[Show abstract][Hide abstract] ABSTRACT: Background. In the US, FTC/TDF is a preferred NRTI backbone with 3TC/ABC as a commonly used alternative. For HIV infected patients virologically suppressed on a boosted PI+3TC/ABC regimen, the merits of switching to FTC/TDF as the NRTI backbone are unknown.Methods. SWIFT was a prospective, randomized, open-label 48-week study to evaluate efficacy and safety of switching to FTC/TDF. Subjects receiving 3TC/ABC+PI+RTV with HIV RNA <200 c/mL≥3 months were randomized to continue 3TC/ABC or switch to FTC/TDF. The primary endpoint was time to loss of virologic response (TLOVR) with non-inferiority measured by delta of 12%. Virologic failure (VF) was defined as confirmed rebound or the last HIV RNA measurement on study drug≥200 c/mL.Results. 311 subjects were treated in this study (155 to PI+RTV+FTC/TDF, 156 to PI+RTV+3TC/ABC). Baseline characteristics were similar between the arms: 85% males, 28% African Americans, median age 46 years, and median CD4 532 cells/mm(3). By TLOVR through Week 48, switching to FTC/TDF was non-inferior compared to continued 3TC/ABC (86.4% vs. 83.3%, treatment difference 3.0% (95% CI -5.1% to 11.2%). Fewer subjects on FTC/TDF experienced VF (3 vs. 11; p=0.034). FTC/TDF showed greater declines in fasting LDL, total cholesterol (TC), and triglycerides (TG) with significant declines in LDL and TC beginning at Week 12 with no TC/HDL ratio change. Switching to FTC/TDF showed improved NCEP thresholds for TC and TG and improved 10-year Framingham TC calculated scores. Decreased eGFR was observed in both arms with a larger decrease in the FTC/TDF arm.Conclusions. Switching to FTC/TDF from 3TC/ABC maintained virologic suppression, had fewer VFs, improved lipid parameters and Framingham scores, but decreased eGFR.
[Show abstract][Hide abstract] ABSTRACT: This retrospective cohort study examined electronic medical records of HIV-positive patients in California (N = 7,834) to find the prevalence of any psychiatric condition and the associations between several factors and the likelihood of these disorders. Approximately 53 % of the patients in this study had a documented psychiatric condition, including 23 % who had a mood disorder, 19 % who had a substance-related disorder, and 16 % who had an anxiety disorder. After controlling for potential confounders, significant positive associations (p < 0.001) were found between female gender and the presence of any mood disorder (adjusted odds ratio [95 % confidence interval, 95 %CI] = 1.58 [1.26-1.99]) or anxiety disorder (AOR = 1.54 [1.18-2.02]) and between homosexual orientation and the presence of any psychiatric condition (AOR = 1.33 [1.15-1.55]), mood disorder (AOR = 1.71 [1.42-2.07]), or anxiety disorder (AOR = 1.41 [1.22-1.88]). There were also significant negative associations between African-American race and the presence of any psychiatric condition (AOR = 0.68 [0.60-0.77]), mood disorder (AOR = 0.74 [0.64-0.86]), anxiety disorder (AOR = 0.43 [0.36-0.52]), or substance-related disorder (AOR = 0.78 [0.67-0.91]) and between state/federal insurance and the presence of any psychiatric condition (AOR = 0.70 [0.62-0.79]), mood disorder (AOR = 0.71 [0.62-0.80]), or anxiety disorder (AOR = 0.77 [0.66-0.89]).
