The substantial decline in the Pneumocystis jirovecii pneumonia (PCP) incidence in HIV-infected patients after the introduction of antiretroviral therapy (ART) in resource-rich settings and the growing number of non-HIV-infected immunocompromised patients at risk leads to considerable epidemiologic changes with clinical, diagnostic, and treatment consequences for physicians. HIV-infected patients usually develop a subacute course of disease, while non-HIV-infected immunocompromised patients are characterized by a rapid disease progression with higher risk of respiratory failure and higher mortality. The main symptoms usually include exertional dyspnea, dry cough, and subfebrile temperature or fever. Lactate dehydrogenase may be elevated. Typical findings on computed tomography scans of the chest are bilateral ground-glass opacities with or without cystic lesions, which are usually associated with the presence of AIDS. Empiric treatment should be initiated as soon as PCP is suspected. Bronchoalveolar lavage has a higher diagnostic yield compared to induced sputum. Immunofluorescence is superior to conventional staining. A combination of different diagnostic tests such as microscopy, polymerase chain reaction, and (1,3)-β-D-glucan is recommended. Trimethoprim/sulfamethoxazole for 21 days is the treatment of choice in adults and children. Alternative treatment regimens include dapsone with trimethoprim, clindamycin with primaquine, atovaquone, or pentamidine. Patients with moderate to severe disease should receive adjunctive corticosteroids. In newly diagnosed HIV-infected patients with PCP, ART should be initiated as soon as possible. In non-HIV-infected immunocompromised patients, improvement of the immune status should be discussed (e.g., temporary reduction of immunosuppressive agents). PCP prophylaxis is effective and depends on the immune status of the patient and the underlying immunocompromising disease.
BackgroundTo evaluate clinical outcomes after either immediate or deferred initiation of antiretroviral therapy in HIV-1-infected patients, presenting late with pneumocystis pneumonia (PCP) or toxoplasma encephalitis (TE).MethodsPhase IV, multicenter, prospective, randomized open-label clinical trial. Patients were randomized into an immediate therapy arm (starting antiretroviral therapy (ART) within 7 days after initiation of OI treatment) versus a deferred arm (starting ART after completing the OI-therapy). All patients were followed for 24 weeks. The rates of clinical progression (death, new or relapsing opportunistic infections (OI) and other grade 4 clinical endpoints) were compared, using a combined primary endpoint. Secondary endpoints were hospitalization rates after completion of OI treatment, incidence of immune reconstitution inflammatory syndrome (IRIS), virologic and immunological outcome, adherence to proteinase-inhibitor based antiretroviral therapy (ART) protocol and quality of life.Results61 patients (11 patients suffering TE, 50 with PCP) were enrolled. No differences between the two therapy groups in all examined primary and secondary endpoints could be identified: immunological and virologic outcome was similar in both groups, there was no significant difference in the incidence of IRIS (11 and 10 cases), furthermore 9 events (combined endpoint of death, new/relapsing OI and grade 4 events) occurred in each group.ConclusionsIn summary, this study supports the notion that immediate initiation of ART with a ritonavir-boosted proteinase-inhibitor and two nucleoside reverse transcriptase inhibitors is safe and has no negative effects on incidence of disease progression or IRIS, nor on immunological and virologic outcomes or on quality of life.
165 treatment-naive patients who first presented at the infectious disease clinic of the University Medical Center Hamburg-Eppendorf from 2009 to 2011 were retrospectively analyzed with emphasis on patients with late presentation (LP). In line with other recent German reports, there was a large proportion of 105 of the 165 treatment-naïve patients (63.6 %) who presented late. Old age, heterosexual transmission risk and migrant background were associated risk factors for late presentation. Thus, further intensified national efforts like the HIV in Europe initiative are needed to identify such patients at high risk for HIV infection.
We analyzed 1,397 HIV-1
pol
sequences of antiretroviral therapy–naive patients in a total of 7 university hospitals in Bonn, Cologne, Frankfurt, Hamburg, Hannover, and Munich, Germany. Phylogenetic and network analysis elucidated numerous cases of shared drug resistance mutations among genetically linked patients; K103N was the most frequently shared mutation.
BackgroundWhile Germany has a long tradition in HIV research with many well-established regional cohorts, there was a lack of collaborative efforts toward harmonized data collection and biobanking, both key strategies for efficient translational research projects. Key challenges are heterogeneity of data systems and privacy concepts, of existing study and data collection protocols, and sample collection, storage, and sharing.MethodsIn 2013, we established the Translational Platform HIV (TP-HIV) with support of the German Centre for Infection Research (DZIF) as a collaboration between university hospitals and specialized HIV care centers throughout Germany. After assessing the individual needs of all partner sites, we have taken comprehensive action to create a common platform for collaboration in all research stages. We developed protocols, rules of operation, biobanking strategies, and privacy concepts for all collaborating partner sites. Patients infected with HIV (PLWH) who sign the informed consent for the TP-HIV are pro- and retrospectively included in the cohort.ResultsTo date, the TP-HIV infrastructure is implemented at 27 member sites from 11 cities, potentially extending to more than 20,000 patients currently treated for HIV across Germany. Facing the special needs in the German research environment, the TP-HIV established a unique data- and biomaterial collection allowing expedited translational research and reduce project overheads, regulatory burden, and data security regulations for investigators. By active surveillance, rapid access to individual patient groups such as patients with acute HIV infection, TP-HIV is an ideal platform for early phase clinical trials with new drug candidates. Researchers with clinical, biological, epidemiological, and statistical expertise have been brought together within the TP-HIV, which enables an effective translational chain from bench to bedside and back. New collaborations have been established with currently 23 active study protocols.ConclusionThe TP-HIV has demonstrated to be a powerful tool for generating and testing research hypotheses in PLWH. In the future, we will work to further expand our network and address the pressing needs in the German research environment.Disclosures
All authors: No reported disclosures.
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