Suppressive valacyclovir therapy: impact on the population spread of HSV-2 infection.

OBJECTIVES: Recent trial results demonstrate that the transmission probability of HSV-2 in monogamous couples is nearly halved by the use of valacyclovir as suppressive therapy. GOAL: The goal of this study is to understand the potential impact of suppressive valacyclovir therapy on the transmission of HSV-2 within a population. STUDY DESIGN: A mathematical model of HSV-2 epidemiology was developed which included suppressive therapy with the efficacy observed in the clinical trial. The model represented HSV-2 spread in an age and sexual activity stratified population where rates of viral shedding declined based on time since infection. The model tested the impact of a range of suppression coverage levels. RESULTS: Suppressive therapy reduces the population incidence of HSV-2. With coverage rates of 3.2%, the incidence of HSV-2 would be reduced by between 1.8% and 2.8%. Higher coverage rates were estimated to reduce the incidence of new cases up to 13%. Starting suppression closer to the time of infection also reduces the incidence of new cases. CONCLUSION: The impact of suppressive therapy on the HSV-2 epidemic is modest at current coverage levels but could be substantially increased with higher rates of diagnosis and a focus on coverage soon after infection.

Understanding patient preferences for HIV medications using adaptive conjoint analysis: feasibility assessment.

OBJECTIVE: Choosing among HIV medications involve making trade-offs among various efficacy, convenience, resistance, and side-effect attributes. This study tested the feasibility of using adaptive conjoint analysis (ACA) to assess preferences (utilities) for HIV medication attributes. METHODS: HIV individuals were recruited through newspaper advertisements. Participants completed a computerized ACA survey that assessed 12 attributes, including side effects, regimen convenience, resistance, and efficacy. Literature on third-agent HIV drugs was used to identify percentage risk and severity level descriptions for each attribute. Based on the ACA-derived utilities, we assessed the relative importance of the attributes by averaging individually calculated importance and estimated the percentages that would prefer selected HIV medications over others. To check validity of the ACA utilities, the survey also had respondents choose among medications with different attribute profiles. RESULTS: The 35 respondents were primarily African Americans (94%) and unemployed (54%). Of these, 28 (80%) provided consistent responses and were analyzed. Of the 12 medication attributes evaluated, the risk of developing resistance, regimen convenience, and the risk of sleep disturbance had the greatest impact on preferences; each accounting for more than 8.5% of the variation in preferences. These were followed by risk of drug failure (8.2%), cholesterol elevation (7.1%), diarrhea (7.1%) and nausea (6.9%). The ACA utilities accurately predicted patients' actual medication choices 75% of the time. CONCLUSIONS: Adaptive conjoint analysis was successful in predicting HIV treatment preferences under different medication scenarios. Resistance, regimen convenience, and sleep disturbance would likely make the most difference in the perceived value of a third-agent HIV medication.

Triple nucleoside treatment with abacavir plus the lamivudine/zidovudine combination tablet (COM) compared to indinavir/COM in antiretroviral therapy-naïve adults: results of a 48-week open-label, equivalence trial (CNA3014).

