130 (94.9%) received ART. In 30 (22%) patients the Framingham score was higher than 10%. In 36 (25.9%) patients, ED was detected in a moderate-severe degree and in 53 (38.1%) SCA was detected. In the multivariate analysis, variables independently associated with the presence of SCA were: older age (OR = 1.22, CI95% 1.1-1.35, p…

Abstract Background To investigate the associations between the perceived barriers and benefits of using HIV pre-exposure prophylaxis medication, including worries about the side effects, disliking taking drugs, perceived burden of taking medication, positive expectations as to the efficacy of the drugs, favourable doctor-patient relationships, and medication adherence among men who have sex with men (MSM) to provide a target for improving medication adherence and reducing HIV infection among MSM. Methods MSM were recruited in western China from April 2013 to October 2014, administered oral tenofovir (TDF) daily and followed up every 12 weeks for 2 years. At each follow-up, the medication rate was calculated based on the self-reported number of missed doses over 2 weeks, and then, the medication adherence was evaluated. The barriers and benefits perceived during medication were obtained by a self-administered questionnaire, and their effects on medication adherence were analysed by linear mixed models. Results A total of 411 participants were enrolled in this study, and 1561 follow-up observation points were obtained. The average medication rate was 0.62 ± 0.37, and the medication rate increased with longer follow-up (P 

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

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

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

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

Hu, Y., Liu, Y., Coates, A.

Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, antibiotic-resistant Enterobacteriaceae is prevalent and extremely difficult to treat. Reusing existing drugs and rejuvenating the therapeutic potential of existing antibiotics represent an attractive novel strategy. Azidothymidine (AZT) is an antiretroviral drug which is used in combination with other antivirals to prevent and to treat HIV/AIDS. AZT is also active against Gram-negative bacteria but has not been developed for that purpose. Here we investigated in vitro and in vivo efficacy of AZT in combination with colistin against antibiotic-resistant Enterobacteriaceae including extended-spectrum beta-lactamase (ESBL), New Delhi metallo-beta-lactamase 1 (NDM) or the mobilized colistin resistance (mcr-1) producing strains. Minimum inhibitory concentration was determined using the broth microdilution method. The combinatory effect of AZT and colistin was examined using the checkerboard method and time-kill analysis. A murine peritoneal infection model was used to test the therapeutic effect of the combination of AZT and colistin. Fractional inhibitory concentration index from checkerboard assay demonstrated that AZT synergized with colistin against 61% and 87% of ESBL-producing Escherichia coli and Klebsiella pneumoniae, respectively, 100% of NDM-1-producing strains and 92% of mcr-1 producing E. coli. Time-kill analysis demonstrated significant synergistic activities when AZT was combined with colistin. In the murine peritoneal infection model, AZT in combination with colistin showed augmented activities of both drugs in the treatment of NDM-1 K. pneumoniae and mcr-1 E. coli infections. AZT and colistin combination poses a potential to be used coherently to treat antibiotic-resistant Enterobacteriaceae infections.…

Shivanthan Shanthikumar

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 10, Page 1348-1349, November 15, 2018. …

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

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

Ambrosioni J, Mosquera M, Miró JM.

To the Editor In the updated Recommendations of the International Antiviral Society–USA Panel for the treatment and prevention of human immunodeficiency virus (HIV) infection in adults, the recommendations for laboratory monitoring have been revised to include the use of baseline HIV genotype to assess transmitted drug resistance. The panel recommended testing only for nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and protease inhibitors, and reserved testing for integrase strand-transfer inhibitor (InSTI) resistance to cases of suspected exposure to a partner with InSTI resistance. All preferred regimens are InSTI-based, favoring dolutegravir and bictegravir and, when those are not available, raltegravir and elvitegravir/cobicistat.

Saag MS, Günthard HF, Smith DM.

In Reply As stated in the panel’s report, the relative absence of resistance-conferring mutations for InSTI drugs supports the recommendation to not test routinely for InSTI resistance before start of HIV treatment. A summary of existing data regarding the relative lack of transmission of InSTI resistance–conferring mutations was published this year.

