Mortality among people living with HIV/AIDS with non-small-cell lung cancer in the modern HAART Era.

People living with HIV (PLWHA) with adequate access to modern combination antiretroviral therapy (cART) are living longer and experiencing reduced AIDS-related morbidity and mortality. However, increases in non-AIDS related conditions, such as certain cancers, have accompanied these therapeutic advances over time. As such, our study objective was to determine the impact of HIV on all-cause and lung cancer-specific mortality amongst PLWHA with diagnoses of non-small-cell lung cancer (NSCLC) and HIV-negative individuals with NSCLC. This analysis was inclusive of PLWHA on and off cART over the age of 19 years and a 10% comparison sample from the BC population ≥19 years, over a 13-year period (2000-2013). Kaplan-Meier estimates, Cox PH models, and competing risk analysis for all-cause and cause-specific mortality (respectively) compared PLWHA to HIV-negative individuals, controlling for age, gender, cancer stage, co-morbidities; and nadir CD4 count, viral load, and injection drug use for a HIV-positive specific analysis. We identified 71 PLWHA and 2463 HIV-negative individuals diagnosed with NSCLC between 2000 and 2013. PLWHA with NSCLC were diagnosed at a significantly younger age than HIV-negative individuals (median age 57 vs 71 years, p < 0.01). We found no significant difference in lung cancer-specific mortality. However, in multivariate analysis, HIV was associated with greater all-cause mortality (adjusted hazard ratio [aHR]:1.44; 95% confidence interval [CI]: 1.08-1.90), with median survival of 4 months for PLWHA, and 10 months for HIV-negative. Higher nadir CD4 count was protective against mortality (aHR: 0.33, 95% CI: 0.17-0.64) amongst PLWHA in multivariate analysis. Our analysis suggests that PLWHA in the modern cART era experience similar lung cancer survival outcomes compared to the general BC population with NSCLC. However, we also observed significantly higher all-cause mortality among PLWHA with NSCLC, which may warrant further inquiry into the role of HIV in exacerbating mortality among PLWHA with comorbidities and cancer.

A cluster of Bacillus cereus bacteremia cases among injection drug users.

Bacillus cereus is a ubiquitous spore-forming organism that is infrequently implicated in extraintestinal infections. The authors report three cases of B cereus bacteremia among injection drug users presenting within one month to an urban tertiary care hospital. Treatment with intravenous vancomycin was successful in all three cases. While temporal association suggested an outbreak, molecular studies of patient isolates using pulsed-field gel electrophoresis did not suggest a common source. A review of the association of B cereus infections with heroin use and treatment of this pathogen is provided.

Le Bacillus cereus est un organisme sporulé omniprésent qui est parfois responsable d'infections extra-intestinales. Les auteurs rendent compte de trois cas de bactériémie à B cereus chez des consommateurs de drogue injectable qui ont consulté au cours du même mois dans un hôpital urbain de soins tertiaires. Dans les trois cas, un traitement intraveineux à la vancomycine a donné de bons résultats. L'association temporelle laissait suggérer une éclosion, mais des études moléculaires d'isolats de patients par électrophorèse en champ pulsé n'évoquaient pas une source commune. Les chercheurs proposent une analyse de l'association des infections à B cereus à la consommation d'héroïne et du traitement de cet agent pathogène.

Risk of anal cancer in HIV-infected and HIV-uninfected individuals in North America.

