Chronic Q fever diagnosis—consensus guideline versus expert opinion

Chronic Q fever, caused by Coxiella burnetii, has high mortality and morbidity rates if left untreated. Controversy about the diagnosis of this complex disease has emerged recently. We applied the guideline from the Dutch Q Fe­ver Consensus Group and a set of diagnostic criteria pro­posed by Didier Raoult to all 284 chronic Q fever patients included in the Dutch National Chronic Q Fever Database during 2006–2012. Of the patients who had proven cas­es of chronic Q fever by the Dutch guideline, 46 (30.5%) would not have received a diagnosis by the alternative cri­teria designed by Raoult, and 14 (4.9%) would have been considered to have possible chronic Q fever. Six patients with proven chronic Q fever died of related causes. Until results from future studies are available, by which current guidelines can be modified, we believe that the Dutch lit­erature-based consensus guideline is more sensitive and easier to use in clinical practice

Decreased exposure to saquinavir in HIV-1-infected patients after long-term antiretroviral therapy including ritonavir and saquinavir

Objective: To explore whether steady-state plasma pharmacokinetics of ritonavir and saquinavir change during long-term treatment in HIV-1-infected patients on antiretroviral treatment including ritonavir and saquinavir. Methods: The pharmacokinetics of ritonavir and saquinavir were assessed during an 8-h period on two occasions in six HIV-1 infected patients on stable twice daily treatment with ritonavir 400 mg, saquinavir 400 mg and stavudine 40 mg with or without lamivudine 150 mg twice daily. Results: The first study day was 4-12 months (median 7 months) after the start of the current regimen. The second study day was 9-15 months (median 10 months) later. No significant differences were observed for the ritonavir pharmacokinetics between the first and second study day. However, median change in plasma trough level of saquinavir between the two study days was -30% (range -79 to +11%; P = 0.06). Median change in maximum plasma concentration was -40% (range -62 to +34%; P = 0.09). The median change in area under the plasma concentration versus time curve over 0-8 h was -33% (range 53 to +21%; P = 0.06). Conclusion: The exposure to saquinavir decreased over time in HIV-infected patients on stable antiretroviral therapy. These data suggest that regular monitoring of plasma drug concentrations should become part of routine patient care even in apparently compliant patients. (C) 2000 Lippincott Williams and Wilkins

A systematic review of a single-class maintenance strategy with nucleoside/nucleotide reverse transcriptase inhibitors in HIV/AIDS

Background: Single-drug class regimens with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) are generally not recommended as initial therapy because they are inferior compared with therapy with two NRTIs plus efavirenz. However, triple-NRTI combinations can be useful in specific circumstances such as in tuberculosis coinfection, pregnancy or dyslipidaemia. Here, we review the potential of such combinations to maintain viral suppression after induction of suppression by standard combination antiretroviral therapy (cART) and to evaluate the trade-off of NRTI-only regimens for metabolic control. Methods: We conducted a systematic search of the literature in two databases from 1 January 1998 up to 1 March 2013: Medline, through the search engine PubMed, and Embase. Results: A total of 11 randomized controlled trials (RCTs) with 2,105 patients and 3 observational studies with 2,639 patients were included. Studies including patients with mono-or dual-NRTI treatment before start of effective cART showed a tendency to higher failure rate because of resistance based on archived viral mutations. In studies with ART-naive subjects before start of cART, triple-NRTI combination showed virological activity comparable to two NRTIs plus a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor in all RCTs, but not in one cohort study. Switching improved serum lipids significantly. Conclusions: Of the studied triple-NRTI combinations only abacavir/lamivudine/zidovudine was sufficiently potent. Triple-NRTI maintenance after successful induction with two-class cART appeared successful in treatment-naive subjects and remains a useful option in specific circumstances, especially when other drugs are not available or drug interactions are an issue

Cerebrospinal fluid HIV-1 RNA during treatment with ritonavir/saquinavir or ritonavir/saquinavir/stavudine

