When to start antiretroviral therapy: The need for an evidence base during early HIV infection

Background Strategies for use of antiretroviral therapy (ART) have traditionally focused on providing treatment to persons who stand to benefit immediately from initiating the therapy. There is global consensus that any HIV+ person with CD4 counts less than 350 cells/μl should initiate ART. However, it remains controversial whether ART is indicated in asymptomatic HIV-infected persons with CD4 counts above 350 cells/μl, or whether it is more advisable to defer initiation until the CD4 count has dropped to 350 cells/μl. The question of when the best time is to initiate ART during early HIV infection has always been vigorously debated. The lack of an evidence base from randomized trials, in conjunction with varying degrees of therapeutic aggressiveness and optimism tempered by the risks of drug resistance and side effects, has resulted in divided expert opinion and inconsistencies among treatment guidelines. Discussion On the basis of recent data showing that early ART initiation reduces heterosexual HIV transmission, some countries are considering adopting a strategy of universal treatment of all HIV+ persons irrespective of their CD4 count and whether ART is of benefit to the individual or not, in order to reduce onward HIV transmission. Since ART has been found to be associated with both short-term and long-term toxicity, defining the benefit:risk ratio is the critical missing link in the discussion on earlier use of ART. For early ART initiation to be justified, this ratio must favor benefit over risk. An unfavorable ratio would argue against using early ART. Summary There is currently no evidence from randomized controlled trials to suggest that a strategy of initiating ART when the CD4 count is above 350 cells/μl (versus deferring initiation to around 350 cells/μl) results in benefit to the HIV+ person and data from observational studies are inconsistent. Large, clinical endpoint-driven randomized studies to determine the individual health benefits versus risks of earlier ART initiation are sorely needed. The counter-argument to this debate topic can be freely accessed here: http://www.biomedcentral.com/1741-7015/11/147 webcite

A Controlled Trial of Isoniazid in Persons with Anergy and Human Immunodeficiency Virus Infection Who Are at High Risk for Tuberculosis

BACKGROUND Patients with human immunodeficiency virus (HIV) infection and latent tuberculosis are at substantial risk for the development of active tuberculosis. As a public health measure, prophylactic treatment with isoniazid has been suggested for HIV-infected persons who have anergy and are in groups with a high prevalence of tuberculosis. METHODS We conducted a multicenter, randomized, double-blind, placebo-controlled trial of six months of prophylactic isoniazid treatment in HIV-infected patients with anergy who have risk factors for tuberculosis infection. The primary end point was culture-confirmed tuberculosis. RESULTS The study was conducted from November 1991 through June 1996. Over 90 percent of the patients had two or more risk factors for tuberculosis infection, and nearly 75 percent of patients were from greater New York City. After a mean follow-up of 33 months, tuberculosis was diagnosed in only 6 of 257 patients in the placebo group and 3 of 260 patients in the isoniazid group (risk ratio, 0.48; 95 percent confidence interval, 0.12 to 1.91; P=0.30). There were no significant differences between the two groups with regard to death, death or the progression of HIV disease, or adverse events. CONCLUSIONS Even in HIV-infected patients with anergy and multiple risk factors for latent tuberculosis infection, the rate of development of active tuberculosis is low. This finding does not support the use of isoniazid prophylaxis in high-risk patients with HIV infection and anergy unless they have been exposed to active tuberculosis

Comparison of the Outcomes of Individuals With Medically Attended Influenza A and B Virus Infections Enrolled in 2 International Cohort Studies Over a 6-Year Period: 2009-2015.

BACKGROUND: Outcome data from prospective follow-up studies comparing infections with different influenza virus types/subtypes are limited. METHODS: Demographic, clinical characteristics and follow-up outcomes for adults with laboratory-confirmed influenza A(H1N1)pdm09, A(H3N2), or B virus infections were compared in 2 prospective cohorts enrolled globally from 2009 through 2015. Logistic regression was used to compare outcomes among influenza virus type/subtypes. RESULTS: Of 3952 outpatients, 1290 (32.6%) had A(H1N1)pdm09 virus infection, 1857 (47.0%) had A(H3N2), and 805 (20.4%) had influenza B. Of 1398 inpatients, 641 (45.8%) had A(H1N1)pdm09, 532 (38.1%) had A(H3N2), and 225 (16.1%) had influenza B. Outpatients with A(H1N1)pdm09 were younger with fewer comorbidities and were more likely to be hospitalized during the 14-day follow-up (3.3%) than influenza B (2.2%) or A(H3N2) (0.7%; P < .0001). Hospitalized patients with A(H1N1)pdm09 (20.3%) were more likely to be enrolled from intensive care units (ICUs) than those with A(H3N2) (11.3%) or B (9.8%; P < .0001). However, 60-day follow-up of discharged inpatients showed no difference in disease progression (P = .32) or all-cause mortality (P = .30) among influenza types/subtypes. These findings were consistent after covariate adjustment, in sensitivity analyses, and for subgroups defined by age, enrollment location, and comorbidities. CONCLUSIONS: Outpatients infected with influenza A(H1N1)pdm09 or influenza B were more likely to be hospitalized than those with A(H3N2). Hospitalized patients infected with A(H1N1)pdm09 were younger and more likely to have severe disease at study entry (measured by ICU enrollment), but did not have worse 60-day outcomes

