Search PubMed⌕ Search

Biomedical subjects

Robert Hogg

Publications and source records attributed to Robert Hogg.

13 recordsLinked to original sources
PubMed2006

Exploring mitochondrial nephrotoxicity as a potential mechanism of kidney dysfunction among HIV-infected patients on highly active antiretroviral therapy.

BACKGROUND: Tenofovir (TDF) exposure has been associated with renal dysfunction. Mitochondrial nephrotoxicity was investigated as an underlying mechanism. Given the interaction between TDF and didanosine (ddl), their concurrent use was also investigated. DESIGN: Relative kidney biopsy mitochondrial DNA (mtDNA) to nuclear DNA ratios were measured retrospectively. HIV+ individuals on TDF within 6 months preceeding the biopsy (HIV+/TDF+, n=21) were compared to HIV+ individuals who never received TDF (HIV+/TDF-, n=10) and to HIV uninfected controls (HIV-,n=22). Twelve of the HIV+/TDF+ individuals received concurrent ddl, 10 of those once at unadjusted ddl dosage. Tubular mitochondria morphology was also examined by electron microscopy. Statistical analyses were done on log-transformed mtDNA/nDNA, using non-parametric tests. RESULTS: Kidney mtDNA levels were different among the three groups (P=0.046). mtDNA ratios were lower in HIV+/TDF+ subjects (7.5 [2.0-12.1]) than in HIV- ones (14.3 [6.0-16.5], P=0.014), but not lower than HIV+/TDF- controls (6.4 [2.8-11.9], P=0.82). Among HIV+ subjects, there was a difference between TDF-, TDF+/ddl- and TDF+/ddl+ (P=0.005), with concurrent TDF/ddl use associated with lower mtDNA (2.1 [1.9-5.5], n=12) than TDF+/ddl- (13.8 [7.5-16.4], n=9, P=0.003). No TDF-/ddl+ biopsies were available. In regression analyses, only HIV infection (P=0.03), and TDF/ddl use (P=0.003) were associated with lower mtDNA. At the ultrastructural level, abnormal tubular mitochondria was more prevalent in HIV+/TDF+ biopsies than HIV+/TDF- and HIV- ones together (P<0.001) but not more so in TDF+/ddl+ biopsies than TDF+/ddl- ones (P=0.67). CONCLUSIONS: Renal dysfunction in this population may be mediated through mitochondrial nephrotoxicity that involves more than one drug and/or pathogenesis. Kidney mtDNA depletion was associated with HIV infection and concurrent TDF/ddl therapy but not TDF use alone, while kidney ultrastructural mitochondrial abnormalities were seen with TDF use. The interaction between TDF and ddl may be relevant in the kidney where both drugs are cleared. The clinical relevance of our findings needs to be evaluated given the current recommendation for reduced doses of ddl when used in conjunction with TDF.

Adenine↗
PubMed2005

Nontuberculous mycobacterial immune reconstitution syndrome in HIV-infected patients: spectrum of disease and long-term follow-up.

BACKGROUND: The long-term outcome and spectrum of disease of nontuberculous mycobacterial immune reconstitution syndrome have not been described. METHODS: We report the findings of an observational study. RESULTS: Among 51 patients (43 with Mycobacterium avium complex [MAC] infection, 2 with Mycobacterium genavense infection, and 6 whose samples were smear positive but culture negative) from 1993-2004, the median follow-up period was 29 months. The incidence of nontuberculous mycobacterial immune reconstitution syndrome was 3.5% among patients initiating highly active antiretroviral therapy (HAART) with a baseline CD4+ cell count of <100 cells/microL. Three main clinical presentations were peripheral lymphadenitis (in 17 patients), pulmonary-thoracic disease (in 15 patients), and intra-abdominal disease (in 13 patients). Six other patients had cases that involved joint, spine, prostate, skin, soft tissue, and spontaneously resolving MAC bacteremia. Disease was usually localized. Median CD4+ cell counts before initiation of HAART and at diagnosis were 20 and 120 cells/microL, respectively, and the median reduction in human immunodeficiency virus (HIV) RNA load was 2.5 log10 copies/mL. Intra-abdominal disease was frequently preceded by disseminated MAC infection (in 62% of cases, compared with 6%-33% of cases for other groups; P=.003) and accounted for 16 (43%) of 36 hospitalizations (compared with 5%-35% for other groups; P=.008). The relapse rate was not higher among 10 patients who received no MAC therapy or received MAC therapy for < or =2 weeks. Prednisone was associated with clinical responses in 8 (89%) of 9 patients with evaluable cases. In total, 7 patients (14%) had 13 subsequent culture-positive MAC events (6 of which were cases of immune reconstitution syndrome, and 7 of which were cases of disseminated MAC infection). Ten patients (20%) died (2 of disseminated MAC infection, 5 of other opportunistic infections, and 3 of HIV-unrelated causes). CONCLUSIONS: Nontuberculous mycobacterial immune reconstitution syndrome has a wide range of clinical presentations and severity. The long-term prognosis is favorable for HAART-adherent patients. Intra-abdominal disease is associated with greater morbidity than is peripheral lymphadenitis. The role of antimycobacterial therapy is uncertain, given the self-limited course of most nonabdominal cases.

Adult↗
PubMed2005

Global IDEA.

Explore the source record for details and available documents.

Biomedical Research↗
PubMed2005

Back to work: correlates of employment among persons receiving highly active antiretroviral therapy.

