Original Article
Class-Sparing Regimens for Initial Treatment of HIV-1 Infection
N Engl J Med 2008; 358:2095-2106May 15, 2008
- Abstract
Background
The use of either efavirenz or lopinavir–ritonavir plus two nucleoside reverse-transcriptase inhibitors (NRTIs) is recommended for initial therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection, but which of the two regimens has greater efficacy is not known. The alternative regimen of lopinavir–ritonavir plus efavirenz may prevent toxic effects associated with NRTIs.
Methods
In an open-label study, we compared three regimens for initial therapy: efavirenz plus two NRTIs (efavirenz group), lopinavir–ritonavir plus two NRTIs (lopinavir–ritonavir group), and lopinavir–ritonavir plus efavirenz (NRTI-sparing group). We randomly assigned 757 patients with a median CD4 count of 191 cells per cubic millimeter and a median HIV-1 RNA level of 4.8 log10 copies per milliliter to the three groups.
Results
At a median follow-up of 112 weeks, the time to virologic failure was longer in the efavirenz group than in the lopinavir–ritonavir group (P=0.006) but was not significantly different in the NRTI-sparing group from the time in either of the other two groups. At week 96, the proportion of patients with fewer than 50 copies of plasma HIV-1 RNA per milliliter was 89% in the efavirenz group, 77% in the lopinavir–ritonavir group, and 83% in the NRTI-sparing group (P=0.003 for the comparison between the efavirenz group and the lopinavir–ritonavir group). The groups did not differ significantly in the time to discontinuation because of toxic effects. At virologic failure, antiretroviral resistance mutations were more frequent in the NRTI-sparing group than in the other two groups.
Conclusions
Virologic failure was less likely in the efavirenz group than in the lopinavir–ritonavir group. The virologic efficacy of the NRTI-sparing regimen was similar to that of the efavirenz regimen but was more likely to be associated with drug resistance. (ClinicalTrials.gov number, NCT00050895.)
Media in This Article
Figure 1
Time to Virologic Failure and Time to Regimen Failure.Figure 2
Virologic Response, According to Study Group.Article Activity
- Article
Current practice guidelines recommend the use of efavirenz or ritonavir-boosted protease inhibitor regimens containing two nucleoside reverse-transcriptase inhibitors (NRTIs) for initial therapy of human immunodeficiency virus type 1 (HIV-1) infection. 1,2 These recommendations are derived from expert opinion and the results of clinical trials, but to our knowledge well-powered, head-to-head comparisons of these regimens have not been performed.3-5
Although NRTIs are included in all recommended antiretroviral regimens, toxic effects, especially lipoatrophy associated with the thymidine analogues,6,7, has raised interest in regimens that do not contain NRTIs. Pilot studies of NRTI-sparing regimens have shown good virologic efficacy, but adequately powered studies comparing these regimens for initial therapy are lacking.3,8 Therefore, we conducted a multicenter, randomized trial to compare the virologic efficacy, immunologic response, side-effect profile, and metabolic complications of efavirenz plus two NRTIs, of lopinavir–ritonavir plus two NRTIs, and of lopinavir–ritonavir plus efavirenz.
Methods
Study Population
The study population consisted of HIV-1–infected male and female patients at least 13 years of age who had not received previous antiretroviral therapy. All patients had a plasma HIV-1 RNA level of at least 2000 copies per milliliter with any CD4 cell count, and acceptable laboratory results. (For details, see the Supplementary Appendix, available with the full text of this article at www.nejm.org.) An institutional review board or ethics committee at each site approved the study, and all patients provided written informed consent. The study was monitored by the data and safety monitoring board of the National Institute of Allergy and Infectious Diseases. The authors who were employed by companies that supplied study drugs participated in the trial design, data accrual, data analysis, and manuscript preparation. All authors vouch for the completeness and accuracy of the data.
Study Design
In this phase 3, randomized, multicenter, open-label trial, eligible patients were randomly assigned with equal probability to receive one of three regimens: 600 mg of efavirenz (Sustiva tablets, Bristol-Myers Squibb) once daily plus two NRTIs (efavirenz group), a combination of 400 mg of lopinavir and 100 mg of ritonavir (Kaletra capsules, Abbott Laboratories) twice daily plus two NRTIs (lopinavir–ritonavir group), or 533 mg of lopinavir and 133 mg of ritonavir twice daily plus 600 mg of efavirenz once daily (NRTI-sparing group).
The NRTIs used in the efavirenz group and the lopinavir–ritonavir group were lamivudine (Epivir, GlaxoSmithKline) for all patients at a dose of 150 mg twice daily or 300 mg once daily plus the choice of one of three other agents: zidovudine (Retrovir, GlaxoSmithKline) at a dose of 300 mg twice daily, stavudine extended release (XR) (Zerit XR, investigational agent, Bristol-Myers Squibb) at a dose of 100 mg once daily (with participants weighing less than 60 kg receiving 75 mg), or tenofovir disoproxil fumarate (DF) (Viread, Gilead Sciences) at a dose of 300 mg once daily. The choice of the second NRTI was made by the site investigator before randomization. Changes in NRTI were not allowed during the study. Lopinavir–ritonavir, efavirenz, stavudine XR, and tenofovir DF were provided by the manufacturer, and other medications were obtained through prescriptions.
Randomization was stratified according to a permuted-block design on the basis of three factors: the screening level of plasma HIV-1 RNA (<100,000 vs. ≥100,000 copies per milliliter), the presence or absence of chronic hepatitis infection (B, C, or both), and the choice of NRTI. After screening, study evaluations were completed before study entry, at entry, and at weeks 1, 4, 8, 12, 16, 20, and 24 and every 8 weeks thereafter for the duration of the study. Plasma HIV-1 RNA was measured at each visit at a central laboratory (Roche Amplicor HIV-1 Monitor assay, ultrasensitive version 1.5). The CD4 cell count was measured before study entry, at entry, and every 8 weeks thereafter.
Patients' adherence to a study-drug regimen was assessed by standardized self-report.9 The adherence questionnaire included a 4-day recall and several questions that included data on doses that were missed during the past week and those that were missed during the past weekend. At week 12, an adherence rate of 100% was defined as all doses taken during the previous 4 days plus no other missed doses, as identified by the additional questions. Body composition was measured by whole-body dual-energy x-ray absorptiometry (DEXA) at study entry and at weeks 48 and 96.10,11 Adverse clinical and laboratory events were assessed by the site investigators and were scored with the use of the adverse-event grading scale of the National Institutes of Health's Division of AIDS (1992 version). The occurrence of clinical lipoatrophy and treatment-limiting toxic effects were determined by the site investigator. Each patient was scheduled for 96 weeks of follow-up after the last enrollment.
Genotyping for resistance to HIV-1 drugs was performed during screening if the site investigator suspected that the patient had been infected with HIV-1 for 1 year or less. Genotyping data were reviewed by the protocol chairs and virologist, and the patient was deemed to be ineligible for the study if any evidence of resistance to a study drug was present.12 At the time of virologic failure, drug-resistance genotyping was performed in a central laboratory (Quest Diagnostics). The genotype was used by the site investigator to choose a new regimen. Patients were allowed to continue the same regimen if it was deemed to be clinically appropriate.
Statistical Analysis
The two primary objectives of the study were to perform pairwise comparisons of the time to virologic failure and the time to regimen failure among the three study groups. Virologic failure was defined as a lack of suppression of plasma HIV-1 RNA by 1 log10 or rebound before week 32 or a lack of suppression to less than 200 copies per milliliter or rebound after week 32. Confirmation of suspected virologic failure was required within 4 weeks. Data from patients whose confirmation sample was missing were included among failure end points. Regimen failure was defined as the first of either virologic failure or toxicity-related discontinuation of any component of the initial randomized treatment regimen.
All patients who underwent randomization and received at least one dose of a study drug were included in the analysis. All analyses were performed on an intention-to-treat basis and were stratified according to the three randomization factors. Patients who discontinued any therapy because of a toxic effect were followed for the occurrence of virologic failure. Data from patients who did not have virologic failure or regimen failure while they were taking a study drug were censored at the time of the last study visit. Missing data due to missed evaluations, loss to follow-up, or censoring were ignored. Prespecified subgroup analyses that were based on the randomization strata were conducted after the completion of the two primary analyses.
Distributions of the time from randomization to virologic failure and to regimen failure were estimated with the use of the Kaplan–Meier method and tested for equality with the use of the stratified log-rank test on the basis of the randomization factors. Cox proportional-hazards models were used to estimate hazard ratios and corresponding confidence intervals. The overall type I error rate was 0.05, with 0.017 (0.05÷3) allocated to each pairwise comparison between study groups; after adjustment for interim analyses, the final type I error rate was 0.014. Thus, only P values of less than 0.014 were considered to have statistical significance in the analyses of primary objectives. The approach outlined by DiRienzo and DeGruttola13 was used to calculate adjusted P values for simultaneous consideration of both primary outcomes. Three interim analyses were conducted by the data and safety monitoring board. At each interim analysis, 0.003 of the total type I error was spent (0.001 for each of the three pairwise comparisons, on the basis of a Peto stopping rule). All reported P values are two-sided.
As originally designed with a total number of 660 patients, the study had a power of approximately 85% to detect a 56% reduction in the risk of virologic failure and a power of 90% to detect a 52% reduction in the risk of regimen failure. The study remained open to enrollment after reaching the initial target of 660 patients to complete enrollment at the South African site and enrollment in a prespecified substudy of endothelial function.14
Results
Patients
A total of 757 patients were enrolled from January 2003 to May 2004. The baseline characteristics of the 753 patients who received study drugs are provided in Table 1Table 1
Baseline Characteristics of the Patients.; 80% of the patients were men, and 64% were nonwhite. At baseline, the median plasma HIV-1 RNA level was 64,203 (4.8 log10) copies per milliliter, and the median CD4 cell count was 191 cells per cubic millimeter. Baseline characteristics of patients were well balanced among the three study groups. Only 5 of 153 participants with available screening data were excluded from enrollment because of HIV-1 drug resistance.The median follow-up was 112 weeks, with no differences among the study groups. A total of 589 of 753 patients (78%) completed the protocol. Of the remaining 164 patients, 19 died, 56 were unable to attend clinic visits, 26 were unwilling to adhere to the protocol, 46 could not be contacted, and 17 had other reasons. There were no significant differences among the three study groups in the reasons for loss to follow-up or the time until patients were lost to follow-up (P=0.66).