Arpadi, Stephen; Lamb, Matthew; Isaie Nzeyimana, N.; Vandebriel, Greet; Anyalechi, Gloria; Wong, Marcia; Smith, Rebecca; Rivadeneira, Emilia D.; Kayirangwa, Eugenie; Malamba, Samuel S.; Musoni, Canisious; Koumans, Emilia H.; Braaten, Mollie; Nsanzimana, Sabin

Abstract: Background: In 2012, Rwanda introduced a Treat All approach for HIV-infected children under age 5. We compared antiretroviral therapy (ART) initiation, outcomes, and retention, before and after this change. Methods: We conducted a retrospective study of children enrolled into care between June 2009-December 2011 (Before Treat All cohort [BTA]) and between July 2012-April 2015 (Treat All cohort [TA]). Setting: Medical records of a nationally representative sample were abstracted for all eligible aged 18-60 months from 100 Rwandan public health facilities. Results: We abstracted 374 medical records: 227 in the BTA and 147 in the TA cohorts. Mean (SD) age at enrollment was (3 years [1.1]). Among BTA, 59% initiated ART within one year, vs. 89% in the TA cohort. Median time to ART initiation was 68 days (IQR 14-494) for BTA and 9 days (IQR 0-28) for TA (p

Abstract Background Incarcerated people carry a high burden of infection, including blood-borne diseases (BBDs). It is also known that one million people contract a sexually transmitted infection (STI) every day worldwide, which represents a global public health challenge. However, data regarding the prevalence of STIs and the risk factors among incarcerated populations are lacking. The objective of this study was to determine the prevalence and associated factors of BBDs and STIs among detainees in the largest pre-trial prison in Switzerland. Methods In a cross-sectional study conducted at the Champ-Dollon pre-trial prison, 273 male detainees answered a standardized questionnaire and were screened for syphilis, herpes simplex virus 2 (HSV-2), HIV, and hepatitis C (HCV). Prevalence rates and associations of BBDs and STIs with risk factors were computed. Results Most participants (90.9%) were migrants from outside Western Europe, and 5.9% were injecting drug users. HCV was diagnosed among 6.2% of participants (antibody prevalence). The prevalence of HCV was higher among injecting drug users (81.2%) than non-injectors (1.6%). The prevalence of HIV, syphilis, and HSV-2 was 0.4%, 1.1%, and 22.4%, respectively. HCV was associated with a history of injecting drug use and HSV-2 with a lower education level and being older than 26 years. Conclusions This study showed the infection prevalence of 2–9 times higher among detainees than in the Swiss community. It also illustrated that these infections are associated with sociodemographic and risk factors. Therefore, the prison environment offers an opportunity to strengthen infectious disease control programs targeting specific subgroups of at-risk people. Such programs would benefit both the prison population and broader society.…

Jumare, Jibreel; El-Kamary, Samer S.; Magder, Laurence; Hungerford, Laura; Umlauf, Anya; Franklin, Donald; Ghate, Manisha; Abimiku, Alash’le; Charurat, Man; Letendre, Scott; Ellis, Ronald J.; Mehendale, Sanjay; Blattner, William A.; Royal, Walter III; Marcotte, Thomas D.; Heaton, Robert K.; Grant, Igor; McCutchan, J. Allen

