HIV Clinical Trials[JOURNAL]
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200 papers
Physician attitudes regarding pregnancy, fertility care, and assisted reproductive technologies for HIV-infected individuals and couples.
Yudin MH, Money DM, Cheung MC … +1 more , Loutfy MR
HIV Clin Trials · 2012 · PMID 23195674 · Publisher ↗
BACKGROUND: Family and pregnancy planning are important for HIV-infected individuals and couples. There is a paucity of data regarding physician attitudes with respect to reproduction in this population, but some evidenc...
BACKGROUND: Family and pregnancy planning are important for HIV-infected individuals and couples. There is a paucity of data regarding physician attitudes with respect to reproduction in this population, but some evidence suggests that attitudes can influence the information, advice, and services they will provide. OBJECTIVE: To determine physician attitudes toward pregnancy, fertility care, and access to assisted reproductive technologies for HIV-infected individuals, and to determine whether attitudes differed based on specific physician characteristics. METHODS: A survey was sent electronically to obstetrician/gynecologists and infectious disease specialists in Canada. Items were grouped into 5 key domains: physician demographics, physician attitudes toward pregnancy and adoption, physician attitudes toward fertility care, physician attitudes toward assisted reproductive technology, and challenges for an HIV-infected population. Attitudes were determined based on answers to individual questions and also for each domain. Univariate and logistic regression analyses were used to determine the influence of specific physician characteristics on attitudes. RESULTS: Completed surveys were received from 165 physicians. Most had positive attitudes regarding pregnancy or adoption (89%), fertility care (72%), and assisted reproductive technology (79%). In multivariate analyses, having cared for HIV-infected patients was significantly associated with having a positive attitude toward fertility care or assisted reproductive technology. CONCLUSIONS: In this national survey of Canadian physicians, most had positive attitudes toward pregnancy, adoption, fertility care, and use of assisted reproductive technology among HIV-infected persons. Physicians who had cared for HIV-infected individuals in the past were more likely to have positive attitudes than those who had not.
Treatment of calcium and vitamin D deficiency in HIV-positive men on tenofovir-containing antiretroviral therapy.
Bech A, Van Bentum P, Telting D … +3 more , Gisolf J, Richter C, De Boer H
HIV Clin Trials · 2012 · PMID 23195673 · Publisher ↗
BACKGROUND: Hypophosphatemia and bone disease are common in HIV-positive (HIV+) patients on tenofovir disoproxil fumarate-containing antiretroviral therapy (TDF-containing ART). The underlying etiology is not completely...
BACKGROUND: Hypophosphatemia and bone disease are common in HIV-positive (HIV+) patients on tenofovir disoproxil fumarate-containing antiretroviral therapy (TDF-containing ART). The underlying etiology is not completely understood. OBJECTIVE: To examine the effects of treatment of calcium and vitamin D deficiency on phosphate metabolism and bone disease in HIV+ patients on tenofovir. METHODS: This was an open-label, pilot study of calcium and phosphate metabolism, bone turnover, and bone density in 24 HIV+ patients on TDF, who were receiving a 1-year treatment for vitamin D and/or calcium deficiency according to a predefined protocol. Eight patients without calcium or vitamin D deficiency served as controls. RESULTS: One-year treatment improved vitamin D levels, decreased serum parathyroid hormone (PTH), and improved calcium balance and bone mineral density. It did not affect the serum levels of PTH-related peptide (PTH-rp) or fibroblast growth factor 23 (FGF-23) nor did it raise serum phosphate levels or decrease renal phosphate loss. CONCLUSION: Treatment of calcium or vitamin D deficiency in HIV+ patients on ART including TDF has favorable effects on bone density, but it does not improve serum phosphate levels. Renal phosphate wasting in these patients is not caused by excess PTH, PTH-rp, or FGF-23 nor by vitamin D or calcium deficiency.
Renal impairment is associated with coronary heart disease in HIV-positive men.
Campbell LJ, Desai M, Hegazi A … +5 more , Ibrahim F, Melikian N, Hay P, Fox JM, Post FA
HIV Clin Trials · 2012 · PMID 23195672 · Publisher ↗
BACKGROUND: Chronic kidney disease is a risk factor for coronary heart disease (CHD). The association between renal impairment and CHD in HIV-positive patients remains poorly described. OBJECTIVE: To describe the CHD inc...