OBJECTIVE: An equivalence (non-inferiority) trial comparing antiviral response, tolerability, and adherence with a triple nucleoside regimen containing abacavir 300 mg (ABC) plus a lamivudine 150-mg/zidovudine 300-mg combination tablet (COM) twice daily vs. a regimen containing the protease inhibitor indinavir (IDV) 800 mg three times daily plus COM twice daily (IDV/COM) in antiretroviral-naïve, HIV-infected patients. METHODS: Adult patients with plasma HIV-1 RNA levels > or = 5000 copies/mL and CD4+ cell counts > or = 100 cells/mm(3) were randomized to receive open-label ABC/COM (n = 169) or IDV/COM (n = 173) for 48 weeks. The intent-to-treat (ITT) population was the primary population evaluated. ITT: switch/missing equals failure (ITT: S/M = F) and as-treated (AT) analyses were used for assessing the proportion of patients achieving plasma HIV-1 RNA level < 400 and < 50 copies/mL at each clinic visit. In the ITT: S/M = F analysis, patients who switched treatment or had missing values were considered treatment failures; the AT analysis examined virologic data only while patients received study treatment. ABC/COM was considered equivalent (non-inferior) to IDV/COM if the lower limit of the 95% confidence intervals (CIs) about the difference in proportions of ABC/COM- vs. IDV/COM-treated patients attaining plasma HIV-1 RNA < 400 copies/mL exceeded -15% at week 48. RESULTS: The study population was diverse with respect to ethnicity (38% Asian, 27% Hispanic, 28% white, 3% black, 4% other) and gender (39% women, 61% men). Baseline median HIV-1 RNA was 4.80 log(10) copies/mL and CD4+ cell count was 315 cells/mm(3). ABC/COM met the criterion of equivalence to IDV/COM. In the ITT: S/M = F analysis at Week 48, a greater proportion of ABC/COM-treated patients achieved HIV-1 RNA < 400 copies/mL (66% [109/164] vs. 50% [82/165]; treatment difference 16.6%, 95% CI (6.0, 27.2), p = 0.002) and HIV-1 RNA < 50 copies/mL (60% [99/164] vs. 50% [83/165]; treatment difference 9.6%, 95% CI [-1.1, 20.2]), whereas the AT analysis showed similar proportions achieving these endpoints (< 400 copies/mL: 85 vs. 83%; < 50 copies/mL: 79 vs 81%). Comparable proportions of patients with screening HIV-1 RNA values > 100 000 copies/mL achieved HIV-1 RNA < 400 copies/mL (ABC/COM: 60% [35/58]; IDV/COM: 51% [33/65]; treatment difference 9.6%, 95% CI [-7.9, 27.1]; ITT: S/M = F analysis). A significantly greater proportion taking ABC/COM were > or = 95% adherent (72% [109/151] vs. 45% [70/154] with IDV/COM, p < 0.001). Median increases from baseline in CD4+ cell counts were similar in the two treatment groups (+148 vs. +152 cells/mm(3)). Significantly more patients on IDV/COM reported drug-related adverse events (87% [142/165] vs. 65% [108/164] with ABC/COM, p < 0.001), similar proportions discontinued treatment due to adverse events (13 vs. 10%), and a slightly greater proportion in the ABC/COM group reported serious adverse events (13 vs. 8%). About half of the latter comprised suspected ABC-related hypersensitivity reactions (overall rate, 6%). Most adverse events were gastrointestinal in nature in both treatment groups. CONCLUSION: ABC/COM was at least equivalent to IDV/COM over 48 weeks in the treatment of antiretroviral-naïve patients. ABC/COM was associated with a significantly higher adherence rate and lower incidence of drug-related adverse events than IDV/COM. The study was limited in that it was not powered to determine equivalence of treatments within high vs. low viral load strata, adherence was not monitored electronically, and bias could not be ruled out due to the open-label study design.

Predictors of adherence and virologic outcome in HIV-infected patients treated with abacavir- or indinavir-based triple combination HAART also containing lamivudine/zidovudine.

OBJECTIVES: To compare dosing convenience and adherence with abacavir (ABC) 300 mg plus a fixed-dose lamivudine 150 mg/zidovudine 300 mg combination tablet (COM) twice daily versus indinavir (IDV) plus COM twice daily in treatment-naïve, HIV-1-infected adults; and to evaluate the association among difficulty taking antiretroviral regimens, adherence, and virologic efficacy. METHODS: An open-label, randomized, multicenter, international study compared the COM/ABC and IDV/COM regimens with respect to self-reported adherence and regimen convenience over 48 weeks. Logistic regression analysis (LRA) was done on a patient sub-sample from both groups to evaluate predictors of adherence and virologic response at last time-point on randomized therapy (LTORT). RESULTS: The study population was diverse with respect to ethnicity (38% Asian, 27% Hispanic, 28% white, 3% black, 4% other) and gender (39% women, 61% men). Baseline median HIV-1 RNA was 4.80 log(10) copies/mL and CD4+ cell count was 315 cells/mm(3). Of 329 patients who were randomized and received treatment, 315 (96%) provided adherence data. Significantly more patients in the ABC/COM group than in the IDV/COM group reported > or = 95% adherence to therapy (76 vs 58%, p < 0.001) and no difficulty in taking their regimen (91 vs 61%, p < 0.001). In both groups, the highest probability of HIV-1 RNA < 400 copies/mL occurred when median adherence was > or = 95%. The probability of HIV-1 RNA < 400 copies/mL declined more rapidly in the IDV/COM group as adherence rates decreased. LRA showed that no difficulty taking any of the drugs in the regimen, ABC/COM treatment group, and male gender were independent significant predictors of > or = 95% adherence (p < 0.05). Median adherence and baseline HIV-1 RNA were significant predictors of HIV-1 RNA < 400 copies/mL (p < 0.05). CONCLUSIONS: Patients reported greater ease of use and superior adherence to ABC/COM than IDV/COM. Patient-reported difficulty taking drugs in a regimen was predictive of reduced adherence, and both of the latter factors were predictive of poorer virologic outcome. Adherence levels of > or = 95% in both treatment groups maximized the probability of patients achieving an HIV-1 RNA < 400 copies/mL.