Mark W. Hull

Optimizing the engagement of care cascade: a critical step to maximize the impact of HIV treatment as prevention.

Purpose of reviewAt present, data from mathematical models, ecologic studies and a clinical trial demonstrate that use of combination antiretroviral therapy (cART) can markedly reduce HIV transmission. Expansion of cART uptake (Treatment as Prevention) is a critical component of biomedical interventions to prevent HIV transmission. Recent findingsSuccessful implementation is dependent on identifying undiagnosed individuals, linking and retaining them in care and initiating durable and potent cART regimens. This continuum is encapsulated within the framework of the ‘Test and Treat’, or ‘Seek, Test, Treat and Retain’ strategies. Currently only 19–28% of all HIV-infected individuals in the USA are estimated to be virologically suppressed. SummaryOptimizing the engagement of care cascade represents a critical step to maximize the individual and societal impact of cART and therefore deliver on the promise of HIV Treatment as Prevention.

Changing Global Epidemiology of Pulmonary Manifestations of HIV/AIDS

Tremendous advances have occurred in the care of patients with HIV/AIDS resulting from the advent of highly active antiretroviral therapy (HAART). This has led to differences in the presentations of HIV-related pulmonary disease. Infections such as bacterial pneumonias, particularly Streptococcus pneumoniae, remain commonplace, while opportunistic agents such as Pneumocystis jirovecii remain a concern in patients without adequate access to optimal medical care. The tuberculosis epidemic, once thought to be slowing, has been re-energized by the spread of HIV, particularly in sub-Saharan Africa. Unusual inflammatory responses due to a phenomenon of immune reconstitution, are now recognized as a consequence of HAART, with a reported incidence of IRIS in this setting ranges from 7 to 45% in retrospective reviews. Noninfectious pulmonary conditions such as chronic obstructive lung disease and pulmonary malignancies are gaining prominence as patients are accessing antiretroviral care and enjoying significantly extended survival.

Ritonavir-boosted protease inhibitors in HIV therapy

Abstract The advent of combination antiretroviral therapy has led to significant improvement in the care of HIV-infected patients. Originally designed as a protease inhibitor (PI), ritonavir is currently exclusively used as a pharmacokinetic enhancer of other protease inhibitors, predominantly due to ritonavirs potent inhibition of the cytochrome P450 3A4 isoenzyme. Ritonavir-boosting of PIs decrease pill burden and frequency of dosing. Boosted PIs are recommended for first-line therapy in treatment and play a key role in the management of treatment-experienced patients. Potential problems associated with PIs include metabolic abnormalities (e.g. dyslipidemia), increased cardiovascular risk, and drug interactions.

Large Community Outbreak of Streptococcus pneumoniae Serotype 5 Invasive Infection in an Impoverished, Urban Population

BACKGROUND Streptococcus pneumoniae is a common cause of sporadic invasive infections, but outbreaks of invasive pneumococcal disease are infrequent. In August 2006, a sudden increase in the number of patients presenting with invasive pneumococcal disease was noted at St. Pauls Hospital (Vancouver, Canada). Most patients with severe disease resided in an area referred to as the Downtown Eastside, a neighborhood known for its high rates of poverty and illicit drug use. METHODS Prospective, laboratory-based surveillance for invasive pneumococcal disease was initiated, including on-site serotyping of S. pneumoniae isolates. A vaccination campaign using 23-valent polysaccharide pneumococcal vaccine was launched in the Downtown Eastside. Multiple logistic regression was used to examine the association of sociodemographic variables and medical risk factors with S. pneumoniae serotype status. RESULTS A single S. pneumoniae serotype (serotype 5) was responsible for 78% of invasive pneumococcal disease cases (137 of 175 cases) during the outbreak period of August 2006-July 2007. The outbreak strain, although fully susceptible to penicillin, caused significant morbidity and placed considerable strain on the acute care system within the Vancouver Coastal Health region. Crack cocaine use was found to be the main independent risk factor associated with invasive pneumococcal disease due to S. pneumoniae serotype 5 (odds ratio, 12.4; 95% confidence interval, 2.22-69.5). CONCLUSIONS A targeted vaccination campaign using polysaccharide pneumococcal vaccine appeared to help control this outbreak. In urban centers with high rates of illicit drug use, vaccination strategies for preventing invasive pneumococcal disease may need to be refined to include individuals who use crack cocaine.

How Generalizable Are the Results From Trials of Direct Antiviral Agents to People Coinfected With HIV/HCV in the Real World?