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: This paper presents the final analysis of once-daily darunavir/ritonavir (DRV/r) vs. lopinavir/ritonavir (LPV/r) in treatment-naïve HIV-1-infected adults. METHODS: ARTEMIS (AntiRetroviral Therapy with TMC114 ExaMined In naïve Subjects; NCT00258557) was a randomized, open-label, phase-III, 192-week trial. Patients were stratified by baseline HIV-1 RNA and CD4 count, and randomized to once-daily DRV/r 800/100 mg or LPV/r 800/200 mg total daily dose (either once or twice daily) plus tenofovir/emtricitabine. RESULTS: Of 689 randomized patients receiving treatment (DRV/r: 343; LPV/r: 346), 85 and 114 patients in the DRV/r and LPV/r arms, respectively, had discontinued by week 192. Noninferiority was shown in the primary endpoint of virological response (HIV-1 RNA < 50 copies/mL) [DRV/r: 68.8%; LPV/r: 57.2%; P < 0.001; intent to treat (ITT)/time to loss of virological response; estimated difference in response 11.6% (95% confidence interval 4.4-18.8%)]. Statistical superiority in virological response of DRV/r over LPV/r was demonstrated for the primary endpoint (P = 0.002) and for the ITT non-virological-failure-censored analysis (87.4% vs. 80.8%, respectively; P = 0.040). No protease inhibitor (PI) primary mutations developed and only low levels of nucleoside reverse transcriptase inhibitor (NRTI) resistance developed in virological failures in both groups. Significantly fewer discontinuations because of adverse events were observed with DRV/r (4.7%) than with LPV/r (12.7%; P = 0.005). Grade 2-4 treatment-related diarrhoea was significantly less frequent with DRV/r than with LPV/r (5.0% vs. 11.3%, respectively; P = 0.003). DRV/r was associated with smaller median increases in total cholesterol and triglyceride levels than LPV/r. Changes in low- and high-density lipoprotein cholesterol were similar between groups. Similar increases in aspartate aminotransferase and alanine aminotransferase for DRV/r and LPV/r were observed. CONCLUSION: Over 192 weeks, once-daily DRV/r was noninferior and statistically superior in virological response to LPV/r, with a more favourable gastrointestinal profile, demonstrating its suitability for long-term use in treatment-naïve patients.
[Show abstract][Hide abstract] ABSTRACT: Objectives
To determine if switching virologically suppressed patients on a regimen containing lopinavir/r (LPV/r) or fosamprenavir (FPV/r) to darunavir/r (DRV/r) or atazanavir/r (ATV/r) results in improved TGs while maintaining virological suppression.
Eligibility criteria were undetectable HIV RNA ≥12 weeks, no PI resistance, receiving LPV/r (n = 46) or FPV/r (n = 3) plus nucleosides, and fasting TGs >200 mg/dl. Patients were randomized to either QD ATV/r or DRV/r (maintaining the same nucleosides). Primary endpoint was change in TGs from baseline to week 24.
66 were screened, 51 enrolled and two withdrew consent after randomization. 24 patients received ATV/r; 25 received DRV/r. Baseline mean CD4 cell count was 569; HIV RNA was <50 copies/mL in 88% of subjects. Mean baseline TGs were 326 mg/dl in ATV/r arm and 342 mg/dl in DRV/r arm. TGs declined from baseline to week 24 by 108 mg/dl (p < 0.001) with a non-significant difference by arm: −88 mg/dl in the ATV/r arm and −126 mg/dl in the DRV/r arm. At week 24, 55% of ATV/r and 48% of DRV/r subjects had TGs <200 mg/dl (OR 1.3; Difference 7%, 95% CI: −22% to 35%). Total and HDL cholesterol decreased and LDL increased (non-significantly). Baseline quality of life (QOL) was 83% and remained high at week 24 (84%). No differences between the groups in CD4 cell counts or HIV RNA levels were noted.
Patients with high TGs who switched from LPV/r or FPV/r to DRV/r or ATV/r had improved TGs, while maintaining virological suppression and high adherence and QOL.