Primary Outcomes
Virologic Failure
As defined in the protocol, virologic failure occurred in 60 of 250 patients (24%) in the efavirenz group, 94 of 253 patients (37%) in the lopinavir–ritonavir group, and 73 of 250 patients (29%) in the NRTI-sparing group. The efavirenz group had a significantly longer time to virologic failure than did the lopinavir–ritonavir group (P=0.006) (Figure 1AFigure 1
Time to Virologic Failure and Time to Regimen Failure. and Table 2Table 2
Hazard Ratios, with 95% Confidence Intervals, for Time to Virologic Failure and Time to Regimen Failure.); the differences between the NRTI-sparing group and the efavirenz group (P=0.49) or the lopinavir–ritonavir group (P=0.13) were not significant.Among patients with HIV-1 RNA levels of 100,000 copies per milliliter or more at screening, the efavirenz group had a longer time to virologic failure than either the lopinavir–ritonavir group (P=0.01) or the NRTI-sparing group (P=0.02) (Figure 1B). For patients with HIV-1 RNA levels of less than 100,000 copies per milliliter at screening, the NRTI-sparing group had a longer time to virologic failure than the lopinavir–ritonavir group (P=0.02), but there was no significant difference between the efavirenz group and the lopinavir–ritonavir group (P=0.13) or the NRTI-sparing group (P=0.26) (Figure 1C). In a multivariable Cox proportional-hazards model stratified according to the three baseline factors, a greater risk of virologic failure was associated with female sex (hazard ratio, 1.38; 95% confidence interval [CI], 1.01 to 1.89), black race as compared with all others (hazard ratio, 1.57; 95% CI, 1.18 to 2.08), a younger age group at baseline, as compared with the next incremental age group (hazard ratio, 1.23; 95% CI, 1.06 to 1.45), and a group with a lower CD4 cell count, as compared with the next incremental cell-count group (hazard ratio, 1.14; 95% CI, 1.01 to 1.27) (Table 1). No other variables were considered in this model.
Regimen Failure
The regimen-failure outcome occurred in 95 of 250 patients (38%) in the efavirenz group, 127 of 253 patients (50%) in the lopinavir–ritonavir group, and 108 of 250 patients (43%) in the NRTI-sparing group. There was a trend toward a longer time to regimen failure in the efavirenz group than in the lopinavir–ritonavir group (P=0.03), but the P value did not reach the significance level of 0.014 with adjustment for multiple comparisons (Figure 1D and Table 2).
Response to Treatment
At week 96, the proportions of patients with fewer than 200 copies per milliliter of plasma HIV-1 RNA were 93% (95% CI, 88 to 96) in the efavirenz group, 86% (95% CI, 80 to 91) in the lopinavir–ritonavir group, and 92% (95% CI, 87 to 96) in the NRTI-sparing group (Figure 2AFigure 2
Virologic Response, According to Study Group.). At the same time, the proportions of patients with fewer than 50 copies per milliliter of plasma HIV-1 RNA were 89% (95% CI, 84 to 93) in the efavirenz group, 77% (95% CI, 71 to 83) in the lopinavir–ritonavir group, and 83% (95% CI, 76 to 88) in the NRTI-sparing group (Figure 2B). (For the comparison between the efavirenz group and the lopinavir–ritonavir group, P=0.04 for fewer than 200 copies per milliliter and P=0.003 for fewer than 50 copies per milliliter; P>0.05 for each of the other pairwise comparisons.)A sustained increase in the CD4 cell count after study entry was observed in all three study groups. At week 96, the median increase from baseline was 230 cells per cubic millimeter (interquartile range, 142 to 353) in the efavirenz group, 287 cells per cubic millimeter (interquartile range, 155 to 422) in the lopinavir–ritonavir group, and 273 cells per cubic millimeter (interquartile range, 176 to 419) in the NRTI-sparing group (see the figure in the Supplementary Appendix). At week 96, the change from baseline in the CD4 cell count was greater in the lopinavir–ritonavir group and the NRTI-sparing group than in the efavirenz group (P=0.01 for the both comparisons by the Wilcoxon rank-sum test). At week 48, there were no significant differences among the three groups in the change from baseline in the CD4 cell count.
Adherence to Treatment
Among patients who were receiving their assigned study drugs at week 12, 405 of 657 (62%) reported having missed no doses since study entry; there were no significant differences among the study groups. Patients in the subgroup with 100% adherence had a longer time to virologic failure than did patients whose rate of adherence was lower, regardless of study-group assignment (P<0.001).
Adverse Events
Toxicity leading to discontinuation of one or more drugs in the initial regimen occurred in 134 of 753 patients (18%). There were no significant differences in the time to the first treatment-limiting adverse event among the three study groups. The most frequent treatment-limiting adverse events are summarized in Table 3Table 3
Treatment-Limiting Adverse Events and New Grade 3 or 4 Clinical Events or Laboratory Abnormalities.. There were 19 deaths, one of which was determined to have a probable association with a study drug. This patient was assigned to the NRTI-sparing group and died of hepatotoxicity at week 14 of the study.From baseline to week 96, the median increase in limb fat as seen on DEXA was 0.05 kg in the the efavirenz group, 0.7 kg in the lopinavir–ritonavir group, and 1.15 kg in the NRTI-sparing group (P≤0.01 for each of the three pairwise comparisons). One or more new or recurrent conditions that define the presence of the acquired immunodeficiency syndrome (AIDS) occurred in 9 of 250 patients (4%) in the efavirenz group, 16 of 253 patients (6%) in the lopinavir–ritonavir group, and 15 of 250 patients (6%) in the NRTI-sparing group, but the differences were not significant (see the table in the Supplementary Appendix).
A total of 131 of 753 patients (17%) had a new grade 3 or 4 sign or symptom, and 259 of 753 patients (34%) had a new grade 3 or 4 laboratory abnormality while receiving their assigned regimen (Table 3). The proportion of patients with at least one new grade 3 or 4 laboratory event was higher in the NRTI-sparing group than in the other two groups (P<0.01 for both comparisons), mainly because of more frequent elevations in fasting triglyceride levels.
Resistance to HIV Drugs
HIV-1 drug-resistance mutations in protease or reverse transcriptase that were detected at the time of virologic failure are shown in Table 4Table 4
Summary of Resistance Mutations at the Time of Virologic Failure.. With the exclusion of minor protease mutations14 and the assumption that no patients with missing genotyping data had resistance mutations, the numbers of patients who had virologic failure and one or more drug-resistance mutations were 22 of 250 (9%) in the efavirenz group, 16 of 253 (6%) in the lopinavir–ritonavir group, and 39 of 250 (16%) in the NRTI-sparing group (P<0.05 for the comparison between the NRTI-sparing group and both the efavirenz group and the lopinavir–ritonavir group). Of the available genotypes from patients with virologic failure, 39 of 56 patients (70%) in the NRTI-sparing group had one or more drug-resistance mutations, as compared with 22 of 46 (48%) in the efavirenz group and 16 of 78 (21%) in the lopinavir–ritonavir group (for the NRTI-sparing group, P<0.001 for the comparison with the lopinavir–ritonavir group and P=0.03 for the comparison with the efavirenz group; P=0.002 for the comparison between the lopinavir–ritonavir group and the efavirenz group).Mutations that were associated with resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) (of which 71% were K103N) were more frequent in the NRTI-sparing group (66%) than in the efavirenz group (43%, P=0.03). There was no significant difference between the lopinavir–ritonavir group and the efavirenz group in the frequency of the M184V mutation (associated with resistance to lamivudine) or those associated with thymidine analogue or any NRTI. Fewer patients in the lopinavir–ritonavir group than in the efavirenz group had mutations associated with resistance to two drug classes (1% vs. 26%, P<0.001) or the K65R substitution (0% vs. 7%, P=0.05).
Discussion
In this 96-week, prospective, randomized comparison of potent regimens for initial therapy for patients with HIV-1 infection, virologic failure was less likely in the group receiving efavirenz plus two NRTIs than in the group receiving lopinavir–ritonavir plus two NRTIs. The NRTI-sparing regimen of lopinavir–ritonavir plus efavirenz had a virologic efficacy similar to that of efavirenz plus two NRTIs, but NNRTI resistance and lipid abnormalities, especially elevated triglycerides, were more frequent. Clinically apparent lipoatrophy was reported infrequently. Recovery of limb fat favored the NRTI-sparing group. There was a trend toward a shorter time to regimen failure in the lopinavir–ritonavir group, as compared with the efavirenz group, but the difference was not significant after adjustment for multiple comparisons. The number of regimen-failure outcomes owing to adverse events was similar among the study groups, and there was no significant difference among the three groups in the time to treatment-limiting toxicity.
Patients who were receiving either of the regimens containing lopinavir–ritonavir had greater increases in the CD4 cell count than did those receiving efavirenz plus two NRTIs at week 96 but not at week 48. It has been suggested that HIV-1 protease inhibitors have antiapoptotic effects on CD4 cells that are independent of the antiviral effects.15 However, it might be expected that a difference between the groups on the basis of this mechanism would be apparent earlier after initiation of treatment. A large, randomized strategy study showed no difference in the change in CD4 cell count for initial therapy with a protease inhibitor (mostly nelfinavir), as compared with an NNRTI-containing regimen.16 In addition, the clinical significance of the differences in recovery in the CD4 cell count that we observed in our study is unclear.
Several factors may be associated with a better virologic response to one antiretroviral regimen over another, including greater potency, better tolerability, and higher rates of adherence. In this study, the regimen of efavirenz plus two NRTIs had greater overall virologic efficacy even when the analysis was restricted to patients with a high level of adherence, and the regimen appeared to suppress HIV-1 RNA levels more rapidly than the regimens containing lopinavir–ritonavir, although the clinical significance of this difference is not known (Figure 2).
HIV-1 drug-resistance testing at the time of virologic failure revealed that NNRTI resistance occurred more frequently in the NRTI-sparing group than in the efavirenz group. This finding was not anticipated but may be explained, in part, by differences in the elimination half-lives of lopinavir–ritonavir and efavirenz. Although this hypothesis is speculative given the long half-life of efavirenz17 and the relatively short half-life of lopinavir–ritonavir, missed doses of lopinavir–ritonavir might result in periods with therapeutic levels of efavirenz but not lopinavir–ritonavir, resulting in the selection of NNRTI-resistant virus.
Previous studies have reported lower frequencies of NRTI resistance at the time of virologic failure among patients receiving lopinavir–ritonavir plus two NRTIs than among those receiving various other regimens.18,19 However, in our study, among patients with virologic failure, the proportion of patients with any NRTI resistance mutation and specifically lamivudine resistance was similar in the lopinavir–ritonavir group and the efavirenz group. The presence of mutations associated with two drug classes, primarily M184V and K103N, was more common in the efavirenz group. The absence of major protease mutations in the lopinavir–ritonavir group was consistent with findings reported previously.19,20
The virologic efficacy of the nucleoside-sparing regimen of lopinavir–ritonavir plus efavirenz in our study clearly shows that NRTIs are not absolutely required for effective antiretroviral therapy. The increased frequency of lipid elevation and NNRTI resistance in the NRTI-sparing group should dampen enthusiasm for routine use of this regimen. However, the data support the use of combined therapy with lopinavir–ritonavir plus efavirenz in specific clinical situations in which options are limited, such as a contraindication for or an intolerance to NRTIs. The virologic efficacy of NRTI-sparing therapy with lopinavir–ritonavir and efavirenz supports the study of potent two-drug NRTI-sparing regimens for initial therapy.
