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Biomedical subjects

Robert Gross

Publications and source records attributed to Robert Gross.

At least 19 recordsLinked to original sources
PubMed2007

Prevalence, risk factors, and outcomes for occult hepatitis B virus infection among HIV-infected patients.

BACKGROUND: Occult hepatitis B virus (HBV) is defined by the presence of HBV DNA in individuals with HBV core antibodies (anti-HBc) but without HBV surface antigen (HBsAg). The prevalence of occult HBV in HIV-infected patients remains controversial, and the risk factors and clinical significance are unknown. OBJECTIVES: To determine the prevalence, risk factors, and clinical significance of occult HBV among HIV-infected patients. Hypothesized risk factors include chronic hepatitis C virus (HCV), CD4 count < 200 cells/mm, HIV RNA level >1000 copies/mL, and lack of use of anti-HBV antiretrovirals. METHODS: We examined randomly selected HBsAg/anti-HBc HIV-infected patients in the Penn Center for AIDS Research Adult/Adolescent Database and Specimen Repository. HBV DNA was qualitatively detected using a transcription-mediated amplification assay. Risk factors and transaminases were ascertained at the time sera were collected. RESULTS: A total of 699 HBsAg/anti-HBc HIV-infected patients were identified. Of 179 randomly selected subjects, 17 (10%; 95% confidence interval [CI]: 5% to 14%) had occult HBV. Differences in the prevalence of HBV surface antibody (anti-HBs) between those with (7 [41%]) and without (94 [58%]) occult HBV were not statistically significant (P = 0.3). An HIV RNA level >1000 copies/mL (adjusted odds ratio [OR] = 4.88, 95% CI: 1.01 to 30.26) and the absence of chronic HCV (adjusted OR = 0.26, 95% CI: 0.05 to 0.95) were associated with occult HBV. Occult HBV did not increase the risk of transaminitis (adjusted OR = 0.42, 95% CI: 0.12 to 1.45). CONCLUSIONS: Occult HBV occurred in a sizable proportion of HIV-infected patients and was associated with detectable HIV and the absence of chronic HCV. It did not increase the risk of transaminitis. The presence of anti-HBs does not rule out occult HBV. Future studies should examine the long-term clinical implications of occult HBV in HIV-infected patients.

Adult↗
PubMed2007

Incidence and risk factors for weight loss during dual HIV/hepatitis C virus therapy.

BACKGROUND: Clinical observations suggest that patients with HIV/hepatitis C virus (HCV) may lose body weight during dual therapy, but this has not been confirmed analytically. OBJECTIVES: To determine if the incidence and degree of weight loss among patients with HIV/HCV receiving highly active antiretroviral therapy (HAART) and pegylated (PEG)-interferon plus ribavirin were greater than in (1) HCV-monoinfected patients receiving PEG-interferon plus ribavirin and (2) HIV-monoinfected patients receiving HAART. Risk factors for weight loss among patients with HIV/HCV were also examined. METHODS: A retrospective cohort study was performed among HIV/HCV-coinfected, HCV-monoinfected, and HIV-monoinfected patients. Body weights were assessed up to 6 months before and up to 12 months after initiation of HCV therapy (HIV/HCV-coinfected and HCV-monoinfected subjects) and over 18 months on HAART (HIV-monoinfected subjects). The primary outcome was clinically significant weight loss (> or =5% of baseline weight). RESULTS: Of 192 subjects, 63 had HIV/HCV, 64 had HCV alone, and 65 had HIV alone. Clinically significant weight loss occurred in 48 (76%) subjects with HIV/HCV versus 25 (39%) subjects with HCV (P < 0.001) and 2 (3%) subjects with HIV (P < 0.001), yielding adjusted hazard ratios (HRs) of 2.76 (95% confidence interval [CI]: 1.67 to 4.55) and 38.5 (95% CI: 8.5 to 174.7), respectively. Receipt of more than 2 nucleoside reverse transcriptase inhibitors increased the risk of clinically significant weight loss (adjusted HR = 8.17, 95% CI: 2.37 to 28.20). CONCLUSIONS: The incidence of weight loss is greater in dually treated patients with HIV/HCV than in treated HCV- or HIV-monoinfected patients. Prospective studies should evaluate additional risk factors for weight loss and changes in body composition to elucidate the mechanism for this weight loss.