BACKGROUND: Chronic kidney disease is a risk factor for coronary heart disease (CHD). The association between renal impairment and CHD in HIV-positive patients remains poorly described. OBJECTIVE: To describe the CHD incidence in a cohort of HIV-positive patients and to examine the relationship between reduced estimated glomerular filtration rate (eGFR) and incident CHD. METHODS: We studied 7,828 HIV-positive patients who were followed up at 3 South London clinics between January 2004 and December 2009. CHD events were identified from electronic records and through elevated troponin levels. Multivariate Poisson regression analysis was used to identify factors associated with CHD among HIV-positive men. RESULTS: The incidence of CHD among men was 1.2 (95% CI, 0.8-1.8) per 1,000 person-years of follow-up, with 28 patients (0.4%) having experienced 32 CHD events. In adjusted analyses, older age (incidence rate ratios [IRR], 2.81; 95% CI, 1.51-5.25) and hepatitis C virus (HCV) status (IRR, 3.94; 95% CI, 1.00-15.5) were significantly associated with CHD. Although eGFR as a continuous variable was not associated with CHD, an eGFR <75 mL/min remained associated with incident CHD (IRR, 4.30; 95% CI, 1.33-14.5) after adjustment for age. No association between CHD and abacavir exposure was observed (IRR, 0.94; 95% CI, 0.30-2.99). CONCLUSIONS: The incidence of CHD in this ethnically diverse cohort was low. Our data suggest that impaired renal function identifies patients at increased risk of CHD events in whom management of traditional CHD risk factors should be prioritized.
Abacavir/lamivudine fixed-dose combination with ritonavir-boosted darunavir: a safe and efficacious regimen for HIV therapy.
Trottier B, Machouf N, Thomas R … +8 more , Gallant S, Longpré D, Vézina S, Boissonnault M, Lavoie S, Legault D, Dion H, Nguyen VK
HIV Clin Trials · 2012 · PMID 23195671 · Publisher ↗
BACKGROUND: Current treatment guidelines recommend the use of tenofovir (TDF) and emtricitabine (FTC) along with a third agent to treat HIV-positive adults. However, other treatment options, including the use of abacavir...
BACKGROUND: Current treatment guidelines recommend the use of tenofovir (TDF) and emtricitabine (FTC) along with a third agent to treat HIV-positive adults. However, other treatment options, including the use of abacavir (ABC) and lamivudine (3TC) when used with ritonavir-boosted darunavir (DRV/r), have rarely been studied. OBJECTIVE: We evaluated the safety and efficacy of the coformulation of ABC/3TC administered with DRV/r in treatment-naïve and treatment-experienced patients. METHODS: HIV-infected adults who received an open-label combination of ABC/3TC/ DRV/r were followed in a community clinic in Montréal. Patients had no resistance to any of the compounds in their regimen. Viral load (VL), CD4 cell count, AST, ALT, and creatinine levels were examined throughout the 48 weeks of follow-up. RESULTS: Sixty-seven patients with a mean age of 45 years were enrolled. Two did not return for follow-up and were excluded. Thirty-five (52%) were treatment- experienced and the remaining were treatment-naïve. HLA-B*5701 test results were available for 56 patients and none were positive. At baseline, mean VL was 4.8 log for treatment-naïve and 2.3 log for experienced patients. Twelve patients discontinued the study regimen prior to reaching the endpoint. At week 48, 79% had a VL <50. Median CD4 cell gain was higher among treatment-naïve patients (273 cells) than among treatment-experienced patients (102 cells) (P = .002). No patient experienced any grade 2 or higher liver enzyme elevation throughout the study. CONCLUSIONS: The new combination of ABC/3TC/DRV/r demonstrates a high rate of antiviral activity with no major toxicity. The drug combination appears to be generally safe and well tolerated.
Comparison of functional status instruments in HIV-infected adults on effective antiretroviral therapy.
Erlandson KM, Allshouse AA, Jankowski CM … +4 more , Duong S, Mawhinney S, Kohrt WM, Campbell TB
HIV Clin Trials · 2012 · PMID 23195670 · Full text
BACKGROUND: The best method for assessment of functional status in human immunodeficiency virus type 1 (HIV-1) infected persons is unknown. OBJECTIVE: We hypothesized that 3 instruments to assess frailty or disability in...
BACKGROUND: The best method for assessment of functional status in human immunodeficiency virus type 1 (HIV-1) infected persons is unknown. OBJECTIVE: We hypothesized that 3 instruments to assess frailty or disability in elderly populations would perform similarly in HIV-1-infected persons. METHODS: HIV-infected subjects 45 to 65 years old with plasma HIV-1 RNA <48 copies/mL were classified prospectively as low, moderate, or high function by Fried's frailty phenotype (FFP), the Short Physical Performance Battery (SPPB), and 400-m walk test. Functional instrument agreement was evaluated by weighted kappa statistic, and relationships with demographic or clinical factors were evaluated by odds ratios (OR). RESULTS: There were 359 participants (85% male, mean age 52 years, mean CD4+ lymphocyte count 551 cells/µL) who were evaluated. Three percent to 8% were low, 31% to 51% were moderate, and 42% to 62% were high function. FFP, SPPB, and 400-m walk test had moderate agreement for functional classification (61%-64%; κ = 0.34-0.41). Across instruments, lower reported physical activity (OR ≯ 5.5; P ≤ .005), no current employment (OR ≯ 4.2; P < .02), arthritis (OR ≯ 6.5; P < .02), neurologic disease (OR ≯ 2.6; P < .05), debilitating pain (OR ≯ 5.4; P < .008), psychiatric disease (OR ≯3.1; P < .03), more comorbidities (OR ≯ 3.6; P ≤ .005), and more non-antiretroviral therapy medications (OR ≯ 3.5; P ≤ .01) were associated with lower function. Current CD4 <200 cells/µL was more likely among low-function (11%) than high-function (2%) persons on FFP (P = .04); other HIV-related characteristics were not significantly different (P > .05) between functional categories on any instrument. CONCLUSIONS: Moderate functional impairment is common among middle-aged HIV-infected persons, with similar frequencies of impairment detected by 3 instruments. Reduction in comorbid disease, increased physical activity, and improved pain symptom management could reduce functional impairment among persons aging with HIV-infection.