BACKGROUND: Anal cancer is one of the most common cancers affecting individuals infected with human immunodeficiency virus (HIV), although few have evaluated rates separately for men who have sex with men (MSM), other men, and women. There are also conflicting data regarding calendar trends. METHODS: In a study involving 13 cohorts from North America with follow-up between 1996 and 2007, we compared anal cancer incidence rates among 34 189 HIV-infected (55% MSM, 19% other men, 26% women) and 114 260 HIV-uninfected individuals (90% men). RESULTS: Among men, the unadjusted anal cancer incidence rates per 100 000 person-years were 131 for HIV-infected MSM, 46 for other HIV-infected men, and 2 for HIV-uninfected men, corresponding to demographically adjusted rate ratios (RRs) of 80.3 (95% confidence interval [CI], 42.7-151.1) for HIV-infected MSM and 26.7 (95% CI, 11.5-61.7) for other HIV-infected men compared with HIV-uninfected men. HIV-infected women had an anal cancer rate of 30/100 000 person-years, and no cases were observed for HIV-uninfected women. In a multivariable Poisson regression model, among HIV-infected individuals, the risk was higher for MSM compared with other men (RR, 3.3; 95% CI, 1.8-6.0), but no difference was observed comparing women with other men (RR, 1.0; 95% CI, 0.5-2.2). In comparison with the period 2000-2003, HIV-infected individuals had an adjusted RR of 0.5 (95% CI, .3-.9) in 1996-1999 and 0.9 (95% CI, .6-1.2) in 2004-2007. CONCLUSIONS: Anal cancer rates were substantially higher for HIV-infected MSM, other men, and women compared with HIV-uninfected individuals, suggesting a need for universal prevention efforts. Rates increased after the early antiretroviral therapy era and then plateaued.

Feasibility of incorporating self-collected rectal swabs into a community venue-based survey to measure the prevalence of HPV infection in men who have sex with men.

BACKGROUND: Inclusion of self-collected rectal swabs (SCRS) into existing community venue-based HIV surveillance systems for men who have sex with men (MSM) may provide a feasible method for monitoring human papillomavirus (HPV) vaccine-related outcomes in this population. We measured the prevalence of HPV and anal dysplasia through incorporating SCRS into ManCount, the Vancouver site of the M-Track HIV surveillance system. METHODS: Participating MSM were provided with a self-collection kit for collection on-site or at a follow-up venue. Swabs were subject to polymerase chain reaction amplification for HPV detection, and cytology slides were reviewed for anal dysplasia. Factors associated with participation were identified through multivariate logistic regression. RESULTS: Of 766 men completing ManCount, 268 (35%) agreed to participate, self-collecting 252 specimens (247 on-site). Of 239 complete specimens, 33.5% did not have detectable ß-globin; in the remainder (159 specimens) the prevalence of HPV infection was 62.3% (23.3% HPV type 16 or 18; 38.4% HPV type 6, 11, 16, or 18). In the 62.3% (149) of specimens adequate for cytology, the prevalence of anal dysplasia was 42.3% (HSIL 11.4%, LSIL 18.8%, ASC-US 6.7%, ASC-H 5.4%). Participation was associated with venue type, availability of on-site collection, and other characteristics. CONCLUSIONS: SCRS can be feasibly integrated within existing community venue-based HIV surveillance systems for MSM, and may be a suitable method for monitoring the impact of HPV vaccination in this population. However, participation may be influenced by venue type and availability of on-site collection, and adequacy of SCRS specimens may be lower in community venues as compared with clinical settings.

Post-exposure prophylaxis against SARS-CoV-2 in close contacts of confirmed COVID-19 cases (CORIPREV): study protocol for a cluster-randomized trial.

