Patient preferences for characteristics of antiretroviral therapies: results from five European countries.

INTRODUCTION: Patient preference to antiretroviral therapy (ART) characteristics should be a key consideration in treatment decisions. ART options exist for people living with HIV (PLWH), however concerns remain related to PLWH satisfaction with current ARTs. The current study examines patient preferences and the strength of preferences for treatment characteristics associated with ART. MATERIALS AND METHODS: Patients' preferences to ART were explored using a discrete choice experiment (DCE). Seven defined treatment characteristics (each with three categories) were identified from a literature review, input from experts, PLWH and physicians. A total of 1582 PLWH from France, Germany, Spain, Italy and the UK were recruited for the study. An adjusted odds ratio <1 signified lower odds of selecting a treatment with this characteristic category, compared to the reference category, independently of other characteristics. RESULTS: The patient preference analyses showed that participants preferred treatments with a rapid reduction in viral load (OR=0.78; 95% CI 0.74-0.81) and CD4 count (OR=0.86; 95% CI=0.82-0.89). Participants had a strong preference for avoiding diarrhoea (Odds ratio, OR=0.36 95% CI=0.33-0.38) and long term health problems (OR=0.30, 95% CI=0.28-0.32). Convenience related issues related to restrictions on taking drugs because of food or drug interactions were important to avoid (OR=0.80, 95% CI=0.76-0.83 and OR=0.72 95% CI=0.69-0.76 respectively). Participants also had a strong preference to avoid drugs which limited the effectiveness of future treatments (OR=0.70, 95% CI=0.67-0.73). CONCLUSIONS: Avoidance of diarrhoea and long-term complications were the most important drivers of patient choice. This study, from a large sample of European patients, demonstrates the importance to patients when different aspects of HIV treatment are considered simultaneously.

Are previous treatment interruptions associated with higher viral rebound rates in patients with viral suppression?

OBJECTIVE: We investigated whether previous treatment interruptions are associated with a raised risk of viral rebound in individuals who have attained virological suppression. METHODS: All patients achieving an undetectable viral load while on therapy were followed until viral rebound or the time of the last viral load. Poisson regression was used to describe the independent impact of treatment interruptions on rebound rates. RESULTS: A total of 12,977 patients from the United Kingdom Collaborative HIV Cohort (UK CHIC) Study achieved a viral load of less than 50 copies/ml. These patients contributed a total of 37,314 person-years of follow-up. The overall rebound rate was 8.07 (7.78, 8.36) per 100 person-years. In adjusted analyses, rates of viral rebound were up to 64% higher (rate ratio 1.64; 1.43, 1.88) in those who had previously interrupted therapy compared with those who had not. Patients who had interrupted at detectable viral loads had up to a 74% (1.74; 1.42, 2.14) higher chance of rebounding compared with those who had not interrupted with a detectable viral load. We found no evidence to suggest interrupting treatment at an undetectable viral load was associated with viral rebound. CONCLUSION: Among patients with an undetectable viral load, having previously interrupted therapy while the viral load was detectable is associated with a raised risk of rebound.

High treatment success rates when switching to once daily nevirapine containing antiretroviral therapy.

INTRODUCTION: Two recent studies have highlighted low rates of virological response to once daily nevirapine containing combination antiretroviral therapy (CART) in treatment naïve HIV-1 infected subjects. AIM: We assessed factors associated with treatment responses in a cohort of HIV-1 infected, therapy naïve individuals, commencing nevirapine CART with two nucleoside reverse transcriptase inhibitors (NRTI) containing either lamivudine or emtricitabine. RESULTS: Between January 2002 and 2006, 173 subjects (80 female) met the study inclusion criteria. All subjects initially commenced on twice daily nevirapine with six different NRTI backbones. Mean follow up was 802 days. 49 (28%) subjects switched to once daily nevirapine, 23 (13%) within the first year. After 48 weeks of therapy, HIV RNA was < 50 copies/mL in 154/173 subjects (89%). A trend was observed towards improved virological outcome (HIV RNA < 50 copies/mL) and switching to once daily nevirapine during the first year of therapy (p=0.051). CONCLUSION: Whilst awaiting the results of prospective studies assessing once daily nevirapine, our data describe high treatment success rates and good safety responses when switching to once daily nevirapine.