Adult↗
PubMed2007

Medication beliefs as mediators of the health literacy-antiretroviral adherence relationship in HIV-infected individuals.

Identifying modifiable barriers to antiretroviral adherence remains an important aim. We hypothesized that mistaken beliefs regarding taking HIV medications mediated the relation between low literacy and poor adherence. We studied 87 HIV-infected individuals on standard antiretroviral regimens for >or= 3 months. Adherence was assessed using pharmacy refill records. Medication beliefs, including an individual's norm for acceptable adherence, were measured using questions developed by expert panel. Literacy was associated with >or=95% adherence (64% for >or=9th grade level vs. 40% for <9th grade level). Participants with <95% adherence had a lower threshold of acceptable adherence than those with >or=95% adherence [80% adherence (interquartile range 70-90%) vs. 90% adherence (interquartile range 80-90%)]. However, the effect was independent of literacy. No other beliefs assessed were associated with adherence. Although the beliefs assessed do not mediate the relation between literacy and adherence, we identified low adherence norms as a potentially modifiable belief associated with adherence.

Adult↗
PubMed2006

A simple, dynamic measure of antiretroviral therapy adherence predicts failure to maintain HIV-1 suppression.

BACKGROUND: High levels of antiretroviral therapy adherence are important for human immunodeficiency virus type 1 (HIV-1) suppression, yet the magnitude of adherence required to maintain it is less well characterized. Furthermore, methods to accommodate changes in adherence over time are lacking. In the present study, our objective was to determine the magnitude of antiretroviral therapy adherence needed to maintain HIV-1 suppression by use of a time-updated adherence measure that has the potential to be of use in a clinical setting. METHODS: We examined a population-based cohort of HIV-1-infected subjects > or =18 years of age, residing in British Columbia, Canada, who started receiving antiretroviral therapy between 1 August 1996 and 30 September 2003, who had at least 2 consecutive viral loads <500 copies/mL and who had prescriptions filled at least 3 times during a follow-up period ending 30 September 2004. Virological failure was defined as the second of 2 consecutive viral loads >1000 copies/mL. Cox proportional hazards model was used to determine the relationship between virological failure and refill-based, time-updated surrogate measure of adherence. RESULTS: Among the 1634 participants > or =18 years of age who initiated triple combination therapy during the study, 606 virological failure events were identified. In multivariate analyses, subjects with < or =95% adherence were 1.66 (95% confidence interval, 1.38-2.01) times more likely to experience virological failure than those with >95% adherence. CONCLUSIONS: The highest levels of antiretroviral therapy adherence are associated with higher rates of maintained virological suppression. This simple, dynamic surrogate measure of adherence overcomes the limitation of single-point-in-time calculations of adherence and may be useful in real time to determine whether an individual is exhibiting incomplete adherence.

Adult↗
PubMed2006

Diagnostic accuracy of CD4 cell count increase for virologic response after initiating highly active antiretroviral therapy.

