Persistence of Activated and Adaptive-Like NK Cells in HIV+ Individuals despite 2 Years of Suppressive Combination Antiretroviral Therapy

Authors: Anna C. Hearps1,2, imagePaul A. Agius3,4, imageJingling Zhou1, imageSamantha Brunt5, imageMkunde Chachage1, imageThomas A. Angelovich1, imagePaul U. Cameron6,7, imageMichelle Giles2,7, imagePatricia Price8, imageJulian Elliott2,7 and imageAnthony Jaworowski1,2*

Innate immune dysfunction persists in HIV+ individuals despite effective combination antiretroviral therapy (cART). We recently demonstrated that an adaptive-like CD56dim NK cell population lacking the signal transducing protein FcRγ is expanded in HIV+ individuals. Here, we analyzed a cohort of HIV+ men who have sex with men (MSM, n = 20) at baseline and following 6, 12, and 24 months of cART and compared them with uninfected MSM (n = 15) to investigate the impact of cART on NK cell dysfunction. Proportions of NK cells expressing markers of early (CD69+) and late (HLA-DR+/CD38+) activation were elevated in cART-naïve HIV+ MSM (p = 0.004 and 0.015, respectively), as were FcRγ− NK cells (p = 0.003). Using latent growth curve modeling, we show that cART did not reduce levels of FcRγ− NK cells (p = 0.115) or activated HLA-DR+/CD38+ NK cells (p = 0.129) but did reduce T cell and monocyte activation (p < 0.001 for all). Proportions of FcRγ− NK cells were not assoc..........

Published at:  2017-06-30

Linkage into care among newly diagnosed HIV-positive individuals tested through outreach and facility-based HIV testing models in Mbeya, Tanzania: a prospective mixed-method cohort study

Erica Samson Sanga1,2, Wondwossen Lerebo2,3, Adiel K Mushi4, Petra Clowes1,5, Willyhelmina Olomi1, Leonard Maboko1, Christina Zarowsky2,6

Linkage to care is the bridge between HIV testing and HIV treatment, care and support. In Tanzania, mobile testing aims to address historically low testing rates. Linkage to care was reported at 14% in 2009 and 28% in 2014. The study compares linkage to care of HIV-positive individuals tested at mobile/outreach versus public health facility-based services within the first 6 months of HIV diagnosis

Published at:  2017-04-12

Trichuris trichiura infection and its relation to environmental factors in Mbeya region, Tanzania: A cross-sectional, population-based study

Kirsi M. Manz ,Petra Clowes,Inge Kroidl,Dickens O. Kowuor,Christof Geldmacher,Nyanda E. Ntinginya,Leonard Maboko,Michael Hoelscher,Elmar Saathoff

The intestinal nematode Trichuris trichiura is among the most common causes of human infectious disease worldwide. As for other soil-transmitted nematodes, its reproductive success and thus prevalence and intensity of infection in a given area strongly depend on environmental conditions. Characterization of the influence of environmental factors can therefore aid to identify infection hot spots for targeted mass treatment.

Published at:  2017-04-06

HIV-1 Genetic Diversity Among Incident Infections in Mbeya, Tanzania

Erik Billings, Eric Sanders-Buell, Meera Bose, Gustavo H. Kijak, Andrea Bradfield, Jacqueline Crossler, Miguel A. Arroyo, Leonard Maboko, Oliver Hoffmann, Steffen Geis, Deborah L. Birx, Jerome H. Kim, Nelson L. Michael, Merlin L. Robb, Michael Hoelscher, and Sodsai Tovanabutra

In preparation for vaccine trials, HIV-1 genetic diversity was surveyed between 2002 and 2006 through the Cohort Development study in the form of a retrospective and prospective observational study in and around the town of Mbeya in Tanzania's Southwest Highlands. This study describes the molecular epidemiology of HIV-1 strains obtained from 97 out of 106 incident HIV-1 infections identified in three subpopulations of participants (one rural, two urban) from the Mbeya area. Near full-genome or half-genome sequencing showed a subtype distribution of 40% C, 17% A1, 1% D, and 42% inter-subtype recombinants. Compared to viral subtyping results previously obtained from the retrospective phase of this study, the overall proportion of incident viral strains did not change greatly during the study course, suggesting maturity of the epidemic. A comparison to a current Phase I-II vaccine being tested in Africa shows ∼17% amino acid sequence difference between the gp120 of the vaccine and subtype C incident strains. Phylogenetic and recombinant breakpoint analysis of the incident........