Our study establishes the use of efavirenz plus two NRTIs as being more effective than lopinavir–ritonavir plus two NRTIs for initial therapy of HIV-1 infection, although the margin of superiority was moderate. Drug resistance was not a common outcome overall, but failure of efavirenz plus two NRTIs was often associated with NNRTI resistance, whereas failure of lopinavir–ritonavir plus two NRTIs was not associated with lopinavir resistance, and NRTI resistance was similar in the two groups. These results highlight the complexity of choosing initial therapy. Selection of initial therapy for an individual patient should take into consideration many factors, including virologic and immunologic response, tolerability, short-term and long-term toxicity, and the resistance consequences associated with virologic failure.
Supported by grants (AI 068636 [AIDS Clinical Trials Group Central Grant], AI 068634, AI 069471, AI 27661, AI 069439, AI 25859, AI 069477, AI 069513, AI 069452, AI 27673, AI 069470, AI 069474, AI 069411, AI 069423, AI 069494, AI 069484, AI 069472, AI 38858, AI 069501, AI 32783, AI 069450, AI 32782, AI 069465, AI 069424, AI 38858, AI 069447, AI 069495, AI 069502, AI 069556, AI 069432, AI 46370, AI 069532, AI 46381, AI 46376, AI 34853, AI 069434, AI 060354, AI 064086, AI 36214, AI 069419, AI 069418, AI 50410, AI 45008, RR 00075, RR 00032, RR 00044, RR 00046, RR 02635, RR 00051, RR 00052, RR 00096, RR 00047, RR 00039, and DA 12121) from the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
Dr. Riddler reports receiving lecture and consulting fees from Bristol-Myers Squibb and Abbott Laboratories and grant support from Schering-Plough; Dr. Haubrich, receiving lecture and consulting fees from Bristol-Myers Squibb, Tanox, Roche, Abbott, Boehringer Ingelheim, Merck, Schering, Tibotec, and Gilead and research support from GlaxoSmithKline, Tibotec, Abbott, and Pfizer; Dr. Powderly, receiving lecture and consulting fees from Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Pfizer, Roche, and Tibotec and grant support from GlaxoSmithKline; Dr. Garren, being an employee of Abbott Laboratories; Dr. George, being an employee of Bristol-Myers Squibb; Dr. Rooney, being an employee of Gilead Sciences; Dr. Murphy, receiving research grants from Bristol-Myers Squibb and Abbott and consulting fees from Gilead Sciences; Dr. Swindells, receiving grant support and consulting fees from Abbott, Bristol-Myers Squibb, Novartis, Tibotec, and Pfizer; and Dr. Mellors, receiving consulting fees from Abbott, Boehringer Ingelheim, Gilead Sciences, GlaxoSmithKline, Merck, Noviro/Idenix, Pfizer, Pharmasset, and Trimeris and grant support from Merck and having an equity interest in Achillion Pharmaceuticals and Pharmasset. No other potential conflict of interest relevant to this article was reported.
Drs. Riddler and Haubrich contributed equally to this article.
We thank the patients for their participation in the study.
Source Information
From the University of Pittsburgh, Pittsburgh (S.A.R., J.W.M.); the University of California, San Diego, San Diego (R.H.); the Harvard School of Public Health, Boston (A.G.D., L.P.); University College Dublin, Dublin (W.G.P.); the Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD (K.L.K.); Abbott Laboratories, Abbott Park, IL (K.W.G.); Bristol-Myers Squibb, Plainsboro, NJ (T.G.); Gilead Sciences, Foster City, CA (J.F.R.); Social and Scientific Systems, Silver Spring, MD (B.B.); the University of KwaZulu Natal, Durban, South Africa (U.G.L.); Northwestern University, Chicago (R.L.M.); the University of Nebraska Medical Center, Omaha (S.S.); and the University of California, San Francisco, San Francisco (D.H.).
Address reprint requests to Dr. Riddler at 613 Falk Bldg., 3601 Fifth Ave., Pittsburgh, PA 15213, or at riddler@dom.pitt.edu.
Ms. Brizz is deceased.
Investigators in the AIDS Clinical Trials Group Study A5142 Team are listed in the Appendix.
Appendix
In addition to the authors, the study team included the following members: P. Cain (Stanford University Medical Center), protocol field representative; M. Cooper, M. Dobson (Frontier Science and Technology Research Foundation), laboratory data coordinators; M. Dorosh (University of Colorado Health Sciences Center), community representative; P. Kondo (University of Hawaii), protocol laboratory technologist; D. Rusin (Frontier Science and Technology Research Foundation), data manager; K. Squires (Thomas Jefferson University), coinvestigator; P. Tran (Division of AIDS, National Institute of Allergy and Infectious Diseases), protocol pharmacist. The following were pharmaceutical representatives: S. Brun, R. Rode (Abbott Laboratories); M. Poblenz, M. Hitchcock (Gilead Sciences).
Other investigators included the following: K. Coleman (Northwestern University); B. Sha (Rush University); O. Adeyemi (Cook County CORE Center); W.K. Henry, W. Calvert (University of Minnesota); M. Morgan, B. Jackson (Vanderbilt University); M. Goldman, J. Hernandez (Indiana University); H.H. Bolivar, M.A. Fischl (University of Miami School of Medicine); C.J. Fichtenbaum, J. Baer (University of Cincinnati); S. Byars, M. Stewart (University of Alabama); H. Edmondson-Melancon, C.A. Funk (University of Southern California); J.N. Connor, M. Torres (Columbia Collaborative HIV/AIDS Clinical Trials Unit); W.E. Maher, L. Laughlin (Ohio State University); M. Adams, C. Hurley (University of Rochester); C. Zelasky, D. Wohl (University of North Carolina–Chapel Hill); D. McMahon, B. Rutecki (University of Pittsburgh); P. Kumar, I. Vvedenskaya (Georgetown University); G.M. Cox, D. Wade (Duke University Medical Center); P. Sax, J. Gothing (Harvard–Boston Medical Center AIDS Clinical Trials Unit); A.A. Amod (Durban International Clinical Trials Unit); B. Rodriguez, B. Philpotts (Case Western Reserve University); H. Friedman, A. Thomas (University of Pennsylvania, Philadelphia); B. Putnam, C. Basler (Colorado AIDS Clinical Trials Unit); W.A. O'Brien, G. Casey (University of Texas Medical Branch–Galveston); I. Wiggins, G. Casey (Johns Hopkins University); M. Carlson, E. Daar (University of California, Los Angeles); A. Olusanya, M. Schreiber (University of California, Davis, Medical Center); C. Davis, B. Boyce (University of Maryland); G.-Y. Kim, K. Gray (Washington University, St. Louis); J. Volinski (University of California, San Francisco); J. Norris, S. Valle (Stanford University); J. Hoffman, S. Cahill (University of California, San Diego); D. Garmon, D. Mildvan (Beth Israel Medical Center); J. Forcht, C. Gonzalez (New York University); K. Tashima, D. Perez (Miriam Hospital); P. Keiser, T. Petersen (University of Texas–Southwestern Medical Center at Dallas); N. Hanks, S. Souza (University of Hawaii at Manoa and Queen's Medical Center); A.C. Collier, S. Storey (University of Washington, Seattle); V. Hughes, T. Stroberg (Cornell University); G. Smith, I. Ofotokun (Emory University).
- References
References
1
Panel on Clinical Practices for Treatment of HIV Infection. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Washington, D.C.: Department of Health and Human Services, October 10, 2006. (Accessed April 18, 2008, at http://AIDSinfo.nih.gov.)
2
Hammer SM ,Saag MS ,Schechter M , et al. Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA panel. JAMA 2006;296:827-843
CrossRef | Web of Science | Medline3
Staszewski S ,Morales-Ramirez J ,Tashima KT , et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. N Engl J Med 1999;341:1865-1873
Full Text | Web of Science | Medline4
Murphy RL ,Brun S ,Hicks C , et al. ABT-378/ritonavir plus stavudine and lamivudine for the treatment of antiretroviral-naïve adults with HIV-1 infection: 48-week results. AIDS 2001;15:F1-F9
CrossRef | Web of Science | Medline5
Gulick RM ,Ribaudo HJ ,Shikuma CM , et al. Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection. N Engl J Med 2004;350:1850-1861
Full Text | Web of Science | Medline6
Carr A ,Miller J ,Law M ,Cooper DA . A syndrome of lipoatrophy, lactic acidaemia and liver dysfunction associated with HIV nucleoside analogue therapy: contribution to protease inhibitor-related lipodystrophy syndrome. AIDS 2000;14:F25-F32
CrossRef | Web of Science | Medline7
Mallal SA ,John M ,Moore CB ,James IR ,McKinnon EJ . Contribution of nucleoside analogue reverse transcriptase inhibitors to subcutaneous fat wasting in patients with HIV infection. AIDS 2000;14:1309-1316
CrossRef | Web of Science | Medline8
Allavena C ,Ferre V ,Brunet-Francois C , et al. Efficacy and tolerability of a nucleoside reverse transcriptase inhibitor-sparing combination of lopinavir/ritonavir and efavirenz in HIV-1-infected patients. J Acquir Immune Defic Syndr 2005;39:300-306
CrossRef | Web of Science | Medline9
Chesney MA ,Ickovics JR ,Chambers DB , et al. Self-reported adherence to antiretroviral medications among participants in HIV clinical trials: the AACTG adherence instruments. AIDS Care 2000;12:255-266
CrossRef | Web of Science | Medline10
Dube MP ,Parker RA ,Tebas P , et al. Glucose metabolism, lipid, and body fat changes in antiretroviral-naive subjects randomized to nelfinavir or efavirenz plus dual nucleosides. AIDS 2005;19:1807-1818
CrossRef | Web of Science | Medline11
Haubrich RH, Riddler S, DiRienzo G, et al. Metabolic outcomes of ACTG 5142: a prospective, randomized, phase III trial of NRTI-, PI-, and NNRTI-sparing regimens for initial treatment of HIV-1 infection. Presented at the 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, February 25–28, 2007.
12
Johnson VA ,Brun-Vezinet F ,Clotet B , et al. Update of the drug resistance mutations in HIV-1: fall 2006. Top HIV Med 2006;14:125-130
Medline13
DiRienzo AG ,DeGruttola V . Design and analysis of clinical trials with a bivariate failure time endpoint: with application to AIDS Clinical Trials Group Study A5142. Control Clin Trials 2003;24:122-134
CrossRef | Medline14
Stein JH ,Cotter BR ,Parker RA , et al. Antiretroviral therapy improves endothelial function in individuals with human immunodeficiency virus infection: a prospective, randomized multicenter trial (Adult AIDS Clinical Trials Group study A5152s). Circulation 2005;112:Suppl II:II-23715
Vlahakis SR ,Bren GD ,Algeciras-Schimnich A ,Trushin SA ,Schnepple DJ ,Badley AD . Flying in the face of resistance: antiviral-independent benefit of HIV protease inhibitors on T-cell survival. Clin Pharmacol Ther 2007;82:294-299
CrossRef | Web of Science | Medline16
MacArthur RD ,Novak RM ,Peng G , et al. A comparison of three highly active antiretroviral treatment strategies consisting of non-nucleoside reverse transcriptase inhibitors, protease inhibitors, or both in the presence of nucleoside reverse transcriptase inhibitors as initial therapy (CPCRA 058 FIRST Study): a long-term randomised trial. Lancet 2006;368:2125-2135
CrossRef | Web of Science | Medline17
Sustiva tablets. New York: Bristol-Myers Squibb, March 2006 (package insert).