Meta-analysis of the safety, tolerability, and efficacy of lopinavir/ritonavir-containing antiretroviral therapy in HIV-1-infected women.
Hermes A, Squires K, Fredrick L … +4 more , Martinez M, Pasley M, Trinh R, Norton M
HIV Clin Trials · 2012 · PMID 23195669 · Publisher ↗
PURPOSE: Women comprise ≯50% of HIV-infected patients, yet safety, tolerability, and efficacy data in women taking antiretrovirals (ARVs) are limited. Lopinavir/ ritonavir (LPV/r)-anchored regimens are globally the most...
PURPOSE: Women comprise ≯50% of HIV-infected patients, yet safety, tolerability, and efficacy data in women taking antiretrovirals (ARVs) are limited. Lopinavir/ ritonavir (LPV/r)-anchored regimens are globally the most widely prescribed HIV-1 protease inhibitor regimens. The objective was to investigate the safety and efficacy of LPV/r-based therapy in women. METHODS: A database query yielded all available data in HIV-1-infected subjects receiving LPV/r-based triple-ARV regimens from randomized clinical trials lasting ≥48 weeks from Abbott or Abbott-supported AIDS Clinical Trials Group studies. Efficacy (HIV-1 RNA levels, CD4+ T-cell counts) and safety and tolerability (treatment discontinuation, treatment-related adverse events [AE], and clinical laboratory abnormalities) at 48 weeks were assessed for total women, women by age (≥50, <50 years) and body mass index (BMI; <25, ≥25 to <30, ≥30 kg/m2), and sex. RESULTS: Nine hundred ninety-two women initiated LPV/r-based therapy (of whom 79.2% were ARV-naïve), with 83.6% completing 48 weeks of treatment. There were 75.5% of women who achieved a threshold of HIV RNA <400 copies/mL by intent-to-treat, non-completer equals failure (ITT, NC = F) analysis, with a mean ± SE CD4+ T-cell count increase of 191.6 ± 4.92 cells/mm3 from baseline. Women aged ≥50 versus <50 years had higher incidence of moderate-to-severe treatment-related AEs and certain laboratory abnormalities, better virologic response (HIV RNA <400 copies/mL by ITT, NC = F), similar immunologic responses, and similar overall incidence of treatment discontinuations. Higher incidences of certain moderate-to-severe treatment-related AEs and laboratory abnormalities occurred in women with BMI ≥30 kg/m2; however, no effect of BMI on efficacy or discontinuation was observed. CONCLUSIONS: LPV/r-based regimens were efficacious and well-tolerated in women without marked differences based on age and BMI categories evaluated.
Design and implementation of a randomized crossover study of valproic acid and antiretroviral therapy to reduce the HIV reservoir.
Routy JP, Angel JB, Spaans JN … +9 more , Trottier B, Rouleau D, Baril JG, Harris M, Trottier S, Singer J, Chomont N, Sékaly RP, Tremblay CL
HIV Clin Trials · 2012 · PMID 23195668 · Full text
BACKGROUND: HIV reservoirs represent the major obstacles for eradication and are defined as a cell type that allows persistence of replication-competent HIV in patients on optimal long-term antiretroviral therapy (HAART)...
BACKGROUND: HIV reservoirs represent the major obstacles for eradication and are defined as a cell type that allows persistence of replication-competent HIV in patients on optimal long-term antiretroviral therapy (HAART). Several pilot clinical trials have been implemented to assess the value of experimental therapy to reduce reservoir size or eradicate HIV. In order to eradicate HIV, valproic acid was used as a new strategy to increase viral gene expression in the nucleus of infected cells with the expectation of generating a direct cell death or destruction by nearby cytotoxic cells. Previous pilot studies using VPA have showed conflicting results on the ability of VPA to reduce the size of HIV reservoirs. PURPOSE: As the role of VPA on HIV reservoirs remains unclear, we conducted a multicenter clinical trial with a specific study design to obtain optimal information on reservoir changes while exposing the smallest number of individuals to the experimental medication. METHOD: To this aim, a randomized, crossover design with 2 different treatment durations was implemented. By doubling the therapeutic period in one study arm, we were in a position to assess the impact of an extended duration of VPA on the size of the HIV reservoir and to evaluate the duration of treatment effects upon VPA withdrawal in the other arm. However, limitations for this type of study design included the logistical complexity of 2 uneven study arms and longer study duration. CONCLUSION: Despite the absence of demonstrable impact of VPA on reservoir size, such crossover study design should be considered in the early stage testing of novel HIV therapeutics targeted to reduce reservoir size or eradicate HIV.
