[Adherence to antiretroviral treatments with a protease inhibitor in HIV-infected patients]. / Enquête sur l'observance des traitements antirétroviraux comportant un inhibiteur de protéase chez les patients infectés par le VIH.

OBJECTIVE: Long-term therapeutic success of powerful antiretroviral treatments dependent on patient adherence. This study was conducted to assess the difficulties HIV-infected patients with advanced-stage disease encounter in adhering to antiretroviral treatments with a protease inhibitor. PATIENTS AND METHODS: A prospective self-administered questionnaire survey was conducted at our outpatient clinic for 2 months. CD4 counts and HIV viral loads were also determined. RESULTS: Seventy-one percent of the study population which included 262 responded to the questionnaire. The survey was made a median 215 days after initiating the antiprotease treatment with indinavir (71% of the cases), ritonavir (13%), saquinavir (6%), or a combination of protease inhibitors (10%). At onset of antiprotease treatment, mean CD4 count was 171+/-150/mm(3) and mean HIV viral load was 75,000 copies/ml. The treatment was considered to be difficult to take by 43% of the patients; 66% stated they had forgotten to take their drugs at least once a month. It was most difficult to take the drugs prescribed for the afternoon. Shifts of 1 hour were observed in 58% of patients. Non-adherence was frequent (1 failure to take drugs per week), observed in 13% of patients. Most often, the patients stated they had forgotten to take their drugs because of occupational or relational difficulties (52%). Non-adherence increased with duration of treatment. The drug most often associated with non-adherence was indinavir (73%). Age and sex did not influence adherence. Mean RNA HIV serum level was lower than at onset of the antiprotease treatment in the most non-adherent patients. At the time of the questionnaire, there was no difference in serum RNA HIV level or in the percentage of patients with an undetectable level between non-adherent and adherent patients. CONCLUSION: This survey confirmed difficulties in adherence are frequent and worsen with time. No relationship was found between non-adherence and reduction in viral load, suggesting that a short-term effect of these very active drugs despite lack of perfect adherence. Other factors (pharmacology, sensitivity to antiretroviral drugs.) also play a major role in therapeutic success.

Plasma cytomegalovirus DNA, pp65 antigenaemia and a low CD4 cell count remain risk factors for cytomegalovirus disease in patients receiving highly active antiretroviral therapy.

OBJECTIVE: To study the natural history and the current risk factors for cytomegalovirus (CMV) disease in the context of highly active antiretroviral therapy (HAART). SETTING: Prospective multicentre cohort in 15 university hospitals in France. METHODS: A group of 198 patients with CD4 cell count < 100 x 10(6) cells/l (or < 200 x 10(6) cells/l under HAART for at least 2 months), no previous CMV disease and CMV-positive serology were followed every 4 months clinically and for virological testing including HIV RNA and CMV blood markers (culture, pp65 antigenaemia, plasma CMV DNA and CMV late mRNA by the polymerase chain reaction). RESULTS: At inclusion, median CD4 was 77 x 10(6) cells/l (0-308) and 85% of the patients received protease inhibitors. The percentage of patients receiving HAART reached 99% at 12 months. After a follow-up of 23.6 months, the incidence of CMV disease was 3.2/100 patient-years [95% confidence interval (CI) 1.3-5.0]. In univariate Cox models, all the CMV markers, a CD4 cell count remaining < 75 x 10(6) cells/l and an HIV viral load > 100,000 copies/ml were predictive for CMV disease. The hazard ratios for CMV disease were 11 for blood culture; 14 and 70 for pp65 antigenaemia of > or = 1 and > or = 100 nuclei/200,000 cells, respectively; 35 for plasma CMV DNA; 6 for CMV mRNA; 29 for CD4 < 75 x 10(6) cells/l; and 12 for HIV RNA > 100,000 copies/ml. In a stepwise multivariate analysis, only three covariates were independently associated with the occurrence of a disease: plasma CMV DNA, pp65 antigenaemia > or = 100 nuclei/200,000 cells and a CD4 count < 75 x 10(6) cells/l. CONCLUSION: CMV blood markers and CD4 count < 75 x 10(6) cells/l remain risk factors for CMV disease in patients receiving HAART. Analysis of plasma CMV DNA by the polymerase chain reaction is a reproducible and standardized tool that could be used as a decision marker for initiating CMV pre-emptive therapy.

