ABSTRACT
This pilot study investigates the feasibility and effect of an intervention based on coaching and directly observed therapy (DOT), aimed at patients who are HIV-positive and have massive adherence problems and treatment failure. Participants were followed six months with coaching, homework and DOT. Eleven were enrolled and seven completed at least six sessions. All seven were satisfied with the intervention. DOT was not usable; six of the seven had more than half of their viral load counts below 500 copies/ml one year after the intervention. Only two of the seven had so before the intervention.
Subject(s)
Counseling/methods , Directly Observed Therapy/psychology , HIV Infections/drug therapy , Medication Adherence/psychology , Adult , Anti-HIV Agents/therapeutic use , Female , HIV Infections/nursing , HIV Infections/psychology , HIV Seropositivity/nursing , HIV Seropositivity/psychology , Health Communication/methods , Humans , Male , Middle Aged , Monitoring, Physiologic , Nurse-Patient Relations , Pilot Projects , Quality of Life , Treatment Failure , Viral LoadABSTRACT
BACKGROUND: Tuberculin is still the only available skin test reagent for the diagnosis of mycobacterial infection. The product has a remarkable sensitivity, but poor specificity. Previous studies, including two human phase I clinical trials, have indicated that rdESAT-6 has a potential as an improved skin test reagent. Animal studies have shown that the sensitivity may be increased by inclusion of the genetically related CFP-10 antigen in the preparation without loosing specificity. METHODOLOGY: In this study a Lactococcus fermented, recombinant skin test reagent consisting of a 1ratio1 wt/wt of rdESAT-6 and CFP-10 was manufactured according to GMP standards and tested for the first time in 42 healthy adult volunteers. The two doses of 0.01 microg or 0.1 microg were injected intradermally by the Mantoux technique with 6 or 12 weeks interval. No serious adverse events and only mild adverse reactions were reported. The reagent elicited a positive skin test reaction after the first injection in one participant, who most likely was latently infected with M. tuberculosis as indicated by an appreciable IFN gamma response just below the Quantiferon(R) cut-off level at the screening visit. None of the remaining participants in the four groups had any skin test reactions and sensitisation by the reagent could therefore be excluded. CONCLUSION: The investigational skin test reagent rdESAT-6 and CFP-10 appeared safe and non-sensitising in this first-in-man clinical trial in human volunteers and can now be tested in larger clinical trials involving individuals with latent M. tuberculosis infection or active TB disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT00793702.
Subject(s)
Antigens, Bacterial , Bacterial Proteins , Tuberculin Test/methods , Tuberculosis/diagnosis , Adult , Antigens, Bacterial/adverse effects , Bacterial Proteins/adverse effects , Humans , Interferon-gamma/metabolism , Recombinant Proteins/adverse effects , Sensitivity and SpecificityABSTRACT
Limited specificity of the tuberculin skin test incited the development of the intradermal Mycobacterium tuberculosis-specific rdESAT-6 skin test. Animal studies have shown, however, that there is a possible risk of sensitization when repeated injections of rdESAT-6 are given. The aim of this phase 1 open clinical trial was to assess the sensitization risk and safety of repeated administration of rdESAT-6 reagent in 31 healthy adult volunteers. Three groups of volunteers received two fixed doses of 0.1 microg rdESAT-6 28, 56 or 112 days apart, respectively. After the second injection, the diameter of induration and/or redness at the injection site was measured and taken as a possible sensitization reaction if >5mm. In vitro interferon gamma (IFN-gamma) responses were measured as supportive evidence. Local adverse reactions at the injection site and adverse events were recorded. One out of 31 (3%) volunteers showed a positive skin reaction (sensitization) upon a second injection of rdESAT-6 after 28days and an increased IFN-gamma response to ESAT-6. For 7 (23%) of the volunteers, local adverse reactions related to the product were registered, but all reactions were mild and predictable. In conclusion, repeated injections of the rdESAT-6 skin test reagent are safe, and sensitization occurs at a low rate, especially if the time span between succeeding doses is wide.
