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Biomedical subjects

G Friedland

Publications and source records attributed to G Friedland.

At least 19 recordsLinked to original sources
PubMed2005

Quality of life in HIV-infected individuals receiving antiretroviral therapy is related to adherence.

This study assesses changes in quality of life (QoL) over time among HIV-infected individuals receiving antiretroviral therapy (ART) and evaluates how this relates to ARTadherence. Prospective, longitudinal data were examined from 1050 participants in two large, randomized, multi-centre antiretroviral clinical trials. QoL was assessed by the SF-12; adherence by the Terry Beirn Community Programs for Clinical Research on AIDS Antiretroviral Medication Self-report. Participants included 20% women, 53% African Americans, 16% Latinos; mean age was 39 years; mean baseline CD4+ cell count 230 cells/mm3; 89% were ART-naïve at entry. Baseline physical and mental health summary QoL scores were 45.4 and 42.9, comparable to scores reported in other advanced HIV populations. Significant improvements in mean QoL scores were seen for the group as a whole after 1 to 4 months on new ART regimens, and persisted for 12 months. Participants reporting 100% ART adherence achieved significantly higher QoL scores at 12 months compared to those with poorer adherence, particularly if 100% adherence was consistent (p < 0.001). Those with at least 80% ART adherence had smaller gains in QoL at 12 months when compared to baseline, while those with < 80% adherence had worsening of QoL. In this analysis, ART adherence was associated with improved QoL, particularly if adherence was sustained.

Adult↗
PubMed2001

Effect of opioid dependence pharmacotherapies on zidovudine disposition.

Injection drug users are frequently infected with human immunodeficiency virus (HIV) and receive opioid dependence pharmacotherapies and zidovudine (ZDV), the latter as a component of highly active antiretroviral therapy. We previously reported that methadone substantially increases ZDV concentrations. We now report on oral ZDV pharmacokinetics in 52 subjects receiving the opioid dependence pharmacotherapies l-alpha-acetylmethadol LAAM, buprenorphine, or naltrexone, and 17 non-opioid-treated controls. Relative to the area under the time-concentration curve (AUC) of ZDV in control subjects, no statistically significant differences in ZDV AUC were observed in participants treated with LAAM (p = .75), buprenorphine (p = .37), or naltrexone (p = .34). While methadone maintenance may result in ZDV toxicity and possibly require dose adjustments, other opioid pharmacotherapies should not produce ZDV toxicity.

Anti-HIV Agents↗
PubMed2000

Two double-blinded, randomized, comparative trials of 4 human immunodeficiency virus type 1 (HIV-1) envelope vaccines in HIV-1-infected individuals across a spectrum of disease severity: AIDS Clinical Trials Groups 209 and 214.

The potential role of human immunodeficiency virus type 1 (HIV-1)-specific immune responses in controlling viral replication in vivo has stimulated interest in enhancing virus-specific immunity by vaccinating infected individuals with HIV-1 or its components. These studies were undertaken to define patient populations most likely to respond to vaccination, with the induction of novel HIV-1-specific cellular immune responses, and to compare the safety and immunogenicity of several candidate recombinant HIV-1 envelope vaccines and adjuvants. New lymphoproliferative responses (LPRs) developed in <30% of vaccine recipients. LPRs were elicited primarily in study participants with a CD4 cell count >350 cells/mm(3) and were usually strain restricted. Responders tended to be more likely than nonresponders to have an undetectable level of HIV-1 RNA at baseline (P=.067). Induction of new cellular immune responses by HIV-1 envelope vaccines is a function of the immunologic stage of disease and baseline plasma HIV-1 RNA level and exhibits considerable vaccine strain specificity.

AIDS Vaccines↗
PubMed2000

Prevalence of multiple dideoxynucleoside analogue resistance (MddNR) in a multicenter cohort of HIV-1-infected Italian patients with virologic failure.

