HIV Clinical Trials[JOURNAL]
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200 papers
Pilot study of younger and older HIV-infected adults using traditional and novel functional assessments.
Sandkovsky U, Robertson KR, Meza JL … +7 more , High RR, Bonasera SJ, Fisher CM, Marsh AJ, Sheehy MK, Fox HS, Swindells S
HIV Clin Trials · 2013 · PMID 23924589 · Full text
OBJECTIVES: Emerging data suggest that HIV disease and its treatment affect the aging process. Accurate and reliable measures of functional status are needed to investigate this further. DESIGN: A pilot study in groups o...
OBJECTIVES: Emerging data suggest that HIV disease and its treatment affect the aging process. Accurate and reliable measures of functional status are needed to investigate this further. DESIGN: A pilot study in groups of younger and older HIV-infected adults using objective measures of function. METHODS: Evaluations included neuropsychological testing, grip strength, balance assessed by the Wii Balance Board, and actigraphy. Surveys were used for depression, fatigue, loneliness, self-reported activity level, and sexual function. Two-samplet test or Wilcoxon rank sum tests were used for continuous variables and exact chi-square tests were used for comparison between groups. RESULTS: Twenty-one participants were 20 to 40 years old (younger; mean age, 31.5), and 20 were more than 50 years old (older; mean age, 56.5). There was no difference between groups for depression, fatigue, or loneliness. Overall, there was a trend to lower scores in the older age group for neuropsychologicalz score (P = .11) and for verbal learning (P = .09). Functioning in the memory domain was significantly lower in older subjects (P = .007). There was no difference in executive function, speed of processing, memory, motor skills, or total activity. Gender differences in sexual function were observed. Four older and 3 younger participants met the definition of frailty. Total activity by actigraphy did not correlate well with self-reported activity. CONCLUSIONS: Objective tests were well accepted and feasible to perform, although not all are suitable for widespread clinical or research use. Objective measurements of activity did not correlate well with patient self-report, which has implications for future studies in this area.
Flow cytometry analysis with a new FITC-conjugated monoclonal antibody-3E12 for HLA-B*57:01 rapid screening in prevention of abacavir hypersensitivity in HIV-1-infected patients.
Rodríguez-Sáinz C, Valor L, Hernández DC … +8 more , Gil J, Carbone J, Pascual-Bernaldez M, Rodríguez-Alcántara F, Martínez I, Vicario JL, Mallal S, Fernández-Cruz E
HIV Clin Trials · 2013 · PMID 23924588 · Publisher ↗
BACKGROUND: Rapid screening for the detection of HLA-B*57:01 in the prevention of abacavir hypersensitivity in HIV-1-infected patients is a hallmark for clinical services. OBJECTIVE: The aim of this work was to analyze t...
BACKGROUND: Rapid screening for the detection of HLA-B*57:01 in the prevention of abacavir hypersensitivity in HIV-1-infected patients is a hallmark for clinical services. OBJECTIVE: The aim of this work was to analyze the utility of flow cytometry with a new FITC-conjugated B-17 monoclonal antibody (mAb3E12) for HLA-B*57:01 screening in a Spanish cohort of 577 HIV-1+ individuals. METHODS: Cryopreserved peripheral blood mononuclear cell samples from HIV-1+ individuals were analyzed by flow cytometry with the mAb 3E12 that recognizes both HLA-B*57 and HLA-B*58 alleles (members of the group specificity, HLA-B17). Patients' DNA samples had been previously typed for HLA-B*57:01 with PCR-SSO or PCR-SSP and additional DNA sequencing (EPI Study). The results obtained by flow cytometry were compared with the results obtained by the DNA-PCR techniques. RESULTS: By flow cytometry, 46 samples (7.97%) were positive for HLA-B17, 530 (91.86%) were negative, and 1 (0.17%) was undetermined. All samples found negative by flow cytometry were negative for HLA-B*57:01 by DNA-PCR. Of the HLA-B17 positive samples, 31 (67.4%) were positive for HLA-B*57:01, 2 (3.25%) were positive for HLA-B*57:03, 11 (26.1%) were positive for HLA-B*58, and 2 (3.25%) were negative for both HLA-B*57 and HLA-B*58 antigens. The undetermined sample was negative for HLA-B*57 and HLA-B*58 alleles by DNA-PCR. CONCLUSIONS: This study shows that flow cytometry with mAb3E12 is a highly sensitive method (no false negatives) to implement prior to DNA-PCR analysis for rapid screening of HLA-B*57:01. Additional confirmation by molecular HLA typing method would be required in less than 10% of the cohort of HIV-1-infected individuals.
Baseline CD4+ T-cell counts predict HBV viral kinetics to adefovir treatment in lamivudine-resistant HBV-infected patients with or without HIV infection.
Cortez KJ, Proschan MA, Barrett L … +8 more , Brust DG, Weatherley B, Formentini E, Davey RT, Masur H, Polis MA, Neumann And AU, Kottilil S
HIV Clin Trials · 2013 · PMID 23924587 · Full text
BACKGROUND: Coinfection with HIV and hepatitis B virus (HBV) substantially alters the course of HBV. Directly acting anti-HBV agents suppress HBV viral levels; however, the kinetics of HBV decline in mono- and coinfected...