Published at:  2017-04-01

Why being an expert – despite xpert –remains crucial for children in high TB burden settings

Authors: Jason M. Bacha, Katherine Ngo, Petra Clowes, Heather R. Draper, Elias N. Ntinginya, Andrew DiNardo, Chacha Mangu, Issa Sabi, Bariki Mtafya & Anna M. Mandalakas

As access to Xpert expands in high TB-burden settings, its performance against clinically diagnosed TB as a reference standard provides important insight as the majority of childhood TB is bacteriologically unconfirmed. We aim to describe the characteristics and outcomes of children with presumptive TB and TB disease, and assess performance of Xpert under programmatic conditions against a clinical diagnosis of TB as a reference standard.

Published at:  2017-02-06

High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial

Authors: Martin J Boeree PhD a †, Norbert Heinrich MD c d †, Rob Aarnoutse PhD b, Andreas H Diacon PhD e, Rodney Dawson PhD g, Sunita Rehal MSc o, Prof Gibson S Kibiki PhD h, Prof Gavin Churchyard FRCP q r t, Ian Sanne FRCP s, Nyanda E Ntinginya MD j, Lilian T Minja MD m, Robert D Hunt BSc n, Salome Charalambous PhD q, Madeleine Hanekom PhD e, Hadija H Semvua PhD h, Stellah G Mpagama PhD i, Christina Manyama MD j, Bariki Mtafya MSc j, Klaus Reither MD k l, Prof Robert S Wallis MD q…Prof Michael Hoelscher FRCP c d

Tuberculosis is now the leading infectious disease killer worldwide. Treatment regimens last at least 6 months, so shorter, safer, and more effective regimens for drug-sensitive tuberculosis are needed as part of the global strategy to eliminate the disease. .......

Published at:  2017-01-15

Limited value of whole blood Xpert® MTB/RIF for diagnosing tuberculosis in children

Authors: Christian Pohl a b c, Liliana K. Rutaihwa a b c, Frederick Haraka c, Martin Nsubuga d, Francesco Aloi d, Nyanda E. Ntinginya e, Daniel Mapamba e, Norbert Heinrich f g, Michael Hoelscher f g, Ben J. Marais h i, Levan Jugheli a b c, Klaus Reither a b c

We evaluated the ability of the Xpert® MTB/RIF assay to detect Mycobacterium tuberculosis in whole blood of children with tuberculosis in tuberculosis endemic settings with high rates of HIV infection. .......

Published at:  2016-10-15

CD25+ FoxP3+ Memory CD4 T Cells Are Frequent Targets of HIV Infection In Vivo

Authors: Mkunde Chachage, Georgios Pollakis, Edmund Osei Kuffour, Kerstin Haase, Asli Bauer, Yuka Nadai, Lilli Podola, Petra Clowes, Matthias Schiemann, Lynette Henkel, Dieter Hoffmann, Sarah Joseph, Sabin Bhuju, Leonard Maboko, Fred Stephen Sarfo, Kirsten Eberhardt, Michael Hoelscher, Torsten Feldt, Elmar Saathoff, Christof Geldmacher

Interleukin 2 (IL-2) signaling through the IL-2 receptor alpha chain (CD25) facilitates HIV replication in vitro and facilitates homeostatic proliferation of CD25+ FoxP3+ CD4+ T cells. CD25+ FoxP3+ CD4+ T cells may therefore constitute a suitable subset for HIV infection and plasma virion production. CD25+ FoxP3+ CD4+ T cell frequencies, absolute numbers, and the expression of CCR5 and cell..........

Published at:  2016-09-29

Effect of Wuchereria bancrofti infection on HIV incidence in southwest Tanzania: a prospective cohort study

Dr Inge Kroidl, MD Elmar Saathoff, PhD Lucas Maganga, MD Williams H Makunde, MD Prof Achim Hoerauf, MD Christof Geldmacher, PhD Petra Clowes, MD Leonard Maboko, PhD Prof Michael Hoelscher, MD

The past decades have seen an ongoing controversial debate about whether the immune activation induced by helminths has an effect on the susceptibility of individuals to HIV. In view of this, we assessed the effect of lymphatic filariasis, a chronic helminth disease elicited by Wuchereria bancrofti, on HIV incidence in southwest Tanzania.

Published at:  2016-08-02

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