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Efficacy and tolerability of high-dose dronabinol maintenance in HIV-positive marijuana smokers: a controlled laboratory study.
Bedi, G, Foltin, RW, Gunderson, EW, Rabkin, J, Hart, CL, Comer, SD, Vosburg, SK, Haney, M
Psychopharmacology. 2010;(4):675-86
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Abstract
RATIONALE Dronabinol (Δ(9)tetrahydrocannabinol) is approved for HIV-related anorexia, yet, little is known about its effects in HIV-positive marijuana smokers. HIV-negative marijuana smokers require higher than recommended dronabinol doses to experience expected effects. OBJECTIVES Employing a within-subjects, double-blind, placebo-controlled design, we assessed the effects of repeated high-dose dronabinol in HIV-positive marijuana smokers taking antiretroviral medication. METHODS Participants (N = 7), who smoked marijuana 4.2 ± 2.3 days/week, resided in a residential laboratory for two 16-day stays, receiving dronabinol (10 mg QID) in one stay and placebo in the other. Efficacy was assessed with objectively verified food intake and body weight. Tolerability was measured with sleep, subjective, and cognitive assessments. For analyses, each inpatient stay was divided into two phases, days 1-8 and 9-16; we compared dronabinol's effects with placebo in each 8-day phase to investigate tolerance. RESULTS Despite sustained increases in self-reported food cravings, dronabinol only increased caloric intake in the initial 8 days of dosing. Similarly, sleep quality was improved only in the first 8 days of dosing. Dronabinol's mood-enhancing effects were sustained across the 16-day inpatient stay. Dronabinol was well tolerated, causing few negative subjective or cognitive effects. CONCLUSIONS In HIV-positive marijuana smokers, high dronabinol doses safely and effectively increased caloric intake. However, repeated high-dose dronabinol appeared to result in selective tolerance to these effects. These findings indicate that HIV-positive individuals who smoke marijuana may require higher dronabinol doses than are recommended by the FDA. Future research to establish optimal dosing regimens, and reduce the development of tolerance, is required.
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Once-daily abacavir/lamivudine/zidovudine plus tenofovir for the treatment of HIV-1 infection in antiretroviral-naïve subjects: a 48-week pilot study.
Elion, R, Cohen, C, DeJesus, E, Redfield, R, Gathe, J, Hsu, R, Yau, L, Ross, L, Ha, B, Lanier, RE, et al
HIV clinical trials. 2006;(6):324-33
Abstract
PURPOSE To assess the safety and efficacy of a 4-drug, 3-tablet, once-daily (qd) regimen consisting of abacavir/lamivudine/zidovudine (ABC/3TC/ZDV; 2 tablets) and tenofovir (TDF) in antiretroviral-naïve patients with plasma HIV-1 RNA 30,000 copies/mL at 48 weeks. METHOD All participants received ABC/3TC/ZDV (300/150/300 mg) and TDF (300 mg) qd in this pilot, open-label, multicenter study. Intent-to-treat (ITT) analyses were conducted to evaluate virologic and immunologic efficacy. RESULTS Of the 123 participants enrolled, 52 (42%) prematurely discontinued study for adverse events (14), were lost to follow-up (13), had virologic nonresponse (12), and withdrew for other reasons (13). At week 48, by ITT missing=failure analysis, 41% (51/123) and 51% (63/123) of participants had plasma HIV-1 RNA <50 copies/mL and <400 copies/mL, respectively; by ITT-observed analysis, 75% (51/68) and 93% (63/68) had plasma HIV-1 RNA <50 copies/mL and <400 copies/mL, respectively; 11% (14/123) met virologic nonresponse criteria. Median week 48 change in CD4+ cell count from baseline was +127 cells/mm3. Median week 48 changes from baseline for fasting lipids were as follows: cholesterol (-9 mg/dL), HDL (+1 mg/dL), LDL (-9 mg/dL), and triglycerides (-4 mg/dL). CONCLUSION A high rate of premature discontinuations contributed to the overall suboptimal virologic response to ABC/3TC/ZDV+TDF qd; however, the regimen was not associated with high rates of virologic failure previously observed with TDF+ABC/3TC.
