Sharon A Riddler

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (76)525.56 Total impact

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    ABSTRACT: Summary There is a paucity of normative bone mineral density (BMD) data in healthy African women. Baseline total hip and lumbar spine BMD was measured in premenopausal women. BMD distribution was comparable to that of a reference population and was impacted by several factors including contraception and duration of lactation. Introduction Normative data on bone mineral density (BMD) and the cumulative impact of lactation, contraceptive use, and other factors on BMD in healthy African women have not been well studied. Objectives The objective of this study was to determine the factors associated with BMD in healthy premenopausal women in Uganda and Zimbabwe. Methods Baseline total hip (TH) and lumbar spine (LS) BMD was measured by dual x-ray absorptiometry in 518 healthy, premenopausal black women enrolling in VOICE, an HIV-1 chemoprevention trial, at sites in Uganda and Zimbabwe. Contraceptive and lactation histories, physical activity assessment, calcium intake, and serum vitamin D levels were assessed. Independent factors associated with BMD were identified using an analysis of covariance model. Results The study enrolled 331 women from Zimbabwe and 187 women from Uganda. Median age was 29 years (IQR 25, 32) and median body mass index (BMI) was 24.8 kg/m2 (IQR 22.2, 28.6). In univariate analyses, lower TH BMD values were associated with residence in Uganda (p p Conclusions Among healthy premenopausal women, TH and LS BMD was higher in Zimbabwe than Uganda. Additional factors independently associated with BMD included BMI, physical activity level, contraceptive use, and lactation.
    Archives of Osteoporosis 12/2015; 10(1):206. DOI:10.1007/s11657-015-0206-7
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    ABSTRACT: We measured plasma HIV-1 RNA by single copy assay from participants (N=334) with viral suppression on antiretroviral therapy (ART). Residual viremia ≥1 copy/mL after 4 years of ART was predicted by higher pre-ART HIV-1 RNA, higher on-treatment CD8 cell count, and lower on-treatment CD4/CD8 ratio, but not by initial ART regimen. In a longitudinal subset (N=64), continued decay of plasma HIV-1 RNA was observed, averaging 6% decline per year and with an estimated half-life of 11.5 years. In contrast to prior reports, persistent viremia continues to slowly decline during years 4-12 of suppressive ART. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail:
    The Journal of Infectious Diseases 09/2015; DOI:10.1093/infdis/jiv433 · 6.00 Impact Factor

  • JAIDS Journal of Acquired Immune Deficiency Syndromes 09/2015; DOI:10.1097/QAI.0000000000000858 · 4.56 Impact Factor
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    AIDS Research and Human Retroviruses 10/2014; 30 Suppl 1(S1):A252-3. DOI:10.1089/aid.2014.5564.abstract · 2.33 Impact Factor

  • AIDS Research and Human Retroviruses 10/2014; 30 Suppl 1(S1):A93. DOI:10.1089/aid.2014.5171.abstract · 2.33 Impact Factor
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    AIDS Research and Human Retroviruses 10/2014; 30 Suppl 1(S1):A173. DOI:10.1089/aid.2014.5365.abstract · 2.33 Impact Factor
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    ABSTRACT: Background: Human immunodeficiency virus type 1 (HIV-1) DNA dynamics during long-term antiretroviral therapy (ART) are not defined. Methods: Blood mononuclear cells obtained during 7-12 years of effective ART were assayed for total HIV-1 DNA and 2-long terminal repeat (LTR) circles by quantitative polymerase chain reaction (qPCR). Slopes of HIV-1 DNA were estimated by participant-specific linear regressions. Plasma was assayed for residual viremia (HIV-1 RNA) by qPCR. Results: Thirty participants were studied. HIV-1 DNA decreased significantly from years 0-1 and 1-4 of ART with median decay slopes of -0.86 (interquartile range, -1.05, -0.59) and -0.11 (-0.17, -0.06) log10(copies/10(6) CD4+ T-cells)/year, respectively (P < .001). Decay was not significant for years 4-7 (-0.02 [-0.06, 0.02]; P = .09) or after year 7 of ART (-0.006 [-0.030, 0.015]; P = .17). All participants had detectable HIV-1 DNA after 10 years (median 439 copies/10(6) CD4+ T-cells; range: 7-2074). Pre-ART HIV-1 DNA levels were positively associated with pre-ART HIV-1 RNA levels (Spearman = 0.71, P < .001) and with HIV-1 DNA at years 4, 7, and 10 on ART (Spearman ≥ 0.75, P < .001). No associations were found (P ≥ .25) between HIV-1 DNA slopes or levels and % activated CD8+ T-cells (average during years 1-4) or residual viremia (n = 18). 