The impact of pre-exposure prophylaxis (PrEP) on HIV epidemics in Africa and India: A simulation study

Background: Pre-exposure prophylaxis (PrEP) is a promising new HIV prevention method, especially for women. An urgent demand for implementation of PrEP is expected at the moment efficacy has been demonstrated in clinical trials. We explored the long-term impact of PrEP on HIV transmission in different HIV epidemics. Methodology/Principal Findings: We used a mathematical model that distinguishes the general population, sex workers and their clients. PrEP scenarios varying in effectiveness, coverage and target group were modeled in the epidemiological settings of Botswana, Nyanza Province in Kenya, and Southern India. We also studied the effect of condom addition or condom substitution during PrEP use. Main outcome was number of HIV infections averted over ten years of PrEP use. PrEP strategies with high effectiveness and high coverage can have a substantial impact in African settings. In Southern India, by contrast, the number of averted HIV infections in different PrEP scenarios would be much lower. The impact of PrEP may be strongly diminished or even reversed by behavioral disinhibition, especially in scenarios with low coverage and low effectiveness. However, additional condom use during low coverage and low effective PrEP doubled the amount of averted HIV infections. Conclusions/Significance: The public health impact of PrEP can be substantial. However, this impact may be diminished, or even reversed, by changes in risk behavior. Implementation of PrEP strategies should therefore come on top of current condom campaigns, not as a substitution

SARS-CoV Pathogenesis Is Regulated by a STAT1 Dependent but a Type I, II and III Interferon Receptor Independent Mechanism

Severe acute respiratory syndrome coronavirus (SARS-CoV) infection often caused severe end stage lung disease and organizing phase diffuse alveolar damage, especially in the elderly. The virus-host interactions that governed development of these acute end stage lung diseases and death are unknown. To address this question, we evaluated the role of innate immune signaling in protection from human (Urbani) and a recombinant mouse adapted SARS-CoV, designated rMA15. In contrast to most models of viral pathogenesis, infection of type I, type II or type III interferon knockout mice (129 background) with either Urbani or MA15 viruses resulted in clinical disease outcomes, including transient weight loss, denuding bronchiolitis and alveolar inflammation and recovery, identical to that seen in infection of wildtype mice. This suggests that type I, II and III interferon signaling play minor roles in regulating SARS pathogenesis in mouse models. In contrast, infection of STAT1−/− mice resulted in severe disease, high virus titer, extensive pulmonary lesions and 100% mortality by day 9 and 30 post-infection with rMA15 or Urbani viruses, respectively. Non-lethal in BALB/c mice, Urbani SARS-CoV infection in STAT1−/− mice caused disseminated infection involving the liver, spleen and other tissues after day 9. These findings demonstrated that SARS-CoV pathogenesis is regulated by a STAT1 dependent but type I, II and III interferon receptor independent, mechanism. In contrast to a well documented role in innate immunity, we propose that STAT1 also protects mice via its role as an antagonist of unrestrained cell proliferation

Raised Venous Lactate and Markers of Intestinal Translocation Are Associated With Mortality Among In-Patients With HIV-Associated TB in Rural South Africa.

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.Introduction: Case fatality among in-patients with HIV-associated tuberculosis (HIV-TB) in Africa is high. We investigated the factors associated with mortality in a rural South African hospital. Methods: This was a prospective observational study of HIV-TB in-patients, with death by 8 weeks the endpoint. Results: Of 99 patients (median CD4 count 72 cells/mm3), 32 (32%) died after median 8-day TB treatment. TB was diagnosed microbiologically in 75/99 and clinico-radiologically in 24, with no mortality difference between these groups [31% versus 38% (P = 0.53)]. Median venous lactate was 5.5 mmol/L (interquartile range 3.9-6.2) in those who died and 3.1 mmol/L (interquartile range 2.2-4.1) in survivors (P < 0.001). In multivariable analysis, lactate ≥4 mmol/L [adjusted odds ratio (aOR) 9.8, 95% confidence interval (CI): 3.0 to 32.2], Glasgow Coma Score <15 (aOR 6.6, 95% CI: 1.5 to 29.6), CD4 count <50 cells per cubic millimeter (aOR 5.5, 95% CI: 1.6 to 18.5), and age ≥50 (aOR 7.7, 95% CI: 1.2 to 46.9) independently predicted death. In a nested case-control study, comparing those who died versus CD4-matched survivors, median plasma lipopolysaccharide concentrations were 93 and 57 pg/mL (P = 0.026) and intestinal fatty acid-binding protein, 132 and 0 pg/mL (P = 0.002). Conclusions: Mortality was high and predicted by elevated lactate, likely reflecting a sepsis-syndrome secondary to TB or bacterial coinfection with intestinal barrier dysfunction appearing to contribute