[Show abstract][Hide abstract] ABSTRACT: Patients virologically suppressed on TDF/FTC + ATV/r may require alternative regimens that maintain suppression while addressing some drug-related side effects. We explored two alternative regimens that replace RTV and/or TDF/FTC. This open-label exploratory pilot trial enrolled 43 patients on TDF/FTC + ATV/r. Subjects were randomized to one of three arms. Arm 1 (n=15) replaced TDF/FTC with RAL 400 mg BID while continuing ATV/r. Arm 2 (n=14) made two changes: TDF/FTC was stopped and RAL BID was used instead; ritonavir was stopped and ATV 300 mg BID was used. Arm CTL (n=14) continued the baseline (BL) regimen. The week 48 final endpoint is summarized. The primary endpoint was maintaining virologic suppression (<40 c/mL); secondary endpoints compared safety measures. Overall mean age was 46, with 74% Caucasian, 21% black race and 12% female; similar characteristics noted across arms. Through week 48, all but two patients maintained virologic suppression; both virologic failures (>200 c/mL on two consecutive tests) were on arm 2; both reported adherence problems and no resistance mutations were detected. Overall CD4 counts were 534/mm(3) at BL and 555/mm(3) at week 48. There was a significant CD4 cell count difference favoring CTL (+52/mm(3)) vs. arm 2 (-14/mm(3)), p=0.03. No significant differences across arms were noted in lipid fractions or other lab tests. There were no clinically significant EKG changes across arms. Among AEs of interest through week 48, there were more neurologic AEs on arm 1 (n=7) and 2 (n=6) vs. CTL (n=1), and more musculoskeletal events noted on arm 2 (n=7) vs. arm 1 (n=3) and CTL (n=1). Quality of life was measured with a self-assessment Likert scale. Scores were similar across arms despite the BID dosing in two arms. Self-reported adherence using 3-day recall was>95% in all three arms at both baseline and week 48. In this randomized pilot study, two of the three arms maintained virologic suppression in all subjects; there were two virologic rebounds in arm 2. No resistance mutations were detected in either, and adherence issues were noted for both subjects. We also noted that the CD4 cell change was significantly less on arm 2, and there were more neurologic and musculoskeletal AEs on arm 2 vs. CTL. In this study, the use of ATV/r with either TDF/FTC or RAL was successful over 48 weeks, but unboosted BID ATV 300 mg+BID RAL 400 mg as an alternative in virologically suppressed patients should be used with caution.
Journal of the International AIDS Society 01/2012; 15(6):18279. · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract HIV-infected patients frequently experience depression, drug use, and unstable housing but are often unable to access supportive services to manage these challenges. Data on barriers to needed supportive services are critical to improving patient access. Data from the Medical Monitoring Project (MMP), a national supplemental surveillance system for HIV-infected persons in care, was used to examine barriers to support service use and factors associated with need and unmet need for services. Interview data for 333 patients in care in 2007 and 2008 in Los Angeles County (LAC) showed that 71% (n=236) reported needing at least one supportive service and of these, 35% (n=83) reported at least one unmet need for services (46% Latino; 25% white; 83% male; 92% 30+; 77% gay/bisexual; 40% response rate). The main reasons that supportive services were not accessed included lack of information (47%; do not know where to go or who to call); an agency barrier (33%; system too confusing, wait list too long); or a financial/practical barrier (18%; too expensive, transportation problems). In a logistic regression that included all participants (n=333), African Americans (OR=3.1, 95% CI: 1.1-8.7) and those with incomes less than $10,000 were more likely to have service needs (odds ratio [OR]=3.5; 95% confidence interval [CI]: 1.3-9.3). Among those with at least one service need (n=236), those who were gay or bisexual were more likely to report at least one unmet service need (OR=2.8; 95% CI: 1.3-6.1). Disparities were found for need and unmet need for supportive services by race/ethnicity; income and sexual orientation. The reported reasons that services were not obtained suggest needed improvements in information dissemination on availability and location of HIV support services and more streamlined delivery of services.
AIDS patient care and STDs 09/2011; 25(9):525-32. · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The development of newer agents such as raltegravir, etravirine and maraviroc has improved the perspective of viral load suppression. However, there is not enough data regarding their use together. In this study, we describe nine patients who were triple-class experienced and were on a salvage regimen consisting of a combination of raltegravir, etravirine, and maraviroc. Our results showed that this regimen is safe with no major side effect and has good virological efficacy with two-thirds of the patients achieving an undetectable viral load by 24 weeks.
Journal of the International Association of Physicians in AIDS Care (JIAPAC) 03/2011; 10(3):135-7.
[Show abstract][Hide abstract] ABSTRACT: Patients with multiclass-resistant HIV-1 have limited treatment options. Raltegravir, an inhibitor of integrase, has shown excellent efficacy when used with protease inhibitors (Pis) in patients with drug-resistant HIV-1. Limited data are available however about the outcomes when using raltegravir without Pis in this population.
Medical records of subjects who received raltegravir as part of the Merck EAP study 0518 were reviewed and abstracted at participating sites. Eligibility criteria included HIV positivity, age ≥ 16 years, limited or no treatment options due to resistance or intolerance to multiple antiretroviral regimens, detectable viremia on current treatment regimen, and documented resistance to at least one drug in each antiretroviral class (PI, NNRTI, and nucleoside analogue). Demographic, clinical, and laboratory data were collected locally using a standardized collection form. Genotypic susceptibility scores (GSS) were determined from the most recent genotypic resistance test available prior to the initiation of raltegravir. The main objective was to compare virologic results in patients who received raltegravir with a PI versus those who received raltegravir without a PI.
