HIV dynamics and natural history studies: Joint modeling with doubly interval-censored event time and infrequent longitudinal data

Hepatitis C virus (HCV) coinfection has become one of the most challenging clinical situations to manage in HIV-infected patients. Recently the effect of HCV coinfection on HIV dynamics following initiation of highly active antiretroviral therapy (HAART) has drawn considerable attention. Post-HAART HIV dynamics are commonly studied in short-term clinical trials with frequent data collection design. For example, the elimination process of plasma virus during treatment is closely monitored with daily assessments in viral dynamics studies of AIDS clinical trials. In this article instead we use infrequent cohort data from long-term natural history studies and develop a model for characterizing post-HAART HIV dynamics and their associations with HCV coinfection. Specifically, we propose a joint model for doubly interval-censored data for the time between HAART initiation and viral suppression, and the longitudinal CD4 count measurements relative to the viral suppression. Inference is accomplished using a fully Bayesian approach. Doubly interval-censored data are modeled semiparametrically by Dirichlet process priors and Bayesian penalized splines are used for modeling population-level and individual-level mean CD4 count profiles. We use the proposed methods and data from the HIV Epidemiology Research Study (HERS) to investigate the effect of HCV coinfection on the response to HAART.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS391 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Malaria-filaria coinfection in mice makes malarial disease more severe unless filarial infection achieves patency

Coinfections are common in natural populations, and the literature suggests that helminth coinfection readily affects how the immune system manages malaria. For example, type 1–dependent control of malaria parasitemia might be impaired by the type 2 milieu of preexisting helminth infection. Alternatively, immunomodulatory effects of helminths might affect the likelihood of malarial immunopathology. Using rodent models of lymphatic filariasis (Litomosoides sigmodontis) and noncerebral malaria (clone AS Plasmodium chabaudi chabaudi), we quantified disease severity, parasitemia, and polyclonal splenic immune responses in BALB/c mice. We found that coinfected mice, particularly those that did not have microfilaremia (Mf), had more severe anemia and loss of body mass than did mice with malaria alone. Even when controlling for parasitemia, malaria was most severe in Mf coinfected mice, and this was associated with increased interferon-g responsiveness. Thus, in Mf mice, filariasis upset a delicate immunological balance in malaria infection and exacerbated malaria-induced immunopathology. Helminth infections are prevalent throughout tropical regions where malaria is transmitted [1–5]. Interactions among infections commonly alter disease severity [6, 7], and malaria-helminth coinfection can either exac

Mathematical analysis of complex SIR model with coinfection and density dependence

An SIR model with the coinfection of the two infectious agents in a single host population is considered. The model includes the environmental carry capacity in each class of population. A special case of this model is analyzed and several threshold conditions are obtained which describes the establishment of disease in the population. We prove that for small carrying capacity $K$ there exist a globally stable disease free equilibrium point. Furthermore, we establish the continuity of the transition dynamics of the stable equilibrium point, i.e. we prove that (1) for small values of $K$ there exists a unique globally stable equilibrium point, and (b) it moves continuously as $K$ is growing (while its face type may change). This indicate that carrying capacity is the crucial parameter and increase in resources in terms of carrying capacity promotes the risk of infection.Comment: 14 page

Rare Coinfection of Scrub Typhus and Malaria in Immunocompetent Person

Scrub Typhus, or tsutsugamushi disease is a febrile illness caused by bacteria of the family Rickettsiaceae and named Orientia tsutsugamushi. Recently it has been found to endemic in Subhimalayan region of India.Malaria is highly endemic in rest of India but its prevalence is low in Subhimalayan region because of the altitude. We report a rare case of a patient having coinfection with scrub typhus and malaria

Astrocyte Apoptosis and HIV Replication Are Modulated in Host Cells Coinfected with Trypanosoma cruzi

The protozoan Trypanosoma cruzi is the etiological agent of Chagas disease. In immunosuppressed individuals, as it occurs in the coinfection with human immunodeficiency virus (HIV), the central nervous system may be affected. In this regard, reactivation of Chagas disease is severe and often lethal, and it accounts for meningoencephalitis. Astrocytes play a crucial role in the environment maintenance of healthy neurons; however, they can host HIV and T. cruzi. In this report, human astrocytes were infected in vitro with both genetically modified-pathogens to express alternative fluorophore. As evidenced by fluorescence microscopy and flow cytometry, HIV and T. cruzi coexist in the same astrocyte, likely favoring reciprocal interactions. In this context, lower rates of cell death were observed in both T. cruzi monoinfected-astrocytes and HIV-T. cruzi coinfection in comparison with those infected only with HIV. The level of HIV replication is significantly diminished under T. cruzi coinfection, but without affecting the infectivity of the HIV progeny. This interference with viral replication appears to be related to the T. cruzi multiplication rate or its increased intracellular presence but does not require their intracellular cohabitation or infected cell-to-cell contact. Among several Th1/Th2/Th17 profile-related cytokines, only IL-6 was overexpressed in HIV-T. cruzi coinfection exhibiting its cytoprotective role. This study demonstrates that T. cruzi and HIV are able to coinfect astrocytes thus altering viral replication and apoptosis.Fil: Urquiza, Javier Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Burgos, Juan Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Ojeda, Diego Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Pascuale, Carla Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Leguizamon, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Quarleri, Jorge Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

Aspergillus fumigatus preexposure worsens pathology and improves control of Mycobacterium abscessus pulmonary infection in mice

ABSTRACT Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Mutations in this chloride channel lead to mucus accumulation, subsequent recurrent pulmonary infections, and inflammation, which, in turn, cause chronic lung disease and respiratory failure. Recently, rates of nontuberculous mycobacterial (NTM) infections in CF patients have been increasing. Of particular relevance is infection with Mycobacterium abscessus , which causes a serious, life-threatening disease and constitutes one of the most antibiotic-resistant NTM species. Interestingly, an increased prevalence of NTM infections is associated with worsening lung function in CF patients who are also coinfected with Aspergillus fumigatus . We established a new mouse model to investigate the relationship between A. fumigatus and M. abscessus pulmonary infections. In this model, animals exposed to A. fumigatus and coinfected with M. abscessus exhibited increased lung inflammation and decreased mycobacterial burden compared with those of mice infected with M. abscessus alone. This increased control of M. abscessus infection in coinfected mice was mucus independent but dependent on both transcription factors T-box 21 (Tbx21) and retinoic acid receptor (RAR)-related orphan receptor gamma t (RORγ-t), master regulators of type 1 and type 17 immune responses, respectively. These results implicate a role for both type 1 and type 17 responses in M. abscessus control in A. fumigatus -coinfected lungs. Our results demonstrate that A. fumigatus , an organism found commonly in CF patients with NTM infection, can worsen pulmonary inflammation and impact M. abscessus control in a mouse model. </jats:p

Does counseling increase sustained benefit of HAART among prison inmates after release to the community?

The lack of sustained effectiveness of HAART after release to the community of HIV-infected inmates treated in prison was well demonstrated by Springer et al. in a recent article. This disappointing result occurred even though all of the patients scheduled for release were referred for transitional case management services to a community-based organization and were provided with a 2-week supply of medications, a medical appointment with an HIV care provider, emergency housing and food, and assistance with other identified unmet needs