Trial results are used to support licensure, inform cost-effectiveness analyses, and guide clinical decision making. We found the majority of coinfected patients were not included in clinical trials of direct-acting antivirals, raising concerns about the generalizability of these trial results.

How generalizable are the results from trials of Direct Antiviral Agents to people coinfected with HIV/Hepatitis C virus in the real world?

Trial results are used to support licensure, inform cost-effectiveness analyses, and guide clinical decision making. We found the majority of coinfected patients were not included in clinical trials of direct-acting antivirals, raising concerns about the generalizability of these trial results.

Epidemic of Lung Cancer in Patients With HIV Infection

The survival of patients with HIV infection has improved dramatically over the past 20 years, largely owing to a significant reduction in opportunistic infections and AIDs-defining malignancies, such as lymphoma and Kaposi sarcoma. However, with improved survival, patients with HIV are experiencing morbidity and mortality from other (non-AIDs-defining) complications, such as solid organ malignancies. Of these, the leading cause of mortality in the HIV-infected population is lung cancer, accounting for nearly 30% of all cancer deaths and 10% of all non-HIV-related deaths. Importantly, the average age of onset of lung cancer in the HIV-infected population is 25 to 30 years earlier than that in the general population and at lower exposure to cigarette smoke. This article provides an overview of the epidemiology of lung cancer in the HIV-infected population and discusses some of the important risk factors and pathways that may enhance the risk of lung cancer in this population.

HIV and hepatitis C virus coinfection in Canada: challenges and opportunities for reducing preventable morbidity and mortality

Hepatitis C virus (HCV) has emerged as an important health problem in the era of effective HIV treatment. However, very few data exist on the health status and disease burden of HIV/HCV‐coinfected Canadians.

Community-associated methicillin-resistant Staphylococcus aureus is prevalent in wounds of community-based injection drug users

Injection drug users (IDUs) have an elevated risk for carriage of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). Cutaneous injection-related infections are common in IDUs but detailed studies are few. Based on a subsample of 218 individuals from a community-recruited cohort of IDUs at a supervised injection facility, we investigated the microbiology and related antibiotic susceptibility profiles of isolates from 59 wounds. Twenty-seven percent of subjects had at least one wound and 25 (43%) were culture positive for S. aureus alone [14 MRSA and 11 (19%) methicillin-susceptible (MSSA) isolates]. Sixteen of 18 MRSA isolates were classified as community associated (CA) by the presence of genes encoding for PVL. MRSA and MSSA occurred in mixed infection with other organisms on three and six occasions, respectively. All CA-MRSA isolates were susceptible to tetracycline, vancomycin and linezolid but only 13% were susceptible to clindamycin compared to 63% of MSSA isolates. The frequency of CA-MRSA is a cause for concern in wound infection in the IDU setting.

Factors Associated With Discordance Between Absolute CD4 Cell Count and CD4 Cell Percentage in Patients Coinfected With HIV and Hepatitis C Virus

BACKGROUND Liver cirrhosis has been associated with decreased absolute CD4 cell counts but preserved CD4 cell percentage in human immunodeficiency virus (HIV)-negative persons. We evaluated factors associated with discordance between the absolute CD4 cell count and the CD4 cell percentage in a cohort of patients coinfected with HIV and hepatitis C virus (HCV). METHODS Baseline data from 908 participants in a prospective, Canadian, multisite cohort of individuals with HIV-HCV coinfection were analyzed. Absolute CD4 cell count and CD4 cell percentage relationships were evaluated. We defined low and high discordance between absolute CD4 cell count/CD4 cell percentage relationships as CD4 cell percentages that differed from the expected CD4 cell percentage, given the observed absolute CD4 cell count, by ±7 percentage points; we defined very low and very high discordance as differences of ±14 percentage points. Factors associated with high or very high discordance, including either end-stage liver disease or aspartate transaminase to platelet ratio index (APRI) of >1.5, were analyzed using multivariate logistic regression models and compared to groups with concordant and low discordant results. RESULTS High/very high discordance was seen in 31% (n = 286), while 35% (n = 321) had concordant values. Factors associated with very high discordance at baseline included history of end-stage liver disease (adjusted odds ratio [aOR], 6.52; 95% confidence interval [CI], 2.27-18.67) and APRI of >1.5 (aOR 4.69; 95% CI, 1.64-13.35). Compared with those with detectable HCV RNA, those who cleared HCV spontaneously were less likely to have very high discordance. CONCLUSIONS Discordance between absolute CD4 cell count and CD4 cell percentage is common in an HIV/HCV-coinfected population and is associated with advanced liver disease and ongoing HCV replication.