Four hundred forty-two subjects were evaluated from the respective sites in the EAP trial, of whom 340 were evaluable. The baseline mean HIV RNA was 4.6 log copies/ mL, and the mean CD4 cell count was 159 cells/μL. The median number of total and new antiretroviral agents in the background regimen was 4 and 2, respectively. Among the 254 patients who received a PI, the most common PI used was darunavir (89%). Etravirine was commonly used in both groups: 39% of the PI group and 67% of the non-PI group. At week 12, 67% of PI patients and 64% of non-PI patients achieved HIV RNA <75 copies/mL and 85% and 86%, respectively, achieved HIV RNA <400 copies/mL GSS, which was similar in both groups at baseline, predicted achieving an HIV RNA of <400 and 75 copies/mL at week 12 (P < .05).
In treatment-experienced patients, the combination of raltegravir with a regimen not containing a PI (used with etravirine in two-thirds of patients) had similar virologic activity when compared to more standard regimens using raltegravir with a PI. The main determinant of efficacy was the number of active drugs as measured by GSS. These data expand the potential utility of raltegravir in patients with multidrug-resistant HIV.
HIV Clinical Trials 01/2011; 12(3):131-40. · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.
[Show abstract][Hide abstract] ABSTRACT: Pyogenic liver abscesses are rarely encountered in HIV-infected patients living outside of temperate climates and are usually polymicrobial in nature, with a majority of the pathogens arising from gastrointestinal flora. We describe the second case of a liver abscess in an HIV-positive individual that was caused by methicillin-resistant Staphylococcus aureus (MRSA), most likely due to a partially treated community-acquired MRSA skin abscess. The liver abscess was successfully managed by percutaneous drainage and intravenous antibiotics. This case underlines the ubiquitous nature of community-acquired MRSA and its possible unusual presentations in immunocompromised hosts.
The American Journal of the Medical Sciences 03/2010; 339(3):290-1. · 1.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gene transfer has potential as a once-only treatment that reduces viral load, preserves the immune system and avoids lifetime highly active antiretroviral therapy. This study, which is to our knowledge the first randomized, double-blind, placebo-controlled, phase 2 cell-delivered gene transfer clinical trial, was conducted in 74 HIV-1-infected adults who received a tat-vpr-specific anti-HIV ribozyme (OZ1) or placebo delivered in autologous CD34+ hematopoietic progenitor cells. There were no OZ1-related adverse events. There was no statistically significant difference in viral load between the OZ1 and placebo group at the primary end point (average at weeks 47 and 48), but time-weighted areas under the curve from weeks 40-48 and 40-100 were significantly lower in the OZ1 group. Throughout the 100 weeks, CD4+ lymphocyte counts were higher in the OZ1 group. This study indicates that cell-delivered gene transfer is safe and biologically active in individuals with HIV and can be developed as a conventional therapeutic product.
Nature medicine 03/2009; 15(3):285-92. · 27.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Maraviroc is a small molecule and a member of a new class of antiretroviral compounds known as CCR5 antagonists, which block R5-tropic HIV entry into CD4 cells. HIV entry into the cell requires binding to a CD4 molecule and, in the majority of cases, to a coreceptor, either chemokine coreceptor 4 (CXCR4) or 5 (CCR5). In August 2007, the US FDA approved maraviroc for use in combination with other antiretroviral agents for treatment-experienced adults infected with CCR5-tropic HIV-1 only and who have evidence of viral replication. Maraviroc prevents the virus from entering uninfected cells by blocking the CCR5 coreceptor. Maraviroc has two dose formulations (150- and 300-mg tablets) and can be taken with or without food. The dosing recommendations are based on concomitant medications due to drug interactions. It is excreted primarily in the feces, with approximately 25% via urine. The safety and efficacy of maraviroc have not been established in pregnant women or pediatric patients. Maraviroc has been shown to achieve an undetectable HIV-1 RNA level in clinically advanced, class 3 antiretroviral treatment-experienced adults with evidence of CCR5-tropic HIV-1 replication despite ongoing antiretroviral therapy. It is generally well tolerated and its development is responding to a desperate need for new classes of antiretroviral agents that can target novel steps of the HIV lifecycle and do not share crossresistance with currently available therapy.