2-LTR circles were detected pre-ART in 20/29 and in 8/30 participants at last follow-up. Conclusions: Decay of HIV-1 DNA in blood is rapid in the first year after ART initiation (86% decline), slows during years 1-4 (23% decline/year), and subsequently plateaus. HIV-1 DNA decay is not associated with the levels of CD8+ T-cell activation or persistent viremia. The determinants of stable HIV-1 DNA persistence require further elucidation. Clinical Trials Registration. NCT00001137.
    Clinical Infectious Diseases 07/2014; 59(9). DOI:10.1093/cid/ciu585 · 8.89 Impact Factor
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    ABSTRACT: Background: Virologic failure (VF) on a first-line ritonavir-boosted protease inhibitor (PI/r) regimen is associated with low rates of resistance, but optimal management after failure is unknown. Methods: The analysis included participants in randomized trials who experienced VF on a first-line regimen of PI/r plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) and had at least 24 weeks of follow-up after VF. Antiretroviral management and virologic suppression (human immunodeficiency virus type 1 [HIV-1] RNA <400 copies/mL) after VF were assessed. Results: Of 209 participants, only 1 participant had major PI-associated treatment-emergent mutations at first-line VF. The most common treatment approach after VF (66%) was to continue the same regimen. The virologic suppression rate 24 weeks after VF was 64% for these participants, compared with 72% for those who changed regimens (P = .19). Participants remaining on the same regimen had lower NRTI resistance rates (11% vs 30%; P = .003) and higher CD4(+) cell counts (median, 275 vs 213 cells/µL; P = .005) at VF than those who changed. Among participants remaining on their first-line regimen, factors at or before VF significantly associated with subsequent virologic suppression were achieving HIV-1 RNA <400 copies/mL before VF (odds ratio [OR], 3.39 [95% confidence interval {CI}, 1.32-8.73]) and lower HIV-1 RNA at VF (OR for <10 000 vs ≥10 000 copies/mL, 3.35 [95% CI, 1.40-8.01]). Better adherence after VF was also associated with subsequent suppression (OR for <100% vs 100%, 0.38 [95% CI, .15-.97]). For participants who changed regimens, achieving HIV-1 RNA <400 copies/mL before VF also predicted subsequent suppression. Conclusions: For participants failing first-line PI/r with no or limited drug resistance, remaining on the same regimen is a reasonable approach. Improving adherence is important to subsequent treatment success.
    Clinical Infectious Diseases 05/2014; 59(6). DOI:10.1093/cid/ciu367 · 8.89 Impact Factor
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    ABSTRACT: Peripheral neuropathy (PN) is a common neurological complication of HIV infection that has debilitating effects on quality of life. While there has been a comprehensive evaluation of the prevalence of neuropathic signs/symptoms and risk factors (RFs) for PN or symptomatic PN (SPN) with initiation of combination antiretroviral therapy (cART) in ART-naïve patients, similar evaluation in ART-experienced patients is limited. This study investigated the prevalence and RFs for PN/SPN in ART-experienced patients enrolled in clinical salvage therapy studies. Between February 2000 and June 2007, 522 ART-experienced participants who experienced virologic failure with a prior regimen and started new regimens were followed longitudinally and annually screened for signs and symptoms of PN. Rates of PN/SPN at 3 years since parent study entry were 52.8 and 24.0 %, respectively. Aging, taller height, protease inhibitor use, and female sex were significant RFs for PN/SPN. The use of statin drugs was significantly associated with lower odds of SPN, and it may prevent progression from no SPN to SPN.
