Outcomes by Sex Following Treatment Initiation With Atazanavir Plus Ritonavir or Efavirenz With Abacavir/Lamivudine or Tenofovir/Emtricitabine

Tierney, Camlin; Mollan, Katie R.; Venuto, Charles S.; Budhathoki, Chakra; Ma, Qing; Sax, Paul E.; Katzenstein, David; Godfrey, Catherine; Fischl, Margaret A.; Daar, Eric S.; Collier, Ann C.; Bolívar, Héctor; Navarro, Sandi L.; Koletar, Susan L.; Gochnour, Diane; Seefried, E.; Hoffman, Julie; Feinberg, Judith; Saemann, M.; Patterson, Kristine B.; Pittard, D.; Upton, Kyle R.; Saag, Michael S.; Ray, G. Thomas; Johnson, Steven C.; Santos, Bartolo; Funk, Clare A.; Morgan, Mike; Jackson, Beth; Tebas, Pablo; Thomas, Aleshia; Kim, G.-Y.; Klebert, Michael; Santana, Jorge; Marrero, Sara; Norris, J.; Valle, Sandra Costa; Cox, Gary M.; Silberman, Martha; Shaik, S.; López, Rosa María; Vasquez, Matthew; Daskalakis, Demetre; Megill, Christina; Shore, Jessica; Taiwo, Babafemi; Goldman, Mitchell; Boston, Mark; Lennox, Jeffrey L.; Río, Carlos del; Lane, Timothy W.; Epperson, K.; Luetkemeyer, Anne F; Payne, Miranda; Gripshover, Barbara; Antosh, Danielle D.; Reid, Joel R.; Adams, M. Jacob; Storey, S. S.; Dunaway, Shelia B.; Gallant, Joel E.; Wiggins, Ilene; Smith, Kimberly Y.; Świątek, Joanna; Timpone, Joseph; Kumar, Priti; Moe, Andrew; Palmer, Maria; Gothing, Jon A; Delaney, Joseph A.; Whitely, K.; Anderson, Albert M.; Hammer, Scott M.; Yin, Michael T.; Jain, Mamta K.; Petersen, Tess; Corales, Roberto; Hurley, Christine; Henry, Keith; Bordenave, B.; Youmans, Anne S.; Albrecht, Mary; Pollard, Richard B.; Olusanya, Aralola; Skolnik, Paul R.; Adams, Bonne J.; Tashima, Karen T.; Patterson, Helen; Ukwu, M.; Rogers, Lisa; Balfour, Henry H.; Fox, K. A.; Swindells, Susan; Meter, F. Van; Robbins, Gregory; Burgett-Yandow, N.; Davis, C. E.; Boyce, Catherine; O’Brien, William A.; Casey, Gerard J.; Morse, Gene D.; Hsaio, C.-B.; Meier, Julian; Stapleton, Jack T.; Mildvan, Donna; Revuelta, Manuel; Currin, D.; Sadr, Wafaa El; Loquere, A.; El-Daher, Nayef; Johnson, Tamara; Gross, Robert; Maffei, K.; Hughes, Valery; Sturge, G.; McMahon, Deborah; Rutecki, B.; Wulfsohn, Michael; Cheng, Andrew; Dix, Lynn P.; Liao, Qiming

doi:10.1093/cid/cit747

Cited by 30 publications

(29 citation statements)

References 13 publications

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“…Sex was not significantly associated with virologic failure, which was primarily in agreement with a study of time to virologic failure in the A5202 study by Smith et al. 19 In addition, there was no significant difference in outcome when evaluating history of IV drug use, the assigned NRTI backbone, and HIV-1 RNA stratification level at screening.…”