We evaluated the prevalence of both Q151M and 6-bp insert at position 69 of RT region responsible for multiple dideoxynucleoside analogue-resistant (MddNR) HIV-1 variants in 177 patients who failed to respond to combination therapy. Patients had received protease inhibitors (PI) and/or nonnucleoside reverse transcriptase inhibitors (NNRTIs) after a long-term experience with nucleoside reverse transcriptase inhibitors (NRTIs) (including zidovudine monotherapy). Two of 177 patients (1.1%) showed the specific complex of Q151M mutation, while 4 (2.3%) had the 69 6-bp insert. Mutations that belong to the 151 set in the absence of the pivotal Q151M substitution were detected in as many as 3.9% of the patients. One patient exhibited a 69S [VG] insert that has not been previously phenotypically characterized. This HIV-1 isolate had high levels of resistance to all NRTIs except stavudine. MddNR is an emerging problem after sequential therapy with this class of compounds among HIV-1-infected patients. Either didanosine (ddI) or zidovudine (ZDV) monotherapy allowed the emergence of MddNR variants containing Q151M complex. Monotherapy with ZDV and ddI or subsequent treatments with various NRTI combinations were the common background in the patients with the 69 insert. The overall prevalence of MddNR (3.4%) in Italy is comparable with that observed in several other European countries (3.4%-6.5%). These data suggest that patients failed by NRTI regimens should be analyzed for the presence of both patterns of MddNR.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Progress in HIV therapeutics and the challenges of adherence to antiretroviral therapy.

The impressive and gratifying advances in antiretroviral therapy have benefited many with HIV disease who are fortunate to have access to these complicated and expensive regimens. It is still early in the era of HAART, and the future of therapeutics is not clear. No other infectious disease has required lifelong therapy, and the challenges of equitable treatment of this chronic infectious disease are daunting; not the least among them is lifelong adherence to medications. To maximize the potential of each drug and drug combination, targeted efforts to increase and maintain excellent adherence in the real-world clinical setting are essential, and are second in importance only to the more widespread availability of HAART and continued development of new and more potent agents. The theoretical basis for improving adherence exists, but more substantial research is required. The aim of providing and maintaining therapeutic benefit necessitates that clinicians develop and employ practical and relevant strategies to support antiretroviral adherence. The marriage of biology and behavior that characterizes clinical care in HIV disease is nowhere more challenging for clinicians than in the issue of adherence, but also nowhere more gratifying.

Anti-HIV Agents↗
PubMed2000

Antiretroviral prophylaxis of health care workers at two urban medical centers.

We examined the influence of job category, source patient HIV status, and exposure type as predictors of whether health care workers initiated antiretroviral prophylaxis after potential blood-borne pathogen exposures. Of 639 exposures over an 18-month period, 82 individuals (13%) elected to receive prophylaxis, of whom 66% took medications for fewer than 96 hours and 12% completed a 4-week course. Reasons for early drug discontinuation included confirmation of source patient HIV-negative serological status (65%), gastrointestinal side effects (13%), headache (4%), and personal decision after counseling/other input (18%). Individuals exposed to HIV-positive source patients were more likely to initiate prophylaxis (odds ratio [OR], 5.1; 95% confidence interval [CI] 2.6 to 9.9). Licensed nurses were less likely than others to accept prophylaxis (OR, 0.5; 95% CI, 0.3 to 0.8), whereas physicians and medical students were more likely to accept prophylaxis (OR, 1.9; 95% CI, 1.1 to 3.3).

Adult↗
PubMed1999

Tuberculosis and HIV Infection.

We review important new recommendations on the treatment and prophylaxis of tuberculosis in HIV-infected individuals. Large-scale studies and expert consensus panels have both concluded that shorter courses and intermittent antituberculous regimens are adequate for the treatment of dually infected individuals. Also, the substitution of rifabutin for rifampin for the treatment and prophylaxis of tuberculosis has been shown to be advantageous, providing equivalent efficacy to regimens containing rifampin, and fewer drug interactions with antiretroviral medications.

Journal Article↗
PubMed1999

Stavudine resistance: an update on susceptibility following prolonged therapy.

The current report summarizes the available published and unpublished data from several investigators on resistance in clinical isolates following prolonged stavudine therapy. Results suggest that stavudine resistance is both modest in degree and infrequent in appearance. Phenotypic evaluation of 61 patients on stavudine therapy showed only modest changes in drug sensitivity following up to 29 months of treatment. The post-treatment isolates from 15 patients exhibited an increase in EC50 value > fourfold (level above variability of assay) when compared with the corresponding pretreatment isolates. However, the vast majority (11) of these pretreatment isolates either had unexpectedly low EC50 levels and/or had post-treatment isolates that lacked any amino acid changes within their reverse transcriptase (RT) gene to account for the observed change in sensitivity. Of the four remaining isolates, two appeared to have a multi-resistant phenotype to several nucleoside analogues and two had no detectable RT amino acid changes to account for the observed change in stavudine sensitivity. To date, clinical HIV-1 isolates displaying stavudine-specific resistance have yet to be reported. Furthermore, full or partial RT sequence analysis of 194 post-treatment isolates failed to identify any consistent amino acid changes. The strain-specific V75T mutation reported to confer stavudine resistance to the HXB2 HIV-1 strain in vitro, was found in only six isolates and did not correlate with stavudine resistance. This low incidence of stavudine resistance is in striking contrast to that observed with other nucleoside analogues and further supports the use of stavudine in first-line combination therapy for HIV patients.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Methadone effects on zidovudine disposition (AIDS Clinical Trials Group 262).

