AR-quiver approach to affine canonical basis elements

AbstractThis is the continuation of [Y. Li, Affine quivers of type A˜n and canonical bases, math.QA/0501175]. We describe the affine canonical basis elements in the case when the affine quiver has arbitrary orientation. This generalizes the description in [G. Lusztig, Affine quivers and canonical bases, Publ. Math. Inst. Hautes Études Sci. 76 (1992) 111–163]

Efficacy of Initial Antiretroviral Therapy for HIV-1 Infection in Adults: A Systematic Review and Meta-Analysis of 114 Studies with up to 144 Weeks' Follow-Up

<div><p>Background</p><p>A comprehensive assessment of initial HIV-1 treatment success may inform study design and treatment guidelines.</p><p>Methods</p><p>Group-based, systematic review and meta-analysis of initial antiretroviral therapy studies, in adults, of ≥48 weeks duration, reported through December 31, 2012. Size-weighted, intention-to-treat efficacy was calculated. Parameters of study design/eligibility, participant and treatment characteristics were abstracted. Multivariable, random effects, linear regression models with backwards, stepwise selection were then used to identify variables associated with efficacy.</p><p>Outcome Measures</p><p>Antiviral efficacy (undetectable plasma viral load) and premature cessation of therapy.</p><p>Results</p><p>114 studies were included (216 treatment groups; 40,124 participants; mean CD4 count 248 cells/µL [SD 81]; mean HIV-1 plasma viral load log₁₀ 4.9 [SD 0.2]). Mean efficacy across all groups was 60% (SD 16) over a mean 82 weeks' follow-up (SD 38). Efficacy declined over time: 66% (SD 16) at 48 weeks, 60% (SD 16) at 96 weeks, 52% (SD 18) at 144 weeks. The most common reason for treatment cessation was participant decision (11%, SD 6.6). Efficacy was higher with ‘Preferred’ than ‘Alternative’ regimens (as defined by 2013 United States antiretroviral guidelines): 75% vs. 65%, respectively, difference 10%; 95%CI 7.6 to 15.4; <i>p</i><0.001. In 98 groups (45%) reporting efficacy stratified by pre-treatment viral load (< or ≥100,000 copies/mL), efficacy was greater for the lower stratum (70% vs. 62%, respectively, difference 8.4%; 95%CI 6.0 to 10.9; <i>p</i><0.001). This difference persisted within ‘Preferred’ regimens. Greatest efficacy was associated with use of tenofovir-emtricitabine (vs. other nucleoside analogue backbones) and integrase strand transfer inhibitors (vs. other third drug classes).</p><p>Conclusion</p><p>Initial antiretroviral treatments for HIV-1 to date appear to have suboptimal long-term efficacy, but are more effective when commenced at plasma viral loads <100,000 copies/mL. Rising viral load should be considered an indication for starting treatment. Integrase inhibitors offer a treatment advantage (vs. other third drug classes).</p></div

Characteristics^* associated with efficacy of initial antiretroviral therapy: February 2013 DHHS ‘Alternative’ regimens (39 groups).

<p>*Dosing relative to food, third drug class, previous AIDS events and pre-treatment CD4 interacted significantly with DHHS regimen type to affect efficacy.</p>†<p>NRTI backbone and pre-treatment CD4 count were not significantly associated with efficacy on univariable analysis.</p><p>DHHS, United States Department of Health and Human Services; SD, standard deviation; CI, confidence interval; TDF, tenofovir; FTC, emtricitabine; 3TC, lamivudine; ABC, abacavir; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; INSTI, integrase strand transfer inhibitor.</p

Included studies and treatment groups.

<p>ABC, abacavir; AZT, zidovudine; APV, amprenavir; AZV, atazanavir; d4T, stavudine; ddI, didanosine; DRV, darunavir; DTG, dolutegravir; EFV, efavirenz; ELV, elvucitabine; ETR, etravirine; EVG, elvitegravir; FPV, fosamprenavir; FTC, emtricitabine; IDV, indinavir; LPV, lopinavir; MVC, maraviroc; NFV, nelfinavir; NVP, nevirapine; r, ritonavir; RPV, rilpivirine; RAL, raltegravir; SQV, saquinavir; TDF, tenofovir; TPV, tipranavir.</p

Characteristics^* associated with efficacy of initial antiretroviral therapy: February 2013 DHHS ‘Preferred’ regimens (27 groups).

<p>*Dosing relative to food, third drug class, previous AIDS events and pre-treatment CD4 interacted significantly with DHHS regimen type to affect efficacy.</p>†<p>Dosing relative to food, NRTI backbone, third drug class and previous AIDS events were not significantly associated with efficacy on univariable analysis.</p><p>DHHS, United States Department of Health and Human Services; SD, standard deviation; CI, confidence interval; TDF, tenofovir; FTC, emtricitabine; 3TC, lamivudine; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; INSTI, integrase strand transfer inhibitor.</p

Study characteristics.

<p>*Prospective cohort studies were considered phase 4 studies.</p>†<p>Includes <400, <200, <40 and <20 copies/mL.</p><p>ITT, intention-to-treat; M = F, missing equals failure; NC = F, non-completer equals failure; TLOVR, time to loss of virological response; ALT, alanine transaminase; AST, aspartate transaminase; IDU, injection drug use; AIDS, acquired immune deficiency syndrome.</p

Characteristics included in linear regression analyses.

<p>*Moderate or greater severity – graded according to 2009 Division of AIDS Classification.</p><p>CDC, Centers for Disease Control and Prevention; HIV, human immunodeficiency virus; NRTI, nucleoside reverse transcriptase inhibitor.</p

PRISMA statement 2009 flow chart.

<p>Diagram depicts each step of the study selection process undertaken in this systematic review and meta-analysis, including the reasons for exclusion.</p

Characteristics^* associated with efficacy of initial antiretroviral therapy: all groups.

<p>*Study phase, genotype/CD4 eligibility restrictions, pills and doses per day were significant on univariable analysis but not multivariable. Co-infection with hepatitis B or C were excluded from the multivariable analysis because >20% of groups were missing data.</p>†<p>Study sponsorship, placebo use, country/region of recruitment, haemoglobin/viral load/liver function eligibility restrictions, race, risk factors for HIV infection, sex, previous AIDS events, pre-treatment viral load/CD4 count, dosing relative to food, serious adverse events, and clinical/laboratory adverse events of at least moderate severity were variables not significant on univariable analysis.</p>‡<p>Coefficient represents the adjusted percentage difference in outcomes relative to a unit increase in any variable (or relative to the reference variable within a category).</p><p>SD, standard deviation; CI, confidence interval; ITT, intention-to-treat; M = F, missing equals failure; NC = F, non-completer equals failure; TLOVR, time to loss of virological response; TDF, tenofovir; FTC, emtricitabine; AZT, zidovudine; 3TC, lamivudine; d4T, stavudine; ddI, didanosine; ABC, abacavir; ELV, elvucitabine; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; INSTI, integrase strand transfer inhibitor; CCR5, chemokine receptor 5 inhibitor.</p

Distribution of prisoner vital status on the basis of record linkage and known vital status.

<p>Distribution of prisoner vital status on the basis of record linkage and known vital status.</p