Comments to Garvey et al.: "Low rates of neurocognitive impairment are observed in neuro-asymptomatic HIV-infected subjects on effective antiretroviral therapy".
Perez-Valero I, Cysique L, Letendre S … +1 more , Heaton R
HIV Clin Trials · 2012 · PMID 23134631 · Full text
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Missing scheduled visits in the outpatient clinic as a marker of short-term admissions and death.
Colubi MM, Pérez-Elías MJ, Elías L … +8 more , Pumares M, Muriel A, Zamora AM, Casado JL, Dronda F, López D, Moreno S, SEAD Study Group
HIV Clin Trials · 2012 · PMID 23134630 · Publisher ↗
INTRODUCTION: It is not uncommon for patients with HIV infection to miss scheduled visits in outpatient clinics without justifying the failure to appear or reschedule the appointment. Few studies have assessed the impact...
INTRODUCTION: It is not uncommon for patients with HIV infection to miss scheduled visits in outpatient clinics without justifying the failure to appear or reschedule the appointment. Few studies have assessed the impact of inconsistent follow-ups on resource use and disease outcomes in this patient population. OBJECTIVE: To assess the effect of missing scheduled visits to the outpatient clinic on the health outcomes of HIV-infected patients. METHODS: Between January and June 2006, we conducted a prospective observational study monitoring assistance at an outpatient HIV/AIDS clinic of a tertiary hospital within a public health care system in a developed country. The short-term subsequent events (deaths and admissions) of the population were observed from January to December 2006. RESULTS: Of the 1,733 HIV patients who were scheduled in the outpatient clinic, 103 met the criteria of missing scheduled visit (5.9%). Hospital admissions and mortality rates were significantly higher in the missing scheduled visit group compared to non-missing scheduled visits (27.2% vs 8.9%; P < .001 and 5.8% vs 0.7%; P < .001, respectively). Patients with missing scheduled visits had a higher risk of hospital admissions (odds ratio [OR] 2.4; 95% CI, 1.4-4) and mortality (OR 6.7; 95% CI, 2.2-18.5) adjusted by age, CD4 cell count, HIV stage, and category of transmission. CONCLUSIONS: Missing scheduled visits was an independent predicting factor for hospital admission and mortality. It is warranted to monitor and implement resources to reduce missed appointments.
Switch from etravirine twice daily to once daily in non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-infected patients with suppressed viremia: the Monetra study.
Schneider L, Ktorza N, Fourati S … +10 more , Assoumou L, Courbon E, Caby F, Blanc C, Tindel M, Agher R, Marcelin AG, Calvez V, Peytavin G, Katlama C
HIV Clin Trials · 2012 · PMID 23134629 · Publisher ↗
BACKGROUND: Etravirine (ETR) is recommended as twice-daily dosing in pretreated patients. There are no data regarding the use of ETR once daily in HIV-experienced patients with prior resistance to first-generation non-nu...
BACKGROUND: Etravirine (ETR) is recommended as twice-daily dosing in pretreated patients. There are no data regarding the use of ETR once daily in HIV-experienced patients with prior resistance to first-generation non-nucleoside reverse transcripase inhibitors (NNRTIs). OBJECTIVES: To evaluate the capacity of once-daily ETR to maintain suppressed viremia over 48 weeks after switching from ETR twice daily in NNRTI-experienced patients. METHODS: In this pilot open-label study, patients with plasma viral load (pVL) <50 copies/mL on a stable ETR 200 mg bid regimen were enrolled to switch to ETR 400 mg qd and followed up over 48 weeks. The primary endpoint was the proportion of patients with pVL <50 copies/mL at week 24. Secondary endpoints included the rate of pVL< 50 copies/mL at week 48, ETR pharmacokinetic parameters, and tolerability and resistance profile. RESULTS: Twenty-four patients were included. They had extensive antiretroviral treatment for a median of 14 years (range, 1-19). All except for 2 had prior resistance to NNRTIs. Seven patients discontinued ETR once daily prior to week 48 for virological failure (3), protocol deviation (3), and side effects (1). At week 24, 95% of patients maintained pVL< 50 copies/mL (95% CI, 78.4-99.7) and 85% at week 48 (95%CI, 65.6-95.8). Two of the 3 patients with virological failure had ETR resistance mutations prior to initiation. The median ETR C(trough) level remained stable after switching from twice daily 515 ng/mL (340-758) to once daily 422 ng/mL (264-655). CONCLUSION: These results suggest that ETR is effective as a once-daily regimen in patients with prior NNRTI experience when HIV is sensitive to ETR. The stability of C(trough) concentrations on a once-daily regimen confirms the once-daily profile of the drug in experienced patients.