Large numbers of injection drug users (IDUs) are infected with HIV and receive both methadone and zidovudine (ZDV) therapy. Pharmacokinetic interactions between these agents may effect drug efficacy, toxicity, and compliance. To confirm and expand previous studies that identified a potential interaction between ZDV and methadone, we performed a within-subject study to determine oral and intravenous ZDV pharmacokinetics in 8 recently detoxified, heroin-addicted patients with HIV disease before and after initiation of methadone treatment. Acute methadone treatment increased oral ZDV in the area under the curve (AUC) by 41% (p = .03) and intravenous ZDV AUC by 19% (p = .06). Clearance was reduced by 21% (p = .007) and 19% (p = .04), respectively. Chronic methadone treatment increased oral ZDV AUC by 29% (p = .15) and intravenous ZDV AUC by 41% (p = .05). Clearance was decreased by 26% for both routes (p = .02). Methadone levels remained in the therapeutic range during ZDV treatment. These effects resulted primarily from inhibition of ZDV glucuronidation, but also from decreased renal clearance of ZDV. This study confirms that methadone-maintained patients receiving standard ZDV doses experience greater ZDV exposure and may be at increased risk for ZDV side effects and toxicity. Increased toxicity surveillance and possibly reduction in ZDV dose are indicated when these two agents are given concomitantly.

Administration, Oral↗
PubMed1998

Public health implications of antiretroviral therapy and HIV drug resistance.

Widespread use of antiretroviral agents and increasing occurrence of human immunodeficiency virus (HIV) strains resistant to these drugs have given rise to a number of important issues. Some of these concerns are distinct from the obvious question of the relationship between drug resistance and treatment failure and have potentially widespread public health implications. The relevant issues include but are not limited to the following: (1) frequency with which drug-resistant virus may be transmitted via sexual, intravenous, or mother-to-child routes; (2) ability of drug-resistant variants to be transmitted, a question that relates, in part, to the relative fitness of such strains; (3) effectiveness of antiviral therapy in diminishing viral burden in both blood and genital secretions, and whether this may be compromised in persons harboring resistant virus; and (4) importance of patient adherence to antiviral therapy and its relationship to sustained reduction in viral load to minimize the appearance in and transmission of drug-resistant virus from both blood and genital secretions. Thus, prevention of both development of HIV drug resistance as well as transmission of drug-resistant variants is a central issue of public health importance. Unless this topic is appropriately addressed, the likelihood is that drug-resistant variants of HIV, if able to successfully replicate, will sustain the epidemic and limit the effectiveness of antiviral therapy.

Anti-HIV Agents↗
PubMed1998

Molecular cloning and characterization of p56dok-2 defines a new family of RasGAP-binding proteins.

Chronic myelogenous leukemia (CML) is a disease characterized by the presence of p210(bcr-abl), a chimeric protein with tyrosine kinase activity. Substrates for p210(bcr-abl) are likely to be involved in the pathogenesis of CML. Here we describe the purification, cDNA cloning, and characterization of a 56-kDa tyrosine phosphorylated protein, p56(dok-2) (Dok-2), from p210(bcr-abl) expressing cells. The human dok-2 cDNA encodes a 412-amino acid protein with a predicted N-terminal pleckstrin homology domain as well as several other features of a signaling molecule, including 13 potential tyrosine phosphorylation sites, six PXXP motifs, and the ability to bind to p120(RasGAP). Dok-2 was shown to be 35% identical to p62(dok-1), a recently identified RasGAP binding protein from CML cells, and analysis of the expressed sequence tag data base revealed the presence of at least four additional proteins containing a Dok homology sequence motif. Dok mRNAs were primarily expressed in tissues of hematopoietic origin. These findings strongly suggest that a family of Dok-related proteins exists that bind to RasGAP and may mediate the effects of p210(bcr-abl) in CML.

Adaptor Proteins, Signal Transducing↗
PubMed1998

End-of-life decisions in HIV-positive patients: the role of spiritual beliefs.