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alpha-Tocopherol as an antiretroviral therapy supplement for HIV-1-infected patients for increased lymphocyte viability.
de Souza Júnior, O, Treitinger, A, Baggio, GL, Michelon, C, Verdi, JC, Cunha, J, Ferreira, SI, Spada, C
Clinical chemistry and laboratory medicine. 2005;(4):376-82
Abstract
The aim of our study was to evaluate the benefits of supplementation with 800 mg/day of alpha-tocopherol with regard to cellular viability in HIV-1 seropositive patients undergoing anti-retroviral therapy. A total of 29 patients participated in the study, of whom 14 were given the supplement and 15 a placebo. The analyses were carried out before treatment commenced and after 60, 120 and 180 days. The plasma levels of HIV-1 RNA showed a significant decrease as a consequence of treatment time in the groups studied (p = 0.0001), although the difference between the treatments over time was not verified (p = 0.7343). The percentage of viable lymphocytes showed a significant increase as a consequence of treatment time in both groups studied (p = 0.0002) and a significant difference between the treatments over time (p = 0.0472). The percentage of lymphocytes in apoptosis showed a significant reduction over time (p = 0.0003), as well as a significant difference between the treatments over time (p = 0.0321). The significant increase in cellular viability indicates that supplementation with alpha-tocopherol offers an additional positive effect on cellular preservation in HIV-1 individuals undergoing anti-retroviral therapy; however, it represents an additional risk of anti-retroviral therapeutic failure, possibly due to drug-drug interaction involving up-regulation of metabolic clearance.
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Switching to atazanavir improves metabolic disorders in antiretroviral-experienced patients with severe hyperlipidemia.
Möbius, U, Lubach-Ruitman, M, Castro-Frenzel, B, Stoll, M, Esser, S, Voigt, E, Christensen, S, Rump, JA, Fätkenheuer, G, Behrens, GM, et al
Journal of acquired immune deficiency syndromes (1999). 2005;(2):174-80
Abstract
OBJECTIVE To describe the efficacy and change in lipid profile in patients with severe hyperlipidemia after switch to an atazanavir-containing highly active antiretroviral therapy regimen. DESIGN AND METHODS Open-field, 24-week, prospective observational cohort study including 33 HIV-infected, antiretroviral-experienced patients with hyperlipidemia. Changes in lipid profiles were evaluated by analyses of triglycerides, total cholesterol, high- and low-density lipoprotein (HDL and LDL) cholesterol, and efficacy by HIV RNA and CD4 cell changes, both from baseline to week 24. RESULTS A rapid and significant decrease of 46% (5.81 +/- 4 mmol/L vs. 3.16 +/- 2.6 mmol/L, P = 0.002) in triglyceride levels was shown. Similarly, a sustained improvement of 18% was observed in total cholesterol levels during the first 24 weeks after switching to atazanavir (6.45 +/- 1.9 mmol/L vs. 5.3 +/- 1.3 mmol/L, P = 0.001). After 24 weeks of treatment there was a significant decrease of 22% in non-HDL cholesterol (5.76 +/- 1.9 mmol/L at baseline vs. 4.5 +/- 1.3 mmol/L at 24 weeks; P = 0.003). HDL and LDL cholesterol profiles did not change significantly as did the viral load or CD4 cell count. CONCLUSIONS Switching to atazanavir results in a significant improvement in HIV therapy-induced hyperlipidemia. A switch to atazanavir is proposed as a valuable option to improve atherogenic lipid profiles while maintaining virologic control.
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Acetyl-l-carnitine: a pathogenesis based treatment for HIV-associated antiretroviral toxic neuropathy.