OBJECTIVE: To derive and internally validate a clinical prediction rule for virologic response based on CD4 cell count increase after initiation of HAART in a resource-limited setting. DESIGN AND METHODS: A retrospective cohort study at two HIV care clinics in Gaborone, Botswana. The participants were previously treatment-naive HIV-1-infected individuals initiating HAART. The main outcome measure was a plasma HIV-1 RNA level (viral load) < or = 400 copies/ml (i.e. undetectable) 6 months after initiating HAART. RESULTS: The ability of CD4 cell count increase to predict an undetectable viral load was significantly better in those with baseline CD4 cell counts < or = 100 cells/microl [area under the ROC curve (AUC), 0.78; 95% confidence interval (CI), 0.67-0.89; versus AUC, 0.60; 95% CI, 0.48-0.71; P = 0.018]. The sensitivity, specificity, and positive and negative predictive values of a CD4 cell count increase of > or = 50 cells/microl for an undetectable viral load in those with baseline CD4 cell counts < or = 100 cells/microl were 93.1, 61.3, 92.5 and 63.3%, respectively. Alternatively, these values were 47.8, 87.1, 95.0 and 24.5%, respectively, if a increase in CD4 cell count of > or = 150 cells/microl was used. CONCLUSIONS: CD4 cell count increase after initiating HAART has only moderate discriminative ability in identifying patients with an undetectable viral load, and the predictive ability is higher [corrected] in patients with lower baseline CD4 cell counts. Although HIV treatment programs in resource-constrained settings could consider the use of CD4 cell count increases to triage viral load testing, more accurate approaches to monitoring virologic failure are urgently needed.

Adolescent↗
PubMed2006

Out-of-pocket costs of HAART limit HIV treatment responses in Botswana's private sector.

A large number of HIV-infected patients in sub-Saharan Africa pay out-of-pocket for HAART. This analysis from Botswana indicates that higher median out-of-pocket regimen costs to patients for the initial 30 days of HAART are associated with failure to achieve a viral load< 400 copies/ml [US$32; interquartile range (IQR), 20-84 compared with US$22; (IQR, 17-36), P = 0.001]. HAART costs should be minimized as scale-up efforts in sub-Saharan Africa progress.

Adult↗
PubMed2006

HIV-1-specific CD4+ T cell responses in chronically HIV-1 infected blippers on antiretroviral therapy in relation to viral replication following treatment interruption.

The impact of transient viral load blips on anti-HIV-1 immune responses and on HIV-1 rebound following treatment interruption (TI) is not known. Clinical and immunological parameters were measured during 40 weeks of antiretroviral therapy (ART) and following TI in an observational cohort of 16 chronically HIV-1-infected subjects with or without observed viral load blips during ART. During therapy, blips in seven subjects were associated with higher anti-HIV-1 (p24) CD4+ T cell lymphoproliferative responses (p = 0.04), without a significant difference in T cell activation or total anti-HIV-1 CD8+ T cell interferon-gamma (IFN-gamma) responses when compared to nine matched non-blippers. Therapy interruption resulted in a significantly higher viral rebound in blippers by 8 week despite retention of higher lymphoproliferative p24 responses (p = 0.01) and a rise in CD3+ T cell activation (p = 0.04) and anti-HIV-1 CD8+ T cell responses in blippers by week 4 when compared to non-blippers. Past week 4 of interruption, therapy re-initiation criteria were also met by a higher frequency in blippers by week 14 (p < 0.04) with no difference between groups by week 24. These data support that blippers have higher anti-HIV lymphoproliferative responses while on ART but experience equal to higher viral rebound as compared to matched non-blippers upon TI.

Anti-HIV Agents↗
PubMed2005

Effect of GB virus C viremia on HIV acquisition and HIV set-point.

We performed both a case-control study and a cohort study to determine whether GB virus C (GBV-C) viremia prevents the acquisition of HIV infection or alters the HIV set-point after infection. The prevalence of GBV-C viremia in HIV-uninfected individuals who did and did not acquire HIV were similar (odds ratio 1.32; 95% confidence interval 0.6-2.6). Pre-existing GBV-C viremia at the time of HIV acquisition was also not associated with lower plasma HIV-RNA levels.

Adult↗
PubMed2005

A tale of 2 epidemics: the intersection between obesity and HIV infection in Philadelphia.