Section: Discussionsupporting

confidence: 87%

Efavirenz Therapeutic Range in HIV-1 Treatment-Naive Participants

Bednasz

Venuto

et al. 2017

Therapeutic Drug Monitoring

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Objectives Efavirenz is currently suggested as an alternative to recommended antiretroviral (ARV) regimens by the Department of Health and Human Services for the treatment of HIV-1 in ARV-naive patients. A mid-dosing interval therapeutic range between 1,000 and 4,000 ng/mL for efavirenz has been proposed in the literature, with patients more likely to experience virologic failure below this range and adverse effects above. The current study reports an analysis of virologic outcome between those above, below, or within the reported efavirenz therapeutic range (1,000–4,000 ng/mL) and within subgroups. Methods This analysis examined efavirenz plasma concentrations obtained from participants enrolled in AIDS Clinical Trials Group Study A5202. This investigation divided subjects into those who experienced virologic failure and those who did not. These subjects were further separated to investigate those who had “high,” “within,” or “low” plasma concentrations, based on the therapeutic range. The association between virologic failure and plasma concentration was statistically examined in addition to the variables race/ethnicity, sex, assigned nucleos(t)ide reverse transcriptase inhibitor backbone, age at study entry, history of intravenous drug use, weight, and screening HIV-1 RNA stratification level. Results In univariate analyses, a statistically significant difference was found when comparing the efavirenz concentration groups, (22 failures among the “low” concentration group [19%], 65 failures among the “within” concentration group [12%], and 11 failures among the “high” concentration group [9%]) when evaluating virologic failure as an outcome (p = 0.04). In addition, the proportion of participants with virologic failure differed across race/ethnicity groups (p = 0.03) with black non-Hispanic participants observed to have the highest rate (17%). Efavirenz concentration group, race/ethnicity, age, weight, and the interaction between efavirenz concentration group and weight were found to be significantly associated with virologic failure in multivariable logistic regression analysis. Conclusions The proposed efavirenz therapeutic range, combined with the impact of a patient’s weight, is associated with virologic failure in HIV-infected ARV-naive individuals in the United States. Additional analysis is recommended to determine the most appropriate concentration value that defines the lower limit of the efavirenz therapeutic range.

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Section: Discussionsupporting

confidence: 87%

Efavirenz Therapeutic Range in HIV-1 Treatment-Naive Participants

Bednasz

Venuto

et al. 2017

Therapeutic Drug Monitoring

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“…The association of ABC with dyslipidemia has been reported in some studies; in the HEAT trial, ABC/3TC was associated with an increase in TC and TG at 96 weeks; however, glucose had no modification related to this backbone [16]. Another study, ACTG5202, found a higher frequency of dyslipidemia with ABC/3TC either with ATV/r or with EFV [17]. Finally, the ASSERT trial, found a statistically significant increase in TC and TG with ABC/LMV regimens compared with TDF/FTC in treatment-naïve infected patients [18].…”

Section: Regimen Tdf/ftc+efv Tdf/ftc+nvp Abc/3tc+lpv/r Abc/3tc+efv Abmentioning

confidence: 85%

Dyslipidemia and Fasting Glucose Impairment among HIV-Infected Patients 48-Weeks after the First Antiretroviral Regimen

Marín¹

2015

J AIDS Clin Res

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BackgroundWith the increased survival of HIV-infected patients, there have emerged a number of unexpected consequences of chronic illness and drugs adverse events, especially in the form of metabolic disease [1].Available data suggest the presence of an accelerated process of coronary atherosclerosis in this population due to multiple factors, including a higher prevalence (compared with non-HIV-infected patients) of conventional risk factors, emerging risk factors (chronic inflammation, immune activation, and senescence related to HIV infection itself), and the role of antiretroviral therapy (ART), regarding metabolic syndrome as one of the major problems [2]. Some studies have showed that the prevalence of metabolic syndrome was higher among HIV-infected patients on ART than among non-HIV-infected healthy controls (15.8 vs. 3.2%) [3]. A high incidence of diabetes mellitus (DM) and impaired fasting glucose (IFG) has been detected in HIV-infected patients receiving ART [4,5]. Another studies have found relationship between some classes of antiretroviral (ARV) drugs such as protease inhibitors (PIs) and nucleos(t)ide retrotranscriptase inhibitors (NRTIs) with a higher frequency of new-onset DM and IFG [6].Dyslipidemia is particularly frequent and is mostly characterized by hypertriglyceridemia and low HDL-cholesterol concentrations. AbstractBackground: People infected with human immunodeficiency virus (HIV) develop lipid and glucose metabolic alterations, which predisposes them to cardiovascular disease. The aim of this study was to evaluate the cumulative incidence of dyslipidemia and fasting glucose impairment after 48 weeks of initiating the first antiretroviral (ART) regimen and the association with the type of ART regimen.

