Individualizing salvage regimens: the inhibitory quotient (Ctrough/IC50) as predictor of virological response.

Increased drug levels could overcome resistance and improve the response to a salvage regimen. We evaluate the inhibitory quotient (IQ, Ctrough/protein-binding corrected IC50) as a predictor of virological response in 52 patients included in two dual protease inhibitor (PI)-based salvage regimens. The HIV-RNA level decrease at 12 weeks was greater in patients who achieved an IQ greater than 1. The IQ could be useful to improve the virological response to a dual PI salvage regimen.

Phenotype or virtual phenotype for choosing antiretroviral therapy after failure: a prospective, randomized study.

BACKGROUND: Resistance testing is useful in the management of virological failure patients, although the best method to be used in clinical practice has not been determined. METHODS: A prospective, randomized, double-blind, multicentre, controlled clinical trial was performed to compare the usefulness of drug resistance testing with a recombinant viral phenotype method or with a virtual phenotype, a genotyping interpretation system. Planned 300 HIV-infected adults failing their current antiretroviral therapy (HIV RNA > 1000 copies/ml) were centrally randomized 1:1 to resistance testing with a recombinant viral phenotype method or with a virtual phenotype, after stratifying according to previous drug exposure (one or two versus three drug classes). Percent of patients with HIV RNA suppression (% < 400 copies/ml) after 24 weeks was the primary outcome variable. Median HIV RNA concentration and change from baseline in HIV RNA concentration were also used to compare effectiveness. An extended analysis was performed at week 48. RESULTS: Of the 300 patients enrolled, a total of 276 patients could be analysed; 139 patients were randomized to the phenotype group and 137 patients were randomized to the virtual phenotype group. After 24 weeks of follow-up, 46.8 and 56.2% of patients had HIV RNA < 400 copies/ml (P = 0.1) in the phenotype and virtual phenotype, respectively. Mean decrease from baseline in viral load was 1.0 and 1.3 log copies/ml in the phenotype and virtual phenotype groups, respectively (P = 0.017). In a multivariate linear regression analysis, after adjusting for baseline HIV RNA and adherence to treatment, the virtual phenotype was associated with a greater mean decrease in plasma HIV RNA (P = 0.0063). The results observed at week 48 were similar. CONCLUSIONS: Virtual phenotype is at least as effective as phenotype when used to select an optimized treatment for patients who have failed one or more antiretroviral regimens.

Overcoming resistance: virologic response to a salvage regimen with the combination of ritonavir plus indinavir.

PURPOSE: To explore the possibility of overcoming resistance to protease inhibitors (PIs) and to determine the resistance cutoff values that continue to predict treatment failure with a dual PI regimen. METHOD: We performed a prospective study of 53 patients who had failed in several PIs and who were included in a ritonavir (RTV) plus indinavir (IDV) salvage regimen. Median HIV RNA level decrease was evaluated according to resistance assays and indinavir trough levels. RESULTS: Eighty-seven percent of patients had previously failed on an IDV-containing regimen. Overall, median HIV RNA decrease was -1.25 log(10) copies/mL after 3 months on therapy. A significant blunted virologic response was observed only in isolates with more than 12 substitutions including the V82A (-0.75 vs. -1.3 log(10) copies/mL; p =.04), or in isolates with more than 30 fold-increase in the IC(50) (-0.43 vs. -1.2 log(10) copies/mL). Higher drug levels were observed in patients with resistant isolates who achieved an HIV RNA decrease greater than 1 log (1742 vs. 1100 ng/mL). CONCLUSION: Our preliminary data suggest the possibility of overcoming resistance with the combination of RTV plus IDV. They also suggest the need for establishing new resistance cutoff values when using PIs in combination.

[In vitro susceptibility study of herpes simplex virus to acyclovir and foscarnet. Are routine susceptibility studies necessary?]. / Estudio de sensibilidad in vitro del virus herpes simple a aciclovir y foscarnet. Son necesarios los estudios de sensibilidad de forma rutinaria?

BACKGROUND: The objective of this study was to investigate the prevalence of resistance of herpes simplex virus to acyclovir and foscarnet. PATIENTS AND METHOD: An in vitro susceptibility study of HSV strains isolated from HIV-infected and non-infected (control group) patients was conducted by means of qualitative screening. When the screening results were positive, the method for reducing cytopathic effect was utilized for calculating ID50. An ID50 < 1 microgram/ml indicated susceptibility to acyclovir, ID50 1-2 microgram/ml was intermediate susceptibility to acyclovir and a value of ID50 >/= 2 microgram/ml denoted resistance. Resistance to foscarnet was considered at ID50 >/= 100 microgram/ml. RESULTS: The study involved investigating 84 HSV strains, 49 HIV-infected patients, and 19 control patients. In the control group, no strains resistant to acyclovir were present and infection recurred in only one patient. In patients with HIV infection, one acyclovir resistant strain was detected and one moderately resistant to acyclovir, with good response to acyclovir treatment. In this group, 24.4% of patients presented recurrent infection. No resistance to foscarnet was detected. CONCLUSION: Percentage of HSV strains resistant to acyclovir is very low and resistance to foscarnet was not detected. These data suggest that routine in vitro susceptibility testing of antiviral drugs against HSV does not seem to be necessary.

Estudio de sensibilidad in vitro del virus herpes simple a aciclovir y foscarnet. ¿Son necesarios los estudios de sensibilidad de forma rutinaria? / In vitro susceptibility study of herpes simplex virus to acyclovir and foscarnet. Are routine susceptibility studies necessary?

FUNDAMENTOS. El objetivo de este estudio es conocer la prevalencia de resistencias del virus herpes simple (VHS) a aciclovir y foscarnet. PACIENTES Y MÉTODO. Se realizó un estudio de sensibilidad in vitro a VHS aislados de pacientes infectados por el virus de la inmunodeficiencia humana (VIH) y no infectados por el VIH (grupo control) mediante una prueba de cribado cualitativo. Cuando la prueba de cribado fue positiva se utilizó el método de reducción de efecto citopático para calcular la DI50. Se consideró sensibilidad al aciclovir a una DI50 < 1 g/ml; una sensibilidad intermedia al aciclovir, a una DI50 1-2 g/ml y resistente, a DI50 2 g/ml. Se consideró resistencia al foscarnet a DI50 100 g/ml. RESULTADOS. Se estudiaron 84 cepas de VHS de 49 pacientes con infección por el VIH y 19 de un grupo control. En el grupo control no existió ninguna cepa resistente al aciclovir y la infección sólo recurrió en un paciente. Los enfermos infectados por el VIH tuvieron una cepa resistente a aciclovir y una cepa moderadamente resistente a este fármaco, con una buena respuesta al tratamiento. En este grupo, el 24,4 por ciento de los pacientes tuvo recurrencia de la infección. No se detectaron resistencias al foscarnet. CONCLUSIONES. La tasa de VHS resistente al aciclovir es muy baja y no se detectó resistencia al foscarnet. La baja tasa de resistencia no justificaría la realización rutinaria de la prueba de sensibilidad in vitro de antivíricos frente al VHS (AU)