BACKGROUND: Obesity and HIV infection are ongoing epidemics in the United States. Obesity predisposes to diabetes and cardiovascular disease, which are complications also associated with HIV and/or its treatment. OBJECTIVE: To determine the prevalence and risk factors for overweight and obesity in HIV-infected individuals. DESIGN AND SETTING: Retrospective cross-sectional study in which 1689 patients enrolled in the University of Pennsylvania Center for AIDS Research Adult/Adolescent Database at 1 university hospital clinic, 2 affiliated practices, and 1 Veterans Administration clinic in Philadelphia had demographic, social, and medical data collected prospectively since 1999. PARTICIPANTS: Body mass index (BMI) data were available for 1669 HIV-infected subjects: 78% were men, and 60% were African American. The median CD4 count was 381 cells/microL, 47% of subjects had a viral load <400 copies/mL, and 9% of subjects were treatment naive. MAIN OUTCOME MEASURES: The prevalence and risk factors for overweight (BMI: 25-29.9 kg/m) and obesity (BMI>or=30 kg/m) in HIV-infected subjects. RESULTS: Obesity and overweight were more prevalent than wasting (14%, 31%, and 9%, respectively; P<0.0005), but they were not more common than in the general population. Although women and men were equally overweight (30% vs. 31%), women were more obese than men (28% vs. 11%; P<0.001). Among women, African American race (odds ratio [OR]=1.8, 95% confidence interval [CI]: 1.1-2.9) and a CD4 count>or=200 cells/microL (OR=2.8, 95% CI: 1.6-4.9) were associated with overweight and obesity. Among men, only a CD4 count>or=200 cells/microL (OR=1.6, 95% CI: 1.04-2.4) was associated with increased BMI. In men and women, smoking was associated with decreased obesity and overweight (OR=0.59, 95% CI: 0.47-0.74 and OR=0.65, 95% CI: 0.43-0.98, respectively). Age, income, employment, education, past or current intravenous drugs, being on HIV treatment, and viral load were not associated with obesity in the multivariate model. There was a positive correlation between BMI and total cholesterol, triglycerides, and glucose. CONCLUSION: Obesity is more common than wasting in this therapeutic era. Women, particularly those of African American race, are at high risk. Obesity might add to metabolic abnormalities associated with HIV or its treatment and contribute to morbidity, as patients with HIV live longer.

Adolescent↗
PubMed2005

Epidemiologic studies of adverse effects of anti-retroviral drugs: how well is statistical power reported.

PURPOSE: To determine whether there is a difference in average statistical power between pharmacoepidemiologic studies of anti-retroviral adverse drug effects (ADEs) sponsored by for-profit versus non-profit organizations. METHODS: We studied all published pharmacoepidemiologic studies of ADEs associated with the 15 anti-retroviral drugs approved through the end of 1999. A priori, the primary outcome was the power of each study to detect a clinically important difference in the risk for an adverse effect among patients exposed to the study drug(s). We could not evaluate this outcome because of the infrequent reporting of power calculations. We instead report the distribution of studies across a 5-tiered measure of adequacy of reporting of statistical power, as well as the sponsorship of these studies. RESULTS: Of 48 studies meeting our inclusion criteria, only 1 (2%) reported either a completed, a priori power calculation or sufficient details for readers to calculate the power to detect a pre-defined, clinically important effect. Thirty-five studies (73%) reported the minimum information required for sophisticated readers to determine the power to detect an event rate of interest to them; 6 additional studies (13%) reported confidence intervals around at least one summary effect measure and 6 (13%) provided no indication of power or uncertainty. Of the 41 studies for which sponsorship was determined, only 3 (7%) were sponsored by for-profit organizations. CONCLUSIONS: The poor reporting of statistical power in this sample suggests a need for guidelines to improve the reporting of pharmacoepidemiologic studies of ADEs. Future research is needed to determine whether the observed paucity of industry-sponsored observational studies of anti-retroviral ADEs extends to other clinical areas, and if so, to identify the causes of this phenomenon.