Objective: To assess the HIV-1-RNA response and drug concentrations in cerebro-spinal fluid (CSF) and serum during treatment with saquinavir (SQV)/ritonavir (RIV) or SQV/RIV plus stavudine (d4T) in HIV-1-infected patients. Design: A multicentre, open-label, randomized controlled trial. Methods: A total of 208 protease inhibitor (PI) and d4T-naive, HIV-1-infected patients were treated with RTV 400 mg twice daily and SQV 400 mg twice daily with or without d4T 40 mg twice daily. Intensification with reverse transcriptase inhibitors was allowed if serum HIV RNA remained above 400 copies/ml after 12 weeks. In 27 volunteers, CSF and serum HIV RNA were measured at baseline, weeks 12 and 48, using the Roche Amplicor and the ultrasensitive assay. In 22 patients, serum and CSF drug concentrations were determined at week 12. Results: The median baseline serum and CSF HIV-RNA concentrations were 4.81 and 3.21 log10 copies/ml, respectively. A difference in the proportion of patients with a CSF HIV-RNA level below the limit of quantification ( LLQ at week 12 in logistic regression analysis (P= 0.005). CSF RIV and SQV concentrations were < LLQ in most patients. Conclusion: RTV/SQV alone cannot suppress detectable CSF HIV-1-RNA levels to < LLQ after 12 weeks of treatment in the majority of patients. CSF drug concentrations of RTV and SQV < LLQ may explain the suboptimal antiretroviral effect in the CSF. (C) 2000 Lippincott Williams and Wilkins

Increasing cerebrospinal fluid chemokine concentrations despite undetectable cerebrospinal fluid HIV RNA in HIV-1-infected patients receiving antiretroviral therapy

Only limited data on cerebrospinal fluid (CSF) HIV-1 RNA responses and markers of local inflammation in CSF during antiretroviral therapy are available. HIV-RNA, soluble tumor necrosis factor (TNF)-receptor (sTNFr)-II, monocyte chemoattractant protein (MCP)-1, and interferon-γ-inducible protein (IP)-10 were measured in the peripheral blood and CSF of 26 antiretroviral-naive HIV-1-positive patients, who were treated with ritonavir (RTV)/saquinavir (SQV) (n = 5), RTV/SQV/stavudine (d4T; n = 8) or zidovudine (AZT)/lamivudine (3TC)/abacavir/nevirapine/indinavir (n = 13). After 8 to 12 weeks of treatment, CSF HIV-RNA dropped to <400 copies/ml in 1 of 5 patients in the RTV/SQV group, 8 of 8 patients in the RTV/SQV/d4T group, and 9 of 10 patients in the five-drag group. CSF sTNFr-II and IP-10 levels increased in patients with detectable CSF HIV-RNA. However, increases in CSF chemokine and sTNFr-II concentrations were also observed in some patients with good CSF HIV-RNA responses. Moreover, CSF MCP-1 concentrations increased in the whole population after 2 months of treatment. Ongoing residual HIV replication in the central nervous system, which cannot be detected with CSF HIV-RNA measurements, may account for this phenomenon

Vaccination with Fendrix of prior nonresponding patients with HIV has a high success rate

BACKGROUND: Patients with HIV have a poor serological conversion rate with the standard vaccination strategy against hepatitis B virus (HBV) of around 50%. Vaccination with Fendrix confers much better results in these patients. In this study, we tested the effect of revaccination with Fendrix in prior nonresponding patients with HIV and aimed to determine which factors are associated with seroconversion. METHODS: Eight Dutch HIV treatment centers participated in this retrospective study. Patients infected with HIV-1 and nonresponding to prior course of vaccination against HBV (anti-HBs <10 IU/ml) and who had Fendrix as a second, third or fourth effort to achieve seroconversion were eligible for inclusion. Primary outcome was the proportion of patients with seroconversion after revaccination with Fendrix. Univariate binary logistic regression analyses were used to determine which factors could be used as predictors for seroconversions. RESULTS: We included 100 patients with HIV. The mean age was 47.3 (±11.0) years and 86% were men. Revaccination with Fendrix showed a seroconversion rate of 81% (95% confidence interval 72-88%). Median nadir CD4 cell count was 300 (20-1040) cells/μl and median CD4 cell count at the time at starting vaccination with Fendrix was 605 (210-1190) cells/μl. Regression analyses showed no significant factor associated with seroconversion. CONCLUSIONS: Revaccination with Fendrix of patients prior nonresponding to other hepatitis B vaccination strategies has a high success rate. Eighty-one percentage responded with seroconversion, irrespective of CD4 cell count

Nguyen Huu Chau, Structures, Institutions et développement économique dans les pays sous-développés

Decouflé André-Clément. Nguyen Huu Chau, Structures, Institutions et développement économique dans les pays sous-développés. In: Tiers-Monde, tome 6, n°21, 1965. pp. 279-280