BACKGROUND: Coinfection with HIV and hepatitis B virus (HBV) substantially alters the course of HBV. Directly acting anti-HBV agents suppress HBV viral levels; however, the kinetics of HBV decline in mono- and coinfected persons have not been evaluated. We investigated the role of baseline CD4+ T-cell counts as a predictor of HBV response to adefovir (ADV) therapy in chronic HBV with and without HIV coinfection. METHODS: We conducted a double-blind, randomized, placebo-controlled study of HIV-infected (n = 12) and uninfected (n = 5) chronic HBV patients treated with ADV. Five HIV uninfected patients received ADV; the HIV+ patients received ADV or placebo for a total of 48 weeks. At the end of 48 weeks, all patients received open-label ADV for an additional 48 weeks. HBV, HIV viral loads, CD4+ T-cell counts, and safety labs were performed on days 0, 1, 3, 5, 7, 10, 14, and 28 and then every 4 weeks. RESULTS: Lower HBV slopes were observed among coinfected compared to monoinfected patients (P = .027 at 4 weeks, P = .019 at 24 weeks, and P = .045 at 48 weeks). Using a mixed model analysis, we found a significant difference between the slopes of the 2 groups at 48 weeks (P = .045). Baseline CD4+ T-cell count was the only independent predictor of HBV decline in all patients. CONCLUSION: HIV coinfection is associated with slower HBV response to ADV. Baseline CD4+ T-cell count and not IL28B genotype is an independent predictor of HBV decline in all patients, emphasizing the role of immune status on clearance of HBV.
Randomized trial to evaluate cardiometabolic and endothelial function in patients with plasma HIV-1 RNA suppression switching to darunavir/ritonavir with or without nucleoside analogues.
Guaraldi G, Zona S, Cossarizza A … +8 more , Vernacotola L, Carli F, Lattanzi A, Beghetto B, Orlando G, De Biasi S, Termini R, Garau M
HIV Clin Trials · 2013 · PMID 23924586 · Publisher ↗
BACKGROUND: We performed a study to evaluate change in cardiometabolic and endothelial function in HIV-infected patients switching to darunavir/ritonavir (DRV/r) monotherapy versus triple therapy. METHODS: The MONARCH tr...
BACKGROUND: We performed a study to evaluate change in cardiometabolic and endothelial function in HIV-infected patients switching to darunavir/ritonavir (DRV/r) monotherapy versus triple therapy. METHODS: The MONARCH trial recruited 30 patients who were taking triple combination therapy and with HIV RNA<40 copies/ mL. Patients were randomized to either DRV/r 800/100 mg once daily (OD) monotherapy or DRV/r 800/100 mg OD plus 2 nucleoside reverse transcriptase inhibitors (NRTIs). The primary objective was to assess endothelial function change from baseline to 24 and 48 weeks in brachial artery flow-mediated dilation (FMD) test; changes in endothelial precursor cells (EPCs) and circulating endothelial cells (CECs) were secondary objectives. RESULTS: At baseline, the median age of participants was 43 years, 77% were men, and median CD4 cell count was 585 cells/μL. The median FMD (%) decreased in both arms in the study period (P ≯ .05), with no statistically significant difference between arms (10.7% at baseline and 6.7% at week 48 in the DRV/r + 2 NRTIs arm; 11.1% at baseline and 8.8% at week 48 in the DRV/r arm). The changes at week 48 were similar in the 2 arms for EPCs and CECs. Total cholesterol and low-density lipoprotein (LDL) cholesterol showed larger rises to week 48 in the DRV/r arm monotherapy group than in the triple-therapy group (+26 vs +9 mg/dL for total cholesterol and +14 vs +5 mg/dL for LDL cholesterol). CONCLUSIONS: In the MONARCH trial, switching from triple combination treatment to DRV/r, with or without nucleoside analogues, did not translate into clinically meaningful reductions in endothelial function as measured by FMD.
Sustained virological response and baseline predictors in HIV-HCV coinfected patients retreated with pegylated interferon and ribavirin after failing a previous interferon-based therapy: systematic review and meta-analysis.
Basso M, Parisi SG, Mengoli C … +6 more , Gentilini V, Menegotto N, Monticelli J, Nicolè S, Cruciani M, Palù G
HIV Clin Trials · 2013 · PMID 23924585 · Publisher ↗
BACKGROUND: Published data on retreatment with pegylated interferon and ribavirin of previously failing HIV-HCV coinfected patients are sparse and limited to observational study. We aimed to evaluate efficacy and pretrea...
BACKGROUND: Published data on retreatment with pegylated interferon and ribavirin of previously failing HIV-HCV coinfected patients are sparse and limited to observational study. We aimed to evaluate efficacy and pretreatment predictors. METHODS: Systematic review and meta-analysis of observational studies. The overall and genotype-related success rate was investigated. A direct comparison was performed between genotypes 1/4 and 2/3 by evaluating the sustained virological response (SVR) rate ratio (RR). The effect of study level variables on the effect size was investigated by meta-regression. Variables that were analyzed included age, gender, advanced hepatic fibrosis, pretreatment of HCV RNA and CD4, and successful antiretroviral treatment (ART). RESULTS: The available evidence was from 5 open-label, cohort studies (275 patients). The overall SVR rate was 0.280 (95% CI,0.171-0.425). The SVR rate in genotype 1/4 infections was 0.174 (95% CI, 0.129-0.230), and in genotype 2/3 infections it was 0.474 (95% CI, 0.286-0.670). The pooled RR comparing the SVR of genotype 1/4 to 2/3 was 0.369 (95% CI, 0.239-0.568), with a decreased probability of response for genotype 1/4 (P < .001). HIV RNA suppression had a significant effect on SVR (P = .005). The other covariates had no effect on the overall SVR rate. CONCLUSIONS: The overall SVR rate was 28%, consistent with the rate reported in the retreatment of mono-infected patients with the same schedule. A substantial relative reduction in the SVR rate of about one-third, when treating genotypes 1/4, was found, with a low SVR rate of 17%. Successful HIV suppression by ART predicted a higher rate of treatment success.