Background: Risk of cognitive impairment is increased among persons with high or low body mass index (BMI) in HIV- and HIV+ populations in resource-rich settings. We examined this association among HIV+ patients in three resource-limited settings. Methods: This secondary analysis included data of 761 HIV+ volunteers pooled from 3 prospective cohort studies conducted in China (n=404; 53%), India (n=200; 26%) and Nigeria (n=157; 21%). World Health Organization (WHO) weight classifications were based on BMI. T scores, adjusted for demographics and practice effects, were derived from a 7-domain neuropsychological battery. Neurocognitive impairment (NCI) was defined as global deficit score (GDS) of ≥ 0.5. Results: Overall prevalence of NCI at baseline was 27.7% (similar across all cohorts). The overweight/obese and underweight constituted 37.3% and 15.5% of the total participants respectively. In a multivariable logistic regression of pooled longitudinal data, adjusting for clinical and demographic variables, the odds of global neurocognitive impairment were 38% higher among the overweight/obese as compared to normal weight participants (OR: 1.38 [95% CI: 1.1, 1.72]; P=0.005). Similarly, the odds of global neurocognitive impairment were 39% higher among the underweight as compared to normal weight participants (OR: 1.39 [95% CI: 1.03, 1.87]; P=0.029). Conclusion: Neurocognitive impairment among HIV-1 infected patients was more prevalent in both overweight/obese and underweight than normal weight individuals in three resource-limited settings, confirming observations in resource rich settings. Mechanisms underlying these associations are unclear, but likely differ for underweight and overweight persons. Corresponding author: E-mail: jibreel.jumare@som.umaryland.edu, Tel: (410) 706-7192, Fax: (410) 706-1944 Conflicts of Interest and Source of Funding: WAB is an editor for JAIDS. Other authors have no conflicts to report. This work was supported by National Institutes of Health grant #R01 P30 MH62512-14 (to Igor Grant), National Institute of Mental Health (NIMH) grant #R01 MH78748 (to Thomas D. Marcotte), National Institutes of Health grant #R01 MH086356 (to William A. Blattner and Walter Royal, III) and by National Institutes of Health Fogarty/AIDS International Training and Research Program grant #2D43TW001041-14 (training support to Jibreel Jumare). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Turan, Bulent; Crockett, Kaylee B.; Buyukcan-Tetik, Asuman; Kempf, Mirjam-Colette; Konkle-Parker, Deborah; Wilson, Tracey E.; Tien, Phyllis C.; Wingood, Gina; Neilands, Torsten B.; Johnson, Mallory O.; Weiser, Sheri D.; Turan, Janet M.

Background: One mechanism through which social stigma of HIV affects health outcomes for people living with HIV (PLWH) is via internalization of stigma. However, this transformation of social stigma in the community into internalized stigma may not be of the same magnitude for all PLWH. We examined the moderating effects of 3 personality traits—fear of negative social evaluation, attachment-related anxiety, and dispositional resilience—in transforming perceived stigma in the community into internalized stigma. Furthermore, we investigated downstream effects of these moderated associations on depressive symptoms and antiretroviral treatment (ART) adherence. Setting/Methods: In Study 1, data from 203 PLWH in the southeast US were analyzed controlling for age, sex, education, race, and time on ART. In Study 2, data from 453 women in a multi-site study were analyzed controlling for age, education, race, time on ART, and substance use. Results: In both studies, fear of negative evaluation and attachment-related anxiety moderated the effect of perceived HIV stigma in the community on internalized HIV stigma: People higher on those moderating variables had stronger associations between perceived stigma in the community and internalized stigma. In study 2, resilience was assessed, and also moderated the effect of perceived HIV stigma in the community on internalized stigma. In moderated mediation models, fear of negative evaluation, attachment-related anxiety, and resilience moderated the indirect effect of perceived HIV stigma in the community on ART adherence and depression through internalized stigma. Conclusions: Interventions to assuage internalization of HIV stigma should focus on bolstering attachment-related security, social competence, and resilience. Corresponding Author (requests for reprints should also be made to): Bulent Turan Email address: bturanb@uab.edu; bturanb@gmail.com Telephone: (650) 387 0251 Address: 415 Campbell Hall, Dept. of Psychology, University of Alabama at Birmingham, Birmingham, AL 35294-1170 * Bulent Turan and Kaylee B. Crockett contributed equally to this manuscript. The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Turan, Bulent; Crockett, Kaylee B.; Buyukcan-Tetik, Asuman; Kempf, Mirjam-Colette; Konkle-Parker, Deborah; Wilson, Tracey E.; Tien, Phyllis C.; Wingood, Gina; Neilands, Torsten B.; Johnson, Mallory O.; Weiser, Sheri D.; Turan, Janet M.