Vitamin D deficiency is common among HIV-infected breastfeeding mothers in Pune, India, but is not associated with mother-to-child HIV transmission.
Mave V, Shere D, Gupte N … +12 more , Suryavanshi N, Kulkarni V, Patil S, Khandekar M, Kinikar A, Bharadwaj R, Bhosale R, Sambarey P, Chandanwale A, Bollinger R, Gupta A, SWEN India and Byramjee-Jeejeebhoy Medical College Clinical Trials Unit Study Team
HIV Clin Trials · 2012 · PMID 23134628 · Publisher ↗
A recent report from Tanzania demonstrated an increased risk of being HIV infected or of dying at birth among children born to breastfeeding mothers with low baseline vitamin D levels. We conducted a nested case-control...
A recent report from Tanzania demonstrated an increased risk of being HIV infected or of dying at birth among children born to breastfeeding mothers with low baseline vitamin D levels. We conducted a nested case-control study among HIV-infected pregnant women in western India to confirm the association between maternal vitamin D levels and mother-to-child transmission (MTCT) of HIV. Vitamin D insufficiency and deficiency were common among HIV-infected pregnant women, but were not associated with mother to child HIV transmission at 1 year postpartum (adjusted odds ratio [AOR], 0.66; 95% CI, 0.30-1.45; P = .30).
Feasibility and reliability of interactive voice response assessment of HIV medication adherence: research and clinical implications.
Hettema JE, Hosseinbor S, Ingersoll KS
HIV Clin Trials · 2012 · PMID 23134627 · Full text
BACKGROUND: There are well-documented negative consequences of nonadherence to HIV medications. Telephone-based interactive voice response (IVR) technologies may hold promise for assessing nonadherence in both research a...
BACKGROUND: There are well-documented negative consequences of nonadherence to HIV medications. Telephone-based interactive voice response (IVR) technologies may hold promise for assessing nonadherence in both research and clinical contexts; however, little psychometric research has been conducted on this topic. OBJECTIVE: In the present pilot study, we test the feasibility and reliability of a simplified patient-initiated, daily IVR system with a convenience sample of HIV patients attending a university-affiliated infectious disease clinic. METHODS: Participants were asked to call in to an IVR system to report adherence daily during 2 weeks of a larger prospective study. Response rates and patterns were analyzed for feasibility and compared to retrospective, self-report timeline follow-back (TLFB) adherence reporting. RESULTS: The IVR protocol showed moderate feasibility, with participants reporting adherence behavior on 63.4% of days. However, agreement with TLFB data was low, particularly for days in which participants reported incomplete adherence. CONCLUSIONS: The IVR protocol tested in the current trial shows some promise. Completion rates were higher than in previous trials. Future research is needed to further enhance the feasibility of IVR for HIV medication adherence and to compare responses to more objective measures on HIV adherence.
Effect of darunavir on lipid profile in HIV-infected patients.
Overton ET, Arathoon E, Baraldi E … +1 more , Tomaka F
HIV Clin Trials · 2012 · PMID 23134626 · Publisher ↗
Highly active antiretroviral therapy regimens, consisting of a ritonavir-boosted protease inhibitor (PI) and 2 nucleoside reverse transcriptase inhibitors, are established first-line regimens for HIV-infected patients. H...
Highly active antiretroviral therapy regimens, consisting of a ritonavir-boosted protease inhibitor (PI) and 2 nucleoside reverse transcriptase inhibitors, are established first-line regimens for HIV-infected patients. However, a common adverse effect in patients receiving PIs is dyslipidemia, characterized by increases in plasma levels of triglycerides, low-density lipoprotein cholesterol, and total cholesterol (TC). These lipid changes, as well as other well-described risk factors, may predispose patients to the development of cardiovascular disease, an important comorbidity, especially as the lifespan of HIV-infected patients has increased dramatically in recent years. Among PIs, ritonavir-boosted atazanavir (ATV/r) and, more recently, ritonavir-boosted darunavir (DRV/r) have demonstrated potent antiviral efficacy with more favorable lipid profiles than other PIs. This review provides an overview of the lipid effects of DRV/r. Studies with DRV/r in healthy volunteers and in both treatment-naïve and -experienced patients have demonstrated that changes in tri-glycerides and TC are comparable to those seen with ATV/r.
Increase in standard cholesterol and large HDL particle subclasses in antiretroviral-naïve patients prescribed efavirenz compared to atazanavir/ritonavir.