Long-term HIV-1 virologic control in patients on a dual NRTI regimen.
Prazuck T, Zucman D, Avettand-Fènoël V … +5 more , Ducasse E, Bornarel D, Mille C, Rouzioux C, Hocqueloux L
HIV Clin Trials · 2013 · PMID 23835514 · Publisher ↗
BACKGROUND: Since the release of protease inhibitors, only 2 randomized trials in the late 1990s have re-assessed the potency of dual nucleoside reverse transcriptase inhibitor (NRTI) combination (2N) as a maintenance st...
BACKGROUND: Since the release of protease inhibitors, only 2 randomized trials in the late 1990s have re-assessed the potency of dual nucleoside reverse transcriptase inhibitor (NRTI) combination (2N) as a maintenance strategy for patients whose HIV RNA was suppressed by tri-therapy. The objective of this study was to describe the characteristics of patients who exhibited durable virologic suppression while receiving 2N. METHODS: A retrospective study was conducted in 2 French hospitals. Using electronic medical records, we identified all HIV-1-infected patients treated with tenofovir/emtricitabine or abacavir/lamivudine (without a third agent) between 2005 and 2012. RESULTS: Out of 1,255 patients, 37 (3%) received a 2N regimen and were included in this study. All received a fixed-dose combination of either tenofovir/emtricitabine (n = 31) or abacavir/lamivudine (n = 6). This regimen was a first-line (n = 8) or a simplification (n = 29) strategy. The total follow-up for patients receiving 2N was 123 patient-years (median, 3.2 years; interquartile range [IQR], 1.3-5.1). At the last visit, 33 of 37 patients were continuing with 2N and had HIV RNA <50 copies/mL (success rate of 89%, snapshot analysis). These patients had received early treatment (median CD4+ nadir, 340/mm3) and had a low HIV RNA zenith (median, 3.9 log/mL) and a low HIV DNA level (median, 2.5 log copies/106 peripheral blood mononuclear cells). Four patients, treated with tenofovir/emtricitabine in the simplify cation group, experienced viral failure. CONCLUSIONS: These results suggest that, in selected patients, a 2N fixed-dose combination is able to maintain viral suppression durably. Such a simple strategy could reduce both the constraints and side effects experienced by patients and the costs for the community.
Pregnancy outcomes in HIV-infected women of advanced maternal age.
Liuzzi G, Pinnetti C, Floridia M … +13 more , Tamburrini E, Masuelli G, Dalzero S, Sansone M, Giacomet V, Degli Antoni AM, Guaraldi G, Meloni A, Maccabruni A, Alberico S, Portelli V, Ravizza M, Italian Group On Surveillance On Antiretroviral Treatment In Pregnancy
HIV Clin Trials · 2013 · PMID 23835513 · Publisher ↗
BACKGROUND: There is limited information on pregnancy outcomes in women with HIV who are of a more advanced maternal age. METHODS: Data from a national observational study in Italy were used to evaluate the risk of nonel...
BACKGROUND: There is limited information on pregnancy outcomes in women with HIV who are of a more advanced maternal age. METHODS: Data from a national observational study in Italy were used to evaluate the risk of nonelective cesarean section, preterm delivery, low birthweight, major birth defects, and small gestational age-adjusted birthweight according to maternal age (<35 and ≥35 years, respectively). RESULTS: Among 1,375 pregnancies with live births, 82.4% of deliveries were elective cesarean sections, 15.8% were nonelective cesarean sections, and 1.8% were vaginal deliveries. Rates of nonelective cesarean section were similar among mothers ≥35 and <35 years (odds ratio [OR], 1.22; 95% CI, 0.90-1.65;P = .19). Preterm delivery and low birthweight were significantly more common among women ≥35 years in univariate but not in multivariate analyses. Newborns from women ≥35 and <35 years showed no differences inZ scores of birthweight, with a similar occurrence of birthweight <10th percentile (12.1% vs 12.0%; OR, 1.02; 95% CI, 0.71-1.46;P = .93). The overall rate of birth defects was 3.4% (95% CI, 2.4-4.4), with no differences by maternal age (≥35 years, 3.5%; <35 years, 3.3%; OR, 1.05; 95% CI, 0.56-1.98;P = .88). DISCUSSION: In this study of pregnant women with HIV, older women were at higher risk of some adverse pregnancy outcomes, such as preterm delivery and low birthweight. The association, however, did not persist in multivariable analyses, suggesting a role of some predisposing factors associated with older age.
Pharmacokinetics, safety, and tolerability of maraviroc in HIV-negative subjects with impaired renal function.
Vourvahis M, Fang J, Checchio T … +4 more , Milton A, Weatherley B, McFadyen L, Heera J
HIV Clin Trials · 2013 · PMID 23835512 · Publisher ↗
PURPOSE: This open-label, nonrandomized, parallel-group study was conducted to explore the pharmacokinetics, safety, and tolerability of maraviroc in renally impaired subjects. METHODS: Subjects with normal renal functio...