    Journal of NeuroVirology 12/2013; 19(6). DOI:10.1007/s13365-013-0216-4 · 2.60 Impact Factor
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    ABSTRACT: Background: In the United States, black individuals infected with human immunodeficiency virus (HIV) have higher rates of virologic failure on antiretroviral therapy (ART) and of death compared to white individuals. The cause for these disparities is uncertain. We sought to examine differences in virologic outcomes among antiretroviral-naive clinical trial participants starting randomized ART and to investigate factors to explain the differences. Methods: Individual-level data from participants initiating ART in 5 AIDS Clinical Trials Group studies were analyzed. Included studies were those conducted during 1998-2006 with a primary outcome of virologic failure. The primary outcome measure was time to virologic failure, regardless of ART changes. Results: A total of 2495 individuals (1151 black; 1344 white) were included with a median follow-up of 129 weeks. Compared to whites, blacks had an increased hazard of virologic failure (hazard ratio [HR]; 1.7; 95% confidence interval [CI], 1.4-1.9; P < .001), with no evidence of heterogeneity across regimens (P = .97); the association remained after adjustment for measured confounders (HR, 1.4; 95% CI, 1.2-1.6; P < .001). Increased hazard of virologic failure was associated with younger age, higher pretreatment HIV type 1 RNA level, lower pretreatment CD4 cell count, hepatitis C antibody, less education, and recent nonadherence to treatment. Sensitivity analyses with different endpoint definitions demonstrated similar results. Conclusions: In this analysis, blacks had a 40% higher virologic failure risk than whites that was not explained by measured confounders. The observation was consistent over a range of regimens, suggesting that the difference may be driven by social factors; however, biological factors cannot be ruled out. Further research should identify the sources of racial disparities and develop strategies to reduce them.
    Clinical Infectious Diseases 09/2013; 57(11). DOI:10.1093/cid/cit595 · 8.89 Impact Factor
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    ABSTRACT: Objective: To compare the longitudinal changes in total bone mineral density (TBMD) across antiretroviral (ARV) regimens. Methods: A5142 was an open-label study comparing 3 ARV regimens for the initial treatment of HIV-1. Subjects were randomized equally to efavirenz (EFV) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs), lopinavir/ritonavir (LPV/r) plus 2 NRTIs, or LPV/r plus EFV without NRTI. The NRTI regimen (lamivudine [3TC] plus zidovudine [ZDV], stavudine [d4T], or tenofovir [TDF]) was selected prior to randomization. TBMD was assessed via whole-body dual-energy X-ray absorptiometry (DXA) at baseline and 48 and 96 weeks. Analysis was modified intent-to-treat (ITT) ignoring regimen changes using all evaluations. Results: Significant mean declines in TBMD at week 48 were observed among subjects. In repeated-measures analysis of changes (including randomized regimen, NRTI used, and time), there was a significant difference in the NRTI-containing arms in mean percentage change in TBMD at week 48 according to NRTI used (P < .001). Subjects taking ZDV had similar changes to those taking d4T (P = .970), whereas those taking TDF had larger declines (P < .001). There was a nonsignificant trend toward greater mean declines among subjects taking LPV/r versus EFV (P = .080). Overall, TDF-containing regimens demonstrated the greatest losses in TBMD, while EFV regimens without TDF had lesser TBMD reductions even compared to the NRTI-sparing arm. From week 48 to 96, all treatment groups continued to lose TBMD at similar rates. Conclusions: Among NRTI-containing arms, NRTI selection, especially use of TDF, had a greater effect on TBMD change than randomized regimen. The long-term clinical significance remains to be demonstrated.