18
Walmsley S ,Bernstein B ,King M , et al. Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection. N Engl J Med 2002;346:2039-2046
Full Text | Web of Science | Medline19
Kempf DJ ,King MS ,Bernstein B , et al. Incidence of resistance in a double-blind study comparing lopinavir/ritonavir plus stavudine and lamivudine to nelfinavir plus stavudine and lamivudine. J Infect Dis 2004;189:51-60
CrossRef | Web of Science | Medline20
Hicks C ,King MS ,Gulick RM , et al. Long-term safety and durable antiretroviral activity of lopinavir/ritonavir in treatment-naive patients: 4 year follow-up study. AIDS 2004;18:775-779
CrossRef | Web of Science | Medline
- Citing Articles (154)
Citing Articles
1
C. William Wester, Ori M. Stitelman, Victor DeGruttola, Hermann Bussmann, Richard G. Marlink, Mark J. van der Laan. (2012) Effect Modification by Sex and Baseline CD4+ Cell Count Among Adults Receiving Combination Antiretroviral Therapy in Botswana: Results from a Clinical Trial.. AIDS Research and Human Retroviruses120206140605008
CrossRef2
T. J. Barber, L. Harrison, D. Asboe, I. Williams, S. Kirk, R. Gilson, L. Bansi, D. Pillay, D. Dunn, . (2012) Frequency and patterns of protease gene resistance mutations in HIV-infected patients treated with lopinavir/ritonavir as their first protease inhibitor. Journal of Antimicrobial Chemotherapy
CrossRef3
Mark Oette, Stefan Reuter, Rolf Kaiser, Thomas Lengauer, Gerd Fätkenheuer, Heribert Knechten, Martin Hower, Herbert Pfister, Dieter Häussinger. (2012) Epidemiology of Transmitted Drug Resistance in Chronically HIV-Infected Patients in Germany: The RESINA Study 2001–2009. Intervirology 55:2, 154-159
CrossRef4
Daniel Röshammar, Ulrika S. H. Simonsson, Håkan Ekvall, Leo Flamholc, Vidar Ormaasen, Jan Vesterbacka, Eva Wallmark, Michael Ashton, Magnus Gisslén. (2011) Non-linear mixed effects modeling of antiretroviral drug response after administration of lopinavir, atazanavir and efavirenz containing regimens to treatment-naïve HIV-1 infected patients. Journal of Pharmacokinetics and Pharmacodynamics 38:6, 727-742
CrossRef5
L. PIROTH, I. FOURNEL, S. MAHY, Y. YAZDANPANAH, D. REY, C. RABAUD, J. P. FALLER, B. HOEN, M. FARDEHEB, C. QUANTIN, P. CHAVANET, C. BINQUET. (2011) A decision tree to help determine the best timing and antiretroviral strategy in HIV-infected patients. Epidemiology and Infection 139:12, 1835-1844
CrossRef6
Johan van Griensven, Sopheak Thai. (2011) Predictors of immune recovery and the association with late mortality while on antiretroviral treatment in Cambodia. Transactions of the Royal Society of Tropical Medicine and Hygiene 105:12, 694-703
CrossRef7
Daniel R Kuritzkes. (2011) Drug resistance in HIV-1. Current Opinion in Virology 1:6, 582-589
CrossRef8
M. Fabbiani, L. Bracciale, E. Ragazzoni, R. Santangelo, P. Cattani, S. Giambenedetto, G. Fadda, P. Navarra, R. Cauda, A. Luca. (2011) Relationship between antiretroviral plasma concentration and emergence of HIV-1 resistance mutations at treatment failure. Infection 39:6, 563-569
CrossRef9
Ricardo Camacho, Eugénio Teófilo. (2011) Antiretroviral therapy in treatment-naïve patients with HIV infection. Current Opinion in HIV and AIDS 6, S3-S11
CrossRef10
Hicham El Annaz, Patricia Recordon-Pinson, Rida Tagajdid, Toufik Doblali, Bouchra Belefquih, Siham Oumakhir, Omar Sedrati, Saad Mrani, Hervé Fleury. (2011) Drug Resistance Mutations in HIV Type 1 Isolates from Patients Failing Antiretroviral Therapy in Morocco. AIDS Research and Human Retroviruses111123134251001
CrossRef11
Baligh R. Yehia, Judith A. Long, Cordelia R. Stearns, Benjamin French, Pablo Tebas, Ian Frank. (2011) Impact of transitioning from HIV clinical trials to routine medical care on clinical outcomes and patient perceptions. AIDS Care1-9
CrossRef12
V. von Wyl, S. Yerly, J. Boni, C. Shah, C. Cellerai, T. Klimkait, M. Battegay, E. Bernasconi, M. Cavassini, H. Furrer, B. Hirschel, P. L. Vernazza, B. Ledergerber, H. F. Gunthard, . (2011) Incidence of HIV-1 Drug Resistance Among Antiretroviral Treatment-Naive Individuals Starting Modern Therapy Combinations. Clinical Infectious Diseases
CrossRef13
Richard H. Haubrich, Sharon A. Riddler, Heather Ribaudo, Gregory DiRenzo, Karin L. Klingman, Kevin W. Garren, David L. Butcher, James F. Rooney, Diane V. Havlir, John W. Mellors. (2011) Initial viral decay to assess the relative antiretroviral potency of protease inhibitor-sparing, nonnucleoside reverse transcriptase inhibitor-sparing, and nucleoside reverse transcriptase inhibitor-sparing regimens for first-line therapy of HIV infection. AIDS 25:18, 2269-2278
CrossRef14
Michael J. Mugavero, Margaret May, Heather J. Ribaudo, Roy M. Gulick, Sharon A. Riddler, Richard Haubrich, Sonia Napravnik, Sophie Abgrall, Andrew Phillips, Ross Harris, M. John Gill, Frank de Wolf, Robert Hogg, Huldrych F. Günthard, Geneviève Chêne, Antonella DʼArminio Monforte, Jodie L. Guest, Colette Smith, Javier Murillas, Juan Berenguer, Christoph Wyen, Pere Domingo, Mari M. Kitahata, Jonathan A. C. Sterne, Michael S. Saag. (2011) Comparative Effectiveness of Initial Antiretroviral Therapy Regimens. JAIDS Journal of Acquired Immune Deficiency Syndromes 58:3, 253-260
CrossRef15
Andrew Scourfield, Laura Waters, Mark Nelson. (2011) Drug combinations for HIV: what’s new?. Expert Review of Anti-infective Therapy 9:11, 1001-1011
CrossRef16
Babafemi Taiwo, Lu Zheng, Sebastien Gallien, Roy M. Matining, Daniel R. Kuritzkes, Cara C. Wilson, Baiba I. Berzins, Edward P. Acosta, Barbara Bastow, Peter S. Kim, Joseph J. Eron. (2011) Efficacy of a nucleoside-sparing regimen of darunavir/ritonavir plus raltegravir in treatment-naive HIV-1-infected patients (ACTG A5262). AIDS 25:17, 2113-2122
CrossRef17
Brian Gazzard, Claudine Duvivier, Christian Zagler, Antonella Castagna, Andrew Hill, Yvonne van Delft, Stephan Marks. (2011) Phase 2 double-blind, randomized trial of etravirine versus efavirenz in treatment-naive patients. AIDS 25:18, 2249-2258
CrossRef18
M. W. Hull, J. S. G. Montaner. (2011) Optimizing Initial Therapy for HIV Infection. Journal of Infectious Diseases 204:8, 1154-1156
CrossRef19
Risa M. Hoffman, Beth D. Jamieson, Ronald J. Bosch, Judith Currier, Christina M. R. Kitchen, Ingrid Schmid, Yuda Zhu, Kara Bennett, Ronald Mitsuyasu. (2011) Baseline Immune Phenotypes and CD4+ T Lymphocyte Responses to Antiretroviral Therapy in Younger versus Older HIV-infected Individuals. Journal of Clinical Immunology 31:5, 873-881
CrossRef20
Roberto Rossotti, Barbara Foglieni, Chiara Molteni, Manuela Gatti, Irene Guarnori, Ennio La Russa, Daniele Prati, Anna Orani. (2011) A cluster of patients with recombinant B/F HIV-1 infection: Epidemiological, clinical, and virological aspects. Journal of Medical Virology 83:9, 1493-1498
CrossRef21
Barbara S. Taylor, Gillian Hunt, Elaine J. Abrams, Ashraf Coovadia, Tammy Meyers, Gayle Sherman, Renate Strehlau, Lynn Morris, Louise Kuhn. (2011) Rapid Development of Antiretroviral Drug Resistance Mutations in HIV-Infected Children Less Than Two Years of Age Initiating Protease Inhibitor-Based Therapy in South Africa. AIDS Research and Human Retroviruses 27:9, 945-956
CrossRef22
Toshibumi Taniguchi, Diana Nurutdinova, Jessica R. Grubb, Nur F. Önen, Enbal Shacham, Michael Donovan, Edgar Turner Overton. (2011) Transmitted Drug-Resistant HIV Type 1 Remains Prevalent and Impacts Virologic Outcomes Despite Genotype-Guided Antiretroviral Therapy. AIDS Research and Human Retroviruses110830063440008
CrossRef23
B. Taiwo, S. Gallien, E. Aga, H. Ribaudo, R. Haubrich, D. R. Kuritzkes, J. J. Eron. (2011) Antiretroviral Drug Resistance in HIV-1-Infected Patients Experiencing Persistent Low-Level Viremia During First-Line Therapy. Journal of Infectious Diseases 204:4, 515-520
CrossRef24
Mark W. Hull, Julio S. G. Montaner. (2011) Ritonavir-boosted protease inhibitors in HIV therapy. Annals of Medicine 43:5, 375-388
CrossRef25
Julieta Díaz-Delfín, M. del Mar Gutiérrez, José M. Gallego-Escuredo, Joan C. Domingo, M. Gracia Mateo, Francesc Villarroya, Pere Domingo, Marta Giralt. (2011) Effects of nevirapine and efavirenz on human adipocyte differentiation, gene expression, and release of adipokines and cytokines. Antiviral Research 91:2, 112-119
CrossRef26
Pierre Frange, Nelly Briand, Véronique Avettand-fenoel, Florence Veber, Despina Moshous, Nizar Mahlaoui, Christine Rouzioux, Stéphane Blanche, Marie-Laure Chaix. (2011) Lopinavir/Ritonavir-based Antiretroviral Therapy in Human Immunodeficiency Virus Type 1-infected Naive Children. The Pediatric Infectious Disease Journal 30:8, 684-688
CrossRef27
Gabriel Vallecillo, Pere Domingo, Josep Mallolas, Jesús Blanch, Elena Ferrer, Manuel Cervantes, Enric Pedrol, Hernando Knobel, Josep M. Llibre. (2011) Evaluation of the Safety and Effectiveness of Nevirapine Plus Coformulated Tenofovir/Emtricitabine as First-Line Therapy in Routine Clinical Practice. AIDS Research and Human Retroviruses110726065827005