PURPOSE: This open-label, nonrandomized, parallel-group study was conducted to explore the pharmacokinetics, safety, and tolerability of maraviroc in renally impaired subjects. METHODS: Subjects with normal renal function; mild, moderate, or severe renal impairment; or end-stage renal disease (ESRD) (n = 6 per group) were enrolled. Subjects with normal function (period 1), severe impairment, and ESRD received a single 300 mg dose of maraviroc. Subjects with normal function (period 2), mild impairment, and moderate impairment received 150 mg for 7 days at adjusted intervals of twice daily, once daily, and every 48 hours, respectively, with saquinavir/ritonavir (SQV/r). Maraviroc was quantified in plasma, urine, and dialysate by tandem high-performance liquid chromatography-mass spectrometry. RESULTS: With SQV/r, geometric mean steady-state maraviroc area under the plasma concentration-time curve for the dosing interval (AUCtau) was 5,341 (coefficient of variation [CV], 27%), 8,119 (35%), and 6,193 (27%) h•ng/mL, in normal function, mild, and moderate impairment groups, respectively. Without SQV/r, 2% to 3% of the maraviroc dose was recovered in urine versus 15% to 25% of steady-state dose when given with SQV/r. Moderate to high intersubject variability in exposure was noted. AUC from zero to infinity (AUCinf) was similar to historical single-dose data in subjects with ESRD: low in those with normal function, and high in those with severe impairment. Dialysis did not influence maraviroc exposure. Maraviroc was well tolerated. CONCLUSIONS: The data suggest that no dosing interval adjustments are required in subjects with renal impairment when maraviroc is administered alone. However, maraviroc dosing interval adjustment is warranted in renally impaired patients receiving potent CYP3A4 inhibitors. Reference to local prescribing information is recommended, because dose recommendations in renally impaired patients may differ between regions.
Pharmacokinetics and pharmacodynamics of etravirine 400 mg once daily in treatment-naïve patients.
Di Perri G, Green B, Morrish G … +6 more , Hill A, Faetkenheuer G, Bickel M, van Delft Y, Kurowski M, Kakuda T
HIV Clin Trials · 2013 · PMID 23835511 · Publisher ↗
BACKGROUND: Etravirine is currently approved for HIV treatment-experienced patients at a dose of 200 mg twice daily. The long terminal elimination half-life of etravirine should support once-daily dosing. METHODS: In the...
BACKGROUND: Etravirine is currently approved for HIV treatment-experienced patients at a dose of 200 mg twice daily. The long terminal elimination half-life of etravirine should support once-daily dosing. METHODS: In the double-blind 48-week SENSE trial, 157 antiretroviral treatment-naïve patients were randomly assigned to receive etravirine 400 mg once daily (n = 79) or efavirenz 600 mg once daily (n = 78), plus 2 nucleoside reverse transcriptase inhibitors (NRTIs). Sparse sampling for etravirine plasma concentrations was conducted during the 48-week trial. Area under the curve over the dosing interval (AUC24h) and trough concentration (C0h) were estimated using a population pharmacokinetic model and compared with previous results using the 200-mg twice-daily dosage. The relationship between etravirine AUC24h and C0h with efficacy and safety was also assessed. RESULTS: By week 48, the percentage of patients in the etravirine arm with HIV RNA <50 copies/ mL was 75.9% in the intent-to-treat switch equals failure analysis and 92.3% in the on-treatment analysis; no patient developed genotypic or phenotypic resistance to NRTIs or non-nucleoside reverse transcriptase inhibitors (NNRTIs) after virologic failure. Seventy-one subjects had evaluable etravirine pharmacokinetics. The median (interquartile range) of etravirine AUC24h and C0h were 12,447 (8,261-15,652) ng•h/mL and 330 (188-472) ng/mL, respectively. There was no correlation between etravirine exposure and virologic response or adverse events. CONCLUSIONS: In the SENSE trial, etravirine 400 mg once daily achieved similar exposures to historical reference data on etravirine when dosed at 200 mg twice daily. There was no apparent relationship between the pharmacokinetics of etravirine and virologic response or adverse events.
Rilpivirine versus efavirenz in HIV-1-infected subjects receiving emtricitabine/tenofovir DF: pooled 96-week data from ECHO and THRIVE Studies.
Nelson MR, Elion RA, Cohen CJ … +11 more , Mills A, Hodder SL, Segal-Maurer S, Bloch M, Garner W, Guyer B, Williams S, Chuck S, Vanveggel S, Deckx H, Stevens M
HIV Clin Trials · 2013 · PMID 23835510 · Publisher ↗
OBJECTIVES: Week 96 efficacy and safety of the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) was compared to efavirenz (EFV) in subset of 1,096 subjects who received emtricitabine/tenofovir dis...
OBJECTIVES: Week 96 efficacy and safety of the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) was compared to efavirenz (EFV) in subset of 1,096 subjects who received emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in pooled data from 2 phase 3 studies. METHODS: ECHO and THRIVE are double-blind, double-dummy, randomized, active-controlled, non-inferiority phase 3 studies of RPV versus EFV plus 2 NRTIs in antiretroviral-naïve adult subjects. The primary and secondary endpoints were the proportion of subjects with HIV-1 RNA <50 copies/ mL using an intent-to-treat, time to loss of virologic response (ITT-TLOVR) analysis at weeks 48 and 96, respectively. Safety, tolerability, immunologic response, adherence level, and other measures were also evaluated. RESULTS: At week 48, noninferior efficacy of RPV+FTC/TDF over EFV+FTC/TDF was established, and at week 96 RPV+FTC/TDF remained noninferior (77% overall response rate in both groups). Through week 96, rates of virologic failure were higher in the RPV+FTC/ TDF group, with low and similar rates of virologic failure and resistance mutations occurring during the second year of follow-up. Treatment with RPV+FTC/TDF was associated with a lower rate of discontinuation due to adverse events and grade 2-4 adverse events including dizziness, abnormal dreams/nightmares, rash, and lipid abnormalities. CONCLUSIONS: The pooled ECHO and THRIVE studies demonstrated noninferiority of RPV+FTC/TDF in achieving virologic response with safety and tolerability advantages over EFV+FTC/TDF through 96 weeks. Higher rates of virologic failure in the RPV+FTC/TDF group were balanced with higher rates of discontinuations due to adverse events in the EFV+FTC/TDF group.
