Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe.

BACKGROUND: Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. METHODS: Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. RESULTS: The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. CONCLUSIONS: Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected.

A forgotten disease in a returning traveler from Thailand.

Cutaneous diphteria is a forgotten disease. We must consider this in our differential diagnosis, not only when a patient presents with a cutaneous ulcer and has travelled to tropical areas, but also in patients who subsist in low socio-economic conditions, especially in homeless people and people with a history of alcohol or drug abuse. Vigilance for this forgotten disease is warranted because most physicians in developed countries have never seen one case. In an era of increasing globalisation, we might see more cases in the future. We report a case of a foot infection with a non toxigenic C. diptheriae biovar gravis in a 16 year old girl, who has travelled to Thailand.

Fever in HIV-infected patients: less frequent but still complex.

Fever was a common symptom in patients with Human Immunodeficiency Virus (HIV) infection in the early phases of the epidemic. Fever of Unknown Origin (FUO) was frequent in HIV-patients and conditions causing FUO were often opportunistic conditions. The HIV-epidemic continues to expand, but access to effective antiretroviral therapy is also expanding, resulting in a growing number of HIV-infected patients less likely to be severely immunocompromised and less likely to present opportunistic conditions. Yet part of newly diagnosed patients continue to present with advanced HIV-infection and are still at high risk of opportunistic conditions. This epidemiological evolution strongly influences the spectrum of conditions causing fever and FUO in HIV-patients. While some patients with HIV-associated fever and FUO may still be suffering from opportunistic conditions classically associated with HIV-related FUO, many others will have causes of fever that are similar to the non-HIV-infected population or to classical FUO. Strategies for diagnosis and treatment of fever and its causes in HIV-infected patients need to take into account this evolution.

Equivalent dynamic human brain NK1-receptor occupancy following single-dose i.v. fosaprepitant vs. oral aprepitant as assessed by PET imaging.

The type 1 neurokinin receptor (NK1R) antagonist aprepitant and its i.v. prodrug fosaprepitant have been approved for prevention of acute and delayed nausea and vomiting associated with chemotherapy. This study evaluated the magnitude and duration of brain NK1R occupancy over a period of 5 days after single-dose i.v. infusion of 150-mg fosaprepitant and single-dose oral administration of 165-mg aprepitant, using serial [(18)F]MK-0999 positron emission tomography (PET) in 16 healthy subjects. Each subject underwent three scans. Brain NK1R occupancy rates after i.v. fosaprepitant at time to peak concentration (T(max); ~30 min), 24, 48, and 120 h after the dose were 100, 100, ≥97, and 41-75%, respectively. After aprepitant, NK1R occupancy rates at these time points (T(max) ~4 h) were ≥99, ≥99, ≥97, and 37-76%, respectively. Aprepitant plasma concentration profiles were comparable for the two dosage forms. The study illustrates the utility of PET imaging in determining central bioequivalence in a limited number of subjects.

[AIDS treatment in Africa: the risk of antiretroviral resistance]. / Aidsbehandeling in Afrika: het risico van antiretrovirale resistentie.

--In recent years, implementation of antiretroviral therapy in developing countries with a high prevalence of HIV-1 has been recognised as a public health priority. Consequently, the availability ofantiretroviral combination therapy for people with HIV is increasing rapidly in sub-Saharan Africa. --HIV treatment programmes are implemented according to the standardised, simplified public health guidelines developed by the World Health Organization (WHO). --However, the implementation of treatment programmes in Africa is hindered by several factors, including the lack of adequate immunological and virological laboratory monitoring, insufficient support for adherence to therapy, vulnerable health care systems and the use of suboptimal drug combinations. --These suboptimal treatment conditions increase the risk that resistant virus strains will emerge that are less susceptible to standard first-line combination therapy, thus threatening the long-term success of the treatment programmes. --The WHO has initiated HIVResNet, an international expert advisory board that has developed a global strategy for surveillance and prevention of antiretroviral drug resistance. --The Dutch initiative known as 'PharmAccess African studies to evaluate resistance' (PASER) is contributing to this strategy by creating a surveillance network in sub-Saharan Africa.

Value of standard laboratory tests for the early recognition of group A beta-hemolytic streptococcal necrotizing fasciitis.

The laboratory data for 17 patients with group A beta-hemolytic streptococcal necrotizing fasciitis (GAS NF) were compared with data for 145 patients hospitalized for cellulitis during the same period. Admission values of C-reactive protein and creatine kinase were higher for patients in the group with GAS NF than for patients in the group with cellulitis (P<.001), suggesting that standard laboratory tests may be useful for the early differential diagnosis of GAS NF and cellulitis.

Positron emission tomography scan in the diagnosis and follow-up of aortitis of the thoracic aorta.

We report a case of a 62-year-old female patient with an inflammatory reaction of the thoracic aortic wall. The diagnosis was made by computed tomographic (CT) scan, magnetic resonance imaging (MRI) and positron emission tomographic scan with 18-fluorodeoxyglucose (FDG-PET). The patient was treated with corticosteroids. The inflammatory parameters as well as FDG-uptake on PET scan returned to normal. Due to its aspecific presentation, the diagnosis of aortitis is often hard to establish. With this case the possible role of FDG-PET scan as a valuable tool in the diagnosis and monitoring of this inflammatory aortic disorder was demonstrated.