The aim of this study was to quantify the level of employment at one-year and to determine potential predictors of future employment among HIV-positive persons on highly active antiretroviral therapy (HAART) in the province of British Columbia. Of the 392 individuals that were initially unemployed at baseline 63 (16.1%) found a job over the subsequent year. Factors associated with becoming employed included a baseline income over 10,000 dollars, having long-term disability or unemployment insurance as an income source, having higher CD4 cell counts, and better physical, social, and role functioning. Factors negatively associated with finding employment included having provincial assistance as an income source and having ever been an injection drug user (IDU). In multivariate analyses, not using provincial assistance as a source of income (Odds Ratio [OR] = 7.39; 95% CI: 3.26-16.7; p < 0.001) and higher MOS-SF role functioning (OR = 1.12 per 10 point increment; 95% CI: 1.03-1.21; p = 0.005) were independent predictors of becoming employed. In conclusion, our study demonstrates that while significant advances have been made in the reduction of HIV-related mortality, the majority of HIV-infected individuals on adequate treatment are still unable to be gainfully employed.

Adolescent↗
PubMed2004

Psychosocial determinants of adherence to highly active antiretroviral therapy among injection drug users in Vancouver.

BACKGROUND: Sub-optimal adherence to highly active antiretroviral therapy (HAART) among injection drug users (IDUs) is a significant concern. As such, there is an urgent need to identify psychosocial determinants of adherence that can be incorporated into interventions designed to promote optimal adherence. OBJECTIVE: To identify psychosocial determinants of adherence to HAART, as well as self-reported reasons for missing doses of HAART among HIV-infected IDUs. METHODS: We developed an eight-item adherence self-efficacy scale comprised of two sub-scales: adherence efficacy and self-regulatory efficacy. We examined correlates between adherence self-efficacy, outcome expectations, socio-demographic characteristics, drug use and risk behaviours, social support and HAART adherence among 108 HIV-infected participants in the Vancouver Injection Drug Users Study (VIDUS). Pharmacy-based adherence to HAART was obtained through a confidential record linkage to the province of British Columbia's HIV/AIDS Drug Treatment Program. Participants were defined as adherent if they picked-up 95% of their HAART prescriptions. Participants were also asked to indicate reasons for missing doses of HAART. Logistic regression was used to identify the factors independently associated with adherence to HAART. RESULTS: Seventy-one (66%) HIV-infected IDUs were less than 95% adherent. Forgetting was the most frequently cited reason (27%) for missing doses of HAART. Factors independently associated with adherence to HAART included adherence efficacy expectations [OR=1.8 (95% CI: 1.0-3.1); P=0.039] and negative outcome expectations [OR=0.8 (95% CI: 0.7-0.9); P=0.027]. CONCLUSIONS: We found low rates of adherence to HAART among IDUs. Psychological constructs derived from self-efficacy theory are highly germane to the understanding of adherence behaviour, and interventions that address these constructs should be developed and tested among HIV-infected drug users.

Adult↗
PubMed2001

Azithromycin prophylaxis for Mycobacterium avium complex during the era of highly active antiretroviral therapy: evaluation of a provincial program.

Mycobacterium avium complex (MAC) disease was evaluated in a provincial program of azithromycin prophylaxis. Highly active antiretroviral therapy (HAART) was prescribed to 383 (65%) of 587 patients eligible for MAC prophylaxis (CD4 <75 cells/mm3). By use of an intent-to-treat analysis, MAC disease was observed in 21 of 271 patients who did not receive prophylaxis (incidence rate, 8 events per 100 person-years). MAC events occurred in 10 of 316 patients who received azithromycin (2.37 events per 100 person-years). Localized lymphadenitis compatible with immune reconstitution disease accounted for 23% of all MAC events, in contrast to studies in the pre-HAART era, where almost all cases were disseminated. None of the MAC isolates from the 10 prophylaxis failures were resistant to azithromycin. Azithromycin appeared to be protective against disseminated MAC in patients who were either unresponsive or nonadherent to HAART, but it did not prevent the development of immune reconstitution disease due to MAC.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes.

BACKGROUND: Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure. METHODS: We undertook collaborative joint analysis of 13 HIV cohorts from Europe, North America, and Australia, involving patients who had had three-class virological failure (viral load >1000 copies per mL for >4 months). Regression analyses were used to quantify the associations between CD4-cell-count slope, HIV-1 RNA concentration, treatment information, and demographic characteristics. Predictors of death were analysed by Cox's proportional-hazards models. FINDINGS: 2488 patients were included. 2118 (85%) had started antiretroviral therapy with single or dual therapy. During 5015 person-years of follow-up, 276 patients died (mortality rate 5.5 per 100 person-years; 3-year mortality risk 15.3% (95% CI 13.5-17.3). Risk of death was strongly influenced by the latest CD4-cell count with a relative hazard of 15.8 (95% CI 9.28-27.0) for counts below 50 cells per microL versus above 200 cells per microL. The latest viral load did not independently predict death. For any given viral load, patients on treatment had more favourable CD4-cell-count slopes than those off treatment. For patients on treatment and with stable viral load, CD4-cell counts tended to be increasing at times when the current viral load was below 10000 copies per mL or 1.5 log10 copies per mL below off-treatment values. INTERPRETATION: In patients for whom viral-load suppression to below the level of detection is not possible, achievement and maintenance of a CD4-cell count above 200 per microL becomes the primary aim. Treatment regimens that maintain the viral load below 10000 copies per mL or at least provide 1.5 log10 copies per mL suppression below the off-treatment value do not seem to be associated with appreciable CD4-cell-count decline.

Adult↗