Hart, AM, Wilson, AD, Montovani, C, Smith, C, Johnson, M, Terenghi, G, Youle, M
AIDS (London, England). 2004;(11):1549-60
Abstract
BACKGROUND Nucleoside analogue reverse transcriptase inhibitors (NRTI) disrupt neuronal mitochondrial DNA synthesis, impairing energy metabolism and resulting in a distal symmetrical polyneuropathy (DSP), an antiretroviral toxic neuropathy (ATN) that causes significant morbidity in HIV disease. Serum acetyl-l-carnitine (ALCAR) levels are decreased in neuropathy associated with NRTI therapy. ALCAR enhances neurotrophic support of sensory neurons and promotes energy metabolism, potentially causing nerve regeneration and symptom relief. OBJECTIVE To assess the efficacy of oral ALCAR (1500 mg twice daily) for up to 33 months in an open cohort of 21 HIV-positive patients with established ATN. METHODS Skin biopsies were excised from the leg before ALCAR treatment, at 6-12 month intervals thereafter and from HIV-negative non-neuropathic controls. Fibre types in epidermal, dermal and sweat gland innervation were quantified immunohistochemically. RESULTS After 6 month's treatment, mean immunostaining area for small sensory fibres increased (epidermis 100%, P = 0.006; dermis 133%, P < 0.05) by more than that for all fibre types (epidermis 16%, P = 0.04; dermis 49%, P < 0.05; sweat glands 60%, P < 0.001) or for sympathetic fibres (sweat glands 41%, P < 0.0003). Compared with controls, epidermal, dermal and sweat gland innervation reached 92%, 80% and 69%, respectively, after 6 month's treatment. Innervation improvements continued (epidermis and dermis) or stabilized (sweat glands) after 24 month's treatment. Neuropathic grade improved in 76% of patients and remained unchanged in 19%. HIV RNA load, CD4 and CD8 cell counts did not alter significantly throughout the study. CONCLUSIONS ALCAR treatment improves symptoms, causes peripheral nerve regeneration and is proposed as a pathogenesis-based treatment for DSP.
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Salvage lopinavir-ritonavir therapy in human immunodeficiency virus-infected children.
Resino, S, Bellón, JM, Ramos, JT, Navarro, ML, Martín-Fontelos, P, Cabrero, E, Muñoz-Fernández, MA
The Pediatric infectious disease journal. 2004;(10):923-30
Abstract
OBJECTIVE To study the control of viral replication in human immunodeficiency virus (HIV)-infected children on different salvage therapies. DESIGN AND SETTING A retrospective observational study in 120 HIV-infected children was conducted. The children were divided into 3 groups according to their salvage therapies: (1) children receiving first line highly active antiretroviral therapy (HAART); (2) protease inhibitor-experienced children receiving second line HAART; (3) protease inhibitor-experienced children receiving HAART including lopinavir-ritonavir (LPV/r). The outcome variables examined were time to achieve viral load (VL) < or =400 copies/mL, success in achieving VL < or =400 copies/mL and time to virologic failure (VL >400 copies/mL). METHODS VL (HIV-RNA copies/mL) was quantified with reverse transcription-polymerase chain reaction molecular assay. For each protocol, survival analyses were conducted to determine the probability of achieving VL < or =400 copies/mL and rebound of VL. RESULTS VL < or =400 copies/mL was achieved by 52.4% of children receiving first line HAART, 48.3% receiving second line HAART and 71.5% receiving HAART including LPV/r. Children receiving HAART including LPV/r reached VL < or =400 copies/mL in a shorter time than children receiving second line HAART (P = 0.017), but quite similar to children receiving first line HAART. In terms of adjusted relative risk, children receiving HAART including LPV/r were 3.36 [95% confidence interval (95% CI), 1.59, 7.07] more likely to achieve VL < or =400 copies/mL than children receiving a different second line HAART. VL rebound occurred in 68.2% children receiving first line HAART, 73.4% receiving second line HAART and 32.4% receiving HAART including LPV/r. Children receiving HAART that includes LPV/r has less incidence of VL rebound (P=0.013) and 3.29 (95% CI 1.04, 10.3) times less risk to achieve a VL rebound than children receiving a different second line HAART. CONCLUSIONS HAART that includes LPV/r is able to control HIV replication more efficiently than other classic salvage antiretroviral therapies.
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Lipid lowering therapy with fluvastatin and pravastatin in patients with HIV infection and antiretroviral therapy: comparison of efficacy and interaction with indinavir.
Benesic, A, Zilly, M, Kluge, F, Weissbrich, B, Winzer, R, Klinker, H, Langmann, P
Infection. 2004;(4):229-33
Abstract
BACKGROUND Lipoprotein disorders in HIV-positive patients receiving highly active antiretroviral therapy (HAART) are becoming a major concern in HIV treatment, since there is growing evidence for an association between HAART-induced hyperlipidemia and increased cardiovascular risk. Yet relatively few data are available on the possible interactions of HAART and treatment with statins. PATIENTS AND METHODS In this prospective study, 25 HIV-positive, treatment-experienced patients (five female, 20 male, all Caucasian) were treated with either fluvastatin or pravastatin. Total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL) levels, and serum triglycerides were determined at regular intervals, as well as therapeutic drug monitoring to assess possible drug interactions. RESULTS In 13 pravastatin-treated patients, a decrease in total cholesterol levels (from 7.12 mmol/l to 6.29 mmol/l) after 12 weeks of therapy was seen. In 12 patients treated with fluvastatin, a permanent reduction of total cholesterol (from 6.46 mmol/l to 5.31 mmol/l) after 12 weeks was observed. The reduction of LDL levels was 30.2% in the fluvastatin group and 14.4% in the pravastatin group. In eight patients receiving an indinavir-containing HAART, indinavir plasma levels were not significantly influenced. No effect on triglycerides or HDL was observed. CONCLUSION Fluvastatin and pravastatin are efficient in lowering total and LDL cholesterol levels in HIV-positive patients receiving HAART. Furthermore, no influence on indinavir plasma levels could be observed. Therefore, both compounds seem to be a viable treatment option in HAART-induced hypercholesterolemia.