Gotti D, Cesana BM, Albini L … +13 more , Calabresi A, Izzo I, Focà E, Motta D, Bellagamba R, Fezza R, Narciso P, Sighinolfi L, Maggi P, Brianese N, Quiros-Roldan E, Guaraldi G, Torti C
HIV Clin Trials · 2012 · PMID 23134625 · Publisher ↗
BACKGROUND: Cardiovascular risk in HIV-infected patients is related, at least in part, to serum lipid alterations before and after HAART. Lipoprotein-particle subclasses may also have an effect, but comparative data afte...
BACKGROUND: Cardiovascular risk in HIV-infected patients is related, at least in part, to serum lipid alterations before and after HAART. Lipoprotein-particle subclasses may also have an effect, but comparative data after standard HAART regimens are limited. METHODS: This was a substudy of a trial in 91 antiretroviral-naïve patients randomized to tenofovir + emtricitabine + atazanavir/ritonavir (ATV/r) or efavirenz (EFV). Over-time trends from baseline to week 48 in total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), HDL particles (HDLp), and TC:HDL-C and TG:HDL-C ratios were analyzed by analysis of covariance (ANCOVA). Furthermore, confidence intervals for differences between the 2 groups at week 48 were calculated. Indications for lipid-lowering interventions and low HDL-C were also studied. RESULTS: ANCOVA showed that, with respect to patients receiving ATV/r, those prescribed efavirenz (EFV) had greater increases reported as mean differences in lipid values at week 48: 14 mg/dL (95% CI, 0.2 to 27) for TC, 14 mg/dL (95% CI, 4 to 25) for LDL-C, 5 mg/dL (95% CI, 2 to 9) for HDL-C, and 2.2 mg/dL (95% CI, 0.4 to 4) for large HDLp. Proportions of subjects with indications for lipid-lowering interventions and with HDL-C <40 mg/dL did not differ significantly. CONCLUSIONS: Patients prescribed EFV had greater increases in TC, LDL-C, and HDL-C. Although no significant differences were detected between the 2 groups for the TC:HDL ratio and for indications to start lipid-lowering interventions, large HDLp increased more in the EFV group compared to the ATV/r group, suggesting a protective effect associated with EFV use.
ARIES 144 week results: durable virologic suppression in HIV-infected patients simplified to unboosted atazanavir/abacavir/lamivudine.
Squires KE, Young B, DeJesus E … +7 more , Bellos N, Murphy D, Ward D, Zhao HH, Ross LL, Shaefer MS, ARIES Study Team
HIV Clin Trials · 2012 · PMID 23134624 · Publisher ↗
BACKGROUND: The open-label study ARIES (ClinicalTrials.gov NCT00440947) utilized a ritonavir (/r)-boosted protease inhibitor treatment simplification strategy. Antiretroviral-naïve subjects received abacavir/lamivudine (...
BACKGROUND: The open-label study ARIES (ClinicalTrials.gov NCT00440947) utilized a ritonavir (/r)-boosted protease inhibitor treatment simplification strategy. Antiretroviral-naïve subjects received abacavir/lamivudine (ABC/3TC) + atazanavir/ ritonavir (ATV/r) from baseline through randomization at week 36, then maintained or discontinued ritonavir for an additional 108 weeks. Non-inferiority of the unboosted regimen was demonstrated at week 84. In this optional extension phase, virologic suppression and adverse events were assessed through week 144. METHODS: Patients were randomized at week 36 if they had confirmed HIV RNA <50 copies/mL by week 30 and no previous virologic failure (VF; defined as failure to achieve HIV RNA <400 copies/mL or confirmed rebound after achieving HIV RNA ≥400 copies/mL). Three hundred sixty-nine subjects who completed 84 weeks in ARIES participated in the extension phase and maintained their randomized regimen for an additional 60 weeks post randomization. RESULTS: At week 144, 146/189 (77%) versus 132/180 (73%) subjects in the unboosted ATV and ATV/r groups, respectively, maintained HIV RNA <50 copies/mL. Post randomization (weeks 36-144), treatment-related grade 2-4 adverse events were more common in the ATV/r-treated (23%) compared to the ATV-treated (13%) group; the most frequently reported was increased serum bilirubin (6% of ATV-treated subjects vs 14 % of ATV/r-treated subjects). During the extension phase, 3% (11/369) of subjects met protocol-defined VF (5 ATV-treated and 6 ATV/ r-treated subjects); one ATV/r-treated subject had treatment-emergent major viral resistance-associated mutations. The median change in fasting triglycerides from baseline to week 144 was significantly different (P=.001) in the ATV-treated (-8.5 mg/dL) compared to the ATV/r-treated (28.5 mg/dL) groups. CONCLUSIONS: These long-term study results demonstrate that ATV in combination with ABC/3TC is a potent, well-tolerated regimen in patients who have achieved initial suppression on a ritonavir-boosted regimen.