BACKGROUND: Post-exposure prophylaxis (PEP) is a well-established strategy for the prevention of infectious diseases, in which recently exposed people take a short course of medication to prevent infection. The primary objective of the COVID-19 Ring-based Prevention Trial with lopinavir/ritonavir (CORIPREV-LR) is to evaluate the efficacy of a 14-day course of oral lopinavir/ritonavir as PEP against COVID-19 among individuals with a high-risk exposure to a confirmed case. METHODS: This is an open-label, multicenter, 1:1 cluster-randomized trial of LPV/r 800/200 mg twice daily for 14 days (intervention arm) versus no intervention (control arm), using an adaptive approach to sample size calculation. Participants will be individuals aged > 6 months with a high-risk exposure to a confirmed COVID-19 case within the past 7 days. A combination of remote and in-person study visits at days 1, 7, 14, 35, and 90 includes comprehensive epidemiological, clinical, microbiologic, and serologic sampling. The primary outcome is microbiologically confirmed COVID-19 infection within 14 days after exposure, defined as a positive respiratory tract specimen for SARS-CoV-2 by polymerase chain reaction. Secondary outcomes include safety, symptomatic COVID-19, seropositivity, hospitalization, respiratory failure requiring ventilator support, mortality, psychological impact, and health-related quality of life. Additional analyses will examine the impact of LPV/r on these outcomes in the subset of participants who test positive for SARS-CoV-2 at baseline. To detect a relative risk reduction of 40% with 80% power at α = 0.05, assuming the secondary attack rate in ring members (p0) = 15%, 5 contacts per case and intra-class correlation coefficient (ICC) = 0.05, we require 110 clusters per arm, or 220 clusters overall and approximately 1220 enrollees after accounting for 10% loss-to-follow-up. We will modify the sample size target after 60 clusters, based on preliminary estimates of p0, ICC, and cluster size and consider switching to an alternative drug after interim analyses and as new data emerges. The primary analysis will be a generalized linear mixed model with logit link to estimate the effect of LPV/r on the probability of infection. Participants who test positive at baseline will be excluded from the primary analysis but will be maintained for additional analyses to examine the impact of LPV/r on early treatment. DISCUSSION: Harnessing safe, existing drugs such as LPV/r as PEP could provide an important tool for control of the COVID-19 pandemic. Novel aspects of our design include the ring-based prevention approach, and the incorporation of remote strategies for conducting study visits and biospecimen collection. TRIAL REGISTRATION: This trial was registered at www.ClinicalTrials.gov ( NCT04321174 ) on March 25, 2020.

Once-Daily Treatments for Methicillin-Susceptible Staphylococcus aureus Bacteremia: Are They Good Enough?

PURPOSE OF THE REVIEW: Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is a common cause of morbidity and mortality. First-line treatment requires frequent daily doses of an anti-staphylococcal beta-lactam. However, some physicians prescribe simpler once-daily regimens to improve compliance and improve healthcare utilization. We reviewed the literature regarding advantages, pitfalls, and efficacy of once-daily treatment options for MSSA bacteremia. RECENT FINDINGS: Several once-daily antibiotics are effective in vitro against MSSA (ceftriaxone, daptomycin, telavancin, dalbavancin, oritavancin, tedizolid, ertapenem, fluoroquinolones, and others), but there is insufficient evidence to support these agents for MSSA bacteremia. Ceftriaxone may be considered for therapy completion with MSSA bacteremia from osteomyelitis, and daptomycin may be considered in patients who cannot tolerate first-line therapy. However, they have not been compared to traditional second-line agents, and their role remains uncertain. Current evidence does not support the use of once-daily treatment options for MSSA bacteremia.

Antiretroviral adherence and HIV treatment outcomes among HIV/HCV co-infected injection drug users: the role of methadone maintenance therapy.