CrossRef28
A. S. Perelson, S. G. Deeks. (2011) Drug Effectiveness Explained: The Mathematics of Antiviral Agents for HIV. Science Translational Medicine 3:91, 91ps30-91ps30
CrossRef29
S. Sahali, G. Carcelain, C. Goujard, J.-F. Delfraissy, J. Ghosn. (2011) Stratégies de restauration immunitaire chez les patients infectés par le virus de l’immunodéficience humaine. La Revue de Médecine Interne 32:7, 425-431
CrossRef30
Matthew Grant, Rafik Samuel, Robert L. Bettiker, Byungse Suh. (2011) Antiretroviral therapy 2010 update: Current practices and controversies. Archives of Pharmacal Research 34:7, 1045-1053
CrossRef31
Anita J. Brogan, Sandra E. Talbird, Calvin Cohen. (2011) Cost-Effectiveness of Nucleoside Reverse Transcriptase Inhibitor Pairs in Efavirenz-Based Regimens for Treatment-Naïve Adults with HIV Infection in the United States. Value in Health 14:5, 657-664
CrossRef32
Signe W. Worm, Jens D. Lundgren. (2011) The metabolic syndrome in HIV. Best Practice & Research Clinical Endocrinology & Metabolism 25:3, 479-486
CrossRef33
Stefano Alcaro, Claudia Alteri, Anna Artese, Francesca Ceccherini-Silberstein, Giosuè Costa, Francesco Ortuso, Lucia Parrotta, Carlo Federico Perno, Valentina Svicher. (2011) Molecular and structural aspects of clinically relevant mutations related to the approved non-nucleoside inhibitors of HIV-1 reverse transcriptase. Drug Resistance Updates 14:3, 141-149
CrossRef34
D.L. Pitrak, R. Estes, R.M. Novak, M. Linnares-Diaz, J.M. Tschampa. (2011) Beneficial Effects of a Switch to a Lopinavir/ritonavir-Containing Regimen for Patients with Partial or No Immune Reconstitution with Highly Active Antiretroviral Therapy Despite Complete Viral Suppression. AIDS Research and Human Retroviruses 27:6, 659-667
CrossRef35
Fernando Lozano, Pere Domingo. (2011) Tratamiento antirretroviral de la infección por el VIH. Enfermedades Infecciosas y Microbiología Clínica 29:6, 455-465
CrossRef36
T. Yamamoto, D. A. Price, J. P. Casazza, G. Ferrari, M. Nason, P. K. Chattopadhyay, M. Roederer, E. Gostick, P. D. Katsikis, D. C. Douek, R. Haubrich, C. Petrovas, R. A. Koup. (2011) Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection. Blood 117:18, 4805-4815
CrossRef37
Estevão Portela Nunes, Marilia Santini de Oliveira, Beatriz Grinsztejn. (2011) Lopinavir: the old champion. Future Virology 6:5, 561-570
CrossRef38
Cecilia Pizzocolo, Antonella Castagna, Adriano Lazzarin. (2011) HIV protease inhibitors: present and future. Future Virology 6:5, 571-580
CrossRef39
Adrian Curran, Esteban Ribera. (2011) From old to new nucleoside reverse transcriptase inhibitors: changes in body fat composition, metabolic parameters and mitochondrial toxicity after the switch from thymidine analogs to tenofovir or abacavir. Expert Opinion on Drug Safety 10:3, 389-406
CrossRef40
Alexandra U Scherrer, Viktor von Wyl, Jürg Böni, Sabine Yerly, Thomas Klimkait, Philippe Bürgisser, Christian Garzoni, Bernard Hirschel, Matthias Cavassini, Manuel Battegay, Pietro L Vernazza, Enos Bernasconi, Bruno Ledergerber, Huldrych F Günthard. (2011) Viral Suppression Rates in Salvage Treatment With Raltegravir Improved With the Administration of Genotypic Partially Active or Inactive Nucleoside/Tide Reverse Transcriptase Inhibitors. JAIDS Journal of Acquired Immune Deficiency Syndromes 57:1, 24-31
CrossRef41
Cynthia L Gay, Ashley J Mayo, Chelu K Mfalila, Haitao Chu, Anna C Barry, JoAnn D Kuruc, Kara S Mcgee, Melissa Kerkau, Joe Sebastian, Susan A Fiscus, David M Margolis, Charles B Hicks, Guido Ferrari, Joseph J Eron. (2011) Efficacy of NNRTI-based antiretroviral therapy initiated during acute HIV infection. AIDS1
CrossRef42
H. J. Ribaudo, C. A. Benson, Y. Zheng, S. L. Koletar, A. C. Collier, J. J. Lok, M. Smurzynski, R. J. Bosch, B. Bastow, J. T. Schouten, . (2011) No Risk of Myocardial Infarction Associated With Initial Antiretroviral Treatment Containing Abacavir: Short and Long-Term Results from ACTG A5001/ALLRT. Clinical Infectious Diseases 52:7, 929-940
CrossRef43
Jessica H Brehm, Christina M Lalama, Michael D Hughes, Richard Haubrich, Sharon A Riddler, Nicolas Sluis-Cremer, John W Mellors. (2011) Failure of Initial Therapy With Two Nucleosides and Efavirenz Is Not Associated With Early Emergence of Mutations in the C-Terminus of HIV-1 Reverse Transcriptase. JAIDS Journal of Acquired Immune Deficiency Syndromes 56:4, 344-348
CrossRef44
Scott R Evans, Ronald J Ellis, Huichao Chen, Tzu-min Yeh, Anthony J Lee, Giovanni Schifitto, Kunling Wu, Ronald J Bosch, Justin C McArthur, David M Simpson, David B Clifford. (2011) Peripheral neuropathy in HIV: prevalence and risk factors. AIDS 25:7, 919-928
CrossRef45
Gert Uves van Zyl, Thijs E van Mens, Helen McIlleron, Michele Zeier, Jean B Nachega, Eric Decloedt, Carolina Malavazzi, Peter Smith, Yong Huang, Lize van der Merwe, Monica Gandhi, Gary Maartens. (2011) Low Lopinavir Plasma or Hair Concentrations Explain Second-Line Protease Inhibitor Failures in a Resource-Limited Setting. JAIDS Journal of Acquired Immune Deficiency Syndromes 56:4, 333-339
CrossRef46
(2011) First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: an open-label, randomised phase 2/3 trial. The Lancet Infectious Diseases 11:4, 273-283
CrossRef47
Judith N Dlamini, Zonghui Hu, Harsha Somaroo, Helene C Highbarger, Dean A Follmann, Robin L Dewar, Alice K Pau. (2011) Lack of Effect from a Previous Single Dose of Nevirapine on Virologic and Immunologic Responses After 6 Months of Antiretroviral Regimens Containing Either Efavirenz or Lopinavir-Ritonavir. Pharmacotherapy 31:2, 158-163
CrossRef48
A. Zoufaly, M. an der Heiden, C. Kollan, J. R. Bogner, G. Fatkenheuer, J. C. Wasmuth, M. Stoll, O. Hamouda, J. van Lunzen, . (2011) Clinical Outcome of HIV-Infected Patients with Discordant Virological and Immunological Response to Antiretroviral Therapy. Journal of Infectious Diseases 203:3, 364-371
CrossRef49
HE Hsu, CE Rydzak, KL Cotich, B Wang, PE Sax, E Losina, KA Freedberg, SJ Goldie, Z Lu, RP Walensky, . (2011) Quantifying the risks and benefits of efavirenz use in HIV-infected women of childbearing age in the USA. HIV Medicine 12:2, 97-108
CrossRef50
K. E. Squires, M. Johnson, R. Yang, J. Uy, L. Sheppard, J. Absalon, D. McGrath. (2011) Comparative gender analysis of the efficacy and safety of atazanavir/ritonavir and lopinavir/ritonavir at 96 weeks in the CASTLE study. Journal of Antimicrobial Chemotherapy 66:2, 363-370
CrossRef51
(2011) Clinical Guidelines for the Diagnosis and Treatment of HIV/AIDS in HIV-infected Koreans. Infection and Chemotherapy 43:2, 89
CrossRef52
Todd Hulgan, Richard Haubrich, Sharon A Riddler, Pablo Tebas, Marylyn D Ritchie, Grace A McComsey, David W Haas, Jeffrey A Canter. (2011) European mitochondrial DNA haplogroups and metabolic changes during antiretroviral therapy in AIDS Clinical Trials Group Study A5142*. AIDS 25:1, 37-47
CrossRef53
Maria Cecilia Vieira, Ritesh N. Kumar, Jeroen P. Jansen. (2011) Comparative Effectiveness of Efavirenz, Protease Inhibitors, and Raltegravir-Based Regimens as First-Line Treatment for HIV-Infected Adults: A Mixed Treatment Comparison. HIV Clinical Trials 12:4, 175-189
CrossRef54
Jacques Reynes, Adebayo Lawal, Federico Pulido, Ruth Soto-Malave, Joseph Gathe, Min Tian, Linda M. Fredrick, Thomas J. Podsadecki, Angela M. Nilius. (2011) Examination of Noninferiority, Safety, and Tolerability of Lopinavir/ritonavir and Raltegravir Compared with Lopinavir/ritonavir and Tenofovir/ Emtricitabine in Antiretroviral-Naïve Subjects: The PROGRESS Study, 48-Week Results. HIV Clinical Trials 12:5, 255-267
CrossRef55
Jade Ghosn. (2011) SENSE makes us rethink the second-generation nonnucleoside reverse transcriptase inhibitor etravirineʼs place in HIV-1 treatment. AIDS 25:3, 383-384
CrossRef56
Beverly E. Sha, Camlin Tierney, Susan E. Cohn, Xin Sun, Robert W. Coombs, Lisa M. Frenkel, Spyros A. Kalams, Francesca T. Aweeka, Barbara Bastow, Arlene Bardeguez, Anne Kmack, Alice Stek. (2011) Postpartum Viral Load Rebound in HIV-1–Infected Women Treated with Highly Active Antiretroviral Therapy: AIDS Clinical Trials Group Protocol A5150. HIV Clinical Trials 12:1, 9-23
CrossRef57
Kit N Simpson, Birgitta Dietz, Robert W Baran, Kevin W Garren, Sharon A Riddler, Menaka Bhor, Richard H Haubrich. (2011) Economic modeling of the combined effects of HIV-disease, cholesterol and lipoatrophy based on ACTG 5142 trial data. Cost Effectiveness and Resource Allocation 9:1, 5
CrossRef58
Carole L. Wallis, John W. Mellors, Willem D. F. Venter, Ian Sanne, Wendy Stevens. (2011) Protease Inhibitor Resistance Is Uncommon in HIV-1 Subtype C Infected Patients on Failing Second-Line Lopinavir/r-Containing Antiretroviral Therapy in South Africa. AIDS Research and Treatment 2011, 1-5