Background: One mechanism through which social stigma of HIV affects health outcomes for people living with HIV (PLWH) is via internalization of stigma. However, this transformation of social stigma in the community into internalized stigma may not be of the same magnitude for all PLWH. We examined the moderating effects of 3 personality traits—fear of negative social evaluation, attachment-related anxiety, and dispositional resilience—in transforming perceived stigma in the community into internalized stigma. Furthermore, we investigated downstream effects of these moderated associations on depressive symptoms and antiretroviral treatment (ART) adherence. Setting/Methods: In Study 1, data from 203 PLWH in the southeast US were analyzed controlling for age, sex, education, race, and time on ART. In Study 2, data from 453 women in a multi-site study were analyzed controlling for age, education, race, time on ART, and substance use. Results: In both studies, fear of negative evaluation and attachment-related anxiety moderated the effect of perceived HIV stigma in the community on internalized HIV stigma: People higher on those moderating variables had stronger associations between perceived stigma in the community and internalized stigma. In study 2, resilience was assessed, and also moderated the effect of perceived HIV stigma in the community on internalized stigma. In moderated mediation models, fear of negative evaluation, attachment-related anxiety, and resilience moderated the indirect effect of perceived HIV stigma in the community on ART adherence and depression through internalized stigma. Conclusions: Interventions to assuage internalization of HIV stigma should focus on bolstering attachment-related security, social competence, and resilience. Corresponding Author (requests for reprints should also be made to): Bulent Turan Email address: bturanb@uab.edu; bturanb@gmail.com Telephone: (650) 387 0251 Address: 415 Campbell Hall, Dept. of Psychology, University of Alabama at Birmingham, Birmingham, AL 35294-1170 * Bulent Turan and Kaylee B. Crockett contributed equally to this manuscript. The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Samik Datta, Catherine H. Mercer, Matt J. Keeling

by Samik Datta, Catherine H. Mercer, Matt J. Keeling Background Understanding the spread of sexually transmitted infections (STIs) in a population is of great importance to the planning and delivery of health services globally. The worldwide rise of HIV since the 1980’s, and the recent increase in common STIs (including HPV and Chlamydia) in many countries, means that there is an urgent need to understand transmission dynamics in order to better predict the spread of such infections in the population. Unlike many other infections which can be captured by assumptions of random mixing, STI transmission is intimately linked to the number and pattern of sexual contacts. In fact, it is the huge variation in the number of new sexual partners that gives rise to the extremes of risk within populations which need to be captured in predictive models of STI transmission. Such models are vital in providing the necessary scientific evidence to determine whether a range of controls (from education to screening to vaccination) are cost-effective. Method and results We use probability sample survey data from Britain’s third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) to determine robust distributions for the rate of new partnerships that involve condomless sex and can therefore facilitate the spread of STIs. Different distributions are defined depending on four individual-level characteristics: age, sex, sexual orientation, and previous sexual experience. As individual behaviour patterns can change (e.g. by remaining in a monogamous relationship for a long period) we allow risk-percentiles to be randomly redrawn, to capture longer term behaviour as measured by Natsal-3. We demonstrate how this model formulation interacts with the transmission of infection by constructing an individual-based SIS-P (Susceptible—Infected—Susceptible—Protected) transmission model for the spread of a generic STI, and observing overall population demographics when varying the transmission probability within a partnership, recovery rate and the level of population protection (e.g. from vaccination where applicable).…

Suresh Pallikkuth, Rajendra Pahwa, Bagavathi Kausalya, Shanmugam Saravanan, Li Pan, R. Vignesh, Syed Iqbal, Sunil S. Solomon, Kailapuri G. Murugavel, Selvamuthu Poongulali, Nagalingeswaran Kumarasamy, Savita Pahwa

by Suresh Pallikkuth, Rajendra Pahwa, Bagavathi Kausalya, Shanmugam Saravanan, Li Pan, R. Vignesh, Syed Iqbal, Sunil S. Solomon, Kailapuri G. Murugavel, Selvamuthu Poongulali, Nagalingeswaran Kumarasamy, Savita Pahwa Recent findings point to a role of Checkpoint Inhibitor (CPI) receptors at the tissue level in immune homeostasis. Here we investigated the role of CPI molecules on immune cells in relation to cardiac function. Participants recruited in Chennai, India consisted of HIV+ ART naive viremic (Gp1 n = 102), HIV+ on ART, virologically suppressed (Gp2, n = 172) and HIV negative healthy controls (Gp3, n = 64). A cross-sectional analysis of cardiac function, arterial resistance and immunologic assessment of CPI expressing T cells was performed. Data indicate that ART naive exhibited cardiac function impairment and greater arterial stiffness than the other groups. Frequencies of CD4+ T cells expressing LAG-3 and PD1 were higher in ART naïve while TIGIT and TIM3 were similar among the patient groups. LAG-3+, PD1+ and dual LAG-3+PD1+ CD4 T cells were inversely correlated with cardiac function and arterial elasticity and directly with arterial stiffness in ART naïve participants and with arterial elasticity in virally suppressed group on ART. We conclude that HIV induced upregulation of LAG-3 singly or in combination with PD1 in immune cells may regulate cardiac health and warrant mechanistic investigations. The implications of these findings have bearing for the potential utility of anti-LAG-3 immunotherapy for cardiac dysfunction in chronic HIV infection.

