The impact of combination antiretroviral therapy and its interruption on anxiety, stress, depression and quality of life in Thai patients.

OBJECTIVE: Investigation on anxiety, stress, depression, and quality of life (QoL) within STACCATO, a randomised trial of two treatment strategies: CD4 guided scheduled treatment interruption (STI) compared to continuous treatment (CT). PARTICIPANTS: Thai patients with HIV-infection enrolled in the STACCATO trial. METHODS: Anxiety, depression assessed by the questionnaires Hospital Anxiety and Depression Scale (HADS) and DASS, stress assessed by the Depression Anxiety Stress Scale (DASS), and QoL evaluated by the HIV Medical Outcome Study (MOS-HIV) questionnaires. Answers to questionnaires were evaluated at 4 time-points: baseline, 24 weeks, 48 weeks and at the end of STACCATO. RESULTS: A total of 251 patients answered the HADS/DASS and 241 answered the MOS-HIV of the 379 Thai patients enrolled into STACCATO (66.2 and 63.6% respectively). At baseline 16.3% and 7.2% of patients reported anxiety and depression using HADS scale. Using the DASS scale, 35.1% reported mild to moderate and 9.6% reported severe anxiety; 8.8% reported mild to moderate and 2.0% reported severe depression; 42.6% reported mild to moderate and 4.8% reported severe stress. We showed a significant improvement of the MHS across time (p=0.001), but no difference between arms (p=0.17). The summarized physical health status score (PHS) did not change during the trial (p=0.15) nor between arm (p=0.45). There was no change of MHS or PHS in the STI arm, taking into account the number of STI cycle (p=0.30 and 0.57) but MHS significant increased across time-points (p=0.007). CONCLUSION: Antiretroviral therapy improved mental health and QOL, irrespective of the treatment strategy.

Absence of resistance mutations in antiretroviral-naive patients treated with ritonavir-boosted saquinavir.

BACKGROUND: There are few data on the selection of resistance by ritonavir-boosted saquinavir (SQV/r), particularly in antiretroviral (ARV)-naive patients. OBJECTIVE: To assess the incidence of virological failure and evolution of resistance in ARV-naive individuals receiving SQV/r in the induction phase of the Staccato trial. METHODS: ARV-naive subjects (n = 272) received SQV/r 1,600/100 mg once daily with two nucleoside reverse transcriptase inhibitors (NRTIs) for at least 24 weeks. Patients were defined as having virological failure (VF) when there were two consecutive HIV-1 RNA measurements > 500 copies/ml after week 12. Viral genotypes (reverse transcriptase [RT] and protease [PRO]) were determined at baseline in all patients and as close as possible to the time of initial failure in patients experiencing VF. RESULTS: VF was observed in 9/272 patients receiving SQV/r 1,600/100 mg once daily with two NRTIs (3.3%) and occurred 19-48 weeks after treatment initiation. Eight of these patients were evaluable at failure. No major PRO mutations were detected, but 2/8 displayed single new minor PRO substitutions (M36I, L10I) at VF that were known or suspected not to have been present at baseline; both these substitutions exist as natural polymorphisms. A third patient displayed a single new RT mutation (M184I). CONCLUSIONS: SQV/r plus two NRTIs (1,600/100 mg once daily) is an effective initial treatment option for ARV-naive patients, resulting in a low rate of viral rebound (3.3%). Furthermore, no major protease mutations were detected following VF, suggesting that future treatment options are preserved.

CD4-guided scheduled treatment interruptions compared with continuous therapy for patients infected with HIV-1: results of the Staccato randomised trial.

BACKGROUND: Stopping antiretroviral therapy in patients with HIV-1 infection can reduce costs and side-effects, but carries the risk of increased immune suppression and emergence of resistance. METHODS: 430 patients with CD4-positive T-lymphocyte (CD4) counts greater than 350 cells per muL, and viral load less than 50 copies per mL were randomised to continued therapy (n=146) or scheduled treatment interruptions (n=284). Median time on randomised treatment was 21.9 months (range 16.4-25.3). Primary endpoints were proportion of patients with viral load less than 50 copies per mL at the end of the trial, and amount of drugs used. Analysis was intention-to-treat. This study is registered at ClinicalTrials.gov with the identifier NCT00113126. FINDINGS: Drug savings in the scheduled treatment interruption group, compared with continuous treatment, amounted to 61.5%. 257 of 284 (90.5%) patients in the scheduled treatment interruption group reached a viral load less than 50 copies per mL, compared with 134 of 146 (91.8%) in the continued treatment group (difference 1.3%, 95% CI-4.3 to 6.9, p=0.90). No AIDS-defining events occurred. Diarrhoea and neuropathy were more frequent with continuous treatment; candidiasis was more frequent with scheduled treatment interruption. Ten patients (2.3%) had resistance mutations, with no significant differences between groups. INTERPRETATION: Drug savings with scheduled treatment interruption were substantial, and no evidence of increased treatment resistance emerged. Treatment-related adverse events were more frequent with continuous treatment, but low CD4 counts and minor manifestations of HIV infection were more frequent with scheduled treatment interruption.

A prospective study of efficacy and safety of once-daily saquinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors in treatment-naive Thai patients.

OBJECTIVE: To assess the efficacy and safety of first-line treatment with once-daily saquinavir/ritonavir with two nucleoside reverse transcriptase inhibitors (NRTIs), as induction therapy before enrollment in a randomized trial of structured treatment interruption strategies. DESIGN: Two-hundred antiretroviral-naive patients with CD4+ cell counts between 200-350 at screening were enrolled in this open-label 24week study. METHODS: Patients were followed up every 8 weeks for CD4+ cells, HIV RNA, and clinical and laboratory toxicities. RESULTS: Two-hundred patients were enrolled with median baseline CD4+ cell count of 267 cells/microl and HIV RNA 50 118 (4.7 log10) copies/mi. After 24 weeks of treatment, 191 of 200 (96%) patients had below 400 copies/ml HIV RNA, with 177/200 (89%) below 50 copies/ml (intent to treat, missing equals failure method), with a median rise in CD4+ cell count of 122 cells/microl. There was no significant correlation between the minimum concentration of saquinavir and HIV RNA reductions at week 8 (P = 0.957) or absolute HIV RNA at week 24 (P = 0.77). CONCLUSION: First-line highly active antiretroviral therapy (HAART) with once-daily saquinavir/ritonavir plus two NRTIs showed strong antiviral efficacy over 24 weeks, and should be evaluated in larger prospective randomized clinical trials.