CrossRef59
Mark Nelson, Hans-Jürgen Stellbrink, Daniel Podzamczer, Dénes Banhegyi, Brian Gazzard, Andrew Hill, Yvon van Delft, Johan Vingerhoets, Thomas Stark, Stephan Marks. (2011) A comparison of neuropsychiatric adverse events during 12 weeks of treatment with etravirine and efavirenz in a treatment-naive, HIV-1-infected population. AIDS 25:3, 335-340
CrossRef60
Mattia C.F. Prosperi, Maurizio Zazzi, Grazia Punzi, Laura Monno, Grazia Colao, Paola Corsi, Simona Di Giambenedetto, Genny Meini, Valeria Ghisetti, Stefano Bonora, Monica Pecorari, Maria Rita Gismondo, Patrizia Bagnarelli, Tiziana Carli, Andrea De Luca. (2010) Low rate of virological failure and maintenance of susceptibility to HIV-1 protease inhibitors with first-line lopinavir/ritonavir-based antiretroviral treatment in clinical practice. Journal of Medical Virology 82:12, 1996-2003
CrossRef61
Mona R Loutfy, Miguel Genebat, David Moore, Janet Raboud, Keith Chan, Tony Antoniou, David Milan, Anya Shen, Marina B Klein, Curtis Cooper, Nima Machouf, Sean B Rourke, Anita Rachlis, Chris Tsoukas, Julio S G Montaner, Sharon L Walmsley, Marek Smieja, Ahmed Bayoumi, Edward Mills, Robert S Hogg. (2010) A CD4+ Cell Count <200 Cells per Cubic Millimeter at 2 Years After Initiation of Combination Antiretroviral Therapy Is Associated With Increased Mortality in HIV-Infected Individuals With Viral Suppression. JAIDS Journal of Acquired Immune Deficiency Syndromes 55:4, 451-459
CrossRef62
Mark A. Boyd, Andrew M. Hill. (2010) Clinical Management of Treatment-Experienced, HIV/AIDS Patients in the Combination Antiretroviral Therapy Era. PharmacoEconomics 28, 17-34
CrossRef63
Peter S. Kim, Sarah W. Read. (2010) Nanotechnology and HIV: potential applications for treatment and prevention. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 2:6, 693-702
CrossRef64
Regina B. Osih, Patrick Taffé, Martin Rickenbach, Angèle Gayet–Ageron, Luigia Elzi, Christoph Fux, Milos Opravil, Enos Bernasconi, Patrick Schmid, Huldrych F Günthard, Matthias Cavassini. (2010) Outcomes of Patients on Dual-Boosted PI Regimens: Experience of the Swiss HIV Cohort Study. AIDS Research and Human Retroviruses 26:11, 1239-1246
CrossRef65
John Hornberger, Kit Simpson, Ashwini Shewade, Birgitta Dietz, Robert Baran, Thomas Podsadecki. (2010) Broadening the perspective when assessing evidence on boosted protease inhibitor-based regimens for initial antiretroviral therapy. Advances in Therapy 27:11, 763-773
CrossRef66
Lockman, S.Hughes, M.D.McIntyre, J.Zheng, Y.Chipato, T.Conradie, F.Sawe, F.Asmelash, A.Hosseinipour, M.C.Mohapi, L.Stringer, E.Mngqibisa, R.Siika, A.Atwine, D.Hakim, J.Shaffer, D.Kanyama, C.Wools-Kaloustian, K.Salata, R.A.Hogg, E.Alston-Smith, B.Walawander, A.Purcelle-Smith, E.Eshleman, S.Rooney, J.Rahim, S.Mellors, J.W.Schooley, R.T.Currier, J.S.. (2010) Antiretroviral Therapies in Women after Single-Dose Nevirapine Exposure. New England Journal of Medicine 363:16, 1499-1509
Full Text67
Jamie D. Croxtall, Caroline M. Perry. (2010) Lopinavir/Ritonavir. Drugs 70:14, 1885-1915
CrossRef68
C. J. Destache, T. Belgum, M. Goede, A. Shibata, M. A. Belshan. (2010) Antiretroviral release from poly(DL-lactide-co-glycolide) nanoparticles in mice. Journal of Antimicrobial Chemotherapy 65:10, 2183-2187
CrossRef69
Camille E. Introcaso, Janet M. Hines, Carrie L. Kovarik. (2010) Cutaneous toxicities of antiretroviral therapy for HIV. Journal of the American Academy of Dermatology 63:4, 563-569
CrossRef70
Keri N Althoff, Amy C Justice, Stephen J Gange, Steven G Deeks, Michael S Saag, Michael J Silverberg, M John Gill, Bryan Lau, Sonia Napravnik, Ellen Tedaldi, Marina B Klein, Kelly A Gebo. (2010) Virologic and immunologic response to HAART, by age and regimen class. AIDS 24:16, 2469-2479
CrossRef71
F. Kearney, A. R. Moore, C. F. Donegan, J. Lambert. (2010) The ageing of HIV: implications for geriatric medicine. Age and Ageing 39:5, 536-541
CrossRef72
Lidia Gazzola, Camilla Tincati, Antonella d’Arminio Monforte. (2010) Noninfectious HIV-related comorbidities and HAART toxicities: choosing alternative antiretroviral strategies. HIV Therapy 4:5, 553-565
CrossRef73
Alba Diaz, Llúcia Alós, Agathe León, Anna Mozos, Miguel Caballero, Antonio Martinez, Montserrat Plana, Teresa Gallart, Cristina Gil, Manuel Leal, Jose M Gatell, Felipe García. (2010) Factors associated with collagen deposition in lymphoid tissue in long-term treated HIV-infected patients. AIDS 24:13, 2029-2039
CrossRef74
José M. Miró, Christian Manzardo, Judith Pich, Pere Domingo, Elena Ferrer, José R. Arribas, Esteban Ribera, Julio Arrizabalaga, Montserrat Loncá, Anna Cruceta, Elisa de Lazzari, Montserrat Fuster, Daniel Podzamczer, Montserrat Plana, José M. Gatell. (2010) Immune Reconstitution in Severely Immunosuppressed Antiretroviral-Naive HIV Type 1-Infected Patients Using a Nonnucleoside Reverse Transcriptase Inhibitor-Based or a Boosted Protease Inhibitor-Based Antiretroviral Regimen: Three-Year Results (The Advanz Trial): A Randomized, Controlled Trial. AIDS Research and Human Retroviruses 26:7, 747-757
CrossRef75
Paul A Volberding, Steven G Deeks. (2010) Antiretroviral therapy and management of HIV infection. The Lancet 376:9734, 49-62
CrossRef76
J. Wang, H. Liang, L. Bacheler, H. Wu, K. Deriziotis, L.M. Demeter, C. Dykes. (2010) The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Virology 402:2, 228-237
CrossRef77
Ravindra K Gupta, Arinder Kohli, Adele L McCormick, Greg J Towers, Deenan Pillay, Chris M Parry. (2010) Full-length HIV-1 Gag determines protease inhibitor susceptibility within in-vitro assays. AIDS 24:11, 1651-1655
CrossRef78
Mark S. Roberts, Kimberly A. Nucifora, R. Scott Braithwaite. (2010) Using Mechanistic Models to Simulate Comparative Effectiveness Trials of Therapy and to Estimate Long-term Outcomes in HIV Care. Medical Care 48, S90-S95
CrossRef79
B. Taiwo, C. Hicks, J. Eron. (2010) Unmet therapeutic needs in the new era of combination antiretroviral therapy for HIV-1. Journal of Antimicrobial Chemotherapy 65:6, 1100-1107
CrossRef80
Graeme Moyle, Ralph DeMasi, Andrew Hill. (2010) Does earlier HIV RNA suppression provide long-term benefits?. AIDS 24:10, 1591-1593
CrossRef81
S. Moreno, J. Lopez Aldeguer, J. R. Arribas, P. Domingo, J. A. Iribarren, E. Ribera, A. Rivero, F. Pulido, . (2010) The future of antiretroviral therapy: challenges and needs. Journal of Antimicrobial Chemotherapy 65:5, 827-835
CrossRef82
Arvid Edén, Lars-Magnus Andersson, Örjan Andersson, Leo Flamholc, Filip Josephson, Staffan Nilsson, Vidar Ormaasen, Veronica Svedhem, Christer Säll, Anders Sönnerborg, Petra Tunbäck, Magnus Gisslén. (2010) Differential Effects of Efavirenz, Lopinavir/r, and Atazanavir/r on the Initial Viral Decay Rate in Treatment Naïve HIV-1–Infected Patients. AIDS Research and Human Retroviruses 26:5, 533-540
CrossRef83
Timothy Schacker. (2010) New tools to track HIV. Nature Medicine 16:4, 373-374
CrossRef84
José M. Gatell Artigas. (2010) Infección por el virus de la inmunodeficiencia humana tipo 1: errores irreversibles que no deberíamos volver a cometer. Medicina Clínica 134:9, 399-401
CrossRef85
Renato Maserati, Annalisa De Silvestri, Alessia Uglietti, Grazia Colao, Antonio Di Biagio, Bianca Bruzzone, Massimo Di Pietro, Maria Carla Re, Carmine Tinelli, Maurizio Zazzi. (2010) Emerging mutations at virological failure of HAART combinations containing tenofovir and lamivudine or emtricitabine. AIDS 24:7, 1013-1018
CrossRef86
J. M. Gatell. (2010) When and why to start antiretroviral therapy?. Journal of Antimicrobial Chemotherapy 65:3, 383-385
CrossRef87
Roos E Barth, Maarten F Schim van der Loeff, Rob Schuurman, Andy IM Hoepelman, Annemarie MJ Wensing. (2010) Virological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: a systematic review. The Lancet Infectious Diseases 10:3, 155-166
CrossRef88
Jean-Michel Molina, Jaime Andrade-Villanueva, Juan Echevarria, Ploenchan Chetchotisakd, Jorge Corral, Neal David, Graeme Moyle, Marco Mancini, Lisa Percival, Rong Yang, Victoria Wirtz, Max Lataillade, Judith Absalon, Donnie McGrath. (2010) Once-Daily Atazanavir/Ritonavir Compared With Twice-Daily Lopinavir/Ritonavir, Each in Combination With Tenofovir and Emtricitabine, for Management of Antiretroviral-Naive HIV-1-Infected Patients: 96-Week Efficacy and Safety Results of the CASTLE Study. JAIDS Journal of Acquired Immune Deficiency Syndromes 53:3, 323-332
CrossRef89
P. Echeverría, E. Negredo, G. Carosi, J. Gálvez, J.L. Gómez, A. Ocampo, J. Portilla, A. Prieto, J.C. López, R. Rubio, A. Mariño, E. Pedrol, C. Viladés, A. del Arco, A. Moreno, I. Bravo, R. López-Blazquez, N. Pérez-Alvarez, B. Clotet. (2010) Similar antiviral efficacy and tolerability between efavirenz and lopinavir/ritonavir, administered with abacavir/lamivudine (Kivexa®), in antiretroviral-naïve patients: A 48-week, multicentre, randomized study (Lake Study). Antiviral Research 85:2, 403-408