Aging and motor control.

The goal of the two experiments of the present study was to determine whether in an aiming task performed within a relatively long movement time (MT) bandwidth, older adults make similar use of visual information for motor control as younger adults. Older and younger subjects practiced a manual aiming task toward one (Experiment 1), or one of many (Experiment 2) small target(s) while only the target to be reached was visible (proprioception only: P) or under normal lighting condition (proprioception+vision: PV). Following practice, all subjects were transferred to the P conditions. The results of both experiments indicate that the older subjects were, during practice, as accurate as the younger ones in the PV condition. Moreover, both groups suffered a large and similar increase in aiming error in the transfer condition. This underlines that a useful source of sensory information, namely vision, has been withdrawn in transfer. This result is different from those of earlier studies in which a shorter target MT had been used (Chaput & Proteau, 1996; Proteau, Charest, & Chaput, 1994). This suggests that older adults process the sensory information available in that type of task similarly to younger subjects but at a lower speed. However, when the temporal constraints of the task are stringent, older adults might rely more on modes of control in which sensory information plays a minimal role when compared to younger subjects. Finally, the results of the second experiment suggest that, when multiple targets are used, older adults appear to program a response which is optimally suited for a "central" target.

Modifications with aging in the role played by vision and proprioception for movement control.

Young and older adults performed manual aiming movements to a visible target for either 40 or 200 trials. Under each level of practice, half of the subjects practiced the task under normal visual conditions (proprioception + vision [PV] condition), whereas the other half were not permitted to see their ongoing movement toward the target (proprioception-only [P] condition). Each acquisition trial was followed with knowledge of results (KR). After the last acquisition trial, all subjects were transferred to a common task in which only the target to be reached was visually available, with no KR. During acquisition, the younger subjects were found to be spatially more accurate than their older counterparts, and this was so regardless of the number of acquisition trials. Withdrawing KR during the transfer test did not modify the spatial accuracy of the subjects who had trained under the P condition. This indicates that the subjects had a reliable reference of the movement to be realized. Withdrawing vision of the moving hand and KR in the transfer test caused a significant increase in spatial error for both the older and the younger subjects. However, the increase in error was less pronounced for the older than for the younger subjects. In fact, the older subjects performed as well in the transfer test as the subjects who had trained in the P condition. This pattern of results suggests that in the transfer test, the older subjects could still guide their movements with the proprioceptive information that was available during both acquisition and transfer. However, such was not the case for the younger subjects. This suggests that, unlike the younger subjects, the older subjects could still rely on the proprioceptive cues available during acquisition in the PV condition. These results are taken to indicate that practicing with numerous sources of afferent information, as was the case in the PV condition, resulted in an integrated reference store for the younger subjects. In contrast, while practicing the task in the PV condition, the older subjects appeared to process independently from each other the different sources of sensory information available.

Differential roles with aging of visual and proprioceptive afferent information for fine motor control.

The goal of this study was to determine whether aging brings modifications to the role played by different sources of afferent information for movement control. Older and younger subjects practiced an aiming task for either 40 or 200 trials while different sources of afferent information were available. Following the practice phase, all subjects were submitted to transfer tests in which the afferent information was either maintained or modified. Results indicate that modifying the sources of afferent information available for motor control from acquisition to transfer minimal effects for the older subjects but caused large increase in error for the younger subjects. These results suggest that learning is specific to the sources of afferent information available while practicing the task for the younger subjects, whereas older subjects show more flexibility in their utilization of afferent information for motor control.