Efficacy of raltegravir versus efavirenz when combined with tenofovir/emtricitabine in treatment-naïve HIV-1-infected patients: week-192 overall and subgroup analyses from STARTMRK.
DeJesus E, Rockstroh JK, Lennox JL … +13 more , Saag MS, Lazzarin A, Zhao J, Wan H, Rodgers AJ, Walker ML, Miller M, DiNubile MJ, Nguyen BY, Teppler H, Leavitt R, Sklar P, STARTMRK Investigators
HIV Clin Trials · 2012 · PMID 22849964 · Publisher ↗
We compared 4 years of antiretroviral therapy with tenofovir/emtricitabine and either raltegravir or efavirenz from the ongoing STARTMRK study of treatment-naïve HIV-infected patients. Through 192 weeks, raltegravir prod...
We compared 4 years of antiretroviral therapy with tenofovir/emtricitabine and either raltegravir or efavirenz from the ongoing STARTMRK study of treatment-naïve HIV-infected patients. Through 192 weeks, raltegravir produced durable and consistent viral suppression and immune restoration compared with efavirenz irrespective of baseline demographic and prognostic factors, including in patients with high viral loads.
Alterations in cerebrospinal fluid chemokines are associated with maraviroc exposure and in vivo metabolites measurable by magnetic resonance spectroscopy.
Vera JH, Garvey LJ, Allsop JM … +5 more , Kaye S, McClure MO, Back D, Taylor-Robinson SD, Winston A
HIV Clin Trials · 2012 · PMID 22849963 · Publisher ↗
BACKGROUND: Cerebrospinal (CSF) fluid biomarkers may be a useful tool for assessing the cerebral effects of antiretroviral therapy. OBJECTIVE: The aim of the study was to investigate the relationship between 4 CSF chemok...
BACKGROUND: Cerebrospinal (CSF) fluid biomarkers may be a useful tool for assessing the cerebral effects of antiretroviral therapy. OBJECTIVE: The aim of the study was to investigate the relationship between 4 CSF chemokines with maraviroc exposure and cerebral metabolite ratios (CMR) measured by magnetic resonance spectroscopy (1H-MRS) in HIV-infected individuals following maraviroc intensification. METHODS: CSF concentration of maraviroc and 4 chemokines (MCP-1, IP-10, MCP-4, and MIP-1β), plasma concentration of maraviroc pre-CSF assessment, and right basal ganglia CMR were assessed in 12 male HIV-infected, neuro-asymptomatic adults after 14 days of antiretroviral therapy intensification with maraviroc 150 mg twice daily. The relationship between CSF analytes with both CMRs and plasma and CSF maraviroc concentrations were examined using Spearman correlation coefficient. RESULTS: Twelve subjects completed study procedures with baseline values as follows: mean (SD) age 42 (8) years, CD4+ cell count 503 (199) cells/µL, and plasma HIV RNA<50 copies/mL in most subjects. Mean (range, pg/mL) chemokine concentrations were IP-10, 1242 (190-8073); MCP-4, 6.52 (1-18); MCP-1, 702 (201-1618); and MIP-1β, 42 (5-153). IP-10, MCP-4, and MIP-1β were significantly associated with CMRs in the right basal ganglia with (1) lower concentrations of IP-10 correlating with higher N-acetyl aspartate to creatine ratios (NAA/Cr) and (2) higher concentrations of MCP-4 and MIP-1β correlating with higher myoinositol to creatine (mI/Cr) ratios. There were no significant associations with MCP-1. Finally lower concentrations of IP-10 were significantly associated with higher maraviroc plasma trough concentration (r=-0.629, P=.028) but not CSF concentration (r=-0.308, P=.331). CONCLUSION: We hypothesize that the relationship between IP-10, MCP-4, and MIP-1β with maraviroc exposure and CMRs may be associated with a direct cerebral effect of maraviroc.
Bone effects of rosiglitazone in HIV-infected patients with lipoatrophy.
Ross AC, Hileman CO, Brown TT … +4 more , Fedarko N, Storer N, Labbato D, McComsey GA
HIV Clin Trials · 2012 · PMID 22849962 · Full text
OBJECTIVES: Thiazoledinediones increase limb fat in HIV+ patients with lipoatrophy. However, their use in the general population has been associated with bone loss and fracture. We sought to determine the effects of rosi...