Leonard E. G. Mboera, Susan F. Rumisha, Emanuel P. Lyimo, Mercy G. Chiduo, Chacha D. Mangu, Irene R. Mremi, Claud J. Kumalija, Catherine Joachim, Coleman Kishamawe, Isolide S. Massawe, Lucas E. Matemba, Evord Kimario, Veneranda M. Bwana, Denna M. Mkwashapi

by Leonard E. G. Mboera, Susan F. Rumisha, Emanuel P. Lyimo, Mercy G. Chiduo, Chacha D. Mangu, Irene R. Mremi, Claud J. Kumalija, Catherine Joachim, Coleman Kishamawe, Isolide S. Massawe, Lucas E. Matemba, Evord Kimario, Veneranda M. Bwana, Denna M. Mkwashapi Background Understanding the causes of inpatient mortality in hospitals is important for monitoring the population health and evidence-based planning for curative and public health care. Dearth of information on causes and trends of hospital mortality in most countries of Sub-Saharan Africa has resulted to wide use of model-based estimation methods which are characterized by estimation errors. This retrospective analysis used primary data to determine the cause-specific mortality patterns among inpatient hospital deaths in Tanzania from 2006–2015. Materials and methods The analysis was carried out from July to December 2016 and involved 39 hospitals in Tanzania. A review of hospital in-patient death registers and report forms was done to cover a period of 10 years. Information collected included demographic characteristics of the deceased and immediate underlying cause of death. Causes of death were coded using international classification of diseases (ICD)-10. Data were analysed to provide information on cause-specific, trends and distribution of death by demographic and geographical characteristics. Principal findings A total of 247,976 deaths were captured over a 10-year period. The median age at death was 30 years, interquartile range (IQR) 1, 50. The five leading causes of death were malaria (12.75%), respiratory diseases (10.08%), HIV/AIDS (8.04%), anaemia (7.78%) and cardio-circulatory diseases (6.31%). From 2006 to 2015, there was a noted decline in the number of deaths due to malaria (by 47%), HIV/AIDS (28%) and tuberculosis (26%). However, there was an increase in number of deaths due to neonatal disorders by 128%. Malaria and anaemia killed more infants and children under 5 years while HIV/AIDS and Tuberculosis accounted for most of the deaths among adults. Conclusion The leading causes of inpatient hospital death were malaria, respiratory diseases, HIV/AIDS, anaemia and cardio-circulatory diseases. Death among children under 5 years has shown an increasing trend. The observed trends in mortality indicates that the country is lagging behind towards attaining the global and national goals for sustainable development. The increasing pattern of respiratory diseases, cancers and septicaemia requires immediate attention of the health system.…

Priya Sharma, Kamnoosh Shahabi, Rachel Spitzer, Michele Farrugia, Rupert Kaul, Mark Yudin

by Priya Sharma, Kamnoosh Shahabi, Rachel Spitzer, Michele Farrugia, Rupert Kaul, Mark Yudin In a prospective study of twenty sexually transmitted infection (STI)-free women, we examined the impact of an intrauterine contraceptive device (IUCD) insertion on cervico-vaginal cytokine levels. Nine women chose the levonorgestrel-containing IUCD and eight chose a copper IUCD. A cervico-vaginal swab was collected for cytokine analysis pre-insertion and four weeks post-insertion. Significant increases were noted in levels of IL-1α (median 483.4 versus 316.6 pg/mL, p = 0.046), IL-1β (median 605.7 versus 147.3 pg/mL, p = 0.018), IL-6 (median 570.1 versus 157.3 pg/mL, p = 0.046), TNFα (median 1.19 versus 0.6 pg/mL, p = 0.029) and the chemokine MCP-1 (median 340.2 versus 135.2 pg/mL, p = 0.003). No significant changes were noted in the levels of GM-CSF, IL-8, MIG, MIP-3α, RANTES, IL-10, IL-17, IP-10, MIP-1β. Whether this increase in pro-inflammatory cytokine levels decreases epithelial barrier integrity and enhances susceptibility to STIs, including HIV, merits further study.