CrossRef90
Krittaecho Siripassorn, Weerawat Manosuthi, Suthat Chottanapund, Aranya Pakdee, Siriwan Sabaitae, Wisit Prasithsirikul, Preecha Tunthanathip, Kiat Ruxrungtham. (2010) Effectiveness of Boosted Protease Inhibitor-Based Regimens in HIV Type 1-Infected Patients Who Experienced Virological Failure with NNRTI-Based Antiretroviral Therapy in a Resource-Limited Setting. AIDS Research and Human Retroviruses 26:2, 139-148
CrossRef91
Johan Vingerhoets, Lotke Tambuyzer, Hilde Azijn, Annemie Hoogstoel, Steven Nijs, Monika Peeters, Marie-Pierre de Béthune, Goedele De Smedt, Brian Woodfall, Gastón Picchio. (2010) Resistance profile of etravirine: combined analysis of baseline genotypic and phenotypic data from the randomized, controlled Phase III clinical studies. AIDS 24:4, 503-514
CrossRef92
Juan Sierra-Madero, Angelina Villasis-Keever, Patricia Méndez, Juan Luis Mosqueda-Gómez, Indiana Torres-Escobar, Fernanda Gutiérrez-Escolano, Irene Juárez-Kasusky, Martín Magana-Aquino, Carmen Ramos-Santos, Leticia Pérez-Saleme, Sigfrido Rangel-Frausto, Barbara Antuna-Puente, Luis Enrique Soto-Ramírez, Vivian Lima, Franciso Belaunzarán-Zamudio, Brenda Crabtree-Ramírez, Julio Montaner. (2010) Prospective, Randomized, Open Label Trial of Efavirenz vs Lopinavir/Ritonavir in HIV+ Treatment-Naive Subjects With CD4+<200 cell/mm3 in Mexico. JAIDS Journal of Acquired Immune Deficiency Syndromes1
CrossRef93
Nathan Ford, Alexandra Calmy. (2010) Improving first-line antiretroviral therapy in resource-limited settings. Current Opinion in HIV and AIDS 5:1, 38-47
CrossRef94
Trevor Hawkins. (2010) Understanding and managing the adverse effects of antiretroviral therapy. Antiviral Research 85:1, 201-209
CrossRef95
Roger Paredes, Bonaventura Clotet. (2010) Clinical management of HIV-1 resistance. Antiviral Research 85:1, 245-265
CrossRef96
Annemarie M.J. Wensing, Noortje M. van Maarseveen, Monique Nijhuis. (2010) Fifteen years of HIV Protease Inhibitors: raising the barrier to resistance. Antiviral Research 85:1, 59-74
CrossRef97
Anton L Pozniak, Javier Morales-Ramirez, Elly Katabira, Dewald Steyn, Sergio H Lupo, Mario Santoscoy, Beatriz Grinsztejn, Kiat Ruxrungtham, Laurence T Rimsky, Simon Vanveggel, Katia Boven. (2010) Efficacy and safety of TMC278 in antiretroviral-naive HIV-1 patients: week 96 results of a phase IIb randomized trial. AIDS 24:1, 55-65
CrossRef98
Tomas Cihlar, Adrian S. Ray. (2010) Nucleoside and nucleotide HIV reverse transcriptase inhibitors: 25 years after zidovudine. Antiviral Research 85:1, 39-58
CrossRef99
Juan Sierra-Madero, Giovanni Di Perri, Robin Wood, Michael Saag, Ian Frank, Charles Craig, Robert Burnside, Jennifer McCracken, Dennis Pontani, James Goodrich, Jayvant Heera, Howard Mayer. (2010) Efficacy and Safety of Maraviroc Versus Efavirenz, Both With Zidovudine/Lamivudine: 96-Week Results From the MERIT Study. HIV Clinical Trials 11:3, 125-132
CrossRef100
José A. Esté, Tomas Cihlar. (2010) Current status and challenges of antiretroviral research and therapy. Antiviral Research 85:1, 25-33
CrossRef101
Philip M. Grant, Sarah Palmer, Eran Bendavid, Annie Talbot, Debbie C. Slamowitz, Pat Cain, Stacy S. Kobayashi, Maya Balamane, Andrew R. Zolopa. (2009) Switch from enfuvirtide to raltegravir in virologically suppressed HIV-1 infected patients: Effects on level of residual viremia and quality of life. Journal of Clinical Virology 46:4, 305-308
CrossRef102
Anna Maria Geretti, Zoe V Fox, Clare L Booth, Colette J Smith, Andrew N Phillips, Margaret Johnson, Jin-Fen Li, Walid Heneine, Jeffrey A Johnson. (2009) Low-Frequency K103N Strengthens the Impact of Transmitted Drug Resistance on Virologic Responses to First-Line Efavirenz or Nevirapine-Based Highly Active Antiretroviral Therapy. JAIDS Journal of Acquired Immune Deficiency Syndromes 52:5, 569-573
CrossRef103
Piedad Arazo Garcés, Esther Valero Tena. (2009) Etravirina en primeras líneas de tratamiento. Enfermedades Infecciosas y Microbiología Clínica 27, 12-20
CrossRef104
Amy C Weintrob, Greg A Grandits, Brian K Agan, Anuradha Ganesan, Michael L Landrum, Nancy F Crum-Cianflone, Erica N Johnson, Claudia E Ordóñez, Glenn W Wortmann, Vincent C Marconi. (2009) Virologic Response Differences Between African Americans and European Americans Initiating Highly Active Antiretroviral Therapy With Equal Access to Care. JAIDS Journal of Acquired Immune Deficiency Syndromes 52:5, 574-580
CrossRef105
Daniel Podzamczer Palter, Elena Ferrer Corbera, Juan Manuel Tiraboschi. (2009) Etravirina en pacientes ampliamente pretratados. Enfermedades Infecciosas y Microbiología Clínica 27, 6-11
CrossRef106
Bluma G Brenner, Dimitrios Coutsinos. (2009) The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications. HIV Therapy 3:6, 583-594
CrossRef107
F. Maggiolo. (2009) Efavirenz: a decade of clinical experience in the treatment of HIV. Journal of Antimicrobial Chemotherapy 64:5, 910-928
CrossRef108
Isaac Bogoch, Sharon Walmsley. (2009) First-line regimen failure of antiretroviral therapy: a clinical and evidence-based approach. Current Opinion in HIV and AIDS 4:6, 493-498
CrossRef109
M.a Eulalia Valencia, Victoria Moreno. (2009) Réplica. Lopinavir/ritonavir en monoterapia: ¿para quién y cuándo?. Enfermedades Infecciosas y Microbiología Clínica 27:9, 553-554
CrossRef110
Yazdan Yazdanpanah. (2009) Multidrug resistance: a clinical approach. Current Opinion in HIV and AIDS 4:6, 499-506
CrossRef111
Enrique Pacios. (2009) Tratamiento de simplificación: lopinavir/ritonavir con o sin efavirenz. Enfermedades Infecciosas y Microbiología Clínica 27:9, 553
CrossRef112
Paul A. Pham. (2009) Antiretroviral Adherence and Pharmacokinetics: Review of Their Roles in Sustained Virologic Suppression. AIDS Patient Care and STDs 23:10, 803-807
CrossRef113
J. Dunning, M. Nelson. (2009) Novel strategies to treat antiretroviral-naive HIV-infected patients. Journal of Antimicrobial Chemotherapy 64:4, 674-679
CrossRef114
Loveleen Bansi, Anna Maria Geretti, David Dunn, Teresa Hill, Hannah Green, Esther Fearnhill, Brian Gazzard, Mark Nelson, Kholoud Porter, Andrew Phillips, Caroline Sabin. (2009) The Impact of Transmitted Drug-Resistance on Treatment Selection and Outcome of First-Line Highly Active Antiretroviral Therapy (HAART). JAIDS Journal of Acquired Immune Deficiency Syndromes1
CrossRef115
C William Wester, Hermann Bussmann, John Koethe, Claire Moffat, Sten Vermund, Max Essex, Richard G Marlink. (2009) Adult combination antiretroviral therapy in sub-Saharan Africa: lessons from Botswana and future challenges. HIV Therapy 3:5, 501-526
CrossRef116
Kees Brinkman. (2009) Stavudine in antiretroviral therapy: is this the end?. AIDS 23:13, 1727-1729
CrossRef117
M. Y. Chowers, B. S. Gottesman, L. Leibovici, U. Pielmeier, S. Andreassen, M. Paul. (2009) Reporting of adverse events in randomized controlled trials of highly active antiretroviral therapy: systematic review. Journal of Antimicrobial Chemotherapy 64:2, 239-250
CrossRef118
Munir Pirmohamed. (2009) Clinical management of HIV-associated lipodystrophy. Current Opinion in Lipidology 20:4, 309-314
CrossRef119
Jennifer A. Johnson, Paul E. Sax. (2009) Antiretroviral therapy for treatment-naïve patients: A review of recent literature and the updated guidelines. Current Infectious Disease Reports 11:4, 311-318
CrossRef120
Cathia Soulié, Lambert Assoumou, Jade Ghosn, Claudine Duvivier, Gilles Peytavin, Zaina Ait-Arkoub, Jean-Michel Molina, Dominique Costagliola, Christine Katlama, Vincent Calvez, Anne-Geneviève Marcelin. (2009) Nucleoside reverse transcriptase inhibitor-sparing regimen (nonnucleoside reverse transcriptase inhibitor + protease inhibitor) was more likely associated with resistance comparing to nonnucleoside reverse transcriptase inhibitor or protease inhibitor + nucleoside reverse transcriptase inhibitor in the randomized ANRS 121 trial. AIDS 23:12, 1605-1608
CrossRef121
R. Landman, C. Capitant, D. Descamps, C. Chazallon, G. Peytavin, C. Katlama, G. Pialoux, M. Bentata, F. Brun-Vezinet, J.-P. Aboulker, P. Yeni, . (2009) Efficacy and safety of ritonavir-boosted dual protease inhibitor therapy in antiretroviral-naive HIV-1-infected patients: the 2IP ANRS 127 study. Journal of Antimicrobial Chemotherapy 64:1, 118-125
CrossRef122
Ravindra K Gupta, Diana M Gibb, Deenan Pillay. (2009) Management of paediatric HIV-1 resistance. Current Opinion in Infectious Diseases 22:3, 256-263
CrossRef123