Increased duration of viral suppression is associated with lower viral rebound rates in patients with previous treatment failures.

OBJECTIVE: We investigated whether the rate of viral rebound decreases with increasing duration of viral suppression and, if so, whether rebound rates in patients previously failing antiretroviral regimens ultimately decline to levels as low as those seen in patients who have never experienced virological failure. METHODS: All patients from the UK CHIC Study (n = 21 256) who achieved a viral load (VL) of < or = 50 copies/ml while receiving HAART were followed until viral rebound (two consecutive VL > 400 copies/ml). Patients could re-enter the analysis if they experienced a subsequent VL < or = 50 copies/ml. Rebound rates were calculated according to the number of regimens previously failed and duration of viral suppression. RESULTS: Of 12 648 patients on HAART 10 237 (80.9%) achieved a VL < or = 50 copies/ml. During 26 494 person-years (PY) of follow-up, 1853 (18.1%) patients experienced at least one viral rebound 'event', with 2460 events in total [rebound rate, 9.3 (range, 8.9-9.7)/100 PY). Within the first year of viral suppression, the rate of viral rebound was 8.3 (7.5-9.1)/100 PY in patients who had not previously failed treatment, increasing to 32.7 (27.6-37.8)/100 PY in patients who had failed more than four regimens. Irrespective of previous treatment failure, rebound rates in those who remained suppressed for > 4 years were similar to those in patients who had at no time experienced treatment failure. CONCLUSION: After around 4 years of viral suppression rebound rates in individuals with multiple prior treatment failures approach those of individuals with no prior treatment failure.

Increased haemoglobin A2 percentage in HIV infection: disease or treatment?

An elevated haemoglobin A2 percentage has been reported in HIV-infected patients, possibly attributable to therapy. In cross-sectional and cohort studies we have established that A2 is often elevated in untreated patients; a further rise during treatment is attributable specifically to zidovudine. The haemoglobin A2 may be high enough to lead to a misdiagnosis of beta thalassemia trait if there is a lack of awareness of this unexpected effect of HIV infection and its treatment.

Atazanavir enhances saquinavir hard-gel concentrations in a ritonavir-boosted once-daily regimen.

OBJECTIVE: To determine the pharmacokinetics of saquinavir hard-gel capsules/ritonavir/atazanavir co-administered once daily at 1600/100/300 mg in HIV-infected individuals. METHODS: Eighteen patients receiving saquinavir/ritonavir switched to 1600/100 mg once daily a minimum of 3 days before the study. On study day 1, levels of saquinavir and ritonavir were determined over 24 h. Atazanavir (300 mg once daily) was then added to the regimen. On day 11, a pharmacokinetic analysis was performed. Atazanavir was discontinued on day 32. Drug concentrations were measured by high-pressure liquid chromatography-tandem mass spectrometry. Geometric mean ratios (GMR) and 95% confidence intervals (CI) were used to compare saquinavir and ritonavir pharmacokinetic parameters, with and without atazanavir. A safety analysis was performed at screening, days 1, 11, 32 and follow-up. RESULTS: After the addition of atazanavir, statistically significant increases in saquinavir trough plasma concentration (Ctrough GMR, 95% CI 2.12, 1.72-3.50), maximum plasma concentration (Cmax 1.42, 1.24-1.94), area under the plasma concentration-time curve from 0-24 h (AUC0-24 1.60, 1.35-2.43) and ritonavir Cmax (1.58, 1.32-2.08), AUC0-24 (1.41, 1.22-1.74) were observed. The pharmacokinetics of atazanavir compared with those obtained in patients receiving atazanavir/ritonavir without saquinavir. Four patients developed scleral icterus and two jaundice. Total and unconjugated bilirubin increased approximately fivefold during atazanavir therapy. CONCLUSION: The addition of atazanavir to saquinavir/ritonavir increased saquinavir Ctrough, Cmax and AUC0-24 by 112, 42 and 60%. Ritonavir Cmax and AUCo-24 increased by 34 and 41%. The regimen was well tolerated, with no significant change in laboratory parameters, except for the occurrence of hyperbilirubinemia.