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“…Response to the ABC/3TC + ATV/r regimen has also undergone gender stratification analysis in the ACTG A5202 study 15. A5202 applied a more restrictive definition of virologic failure than ARIES and reported more virologic failures among the female than male subjects while they were receiving ABC/3TC + ATV/r over the 192-week randomization period (hazard ratio, 1.72 in multivariable analysis), although adherence was similar between genders.…”

Section: Discussionmentioning

confidence: 99%

Response by gender of HIV-1-infected subjects treated with abacavir/lamivudine plus atazanavir, with or without ritonavir, for 144 weeks

Squires¹,

Young²,

Santiago³

et al. 2017

HIV

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PurposeThe 144-week results of the open-label, multicenter Atazanavir/Ritonavir Induction with Epzicom Study (ARIES) were stratified by gender to compare treatment responses.MethodsA total of 369 HIV-infected, antiretroviral-naïve subjects receiving once-daily abacavir/lamivudine + atazanavir/ritonavir (ATV/r) whose HIV-1 RNA was <50 copies/mL by week 30 were randomized 1:1 at week 36 to maintain or discontinue ritonavir for 108 subsequent weeks. Between- and within-treatment gender-related efficacy and safety differences were analyzed.ResultsSubjects were 85% male; 64% white; and had a mean age of 39 years, baseline median HIV-1 RNA of 114,815 copies/mL, and median CD4+ cell count of 198 cells/mm3. Gender (ATV [n=189]: 29 females/160 males; ATV/r [n=180]: 25 females/155 males) and most other demographics were similar between groups; more females than males were black (65% vs 25%) and fewer females had baseline HIV-1 RNA ≥100,000 copies/mL (41% vs 58%). At week 144, no significant differences between genders were observed in proportion maintaining HIV-1 RNA <50 copies/mL (ATV, 79% vs 77%; ATV/r, 60% vs 75%) or <400 copies/mL (ATV, 83% vs 84%; ATV/r, 68% vs 82%) (intent-to-treat-exposed: time to loss of virologic response analysis); median CD4+ change from baseline (ATV, +365 vs +300 cells/mm3; ATV/r, +344 vs +301 cells/mm3); proportion with treatment-related grade 2–4 adverse events (baseline to week 144: ATV, 41% vs 31%; ATV/r, 36% vs 43%; weeks 36 to 144: ATV, 14% vs 13%; ATV/r, 24% vs 23%); or proportion developing fasting lipid changes. Female and male virologic failure rates (ATV, 0 vs 5; ATV/r, 2 vs 4) and proportions completing the study were similar during the extension phase. Primary withdrawal reasons were loss to follow-up and pregnancy for females and loss to follow-up and other for males.ConclusionOver 144 weeks, no significant gender differences were observed in efficacy, safety, or fasting lipid changes with abacavir/lamivudine +ATV or abacavir/lamivudine +ATV/r.

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Outcomes by Sex Following Treatment Initiation With Atazanavir Plus Ritonavir or Efavirenz With Abacavir/Lamivudine or Tenofovir/Emtricitabine

Abstract: NCT00118898.

Cited by 30 publications

References 13 publications

Efavirenz Therapeutic Range in HIV-1 Treatment-Naive Participants

Efavirenz Therapeutic Range in HIV-1 Treatment-Naive Participants

Dyslipidemia and Fasting Glucose Impairment among HIV-Infected Patients 48-Weeks after the First Antiretroviral Regimen

Response by gender of HIV-1-infected subjects treated with abacavir/lamivudine plus atazanavir, with or without ritonavir, for 144 weeks

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