High-grade anal intraepithelial neoplasia among HIV-1-infected men screening for a multicenter clinical trial of a human papillomavirus vaccine.
Wilkin T, Lee JY, Lensing SY … +9 more , Stier EA, Goldstone SE, Berry MJ, Jay N, Aboulafia DM, Einstein MH, Saah A, Mitsuyasu RT, Palefsky JM
HIV Clin Trials · 2013 · PMID 23611828 · Full text
PURPOSE: High-grade anal intraepithelial neoplasia (HGAIN) is the precursor lesion to invasive anal cancer. Human papillomavirus (HPV) vaccination holds great promise for preventing anal cancer. METHODS: We examined 235...
PURPOSE: High-grade anal intraepithelial neoplasia (HGAIN) is the precursor lesion to invasive anal cancer. Human papillomavirus (HPV) vaccination holds great promise for preventing anal cancer. METHODS: We examined 235 HIV-1-infected men screening for participation in a multisite clinical trial of a quadrivalent HPV vaccine. All participants had anal swabs obtained for HPV testing and cytology and high-resolution anoscopy with biopsies of visible lesions to assess for HGAIN. RESULTS: HPV types 16 and 18 were detected in 23% and 10%, respectively; abnormal anal cytology was found in 56% and HGAIN in 30%. HGAIN prevalence was significantly higher in those with HPV16 detection compared to those without (38% vs 17%; P = .01). Use of antiretroviral therapy and nadir and current CD4+ cell count were not associated with abnormal anal cytology or HGAIN. CONCLUSION: HGAIN is highly prevalent in HIV-infected men. Further studies are needed on treatment and prevention of HGAIN.
Measurement issues in using pharmacy records to calculate adherence to antiretroviral drugs.
Grimes DE, Andrade RA, Niemeyer CR … +1 more , Grimes RM
HIV Clin Trials · 2013 · PMID 23611827 · Publisher ↗
BACKGROUND: Researchers often use pharmacy records to calculate adherence to antiretrovirals. Variability in the findings may be due to inconsistent methods of calculating adherence. OBJECTIVE: Determine the impact on ad...
BACKGROUND: Researchers often use pharmacy records to calculate adherence to antiretrovirals. Variability in the findings may be due to inconsistent methods of calculating adherence. OBJECTIVE: Determine the impact on adherence rates of 6 different calculations that include accounting for whether filled antiretroviral prescriptions were picked up and whether the patient had medications at the start of the observation period. METHODS: Fifty-six patients of a public care system, who had ordered, but failed to pick up, antiretroviral prescriptions from the clinic pharmacy at least once from September thru December, were identified using an electronic pharmacy database. Their adherence during the 4 months was calculated using refilled doses and picked up doses as a percent of prescribed doses. The effect on the calculation of adherence of medications in the patients' possession from August was examined. RESULTS: When medications in the patients' possession from August were considered in calculating adherence, the rate was 54% based on the prescription refill date and 33.4% based on the prescription pick-up date. If medications in the patients' possession at the beginning of the observation period were ignored, adherence based on refill was 48.9% and 28.1% based on pick-up. If the start date for calculating adherence was the date of the first refill or pick-up during the first month of the observation period, adherence rates were 56.2% and 41%, respectively. CONCLUSIONS: This study demonstrated that 6 different methods of calculating adherence from pharmacy records yielded adherence rates of 28.1% to 56.2%. Studies using pharmacy records should specify how adherence is calculated.
Immune Activation While on Potent Antiretroviral Therapy Can Predict Subsequent CD4+ T-Cell Increases Through 15 Years of Treatment.
Zhang X, Hunt PW, Hammer SM … +3 more , Cespedes MS, Patterson KB, Bosch RJ
HIV Clin Trials · 2013 · PMID 23611826 · Full text
BACKGROUND: While persistent T-cell activation has been cross-sectionally associated with poor CD4+ T-cell restoration in HIV-infected individuals maintaining antiretroviral treatment (ART)-mediated viral suppression, it...
BACKGROUND: While persistent T-cell activation has been cross-sectionally associated with poor CD4+ T-cell restoration in HIV-infected individuals maintaining antiretroviral treatment (ART)-mediated viral suppression, it remains unclear whether CD8+ T-cell activation is of predictive effect on CD4+ T-cell recovery. OBJECTIVE: We assessed whether the extent of persistent CD8+ T-cell activation (% CD38+/HLA-DR+) in the first few years of ART-mediated viral suppression predicted subsequent CD4+ T-cell recovery in 95 subjects with up to 15 years of observation on suppressive ART. RESULTS: Lower CD8+ T-cell activation and higher naïve CD4+ T-cell frequencies (CD45RA+/CD62L+) measured at year 3 to 5 after starting ART independently predicted greater subsequent CD4+ T-cell increases. The mean CD4 count increase from year 0 to year 5 and the increase to the average of year 10 to 15 in the low CD8 activation group (≤18.5%; mean = 13%) were 342 and 458 cells/mm,3 and the increases were 248 and 349 cells/mm3 for the high CD8 activation group (≯18.5%; mean = 29%) (P = .002 and P = .016, respectively, comparing groups). At years 10 to 15, the mean CD4 counts in the groups were 579 and 484 cells/mm3, respectively (P = .026). CONCLUSION: These findings support the need to identify approaches to reduce immune activation in treated HIV disease.
