Monitoring CD27 Expression to Evaluate Mycobacterium Tuberculosis Activity in HIV-1 Infected Individuals In Vivo

Alexandra Schuetz ,Antelmo Haule,Klaus Reither,Njabulo Ngwenyama,Andrea Rachow,Andreas Meyerhans,Leonard Maboko,Richard A. Koup,Michael Hoelscher,Christof Geldmacher

The level of bacterial activity is only poorly defined during asymptomatic Mycobacterium tuberculosis (MTB) infection. The objective was to study the capacity of a new biomarker, the expression of the T cell maturation marker CD27 on MTB-specific CD4 T cells, to identify active tuberculosis (TB) disease in subjects from a MTB and HIV endemic region. The frequency and CD27 expression of circulating MTB-specific CD4 T cells was determined in 96 study participants after stimulation with purified protein derivative (PPD) using intracellular cytokine staining for IFNgamma (IFNγ). Subjects were then stratified by their TB and HIV status. Within PPD responders, a CD27− phenotype was associated with active TB in HIV− (p = 0.0003) and HIV+ (p = 0.057) subjects, respectively. In addition, loss of CD27 expression preceded development of active TB in one HIV seroconverter. Interestingly, in contrast to HIV− subjects ..........

Published at:  2011-11-07

Scarcity or Absence of Humoral Immune Responses in the Plasma and Cervicovaginal Lavage Fluids of Heavily HIV-1-Exposed But Persistently Seronegative Women

Jiri Mestecky, Peter F. Wright, Lucia Lopalco, Herman F. Staats, Pamela A. Kozlowski, Zina Moldoveanu, Rashada C. Alexander, Rose Kulhavy, Claudia Pastori, Leonard Maboko, Gabriele Riedner, Yuwei Zhu, Terri Wrinn, and Michael Hoelscher

To address an existing controversy concerning the presence of HIV-1-specific antibodies of the IgA isotype in the female genital tract secretions of highly-exposed but persistently seronegative (HEPSN) women, 41 samples of plasma and cervicovaginal lavage (CVL) fluid were distributed to six laboratories for their blinded evaluation using ELISA with 10 different HIV-1 antigens, chemiluminescence-enhanced Western blots (ECL-WB), and virus neutralization. HIV-specific IgG or IgA antibodies in plasma samples from HEPSN women were absent or detectable only at low levels. In CVL, 11/41 samples displayed low levels of reactivity in ELISA against certain antigens. However, only one sample was positive in two of five...........

Published at:  2011-05-04

Defining the human immunodeficiency virus type 1 transmission genetic bottleneck in a region with multiple circulating subtypes and recombinant forms

Andile Nofemela a 1, Gama Bandawe a 1, Ruwayhida Thebus a, Jinny Marais a, Natasha Wood b, Oliver Hoffmann e, Leonard Maboko d, Michael Hoelscher d e, Zenda Woodman c, Carolyn Williamson a

The Mbeya region of Tanzania has a genetically complex HIV epidemic with multiple subtypes and recombinant forms circulating, together with a high frequency of dual infections with more than one subtype. This study aimed to determine whether this impacted the HIV-1 transmission bottleneck. A total of 210 env sequences from 22 participants were generated from recently infected women from Mbeya using the single genome amplification approach. Participants were.......

Published at:  2011-05-04

Risk factors for HIV-1 infection in a longitudinal, prospective cohort of adults from the Mbeya Region, Tanzania

Steffen Geis, MD,1,2,* Leonard Maboko, MD, PhD,2,* Elmar Saathoff, PhD,1 Oliver Hoffmann, MD, PhD,1,2 Christof Geldmacher, PhD,1,2 Donan Mmbando, MD,3 Eleuter Samky, MD,4 Nelson L. Michael, MD, PhD,5,6 Deborah L. Birx, MD,7 Merlin L. Robb, MD,5,8 and Michael Hoelscher, MD, PhD1,2

To control the global HIV epidemic targeted interventions to reduce the incidence of HIV infections are urgently needed until an effective HIV vaccine is available. This study describes HIV-1 incidence and associated risk factors in a general population cohort of adults from Mbeya Region, Tanzania, who participated in a vaccine preparedness study.

Published at:  2011-04-15

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