    HIV Clinical Trials 09/2013; 14(5):224-234. DOI:10.1310/hct1405-224 · 2.63 Impact Factor
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    ABSTRACT: Background: Bone mineral density (BMD) decreases 2%-6% in the 2 years after antiretroviral therapy (ART) initiation. Pre-ART immune deficiency and early immune recovery may contribute to this loss. Methods: We pooled data from 3 studies of ART initiation in treatment-naive patients in which serial whole-body dual-energy X-ray absorptiometry scans were performed. We used linear regression to evaluate effects of baseline CD4(+) and 16-week CD4(+) change (both absolute and relative) on 96-week total BMD change from baseline. We performed multivariable linear regression to assess associations between baseline variables of age, sex, race/ethnicity, body mass index (BMI), hepatitis C status, parent study, human immunodeficiency virus type 1 (HIV-1) RNA level, and assignment to a protease inhibitor (PI)- or tenofovir-containing regimen on 96-week total BMD change. Results: The included 796 subjects had mean 96-week total BMD loss of 2.0%. In multivariable analysis, baseline CD4(+) cell count was significantly associated with 96-week BMD loss; individuals with baseline CD4(+) <50 cells/µL lost significantly more BMD compared to those with CD4(+) ≥500 cells/µL. A greater relative, but not absolute, 16-week increase in CD4(+) count was significantly associated with greater declines in BMD, but not after controlling for baseline CD4(+) count. In multivariable analysis, older age, female sex, lower BMI, higher HIV-1 RNA levels, and PI and tenofovir assignment were also associated with greater BMD decline. Conclusions: Low pretreatment CD4(+) count, but not greater CD4(+) count increase, is a strong and independent risk factor for bone loss after ART initiation. ART initiation at higher CD4(+) counts may reduce the burden of osteoporosis and fragility fractures.
    Clinical Infectious Diseases 08/2013; 57(10). DOI:10.1093/cid/cit538 · 8.89 Impact Factor
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    ABSTRACT: The role of the adenosine (ADO) suppression pathway, specifically CD39-expressing and CD73-expressing CD4 T cells in HIV-1 infection is unclear. We evaluated the frequency and numbers of CD4CD39 and CD4CD73 T cells, activated T cells, and plasma C reactive protein (CRP) levels in 36 HIV-1-positive individuals and 10 normal controls (NC). Low-level plasma viremia was evaluated using single copy assay. Mass spectrometry was used to measure hydrolysis of ATP by ectoenzyme-expressing CD4 T cells, whereas cyclic adenosine monophosphate (cAMP) levels were measured using enzyme immunoassay. Suppression of T-cell function by exogenous ADO and CD4CD73 T cells was tested by flow cytometry. CD39 and CD73 are expressed in different CD4 T-cell subsets. CD4CD73 T cells do not express CD25 and FOXP3, and their frequency and numbers were lower in HIV-1-positive individuals regardless of virologic suppression (P = 0.005 and P < 0.001, respectively). CD4CD73 numbers inversely correlated with CD4CD38DR (P = 0.002), CD8CD38DR T-cell frequency (P = 0.05), and plasma CRP levels (P = 0.01). Both subsets are required for hydrolysis of exogenous ATP to ADO and can increase CD4 T-cell cAMP levels when incubated with exogenous ATP. Low-level viremia did not correlate with activated T-cell frequency. In vitro, ADO suppressed T-cell activation and cytokine expression. CD4CD73 T cells suppressed T-cell proliferation only in the presence of exogenous 5'-AMP. The ADO-producing CD4CD73 subset of T cells is depleted in HIV-1-positive individuals regardless of viral suppression and may play a key role in controlling HIV-1-associated immune activation.