OBJECTIVES: Thiazoledinediones increase limb fat in HIV+ patients with lipoatrophy. However, their use in the general population has been associated with bone loss and fracture. We sought to determine the effects of rosiglitazone on bone metabolism in HIV-infected patients. METHODS: HIV+ patients with lipoatrophy were randomized to rosiglitazone versus placebo for 48 weeks in a double-blind, placebo-controlled trial. Limb fat, bone mineral density (BMD), bone formation markers (procollagen type 1 amino-terminal propeptide [P1NP], osteocalcin [OC]) and bone resorption markers (C-terminal telopeptide of type I collagen [CTX]) were measured, along with receptor activator for nuclear factor kappa β ligand (RANKL), osteoprotegerin (OPG), and inflammatory cytokines. RESULTS: Seventy-one subjects were randomized to rosiglitazone or placebo: 17% female and 51% white. Total BMD did not change significantly in either group. In the rosiglitazone group, P1NP showed statistically significant decreases at 24 and 48 weeks; however, changes compared to placebo were only significant at 24 weeks. OC decreased significantly in the rosiglitazone group at 24 weeks, but there were no between-group differences. CTX, RANKL, or OPG did not change for either group. Multivariable regression within the rosiglitazone arm showed P1NP changes were inversely associated with limb fat changes, protease inhibitors, and tenofovir use. CONCLUSION: Rosiglitazone use was associated with decreased bone formation, but it did not alter bone resorption or total BMD. The increase in limb fat that accompanies rosiglitazone use appears to be associated with decreased osteoblast activity. Further studies are needed to determine the effect of thiazoledinediones on bone health in HIV-infected persons.
Renal toxicity associated with antiretroviral therapy.
Calza L
HIV Clin Trials · 2012 · PMID 22849961 · Publisher ↗
Renal disease is becoming an increasingly prevalent comorbidity in patients with human immunodeficiency virus (HIV) infection. The increase in life expectancy following the introduction of highly active antiretroviral th...
Renal disease is becoming an increasingly prevalent comorbidity in patients with human immunodeficiency virus (HIV) infection. The increase in life expectancy following the introduction of highly active antiretroviral therapy (HAART) and the long-term development of metabolic complications (such as diabetes and dyslipidaemia), hypertension, and vascular diseases can contribute to the increasing frequency in the recognition of renal impairment in HIV-infected patients. Some antiretroviral agents, and particularly tenofovir, have been associated with nephrotoxic drug effects, including decline in glomerular filtration rate, proximal tubular damage, and acute kidney injury. The occurrence of clinically evident renal toxicity in patients treated with HAART seems to be very low, but glomerular or tubular subclinical dysfunction may occur more frequently. Therefore, careful clinical and laboratory monitoring for the early recognition of renal abnormalities is recommended for all subjects receiving antiretroviral treatment. In this article, the current knowledge about the nephrotoxic effects of antiretroviral agents has been reviewed, and an algorithm for screening and management of HAART-related kidney disease is proposed in the light of the most recent clinical studies and international guidelines.
A pilot, prospective, open-label simplification study to evaluate the safety, efficacy, and pharmacokinetics of once-daily lopinavir-ritonavir monotherapy in HIV-HCV coinfected patients: the MONOCO study.
Cooper C, la Porte C, Tossonian H … +3 more , Sampalis J, Ackad N, Conway B
HIV Clin Trials · 2012 · PMID 22849960 · Publisher ↗
BACKGROUND: A safe, effective, easy-to-dose antiretroviral therapy that minimizes hepatic complication risk is essential in optimizing HIV-HCV treatment. Nucleoside-sparing boosted protease inhibitor monotherapy may achi...
BACKGROUND: A safe, effective, easy-to-dose antiretroviral therapy that minimizes hepatic complication risk is essential in optimizing HIV-HCV treatment. Nucleoside-sparing boosted protease inhibitor monotherapy may achieve this goal. METHODS: A prospective, open-label pilot simplification study of once-daily lopinavir/ritonavir (LPV/r) monotherapy in HIV-HCV coinfected patients was conducted in patients on HAART with undetectable HIV RNA for ≥6 months. The primary outcome was maintenance of HIV RNA<50 copies/mL through week 48. HIV RNA, immune measures, metabolic markers, and pharmacokinetics were assessed. RESULTS: Twenty participants received once-daily LPV/r monotherapy. Mean baseline age was 46.9 years and CD4 467 cells/L. By per protocol analysis, 71.4% (95% CI, 45.4-88.3) remained on once-daily LPV/r monotherapy with virologic suppression at week 48. Virologic breakthrough (HIV RNA>50 copies/mL on 2 consecutive measures) occurred in 7 patients (mean standard error [SE] time to breakthrough, 38.3 [4.8] weeks). Resuppression occurred with improved adherence in 2 participants and improved adherence plus addition of nucleosides in 2 others. LPV C min was <1 mg/L in 8 patients and was associated with virologic breakthrough in 2 cases but with no development of resistance. No clinically significant changes in CD4, lipids, or glucose were noted. Three participants developed transient≥5-fold liver enzyme elevations. None of 9 severe adverse events were LPV/r- or liver-related. Six discontinued participation for withdrawal of consent (n=1), poor adherence (n=3), or drug intolerance (n=2). CONCLUSIONS: Once-daily LPV/r monotherapy in HIV-HCV coinfected individuals offers a safe and effective approach to the management of the HIV infection, with a predictable pharmacokinetic profile.
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