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Background: A simple real-time PCR assay using one set of primer and probe for rapid, sensitive and quantitative detection of Plasmodium species, with simultaneous differentiation of Plasmodium falciparum from the three other Plasmodium species (Plasmodium vivax, Plasmodium ovale and Plasmodium malariae) in febrile returning travellers and migrants was developed and evaluated.

Non-B HIV-1 viruses are predominant in developing countries where access to antiretroviral drugs (ARVs) is progressively being intensified. It is important to obtain more data on the susceptibility of these viruses to available ARVs. CRF01_AE, CRF02_AG, and subtype C strains of HIV-1 obtained from untreated patients from Vietnam, Cote d'Ivoire, and India were analyzed for their in vitro susceptibility to NRTIs, NNRTIs, PIs, and an entry inhibitor (T-20) using a recombinant viral assay (PHENOSCRIPT). The corresponding viruses, which had been previously sequenced in reverse transcriptase (RT), protease (prot), plus envelope (env) C2/V3 genes and had therefore been fully characterized, were further sequenced in env HR1 + HR2 regions. CRF01_AE isolates are sensitive to NRTIs and NNRTIs with the exception of one isolate that exhibits a decreased susceptibility to NNRTIs associated with a I135T substitution in RT. CRF02_AG and subtype C viruses are sensitive to NRTIs and NNRTIs but some CRF02_AG isolates tend to be resistant to abacavir, potentially related to associated substitutions of RT at positions 123 (D123N) plus 135 (I135V). Whereas all but one CRF01_AE isolates are fully susceptible to PIs, some CRF02_AG and, more frequently, some subtype C isolates are resistant to atazanavir. The role of substitutions in prot at positions of secondary resistance mutations 20, 36, 63, and 82 is raised with a potentially crucial role of the V82I substitution. Finally, all viruses tested, regardless of the CRF or subtype, are fully susceptible to T-20.

In this study, named the Zephir study (Telzir-pharmacokinetics), 121 antiretroviral-experienced human immunodeficiency virus (HIV) patients failing on highly active antiretroviral therapy (HAART) were included in a prospective cohort and received a fosamprenavir-ritonavir (700 mg/100 mg twice a day)-based regimen. The impact of baseline HIV type 1 (HIV-1) mutations, pharmacokinetic (PK) parameters, and genotype inhibitory quotient (GIQ) on the virological response at week 12 (W12) was assessed. HIV reverse transcriptase and protease were sequenced at W0. The response at W12 was defined as <2.3 log 10 HIV-1 RNA copies/ml or a virus load decrease of >1 log 10 copies/ml. W4 amprenavir PK were determined by high-performance liquid chromatography. Patients had a median of nine previous treatments over 8 years. Median W0 values were as follows: 295 CD4 ؉ /l, 4.4 log 10 HIV-1 RNA copies/ml, and 6 protease-and 5 nucleotide reverse transcription inhibitor-related mutations. Respective values for minimum concentration of drug in serum (C min ) and area under the concentration-time curve (AUC) from 0 to 24 h were 1,400 ng/ml and 35 mg ⅐ h/ml. At W12, 52% of the patients were successes, with a median decrease of ؊0.7 log 10 HIV-1 RNA copies/ml. The Zephir mutation score included 12 IAS protease mutations associated with poorer virological response: L10I/F/R/V, L33F, M36I, M46I/L, I54L/M/T/V, I62V, L63P, A71I/L/V/T, G73A/C/F/T, V82A/F/S/T, I84V, L90M, and polymorphism mutations I13V, L19I, K55R, and L89M. Comparing <4 versus >4 mutations, HIV-1 RNA decreases were ؊2.3 log 10 copies/ml versus ؊0.1 log 10 copies/ml (P < 10 ؊4 ) with 93% versus 19% successes (P < 10 ؊4 ), respectively. This score predicted W12 failure with 94% sensitivity, versus 31% for the ANRS 2005 algorithm. C min (<1,600 ng/ml), AUC (<40 mg ⅐ h/ml), and GIQ (<300) values were associated with failure (all P values were <10 ؊4 ). The need to test genotype-based algorithms using different patient databases before their implementation in clinical practice is highlighted. Specific mutations, PK and GIQ, provide relevant information for monitoring fosamprenavir-ritonavir-based HAART.Pharmacokinetic (PK) parameters and virological characteristics have been associated with virological responses to highly active antiretroviral therapy (HAART) (2,9,13,19,20,28,29,30,39). The human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) fosamprenavir (FPV)-an amprenavir (APV) prodrug-is rapidly hydrolyzed during absorption into its APV parent form by cellular phosphatases in the gut epithelium (Lexiva [prescribing information]; GlaxoSmithKline, Research Triangle Park, NC). APV undergoes CYP450-based catabolism in the gastrointestinal tract and liver and has been shown to inhibit and induce different isoforms of this system (6, 15). Coadministration of ritonavir, a potent CYP450 inhibitor, decreases APV elimination (34), resulting in clinically significant increases of APV exposure (10, 14, 33); plasma APV levels are similarly boosted when ritonavir is coadminis...