    AIDS (London, England) 06/2013; 27(10):1545-1555. DOI:10.1097/QAD.0b013e328360c7f3 · 5.55 Impact Factor
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    ABSTRACT: OBJECTIVE:: To facilitate collection of cumulative data on longitudinal HIV disease outcomes during HIV prevention studies by developing recommendations for follow-up of the relatively few study participants with breakthrough infections. DESIGN:: We formed a working group to compare and contrast the various approaches taken in recent HIV prevention trials, to summarize the advantages and disadvantages associated with each, and to explore the feasibility of developing protocols for the long-term follow-up of seroconverters. METHODS:: We reviewed study designs, objectives, and assessments in 15 interventional studies that followed HIV seroconverters. Protocol team members joined discussions of the various approaches and developed recommendations. RESULTS:: Most HIV prevention clinical trials share a core set of objectives, including the description/comparison of virological, immunological and clinical course of HIV, and sometimes a comparison of pre-and post-seroconversion behavior. Long-term follow-up of seroconverters can be conducted in separate studies if the transition from parent protocol is effectively managed. CONCLUSION:: We recommend the development of harmonized seroconverter protocols. Although specific research questions in the post-seroconversion period may differ depending on prevention modality, harmonizing key evaluations would create an opportunity to ask overarching questions that inform the prevention field with respect to design and implementation of future combination prevention studies. Follow-up immediately post-seroconversion should be conducted in the parent protocol before rollover into a follow-up protocol. Development of specimen repositories with ample volumes for future assays, standardized definitions of infection, diagnosis and seroconversion dates, and harmonization of study objectives and sample collections at key time points are important.
    AIDS (London, England) 12/2012; 27(7). DOI:10.1097/QAD.0b013e32835dc08e · 5.55 Impact Factor
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    ABSTRACT: HLA class I-associated polymorphisms identified at the population level mark viral sites under immune pressure by individual HLA alleles. As such, analysis of their distribution, frequency, location, statistical strength, sequence conservation and other properties offers a unique perspective from which to identify correlates of protective cellular immunity. We analyzed HLA-associated HIV-1 subtype B polymorphisms in 1888 treatment-naïve, chronically-infected individuals using phylogenetically-informed methods, and identified characteristics of HLA-associated immune pressures that differentiate protective and non-protective alleles. Over 2100 HLA-associated HIV-1 polymorphisms were identified, approximately one-third of which occurred inside or within 3 residues of an optimally-defined CTL epitope. Differential CTL escape patterns between closely related HLA alleles were common, and increased with greater evolutionary distance between allele group members. Among 9-mer epitopes, mutations at HLA-specific anchor residues represented the most frequently detected escape type: these occurred nearly twofold more frequently than expected by chance, and were computationally predicted to reduce peptide-HLA binding nearly tenfold on average. Characteristics associated with protective HLA alleles (defined using hazard ratios for progression to AIDS from natural history cohorts) included the potential to mount broad immune selection pressures across all HIV-1 proteins except Nef, the tendency to drive multi-site and/or anchor residue escape mutations within known CTL epitopes, and the ability to strongly select mutations in conserved regions within HIV's structural and functional proteins. Thus, the factors defining protective cellular immune responses may be more complex than simply targeting conserved viral regions. Study results provide new information to guide vaccine design and immunogenicity studies.