OBJECTIVE: To describe the role of spiritual beliefs in HIV-positive patients' end-of-life decisions. DESIGN: Inperson, cross-sectional survey. SETTING: An HIV/AIDS floor of an urban, university teaching hospital. PATIENTS: Ninety hospitalized HIV-positive patients. MAIN OUTCOME MEASURES: Prior discussions about advance directives, possession of a living will (written advance directive), fear of death, professions of hope and purpose in life, religious beliefs and practices, guilt about HIV infection, and perception of HIV as punishment. RESULTS: Of 104 eligible patients, 90 agreed to be interviewed. Twenty-four per cent of patients had discussed their resuscitation status with a physician and 17% possessed a living will; 44% of patients felt guilty about their HIV infection, 32% expressed fear of death, and 26% felt their disease was some form of punishment. Prior discussions about resuscitation status were less likely in those who perceived HIV as punishment (P=0.009) and more likely in those who believed in God's forgiveness (P=0.043). A living will was more common in those who prayed daily (P=0.025) and in those whose belief in God helped them when thinking about death (P=0.065). Fear of death was more likely in those who perceived HIV as punishment (P=0.01) or felt guilty about having HIV (P=0.039), and less likely in those who read the Bible frequently (P=0.01) or attended church regularly (P=0.015). Outcome measures did not vary significantly according sex, race, HIV risk factors, or education level. CONCLUSIONS: In this HIV-positive population, spiritual beliefs and religious practices appeared to play a role in end-of-life decisions. Discussions about end-of-life decisions may be facilitated by a patient's belief in a forgiving God and impeded by a patient's interpretation of HIV infection as punishment. Health-care providers need to recognize patients' spiritual beliefs and incorporate them into discussions about terminal care.

Advance Care Planning↗
PubMed1996

Use of a quantitative cytomegalovirus (CMV) antigenemia test in evaluating HIV+ patients with and without CMV disease.

Cytomegalovirus (CMV) infection remains a life-threatening infection in patients with HIV disease. A rapid, quantitative diagnostic technique is needed to adi in the diagnosis of CMV disease. This study was undertaken to evaluate the CMV antigenemia test in patients with HIV disease who are at risk for CMV disease. The study included 22 patients who underwent ophthalmologic exams or selected diagnostic techniques in whom CMV cultures and CMV antigenemia tests were performed. All of 11 patients with CMV disease had positive CMV antigenemia assays [range, 48-1,000 positive cells/2 x 10(5) peripheral blood leukocytes (PBL)], and 10 were also CMV viremic. There was no clinical evidence of CMV disease in 11 patients, including seven in whom the CMV antigenemia assay was negative and who remained without evidence of CMV disease after a median follow-up of 159 days. Four patients had low antigenemia levels. Of these four, two subsequently developed CMV retinitis. In conclusion, a positive CMV antigenemia result with > or = 48 positive cells/2 x 10(5) PBL correlated with concurrent CMV disease. The CMV antigenemia test appears to be a valuable tool for the rapid diagnosis of CMV disease in HIV-infected individuals.

AIDS-Related Opportunistic Infections↗
PubMed1996

Invasive pneumococcal disease: clinical features, serotypes, and antimicrobial resistance patterns in cases involving patients with and without human immunodeficiency virus infection.

We reviewed 153 episodes of invasive pneumococcal disease involving 147 hospitalized patients with and without human immunodeficiency virus (HIV) disease to examine and compare epidemiologic and clinical features, capsular serotypes, and antibiotic susceptibility patterns. HIV infection was the most common risk factor for invasive pneumococcal disease. Pneumococcal disease in HIV-infected individuals was characterized by the greater frequency with which pneumonia was the source of bacteremia (90% vs. 63%) (P < .01) and an increased recurrence rate (15% vs. < 1%) (P < .01). The overall mortality rate was 12% and did not vary by HIV serostatus. Capsular-type data were available for 149 episodes; 90% of the types were among those found in the polyvalent pneumococcal vaccine. The four most common capsular types causing invasive disease were 14, 6b, 9v, and 22f; capsular type 9v was significantly more common among HIV-infected patients (P < .01). Penicillin-resistant isolates were identified in 7.2% of all cases, and their presence did not vary by HIV status; 20% of isolates from cerebrospinal fluid were resistant. The majority of the resistant isolates were of capsular type 9v. Given the worldwide increase in both HIV and penicillin-resistant pneumococcal infections, better preventative and therapeutic strategies are greatly needed.

Adult↗