Richard H Haubrich, Sharon A Riddler, A Gregory DiRienzo, Lauren Komarow, William G Powderly, Karin Klingman, Kevin W Garren, David L Butcher, James F Rooney, David W Haas, John W Mellors, Diane V Havlir. (2009) Metabolic outcomes in a randomized trial of nucleoside, nonnucleoside and protease inhibitor-sparing regimens for initial HIV treatment. AIDS 23:9, 1109-1118
CrossRef124
Antoine Bénard, Florence Damond, Pauline Campa, Gilles Peytavin, Diane Descamps, Caroline Lascoux-Combes, Audrey Taieb, François Simon, Brigitte Autran, Françoise Brun-Vézinet, Geneviève Chêne, Sophie Matheron. (2009) Good response to lopinavir/ritonavir-containing antiretroviral regimens in antiretroviral-naive HIV-2-infected patients. AIDS 23:9, 1171-1173
CrossRef125
Edward M Gardner, William J Burman, John F Steiner, Peter L Anderson, David R Bangsberg. (2009) Antiretroviral medication adherence and the development of class-specific antiretroviral resistance. AIDS 23:9, 1035-1046
CrossRef126
F. Chaix, C. Goujard. (2009) Actualités sur les traitements de l’infection par le virus de l’immunodéficience humaine. La Revue de Médecine Interne 30:6, 543-554
CrossRef127
Edwin DeJesus, Benjamin Young, Javier O Morales-Ramirez, Louis Sloan, Douglas J Ward, John F Flaherty, Ramin Ebrahimi, Jen-Fue Maa, Karen Reilly, Janet Ecker, Damian McColl, Daniel Seekins, Awny Farajallah. (2009) Simplification of Antiretroviral Therapy to a Single-Tablet Regimen Consisting of Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate Versus Unmodified Antiretroviral Therapy in Virologically Suppressed HIV-1-Infected Patients. JAIDS Journal of Acquired Immune Deficiency Syndromes 51:2, 163-174
CrossRef128
Mark A Boyd. (2009) Improvements in antiretroviral therapy outcomes over calendar time. Current Opinion in HIV and AIDS 4:3, 194-199
CrossRef129
M. C. F. Prosperi, R. D'Autilia, F. Incardona, A. De Luca, M. Zazzi, G. Ulivi. (2009) Stochastic modelling of genotypic drug-resistance for human immunodeficiency virus towards long-term combination therapy optimization. Bioinformatics 25:8, 1040-1047
CrossRef130
Sharon Walmsley, Anchalee Avihingsanon, Jihad Slim, Douglas J Ward, Kiat Ruxrungtham, Jason Brunetta, U Fritz Bredeek, Dushyantha Jayaweera, Carol Jean Guittari, Peter Larson, Malte Schutz, François Raffi. (2009) Gemini: A Noninferiority Study of Saquinavir/Ritonavir Versus Lopinavir/Ritonavir as Initial HIV-1 Therapy in Adults. JAIDS Journal of Acquired Immune Deficiency Syndromes 50:4, 367-374
CrossRef131
Panel de expertos de Gesida, Plan Nacional sobre el Sida. (2009) Recomendaciones de Gesida/Plan Nacional sobre el Sida respecto al tratamiento antirretroviral en adultos infectados por el virus de la inmunodeficiencia humana (actualización febrero de 2009). Enfermedades Infecciosas y Microbiología Clínica 27:4, 222-235
CrossRef132
P. Tebas, J. Zhang, R. Hafner, K. Tashima, A. Shevitz, K. Yarasheski, B. Berzins, S. Owens, J. Forand, S. Evans, R. Murphy. (2009) Peripheral and visceral fat changes following a treatment switch to a non-thymidine analogue or a nucleoside-sparing regimen in HIV-infected subjects with peripheral lipoatrophy: results of ACTG A5110. Journal of Antimicrobial Chemotherapy 63:5, 998-1005
CrossRef133
L. Gazzola, C. Tincati, G. M. Bellistre, A. d'Arminio Monforte, G. Marchetti. (2009) The Absence of CD4+ T Cell Count Recovery Despite Receipt of Virologically Suppressive Highly Active Antiretroviral Therapy: Clinical Risk, Immunological Gaps, and Therapeutic Options. Clinical Infectious Diseases 48:3, 328-337
CrossRef134
Lidia Gazzola, Camilla Tincati, Giusi Maria Bellistrì, Antonella d’Arminio Monforte, Giulia Marchetti. (2009) The Absence of CD4 + T Cell Count Recovery Despite Receipt of Virologically Suppressive Highly Active Antiretroviral Therapy: Clinical Risk, Immunological Gaps, and Therapeutic Options. Clinical Infectious Diseases 48:3, 328-337
CrossRef135
C. Allavena, O. Mounoury, A. Rodallec, V. Reliquet, E. Billaud, F. Raffi. (2009) Efficacy and Safety of an NRTI-Sparing Dual Regimen of Raltegravir and Ritonavir-Boosted Protease Inhibitor in a Triple Antiretroviral Class-Experienced Population. HIV Clinical Trials 10:5, 337-340
CrossRef136
Albert ML Anderson, Jeffrey L Lennox. (2009) Abacavir/lamivudine fixed dose combination in the treatment of patients with HIV infection. HIV Therapy 3:1, 19-29
CrossRef137
Dushyantha Jayaweera, Edwin DeJesus, Kim L. Nguyen, Kristy Grimm, David Butcher, Daniel W. Seekins. (2009) Virologic Suppression, Treatment Adherence, and Improved Quality of Life on a Once-Daily Efavirenz-Based Regimen in Treatment-Naïve HIV-1–Infected Patients Over 96 Weeks. HIV Clinical Trials 10:6, 375-384
CrossRef138
Filip Josephson, Jan Albert, Leo Flamholc, Magnus Gisslén, Olof Karlström, Lars Moberg, Lars Navér, Veronica Svedhem, Bo Svennerholm, Anders Sönnerborg. (2009) Treatment of HIV infection: Swedish recommendations 2009. Scandinavian Journal of Infectious Diseases 41:11-12, 788-807
CrossRef139
Anton Pozniak, Ravindra K. Gupta, Deenan Pillay, Jose Arribas, Andrew Hill. (2009) Causes and Consequences of Incomplete HIV RNA Suppression in Clinical Trials. HIV Clinical Trials 10:5, 289-298
CrossRef140
Esteban Ribera Pascuet, Adrià Curran. (2008) Utilidad clínica de atazanavir. Enfermedades Infecciosas y Microbiología Clínica 26, 55-67
CrossRef141
D. Rey, B. Hoen, P. Chavanet, M. P. Schmitt, G. Hoizey, P. Meyer, G. Peytavin, B. Spire, C. Allavena, M. Diemer, T. May, J. L. Schmit, M. Duong, V. Calvez, J. M. Lang. (2008) High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients. Journal of Antimicrobial Chemotherapy 63:2, 380-388
CrossRef142
Alexandra Calmy, Cecilia Pizzocolo, Louis Pizarro, Gilles Brücker, Robert Murphy, Christine Katlama. (2008) The marriage of science and optimized HIV care in resource-limited settings. AIDS 22:17, 2227-2230
CrossRef143
Cristina Mussini, Christian Manzardo, Margaret Johnson, Antonella dʼArminio Monforte, Caterina Uberti-Foppa, Andrea Antinori, M John Gill, Laura Sighinolfi, Vanni Borghi, Adriano Lazzarin, José M Miró, Caroline Sabin. (2008) Patients presenting with AIDS in the HAART era: a collaborative cohort analysis. AIDS 22:18, 2461-2469
CrossRef144
Christoph Boesecke, David A Cooper. (2008) Toxicity of HIV protease inhibitors: clinical considerations. Current Opinion in HIV and AIDS 3:6, 653-659
CrossRef145
Julian H Elliott, Sanjay Pujari. (2008) Protease inhibitor therapy in resource-limited settings. Current Opinion in HIV and AIDS 3:6, 612-619
CrossRef146
Marie-Laure Chaix, Sabrinel Sahali, Coralie Pallier, Aurélie Barrail-Tran, Jean-François Delfraissy, Jade Ghosn. (2008) Switching to darunavir/ritonavir achieves viral suppression in patients with persistent low replication on first-line lopinavir/ritonavir. AIDS 22:17, 2405-2407
CrossRef147
Nina Khanna, Milos Opravil, Hansjakob Furrer, Matthias Cavassini, Pietro Vernazza, Enos Bernasconi, Rainer Weber, Bernard Hirschel, Manuel Battegay, Gilbert R. Kaufmann, . (2008) CD4 + T Cell Count Recovery in HIV Type 1–Infected Patients Is Independent of Class of Antiretroviral Therapy. Clinical Infectious Diseases 47:8, 1093-1101
CrossRef148
Julian H Elliott, Lut Lynen, Alexandra Calmy, Andrea De Luca, Robert W Shafer, Maria Zolfo, Bonaventura Clotet, Sarah Huffam, Charles AB Boucher, David A Cooper, Jonathan M Schapiro. (2008) Rational use of antiretroviral therapy in low-income and middle-income countries: optimizing regimen sequencing and switching. AIDS 22:16, 2053-2067
CrossRef149
(2008) Initial Treatment of HIV-1 Infection. New England Journal of Medicine 359:9, 970-971
Full Text150
Carlo Torti, Ian Frank. (2008) A king in the CASTLE? Optimum initial HIV protease inhibitor. The Lancet 372:9639, 604-606
CrossRef151
Francesca J. Torriani, Lauren Komarow, Robert A. Parker, Bruno R. Cotter, Judith S. Currier, Michael P. Dubé, Carl J. Fichtenbaum, Mariana Gerschenson, Carol K.C. Mitchell, Robert L. Murphy, Kathleen Squires, James H. Stein. (2008) Endothelial Function in Human Immunodeficiency Virus-Infected Antiretroviral-Naive Subjects Before and After Starting Potent Antiretroviral Therapy. Journal of the American College of Cardiology 52:7, 569-576
CrossRef152
A. C. Bailey, M. Fisher. (2008) Current use of antiretroviral treatment. British Medical Bulletin 87:1, 175-192
CrossRef153
C. Duvivier, J. Ghosn, L. Assoumou, C. Soulie, G. Peytavin, V. Calvez, M. A. Genin, J.-M. Molina, O. Bouchaud, C. Katlama, D. Costagliola, . (2008) Initial therapy with nucleoside reverse transcriptase inhibitor-containing regimens is more effective than with regimens that spare them with no difference in short-term fat distribution: Hippocampe-ANRS 121 Trial. Journal of Antimicrobial Chemotherapy 62:4, 797-808
CrossRef154
Hirschel, Bernard, Calmy, Alexandra, . (2008) Initial Treatment for HIV Infection — An Embarrassment of Riches. New England Journal of Medicine 358:20, 2170-2172
Full Text
- Letters