    Journal of Virology 10/2012; 86(24). DOI:10.1128/JVI.01998-12 · 4.44 Impact Factor

  • 19th International AIDS Conference; 01/2012
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    ABSTRACT: To evaluate the effects of sex and initial antiretroviral regimen on decay of HIV-RNA and virologic outcome. We conducted a viral dynamics substudy of A5142, a trial comparing lopinavir (LPV)/ritonavir with efavirenz (LPV/EFV) versus LPV and two nucleoside reverse transcriptase inhibitor (NRTI) (LPV) versus EFV and two NRTI (EFV) in antiretroviral (ARV)-naive individuals. HIV-RNA was measured at days 2, 10, and 14 in the substudy and at weeks 1, 4, and 8 in A5142 participants. Two-phase viral decay was estimated in the substudy with biexponential mixed-effects modeling and compared using Wilcoxon tests. Week 1 HIV-RNA change was assessed as a predictor of virologic failure (HIV-RNA above 50 or 200  copies/ml) at weeks 24-96 using logistic regression. Sixty-eight individuals were enrolled in the substudy (median HIV-RNA 4.9 log(10)  copies/ml). Median rates of phase 1 viral decay by treatment were 0.61(EFV/LPV), 0.53(LPV), and 0.63(EFV) per day. Phase 1 decay was significantly faster for EFV than LPV (P = 0.023); other comparisons were not significant (P > 0.11). Viral decay did not differ by sex (P = 0.10). Week 1 HIV-RNA change, calculated in 571 participants of A5142, was greater for the EFV (median -1.47 log(10)  copies/ml) than either the LPV/EFV or LPV groups (-1.21 and -1.16 log(10 ) copies/ml, respectively; P < 0.001). Week 1 HIV-RNA change was associated with virologic failure above 50  copies/ ml at weeks 24 and 48 (P < 0.018), but not above 200  copies/ml at these time points or for any value at week 96. Phase 1 decay was faster for EFV than LPV or LPV/EFV. Week 1 HIV-RNA change predicted virologic outcome up to week 48, but not at week 96.
    AIDS (London, England) 09/2011; 25(18):2269-78. DOI:10.1097/QAD.0b013e32834d0c20 · 5.55 Impact Factor
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    ABSTRACT: Strong statistical associations between polymorphisms in HIV-1 population sequences and carriage of HLA class I alleles have been widely used to identify possible sites of CD8 T cell immune selection in vivo. However, there have been few attempts to prospectively and systematically test these genetic hypotheses arising from population-based studies at a cellular, functional level. We assayed CD8 T cell epitope-specific IFN-γ responses in 290 individuals from the same cohort, which gave rise to 874 HLA-HIV associations in genetic analyses, taking into account autologous viral sequences and individual HLA genotypes. We found immunological evidence for 58% of 374 associations tested as sites of primary immune selection and identified up to 50 novel HIV-1 epitopes using this reverse-genomics approach. Many HLA-adapted epitopes elicited equivalent or higher-magnitude IFN-γ responses than did the nonadapted epitopes, particularly in Nef. At a population level, inclusion of all of the immunoreactive variant CD8 T cell epitopes in Gag, Pol, Nef, and Env suggested that HIV adaptation leads to an inflation of Nef-directed immune responses relative to other proteins. We concluded that HLA-HIV associations mark viral epitopes subject to CD8 T cell selection. These results can be used to guide functional studies of specific epitopes and escape mutations, as well as to test, train, and evaluate analytical models of viral escape and fitness. The inflation of Nef and HLA-adapted variant responses may have negative effects on natural and vaccine immunity against HIV and, therefore, has implications for diversity coverage approaches in HIV vaccine design.