OBJECTIVE: We examined the association of methadone maintenance therapy (MMT) with highly active antiretroviral therapy (HAART) adherence and HIV treatment outcomes among a cohort of HIV/HCV co-infected injection drug users (IDUs). METHODS: We obtained demographic, drug use, and addiction care history from the Vancouver Injection Drug User Study (VIDUS), which is an open cohort study of IDUs. The questionnaires were longitudinally linked to the British Columbia HIV/AIDS Drug Treatment Program to obtain HAART adherence and HIV treatment outcome data. There were 278 VIDUS participants who accessed HAART from August 1, 1996 to November 24, 2003. We constructed longitudinal logistic models using generalized estimating equations to examine the independent associations between methadone maintenance therapy and the following outcomes: HAART adherence; plasma HIV-1 RNA suppression; and CD4 cell rise of 100cells/mm(3). RESULTS: Among participants who reported at least weekly heroin use, MMT was independently associated with lower odds of subsequent weekly heroin use during the follow-up period (adjusted odds ratio; 95% confidence interval [AOR; 95% CI]: 0.24; 0.14-0.40). We also found that MMT was positively associated with adherence (AOR 1.52; 95% CI 1.16-2.00), HIV-1 RNA suppression (AOR 1.34; 95% CI 1.00-1.79), and CD4 cell count rise (AOR 1.58; 95% CI 1.26-1.99). CONCLUSIONS: Among HIV/HCV co-infected IDUs on HAART, enrollment in MMT was associated with reduced heroin use, and improved adherence, HIV-1 RNA suppression and CD4 cell count response. Integrating opiate addiction care and HIV care may provide improved health outcomes for this vulnerable population and should be further explored.

HAART slows progression to anal cancer in HIV-infected MSM.

OBJECTIVE: Antiretrovirals do not prevent anal intraepithelial neoplasia. However, the influence of antiretrovirals in the natural history of invasive anal cancer is less clear. The objective is to investigate the impact of antiretrovirals in the time to the development of anal cancer in HIV-positive MSM. DESIGN: A retrospective analysis of cases of anal cancer in a cohort of HIV-positive MSM receiving antiretrovirals between 1988 and 2008. METHODS: Time from first CD4 cell count or HIV RNA viral load test to anal cancer diagnosis was analysed using Cox regression and Kaplan-Meier curves. Anal cancer cases treated in the era prior to HAART (<1996) were compared with those treated later (1996-2008). RESULTS: Anal cancer cases (n = 37) were compared with a cohort of 1654 HIV-positive MSM on antiretrovirals. Antiretrovirals were started in the pre-HAART era by 70% of cancer cases, and median CD4 cell count nadir was 70 cells/µl (10-130). Time to development of anal cancer was shorter for cases treated during the pre-HAART era [adjusted hazard ratio (AHR) 3.04, 95% confidence interval (95% CI) 1.48-6.24, P = 0.002], with a CD4 cell count nadir less than 100 cells/µl (AHR 2.21, 95% CI 1.06-4.62, P = 0.035) and longer duration of CD4 cell count less than 100 cells/µl (AHR 1.33, 95% CI 1.11-1.58, P = 0.002). CONCLUSION: Results show that severe immunosuppression and starting therapy pre-HAART are associated with an increased risk of anal cancer. HIV-positive MSM initiating antiretrovirals during the HAART era (1996-2008) had a longer time to the development of anal cancer than those treated pre-HAART. Our results suggest that early use of HAART may delay progression to anal cancer.

Intermittent use of triple-combination therapy is predictive of mortality at baseline and after 1 year of follow-up.

OBJECTIVE: To characterize the impact of intermittent use of triple drug antiretroviral therapy on survival. DESIGN, SETTING AND PARTICIPANTS: Population-based analysis of 1282 antiretroviral therapy naive HIV-positive individuals aged 18 years and older in British Columbia who started triple-combination therapy between August 1996 and December 1999. Therapy use was estimated by dividing the number of months of medications dispensed by the number of months of follow-up. Intermittent therapy was defined as the participant having obtained less than 75% of their medication in the first 12 months. MAIN OUTCOME MEASURE: Cumulative all-cause mortality rates from the start of triple drug antiretroviral therapy to 30 September 2000. RESULTS: As of 30 September 2000, 106 subjects had died. Cumulative mortality was 3.9% (+/- 0.5%) at 12 months. In a multivariate model, after controlling for other variables that were significant in the univariate analyses each 100 cell decrement in baseline CD4 cell count and the intermittent use of antiretroviral drugs were associated with increased mortality with risk ratios of 1.31 [95% confidence interval (CI), 1.16-1.49; P < 0.001] and 2.90 (95% CI, 1.93-4.36; P < 0.001), respectively. In order to control for downward drift, intermittent use of therapy was measured over the first year whereas other factors were measured at the end of year 1. After adjusting for all other factors, those participants who used antiretroviral drugs intermittently were 2.97 times (95% CI, 1.33-6.62; P = 0.008) more likely to die. CONCLUSION: Our study demonstrates that even after adjusting for other prognostic factors intermittent use of antiretroviral therapy was associated with increased mortality.