Cholecalciferol supplementation in HIV-infected youth with vitamin D insufficiency: effects on vitamin D status and T-cell phenotype: a randomized controlled trial.
Giacomet V, Vigano A, Manfredini V … +6 more , Cerini C, Bedogni G, Mora S, Borelli M, Trabattoni D, Zuccotti GV
HIV Clin Trials · 2013 · PMID 23611825 · Publisher ↗
OBJECTIVES: In addition to its known effects on bone metabolism, vitamin D may regulate immune function. DESIGN: We performed a randomized controlled trial (RCT) to test whether cholecalciferol supplementation can improv...
OBJECTIVES: In addition to its known effects on bone metabolism, vitamin D may regulate immune function. DESIGN: We performed a randomized controlled trial (RCT) to test whether cholecalciferol supplementation can improve vitamin D status and affect the T-cell phenotype in HIV-infected youth with vitamin D insufficiency. METHODS: Fifty-two HIV-infected patients aged 8 to 26 years and with serum 25(OH) D <30 ng/mL were randomized to receive orally vitamin D3 100,000 IU or placebo every 3 months for 4 doses. Serum 25(OH)D, 1,25(OH)2D, PTH, and CD4+ T cells were assessed 3 months before baseline and at 0, 3, 6, 9, and 12 months, while Th1-, Th2-, Th17-, and Treg-subsets and T-lymphocyte vitamin D receptor were assessed at 0, 3, and 12 months. RESULTS: Forty-eight subjects (25 receiving vitamin D and 23 receiving placebo) completed the RCT. Cholecalciferol supplementation produced an early (3 months) decrease in PTH, a concomitant increase in 25(OH)D, and a later (6 months) increase in 1,25(OH)2D levels, all persisting at 12 months. The frequency of vitamin D insufficiency at 12 months was 20% versus 60% in the intervention versus placebo group (P = .007). Cholecalciferol supplementation had no effect on CD4+ T-cell counts but was associated with a decreased Th17:Treg ratio at 3 months. CONCLUSIONS: In our cohort of HIV-infected youth, a 12-month cholecalciferol supplementation increased 25(OH)D and 1-25(OH)2D and decreased PTH levels but had no effect on CD4+ T-cells. However, it was associated with changes in CD4+ T-cell phenotype, warranting further investigation.
Dynamics of cellular HIV-1 DNA levels over 144 weeks of darunavir/ritonavir monotherapy versus triple therapy in the MONET trial.
Geretti AM, Arribas JR, Lathouwers E … +6 more , Foster GM, Yakoob R, Kinloch S, Hill A, van Delft Y, Moecklinghoff C
HIV Clin Trials · 2013 · PMID 23372114 · Publisher ↗
BACKGROUND: In patients receiving combination antiretroviral therapy (ART), switching to monotherapy with ritonavir-boosted darunavir (DRV/r) can maintain plasma HIV-1 RNA suppression with no treatment-emergent drug resi...
BACKGROUND: In patients receiving combination antiretroviral therapy (ART), switching to monotherapy with ritonavir-boosted darunavir (DRV/r) can maintain plasma HIV-1 RNA suppression with no treatment-emergent drug resistance; effects on cellular HIV-1 DNA burden are less well characterized. METHODS: In MONET, patients on stable combination ART for at least 6 months with plasma HIV-1 RNA <50 copies/mL and no history of virologic failure switched to DRV/r 800/100 mg once daily, either alone (n = 127) or with 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) (n = 129). In a representative subset of 146 patients, total HIV-1 DNA load in peripheral blood mononuclear cells (PBMC) was tested retrospectively at baseline, week 48, week 96, and week 144. RESULTS: Mean HIV-1 DNA levels at baseline vs week 144 were 2.50 vs 2.49 log10 copies/106 PBMC in the monotherapy arm and 2.59 vs 2.61 log10 copies/106 PBMC in the triple therapy arm, with mean (median) changes of -0.05 (-0.03) and +0.03 (+0.01) log10 copies/106 PBMC in the 2 arms, respectively. Overall baseline HIV-1 DNA levels were higher in patients with nadir CD4 counts <200 cell/µL (P<.05) and in patients who over 144 weeks experienced at least 1 HIV-1 RNA measurement >50 copies/mL (P < .05). CONCLUSIONS: In this substudy of the MONET trial, HIV-1 DNA levels remained stable during 144 weeks of either DRV/r monotherapy or triple therapy with DRV/r + 2 NRTIs. In both treatment arms, baseline HIV-1 DNA levels were predicted by the nadir CD4 cell count and predictive of plasma HIV-1 RNA detection during follow-up.
HIV-1 drug resistance and associated factors among adults failing first-line highly active antiretroviral therapy in Ho Chi Minh City, Vietnam.