    The Journal of Immunology 09/2011; 187(5):2502-13. DOI:10.4049/jimmunol.1100691 · 4.92 Impact Factor
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    ABSTRACT: The generalizability of antiretroviral therapy (ART) clinical trial efficacy findings to routine care settings is not well studied. We compared the relative effectiveness of initial ART regimens estimated in AIDS Clinical Trial Group (ACTG) randomized controlled trials with that among patients receiving ART at Antiretroviral Therapy Cohort Collaboration (ART-CC) study sites. Treatment-naive HIV-infected patients initiating identical ART regimens in ACTG trials (A5095 and A5142) and at 15 ART-CC cohort study sites were included. Virological failure (HIV-1 RNA >200 copies/mL) at 24 and 48 weeks, incident AIDS-defining events and mortality were measured according to study design (ART-CC cohort vs. ACTG trial) and stratified by third drug [abacavir (ABC), efavirenz (EFV), and lopinavir/r (LPV/r)]. We used logistic regression to estimate and compare odds ratios (OR) for virological failure between different regimens and study designs, and used Cox models to estimate and compare hazard ratios for AIDS and death. Compared with patients receiving ABC, those receiving EFV had roughly half the odds of 24-week virologic failure (>200 copies/mL) in both ACTG 5095 (OR = 0.53, 95% confidence interval: 0.36 to 0.79) and ART-CC (0.46, 0.37 to 0.57). Virologic superiority of EFV (vs. ABC) seemed comparable in ART-CC and ACTG 5095 (ratio of ORs 0.86, 95% confidence interval: 0.54 to 1.35). Odds ratios for 48-week virologic failure, comparing EFV with LPV/r, were also comparable in ACTG 5142 and ART-CC (ratio of ORs: 0.87, 0.45 to 1.69). Between ART regimen virologic efficacy of third drugs ABC, EFV, and LPV/r observed in the ACTG 5095 and 5142 trials seem generalizable to the routine care setting of ART-CC clinical cohorts.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 08/2011; 58(3):253-60. DOI:10.1097/QAI.0b013e318230372e · 4.56 Impact Factor
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    ABSTRACT: This study examines the cost and consequences of initiating an ARV regimen including Lopinavir/ritonavir (LPV/r) or Efavirenz (EFV), using data from a recent clinical trial in a previously published model of HIV-disease. We populated the Markov model of HIV-disease with data from ACTG 5142 study to estimate the economic outcomes of starting ARV therapy with a PI-containing regimen as compared to an NNRTI-containing regimen, given their virologic and immunologic efficacy and effects on cholesterol and lipoatrophy. CNS toxicities and GI tolerability were not included in the model because of their transient nature or low cost remedies, and therefore lack of economic impact. CD4+ T-cell counts and the HIV-1 RNA (viral load) values from the study were used to assign a specific health state (HS) to each patient for each quarter year. The resulting frequencies used as "raw" data directly into the model obviate the reliance on statistical tests, and allow the model to reflect actual patient behavior in the clinical trial. An HS just below the last observed HS was used to replace a missing value. The modeled estimates (undiscounted) for the LPV/r-based regimen resulted in 1.41 quality-adjusted life months (QALMs) gained over a lifetime compared to the EFV-based regimen. The LPV/r-based regimen incurred $7,458 (1.8%) greater cost over a lifetime due to differences in drug costs and survival. The incremental cost effectiveness ratio using the discounted cost and QALYs was $88,829/QALY. Most of the higher costs accrue before the 7th year of treatment and were offset by subsequent savings. The estimates are highly sensitive to the effect of lipoatrophy on Health-related Quality of Life (HRQOL), but not to the effect of cholesterol levels. The cost effectiveness of ARV regimens may be strongly affected by enduring AEs, such as lipoatrophy. It is important to consider specific AE effects from all drugs in a regimen when ARVs are compared. ( number, NCT00050895http://[]).
    Cost Effectiveness and Resource Allocation 05/2011; 9(1):5. DOI:10.1186/1478-7547-9-5 · 0.87 Impact Factor

Publication Stats

4k Citations
525.56 Total Impact Points


  • 1994-2014
    • University of Pittsburgh
      • • Division of Infectious Diseases
      • • Department of Infectious Diseases and Microbiology
      • • Department of Medicine
      Pittsburgh, Pennsylvania, United States
  • 2011
    • Royal Perth Hospital
      Perth City, Western Australia, Australia
  • 2008
    • Pittsburg State University
      Kansas, United States
  • 2001-2003
    • Johns Hopkins University
      • Department of Epidemiology
      Baltimore, Maryland, United States
  • 2002
    • University of California, San Diego
      San Diego, California, United States
  • 1996
    • Research Triangle Park Laboratories, Inc.
      Raleigh, North Carolina, United States