Total lymphocyte count as a possible surrogate of CD4 cell count to prioritize eligibility for antiretroviral therapy among HIV-infected individuals in resource-limited settings.

OBJECTIVE: To characterize the value of total lymphocyte counts in predicting risk of death among patients initiating triple combination antiretroviral therapy. METHODS: Study subjects included antiretroviral-naive persons aged 18 years or older who initiated treatment with triple combination therapy between August 1 1996 and September 30 1999 in a population-based observational cohort of HIV-infected individuals. Total lymphocyte counts as well as CD4 count and plasma viral load were assessed at baseline. Separate Cox proportional hazards models were devised to evaluate the effect on survival of total lymphocyte count in lieu of or with CD4 count after adjustment for other prognostic factors including plasma viral load. RESULTS: A total of 733 antiretroviral-naive persons initiated triple drug combination antiretroviral therapy over the study period with a median follow-up of 29.5 months. In the first analysis, only baseline CD4 cell counts of 50-199 cells/microl or less than 50 microl were associated with an increased risk of mortality [adjusted relative risk (ARR) 2.90; 95% CI: 1.40, 5.98] and (ARR 6.30; 95% CI: 2.93, 13.54), respectively. When CD4 counts were excluded from the analysis as if unavailable, total lymphocyte count of between 0.8 and 1.4 G/I, and less than 0.8 G/I were both significantly associated with an increased risk of mortality (ARR 2.36; 95% CI: 1.16, 4.78) and (ARR 6.17; 95% CI: 2.93, 13.01), respectively. CONCLUSION: Total lymphocyte count may provide a simple and cost-effective alternative for prioritizing therapy initiation in resource-limited settings. Our results suggest that, if appropriately validated, judicious application of total lymphocyte counts could overcome one of the practical obstacles to more widespread provision of antiretroviral therapy in resource-poor settings.

Case series assessing the safety of mycophenolate as part of multidrug rescue treatment regimens.

BACKGROUND: Mycophenolate mofetil (MMF), an inhibitor of lymphocyte proliferation, is emerging as a potential adjunct in the treatment of HIV-1 infection. By potentiating the activity of abacavir, MMF may improve antiviral efficacy. However, it may also lead to myelosuppression, such as was seen in patients taking hydroxyurea-containing regimens. PURPOSE: To assess the safety of MMF as adjunctive therapy for HIV infection. METHOD: Eighteen HIV-positive outpatients, given MMF (500 mg po bid) on a compassionate basis as part of their salvage therapy, were monitored for adverse effects. RESULTS: Five patients discontinued MMF between 26-68 days of follow-up due to adverse effects likely related to other factors. Among the remaining 13 patients, no new clinically significant cytopenias occurred over 107-154 days of follow-up. Three patients exhibited decreases in CD4 counts, despite decreases in plasma HIV-1 RNA. CONCLUSION: Short-term follow-up suggests that MMF (500 mg po bid) does not cause lymphocyte suppression. However, further studies are ongoing to determine its safety and efficacy profile in HIV infection.

Resolution of diabetes after initiation of antiretroviral therapy in two human immunodeficiency virus-infected patients.