Pham QD, Huynh TK, Luong TT … +3 more , Tran T, Vu TX, Truong LX
HIV Clin Trials · 2013 · PMID 23372113 · Publisher ↗
BACKGROUND & OBJECTIVES: Little is known about HIV-1 drug resistance (HIVDR) in people failing first-line highly active antiretroviral therapy (HAART) in Vietnam. The aim of this study was to investigate the frequency of...
BACKGROUND & OBJECTIVES: Little is known about HIV-1 drug resistance (HIVDR) in people failing first-line highly active antiretroviral therapy (HAART) in Vietnam. The aim of this study was to investigate the frequency of HIV-1 drug resistance mutations (DRMs) and determine correlates of acquiring genotypic HIVDR among Vietnamese adults (age ≥ 18) who met the immunological or clinical criteria of first-line HAART failure according to the guidelines of the World Health Organization (WHO). METHODS: A total of 138 individuals participated in a descriptive study in Ho Chi Minh City between 2006 and 2009. Blood samples were collected for performing HIV-1 viral load (VL) and genotyping for specimens with VL ≥ 1,000 copies/mL. Stanford algorithm was used to interpret DRMs and multivariate analyses were performed to investigate predictors of HIVDR acquisition. RESULTS: Of the study population, most participants failed either stavudine/lamivudine/nevirapine or stavudine/lamivudine/efavirenz (116 individuals). Up to 51 people obtained a VL <1,000 copies/mL. Among 87 participating individuals with VL ≥1,000 copies/mL, 11 people still harbored a wild-type strain, while 76 participants harbored a HIV-1 drug-resistant strain (2 of which were against protease inhibitors); common DRMs were M184I/V (74%), Y181I/C/V (39%), G190A/S (32%), T215Y/F (32%), and K103N (31%). The proportions of K65R, Q151M, and T69 insertion were 13%, 11%, and 5%, respectively. Being antiretroviral-exposed before initiating first-line HAART in a public and free-of-charge outpatient clinic, having nonadherence to first-line HAART, per 12-month increase of duration on first-line HAART, and having clinical failure criteria were significantly associated with a genotypic HIVDR acquisition. CONCLUSIONS: In the absence of VL for the population with WHO immunological/ clinical treatment failure criteria, a large proportion of people still achieved a VL <1,000 copies/mL, while a high prevalence of HIVDR was observed in those with VL ≥1,000 copies/mL. Thus, VL monitoring should be implemented now for the HAART-treated population in Vietnam.
Determinants of antiretroviral therapy initiation and treatment outcomes for people living with HIV in Vietnam.
Tran DA, Shakeshaft A, Ngo AD … +4 more , Mallitt KA, Wilson D, Doran C, Zhang L
HIV Clin Trials · 2013 · PMID 23372112 · Publisher ↗
OBJECTIVES: This study explores patient characteristics that are significantly associated with very late combination antiretroviral therapy (cART) initiation (CD4 count ≤100 cells/mm³) and examines the association betwee...
OBJECTIVES: This study explores patient characteristics that are significantly associated with very late combination antiretroviral therapy (cART) initiation (CD4 count ≤100 cells/mm³) and examines the association between patient characteristics and treatment outcomes, CD4 recovery, and mortality. DESIGN: Data were obtained from the clinical records of 2,198 HIV/AIDS patients in 13 outpatient clinics across 6 provinces in Vietnam. METHODS: Multivariate logistic regression and Cox proportional hazards regression were used to identify patient characteristics that are significantly associated with very late cART initiation and to measure relationships between patient characteristics and treatment outcomes. RESULTS: Very late cART initiation was significantly associated with being male compared with female (odds ratio [OR], 0.36; 95% CI, 0.23-0.58), becoming HIV infected through injecting drugs (OR, 2.13; 95% CI, 1.09-4.14), and having opportunistic infections at cART initiation (OR, 1.69; 95% CI, 1.02-2.86). Being male (female vs male: hazard ratio [HR], 0.45; 95% CI, 0.20-0.98), very late cART initiation (timely vs late: HR, 0.18; 95% CI, 0.04-0.72), low baseline body mass index (BMI) (HR, 0.95; 95% CI, 0.92-0.98), and later baseline WHO clinical stage (WHO clinical stage IV vs combined group of stage I and II: HR, 5.70; 95% CI, 3.90-7.80) were significantly associated with death, whereas being female compared with male (HR, 1.51; 95% CI, 1.14-1.99) and timely cART initiation (HR, 35.45; 95% CI, 13.67-91.91) were significant predictors of CD4 recovery. CONCLUSIONS: Timely testing of patients for HIV, increasing use of CD4 count testing services, and starting cART earlier are essential to reduce mortality and improve treatment outcomes.
Isolated anti-HBc among HIV-infected patients in Istanbul, Turkey.
Karaosmanoglu HK, Aydin OA, Nazlican O
HIV Clin Trials · 2013 · PMID 23372111 · Publisher ↗
BACKGROUND: Isolated antibody to hepatitis B core antigen (anti-HBc) is frequent in HIV-infected patients, and it may be a marker of occult hepatitis B. We aimed to determine the prevalence and associated risk factors of...