Adverse Drug Reaction Reporting Systems↗
PubMed2005

The odds that clinically unrecognized poor or partial adherence confuses population pharmacokinetic/pharmacodynamic analyses.

Electronic compilation of ambulatory patients' or trial participants' dosing histories has revealed that a wide range of dosing patterns, markedly skewed toward underdosing, occur in virtually every disease and treatment situation so far studied. In planning ambulatory trials and their analyses, one should recognize that patients' variable exposure to test drugs, created by their diversely erratic execution of protocol-specified dosing regimens, is generally the single largest source of variance in drug responses. Trial subjects' erratic dosing behaviour may, if ignored, weaken the trial's assay sensitivity. In contrast, reliably compiled and soundly analyzed dosing histories may greatly inform the analysis of the trial. Dosing histories found to be associated with suboptimal clinical results can highlight particular dosing patterns that should be avoided. Thus begins the sequence leading from first observations, to repeat observations, to ethically possible experimental designs, to causal inference, i.e., learning and then confirming. With the broadening use of electronic monitoring to estimate longitudinal drug exposure, the need exists for an explicit discipline that concerns itself with "what the patient does with the drug". It is called Pharmionics.

Anti-HIV Agents↗
PubMed2004

Randomized, controlled trial of therapy interruption in chronic HIV-1 infection.

BACKGROUND: Approaches to limiting exposure to antiretroviral therapy (ART) drugs are an active area of HIV therapy research. Here we present longitudinal follow-up of a randomized, open-label, single-center study of the immune, viral, and safety outcomes of structured therapy interruptions (TIs) in patients with chronically suppressed HIV-1 infection as compared to equal follow-up of patients on continuous therapy and including a final therapy interruption in both arms. METHODS AND FINDINGS: Forty-two chronically HIV-infected patients on suppressive ART with CD4 counts higher than 400 were randomized 1:1 to either (1) three successive fixed TIs of 2, 4, and 6 wk, with intervening resumption of therapy with resuppression for 4 wk before subsequent interruption, or (2) 40 wk of continuous therapy, with a final open-ended TI in both treatment groups. Main outcome was analysis of the time to viral rebound (>5,000 copies/ml) during the open-ended TI. Secondary outcomes included study-defined safety criteria, viral resistance, therapy failure, and retention of immune reconstitution. There was no difference between the groups in time to viral rebound during the open-ended TI (continuous therapy/single TI, median [interquartile range] = 4 [1-8] wk, n = 21; repeated TI, median [interquartile range] = 5 [4-8] wk, n = 21; p = 0.36). No differences in study-related adverse events, viral set point at 12 or 20 wk of open-ended interruption, viral resistance or therapy failure, retention of CD4 T cell numbers on ART, or retention of lymphoproliferative recall antigen responses were noted between groups. Importantly, resistance detected shortly after initial viremia following the open-ended TI did not result in a lack of resuppression to less than 50 copies/ml after reinitiation of the same drug regimen. CONCLUSION: Cycles of 2- to 6-wk time-fixed TIs in patients with suppressed HIV infection failed to confer a clinically significant benefit with regard to viral suppression off ART. Also, secondary analysis showed no difference between the two strategies in terms of safety, retention of immune reconstitution, and clinical therapy failure. Based on these findings, we suggest that further clinical research on the long-term consequences of TI strategies to decrease drug exposure is warranted.

Adult↗
PubMed2004

A time-to-prescription-refill measure of antiretroviral adherence predicted changes in viral load in HIV.