OBJECTIVE: To describe two cases of human immunodeficiency virus (HIV)-infected patients who had diabetes mellitus, which resolved after initiation of antiretroviral therapy. METHODS: We present the clinical and laboratory findings and describe the clinical course of these two patients. RESULTS: A 48-year-old HIV-infected black woman presented with multiple infections and hyperglycemia. After her acute infections were treated and she was feeling well, she continued to have diabetes that necessitated insulin therapy. Administration of a protease inhibitor-based antiretroviral regimen resolved her diabetes and eliminated the need for insulin or oral therapy. Our second patient, a 37-year-old HIV-infected black man, presented with polyuria and polydipsia and a hemoglobin A1c value of 11%. He received antiretroviral therapy, and his diabetes resolved after a period of 2 1/2 months. CONCLUSION: Protease inhibitor-based antiretroviral therapy is associated with diabetes mellitus in up to 6% of HIV-infected patients. Although most HIV-infected patients in whom diabetes develops have this disorder after initiation of protease inhibitor therapy, the current two cases illustrate patients in whom diabetes resolved after use of antiretroviral therapy. This finding supports the presence of other mechanisms that affect glucose metabolism in patients infected with HIV and suggests that control of HIV infection may have a role in controlling diabetes.

Colorectal and anal cancer in HIV/AIDS patients: a comprehensive review.

Highly active antiretroviral therapy (HAART) has significantly altered the epidemiology of cancer that is diagnosed in individuals who are infected with the human immunodeficiency virus (HIV). Studies have shown a dramatic decrease in the incidence of and mortality from AIDS-related malignancies (primarily Kaposi sarcoma and non-Hodgkin's lymphoma), while the incidence of and mortality from non-AIDS defining malignancies is on the rise. While the risk of colorectal cancer (CRC) in HIV-infected individuals is controversial and has received limited study, there has been accumulating evidence that suggests an increased risk of developing anal cancer (AC) during the HAART era. This article reviews the current literature reporting on CRC and AC in the HIV-infected population, with a specific on cancer: incidence, screening, clinical characteristics, and treatment outcomes.

Prevalence of sexually transmitted infections and high-risk sexual behaviors in heterosexual couples attending sexually transmitted disease clinics in Peru.

OBJECTIVES: The objectives of this study were to determine the prevalence of sexually transmitted infection (STIs) in heterosexual couples and the sexual behaviors associated with their acquisition. GOAL: The goal of this study was to better direct educational efforts to decrease STI among heterosexual couples in Lima, Peru. STUDY DESIGN: We conducted a case-control study in 195 heterosexual couples without HIV infection who attended 2 sexually transmitted disease clinics in Lima, Peru. A case was defined as an individual with one or more newly diagnosed STIs such as gonorrhea, chlamydia, trichomoniasis, herpes simplex, syphilis, mycoplasma, or ureaplasma. RESULTS: Thirty-three percent of individuals (41 men and 89 women) had at least one STI and 26 couples (13%) had the same STI detected. Men who have sex with men (MSM) accounted for 13% of all men, had higher rate of STIs and higher risk behaviors than non-MSM. Ureaplasma infection was the most prevalent STI found in both men and women and was associated with oral sexual contact. In heterosexual pairs, condom use during anal sex occurred less than 10% of the time. CONCLUSIONS: The heterosexual couples in sexually transmitted disease clinics have high-risk behaviors and STIs are frequent. The educational effort concerning prevention of STIs requires higher effort.

Virologic and immunologic response, clinical progression, and highly active antiretroviral therapy adherence.

A growing body of evidence suggests that a high degree of adherence is required to achieve and maintain a successful virologic response both in the short and long term. This holds true despite the definition of adherence or how it is measured. Reported differences in the degree of adherence required are likely due to differences in study design, difficulty measuring patient adherence, patient population studied, and the antiretroviral regimen studied. Virologic suppression and immunologic response often go hand in hand, but the impact of adherence on change in CD4 count tends to be delayed and, therefore, less apparent than the impact on HIV viral load. Degree of adherence has also been shown to be associated with AIDS-related morbidity, mortality, and hospitalizations.

Adverse effects of antiretroviral therapy for HIV infection.

Long-term remission of HIV-1 disease can be readily achieved by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients.