Highly active antiretroviral therapy (HAART) induces beneficial changes in various immunological parameters even when it is initiated early during asymptomatic HIV infection with high CD4 cell counts . Until now, however, the impact of an early initiation of HAART on the quality of life (QoL) in asymptomatic, treatment-naive, HIV-infected individuals has not been reported. Recently, ritonavir in combination with other antiretroviral medications has been shown to influence positively the functioning and well-being in patients with advanced disease .
Within the ongoing Early Antiretroviral Therapy (EARTH) study , 41 asymptomatic individuals with CD4 cell counts of over 400×106/l were randomly assigned to either double therapy (n=19), consisting of zidovudine (300mg twice a day) and lamivudine (150mg twice a day), or triple therapy (n=22), consisting of zidovudine (300mg twice a day), lamivudine (150mg twice a day) and ritonavir (600mg twice a day). We report here the treatment-induced changes in QoL by assessing the HIV Medical Outcome Study (HIV-MOS)  and the Karnofsky score at baseline and at weeks 12 and 24. The HIV-MOS is a well established generic instrument [5-7]. It is a self-administered questionnaire, consisting of 36 questions assessing 11 dimensions (overall health, physical-, role-, social- and cognitive function, pain, mental health, energy/fatigue, health distress, QoL as well as health transition) of health-related QoL. We assessed mean changes in 10 out of 11 dimensions of the HIV-MOS (data regarding overall health was not recorded in the MOS version used) and Karnofsky score.
At baseline, all 41 individuals reported well-being with a Karnofsky score of 100; there were no significant differences in QoL between the randomized groups. Both treatment groups scored lowest at week 12 in nearly all HIV-MOS dimensions, also exemplified by a significant decline in the Karnofsky score (Table 1, intent-to-treat analysis). All study participants taken together showed a significant decline in QoL at week 12 in social function, pain, energy/fatigue and QoL. However, these changes were solely explained by the decline in QoL of the group receiving triple therapy. In addition to the above-mentioned dimensions, role function scored significantly lower in the triple therapy arm at week 12. The decline in the various QoL scores in the triple therapy group correlated with the occurrence of adverse events to ritonavir: Between weeks 0 and 12, two patients receiving triple therapy stopped ritonavir and either continued on double nucleoside therapy or changed to another protease inhibitor, respectively. Between weeks 12 and 24, six additional patients receiving triple therapy changed regimens: two continued with a double therapy, two replaced ritonavir with another protease inhibitor and two dropped out. In view of these treatment modifications and the cessation of ritonavir-associated intolerance, the differences of each group to baseline were no longer statistically significant at week 24.
The comparison of changes between the two groups confirmed significant differences in the dimensions role function, health distress and QoL, which persisted up to week 24 (intent-to-treat analysis), in the presence of rising scores in both arms. An on-treatment analysis of our data did not reveal any new information (results not shown) due to the fact that the above-mentioned six patients scored higher after they discontinued ritonavir.
The only other description of the impact on QoL of HAART including ritonavir describes advanced symptomatic individuals with CD4 cell counts of less than 100×106/l, in whom treatment improved scores in various dimensions of the HIV-MOS . A direct comparison of asymptomatic individuals with patients suffering from AIDS is difficult. For example, in a study  comparing three different regimens of combinations of nucleoside agents there was a difference between the AIDS and non-AIDS (CD4 cell count >200/μl) groups in the mean change in scores from baseline. Therefore, it is important to distinguish between the impact of disease versus that of therapy on the QoL outcomes.
In conclusion, the early initiation of triple therapy in asymptomatic individuals caused a significant short-term impairment of QoL, mainly due to the known adverse effects of ritonavir, 600mg twice a day . However, the impairment was not severe and reversed towards baseline values at week 24 for the entire group, particularly after those patients with the strongest adverse events modified their treatment regimen. The double therapy with zidovudine and lamivudine was well tolerated and did not adversely affect the QoL, but its virological efficacy was inferior . The divergent aspects of the desired full viral suppression, the immunological and clinical benefit of treatment, versus its effect on QoL are important considerations both for the physician and the patient, particularly if HAART is initiated in individuals who previously felt healthy.
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