OBJECTIVE: The goal of this study was to determine the validity and utility of a pharmacy-based time-to-refill measure of antiretroviral therapy adherence. METHODS: We performed an observational cohort study of 110 HIV-infected subjects on a stable, highly active antiretroviral regimen for at least 3 months at a Veterans' Affairs Medical Center in Philadelphia, Pennsylvania. RESULTS: The viral load decreased by 0.12 log c/mL (95% confidence interval [CI] 0.01-0.23 log c/mL) for each 10% increase in pharmacy-based time-to-refill defined adherence as compared with 0.05 log c/mL (95% CI -0.14-0.25 log c/mL) for the self-reported adherence measure. Thus, only the refill-defined measure was statistically significantly associated with viral load change. When adherence was classified as good (> or = 85%) versus poor (<85%), both measures demonstrated a significant difference in outcome between groups. Yet, in individuals self-reporting 100% adherence, those classified as good adherers using the pharmacy-based measure had greater viral load reductions than poor adherers (2.4 log c/mL [interquartile range 1.4-3.4] vs. 1.5 log c/mL [interquartile range 0.8-2.4, P=.03). CONCLUSIONS: The pharmacy-based technique is a valid measure of antiretroviral therapy adherence. Because it provides clinically relevant information in subjects who self-report 100% adherence, it should be incorporated into clinical practice and adherence research.

Adult↗
PubMed2004

Natural history of patients with low-level HIV viremia on antiretroviral therapy.

Ultrasensitive assays for HIV RNA have identified a significant number of patients with persistent low-level viremia despite antiretroviral therapy. The clinical implications of maintaining antiretroviral therapy during low-level HIV viremia remain unclear. The primary objective of this study was to determine the rate and risk factors for virological increase in subjects with low-level HIV viremia who did not change antiretroviral therapy. Between July 1998 and February 2002, we retrospectively observed 79 HIV-infected adults with low-level HIV viremia (between 50 and 500 copies per milliliter) who had been on a stable antiretroviral regimen for at least 3 months and continued that regimen for at least 3 more months. Virologic increase, defined as HIV RNA levels greater than 1000 copies per milliliter, was observed in 29 of the 79 (37%) subjects. The CD4 cell counts decreased by a median of 1.8 cells/mm(3) per month (interquartile range [IQR], -19.6 to 2.3 cells/mm3) in this group but increased by a median of 0.5 cells/mm3 per month (IQR, -6.3 to 5.8 cells/mm3) in the 50 subjects who did not experience virologic increase. A Kaplan-Meier estimate showed that at 3 years of follow-up, approximately 40% of the observed cohort had not experienced virologic increase. There was a higher rate of virologic increase per log increase in HIV viral load at entry into the cohort (adjusted hazards ratio [HR] 3.7; 95% confidence interval [CI], 1.1 to 12.6). Subjects of white race were also more likely to experience virological increase (adjusted HR 2.6; CI, 1.2 to 5.8). Maintenance of antiretroviral therapy despite low-level HIV viremia provided sustained immunological benefit over a 2-year period in approximately two thirds of our cohort. Higher initial HIV RNA levels and white race were predictors for virologic increase.

Adult↗
PubMed2003

Presence of human immunodeficiency virus-1-specific CD4 and CD8 cellular immune responses in children with full or partial virus suppression.

The present study assessed antiviral T cell immune responses in 48 human immunodeficiency virus (HIV)-infected children with a stable or decreasing CD4(+) T cell counts and different levels of viral control, in the presence or absence of antiretroviral therapy. Children with full (<40 copies/mL) or partial (<50,000 copies/mL) virus suppression and with a history of stable CD4(+) T cell counts had significantly increased levels of anti-HIV CD4(+) T cell lymphoproliferative responses, lower levels of CD38(+), and higher CD8(+)/CD28(+) T cell percentage, compared with those in treated children with a lack of virus suppression (>50,000 copies/mL). Levels of anti-HIV CD8(+) T cell activity, although higher in treated children with a lack of virus suppression, were not significantly different between the groups. Although levels of anti-HIV CD4(+) and CD8(+) T cell responses were not associated, these levels of responses were associated with the percentage of specific T cell subsets. Overall, a history of stable CD4(+) T cell counts, as a result of therapy that imparted full or partial virus suppression, was associated with increased levels of anti-HIV CD4(+) T helper responses and decreased T cell activation.

Adolescent↗