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Antenatal vitamin A supplementation increases birth weight and decreases anemia among infants born to human immunodeficiency virus-infected women in Malawi.
Kumwenda, N, Miotti, PG, Taha, TE, Broadhead, R, Biggar, RJ, Jackson, JB, Melikian, G, Semba, RD
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2002;(5):618-24
Abstract
Vitamin A is essential for immunity and growth. A controlled clinical that involved 697 human immunodeficiency virus (HIV)-infected pregnant women was conducted to determine whether vitamin A prevents anemia, low birth weight, growth failure, HIV transmission, and mortality. Women received daily doses of iron and folate, either alone or combined with vitamin A (3 mg retinol equivalent), from 18-28 weeks' gestation until delivery. In the vitamin A and control groups, respectively, the mean (+/-SE) birth weights were 2895+/-31 g and 2805+/-32 g (P=.05), the proportions of low-birth-weight infants were 14.0% and 21.1% (P=.03), the proportions of anemic infants at 6 weeks postpartum were 23.4% and 40.6% (P<.001), and the respective cumulative proportions of infants who were HIV infected at 6 weeks and 24 months of age were 26.6% and 27.8% (P=.76) and 27.7% and 32.8% (P=.21). Receipt of vitamin A improved birth weight and neonatal growth and reduced anemia, but it did not affect perinatal HIV transmission.
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Put this in your pipe and smoke it: medicinal marijuana study.
TreatmentUpdate. 2001;(12):19
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Dose-finding study of a once-daily indinavir/ritonavir regimen.
Hugen, PW, Burger, DM, ter Hofstede, HJ, Koopmans, PP, Stek, M, Hekster, YA, Reiss, P, Lange, JM
Journal of acquired immune deficiency syndromes (1999). 2000;(3):236-45
Abstract
In antiretroviral therapy, to improve compliance the need is increasing to develop regimens that combine potency and safety with convenient dosing. The objective of our study was to find a once-daily dosing regimen of a HIV-protease inhibitor, indinavir (IDV), by combining it with ritonavir (RTV). In the study, 12 healthy volunteers took a single IDV dose of 800 mg on day 1. Plasma and urine sampling was done for 12 hours. From day 2 to day 21, participants took RTV liquid 200 mg (group A) or 400 mg (group B) once daily. Repeated pharmacokinetic sampling was performed over the course of 24 hours, after single doses of indinavir 400 mg (day 15), 800 mg (day 18), and 1200 mg (day 21). The best dosage regimen in this pharmacokinetic study was selected based on efficacy and tolerability criteria. The study comprised 10 male and 2 female healthy volunteers, mean age, 25 years (range, 18-50 years), mean weight, 70 kg (range, 52-83 kg). One male participant discontinued on day 8 due to influenza. All other participants completed the study without the occurrence of serious adverse events. RTV inhibited indinavir plasma clearance by 51% to 70%, leading to increased and prolonged IDV exposure. Renal clearance was influenced by the addition of RTV and dosage increments of IDV. The efficacy criterion was best fulfilled by 1200 mg IDV/400 mg RTV, whereas this combination performed most poorly on tolerability criteria. Based on the single dose data, a once-daily regimen of IDV with a low dose of RTV is possible. The best dosage regimen to start with among those studied here appears to be 1200 mg IDV/400 mg RTV, which could be decreased at steady state to 800 IDV/400 RTV or 1200 IDV/200 RTV if toxicity occurs. Steady-state pharmacokinetic data of once-daily IDV/RTV regimens in HIV-infected patients are warranted.