BACKGROUND: Isolated antibody to hepatitis B core antigen (anti-HBc) is frequent in HIV-infected patients, and it may be a marker of occult hepatitis B. We aimed to determine the prevalence and associated risk factors of isolated anti-HBc among HIV-infected patients in Turkey, which is classified as an intermediate HBV, low HIV endemic region. METHOD: HIV/AIDS patients followed by the Infectious Diseases and Clinical Microbiology Outpatient Clinic of Haseki Training and Research Hospital between January 2006 and March 2011 were included in this study. Medical records were reviewed to determine the prevalence of isolated anti-HBc and to identify the risk factors associated with isolated anti-HBc. The frequency of isolated anti-HBc in 209 HIV-infected patients was compared with 83 volunteer blood donors. RESULTS: Of 209 HIV-infected patients, 40 subjects (19.1%) had isolated anti-HBc compared with control group, which consisted of 83 volunteer blood donors who had similar age (P = .13) and sex (P = .29). In the control group, only 2 (2.4%) had isolated anti-HBc. Isolated anti-HBc was significantly more frequent in HIV-infected patients (P < .001). The characteristics such as age, gender, injecting drug use, anti-HCV seropositivity, and CD4 cell counts were not significantly different between HIV-infected patients with or without isolated anti-HBc. Only 3 (7.5%) of HIV-infected patients had occult infection. CONCLUSION: Prevalence of isolated anti-HBc in Turkish HIV-infected patients was 19.1%, which was significantly more frequent than in blood donors. Isolated anti-HBc could be associated with occult infection. Thus, all HIV-infected patients should be screened for anti-HBc before starting antiretroviral therapy.
Prevalence of primary resistance mutations to integrase inhibitors in treatment-naïve and -experienced patients infected with B and non-B HIV-1 variants.
Gutiérrez C, Hernández-Novoa B, Pérez-Elías MJ … +5 more , Moreno AM, Holguín A, Dronda F, Casado JL, Moreno S
HIV Clin Trials · 2013 · PMID 23372110 · Publisher ↗
BACKGROUND: Raltegravir (RAL) constitutes the first available integrase strand transfer inhibitor (INSTI) available in clinical practice. Three independent pathways have been described to confer resistance to RAL. Second...
BACKGROUND: Raltegravir (RAL) constitutes the first available integrase strand transfer inhibitor (INSTI) available in clinical practice. Three independent pathways have been described to confer resistance to RAL. Secondary mutations with little effect on INSTI susceptibility and additional substitutions with an uncertain role have also been described especially in HIV-1 non-B variants. METHODS: We evaluated the prevalence of primary, secondary, and additional resistance mutations to INSTIs in patients naïve to RAL or elvitegravir (EGV) carrying different HIV-1 variants. RESULTS: A total of 83 patients infected by B HIV-1 subtype (64%) or non-B HIV-1 variants (36%) were evaluated. No primary mutations to RAL or EGV were found in the inte-grase sequences analyzed. Secondary mutations were detected in only 5 patients. Additional mutations were found in both in B and non-B variants. According to the geno2pheno algorithm, some of the secondary mutations detected (L74V, E138K, G163RS, and V151I) have been associated with a reduced estimated susceptibility to RAL and only the E138K mutation has been associated with a decreased estimated susceptibility to EGV. No virological failure was observed after RAL was administrated in 17 patients carrying 1 or more additional substitutions in the absence of primary or secondary mutations. CONCLUSIONS: No primary resistance mutations to INSTI were found in treatment-naïve or -experienced patients infected with B or non-B HIV-1 variants. The vast majority had some polymorphic and non-polymorphic substitutions; however response to RAL was excellent in patients who harbored one or more of these mutations. We could not identify any clinical factors associated with the presence of any of these mutations.
Lipid-lowering effect and efficacy after switching to etravirine in HIV-infected patients with intolerance to suppressive HAART.
Casado JL, de Los Santos I, Del Palacio M … +4 more , García-Fraile L, Pérez-Elías MJ, Sanz J, Moreno S
HIV Clin Trials · 2013 · PMID 23372109 · Publisher ↗
PURPOSE: Etravirine (ETR) has shown a good lipid profile in previous studies. The aim of this study was to determine the virologic, immunologic, and lipid outcome in HIV-infected patients switching to an ETR-based antire...
PURPOSE: Etravirine (ETR) has shown a good lipid profile in previous studies. The aim of this study was to determine the virologic, immunologic, and lipid outcome in HIV-infected patients switching to an ETR-based antiretroviral regimen due to intolerance or toxicity. METHODS: Observational cohort study of 125 HIV-infected patients who switched therapy to an ETR-based regimen. The lipid profile, including total triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was compared after 24 weeks. RESULTS: Patients changed from efavirenz (n = 34; 28%) and ritonavir-boosted protease inhibitors (PI/r; 67 cases: 21 atazanavir, 21 lopinavir, 11 fosamprenavir, 14 darunavir). Hyperlipidemia was the cause in only 22 patients (18%). At 24 weeks, a significant decrease was observed in mean TC level (-8%), LDL-C (-8%), TC:HDL ratio (-6%), and TG level (-20%). For patients receiving previously efavirenz, there was a significant reduction in TC (-23 mg/dL; -13%) and LDL-C (-25 mg/dL; -21%) levels and a trend to a better TG level (-38 mg/dL; -21%;P = .06). In the case of prior PI/r therapy, there was also a significant reduction in TC (-14 mg/dL; -6%) and TG levels (-58 mg/dL; -16%), mostly in prior lopinavir- or fosamprenavir-based therapy (TC -15%; TG -53%). Median CD4+ count increased from 513 to 621 cells/µL (P = .03), and there were only 3 cases of virologic failure (2%). CONCLUSIONS: In patients switching to an ETR-containing regimen, there is a significant improvement of lipids and maintenance of immunologic and virologic response. This lipid-lowering effect was irrespective of the presence of previous hyperlipidemia and for patients receiving different antiretroviral drugs.
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