Rates of Tuberculosis Infection in Healthcare Workers Providing Services to HIV-Infected Populations

Objective: To assess the prevalence of tuberculosis (TB) or a positive skin test in healthcare workers (HCWs) providing services to human immunodeficiency virus (HIV)-infected individuals and to determine prospectively the incidence of new infections in this population. Design: This prospective cohort study enrolled 1,014 HCWs working with HIV-infected populations from 10 metropolitan areas. Purified protein derivative (PPD) tuberculin skin tests were placed at baseline and every 6 months afterwards on those without a history of TB or a positive PPD. Demographic, occupational, and TB exposure data also were collected. Setting: Outpatient clinics, hospitals, private practice offices, and drug treatment programs providing HIV-related healthcare and research programs. Participants: A voluntary sample of staff and volunteers from 16 Community Programs for Clinical Research on AIDS units. Results: Factors related to prior TB or a positive skin test at baseline included being foreign-born, increased length of time in health care, living in New York City, or previous bacille Calmette-Guerín vaccination. The rate of PPD conversion was 1.8 per 100 person years of follow-up. No independent relation was found between the amount or type of contact with HIV-infected populations and the risk of TB infection. Conclusion: These data provide some reassurance that caring for HIV-infected patients is not related to an increased rate ofTB infection among HCWs in these settings

The impact of human immunodeficiency virus infection on drug-resistant tuberculosis.

Infection with human immunodeficiency virus (HIV) has been associated with increased rates of single- and multidrug-resistant (MDR) tuberculosis in the New York City area. In order to examine the relationship of HIV infection to drug-resistant tuberculosis in other selected regions of the United States, we established a registry of cases of culture-proven tuberculosis. Data were collected from sites participating in an NIH-funded, community-based HIV clinical trials group. All cases of tuberculosis, regardless of HIV status, which occurred between January 1992 and June 1994 were recorded. Overall, 1,373 cases of tuberculosis were evaluated, including 425 from the New York City area, and 948 from seven other metropolitan areas. The overall prevalence of resistance to one or more drugs was 20.4%, and 5.6% of isolates were resistant to both isoniazid and rifampin (MDR). In the New York City area, HIV-infected patients were significantly more likely than persons not known to be HIV-infected, to have resistance to at least one drug (37% versus 19%) and MDR (19% versus 6%). In other geographic areas, overall drug resistance was 16%, and only 2.2% of isolates were MDR. In multiple logistic regression analyses, HIV infection was shown to be a risk factor for drug-resistant tuberculosis, independent of geographic location, history of prior therapy, age, and race. We concluded that HIV infection is associated with increased rates of resistance to antituberculosis drugs in both the New York City area and other geographic areas. MDR tuberculosis is occurring predominantly in the New York City area and is highly correlated with HIV infection

The impact of human immunodeficiency virus infection on drug-resistant tuberculosis.

Infection with human immunodeficiency virus (HIV) has been associated with increased rates of single- and multidrug-resistant (MDR) tuberculosis in the New York City area. In order to examine the relationship of HIV infection to drug-resistant tuberculosis in other selected regions of the United States, we established a registry of cases of culture-proven tuberculosis. Data were collected from sites participating in an NIH-funded, community-based HIV clinical trials group. All cases of tuberculosis, regardless of HIV status, which occurred between January 1992 and June 1994 were recorded. Overall, 1,373 cases of tuberculosis were evaluated, including 425 from the New York City area, and 948 from seven other metropolitan areas. The overall prevalence of resistance to one or more drugs was 20.4%, and 5.6% of isolates were resistant to both isoniazid and rifampin (MDR). In the New York City area, HIV-infected patients were significantly more likely than persons not known to be HIV-infected, to have resistance to at least one drug (37% versus 19%) and MDR (19% versus 6%). In other geographic areas, overall drug resistance was 16%, and only 2.2% of isolates were MDR. In multiple logistic regression analyses, HIV infection was shown to be a risk factor for drug-resistant tuberculosis, independent of geographic location, history of prior therapy, age, and race. We concluded that HIV infection is associated with increased rates of resistance to antituberculosis drugs in both the New York City area and other geographic areas. MDR tuberculosis is occurring predominantly in the New York City area and is highly correlated with HIV infection

Mycobacterium szulgai infection of the lung: Case report and review of an unusual pathogen

The nontuberculous mycobacteria are responsible for considerable morbidity in the immunocompromised and immunocompetent host, especially in the older patient with chronic fibrotic or cavitary disease of the lung. Mycobacterium szulgai is a slow growing mycobacterium infrequent in nature and man. Except from a snail and a tropical fish, it has been isolated only from humans and nearly always represents a true pathogen. Three-drug therapy using in vitro susceptibilities as a guide for 12 to 18 months increases the likelihood of success. We present a patient who developed M szulgai pulmonary infection 30 years after an episode of pulmonary tuberculosis. After successful therapy for his M szulgai infection, this patient developed chronic pulmonary histoplasmosis. We review the 25 years of clinical experience with this mycobacteria; particular emphasis is on the presentation and treatment of this very unusual infection

Assessing targeted screening and low rates of HIV testing

Objectives. We assessed rates of HIV testing based on targeting patients with identified risk factors at the Veterans Affairs Medical Center in Washington, DC (VAMC-DC), where written informed consent along with pretest and posttest counseling had, until recently, been required by federal law. Methods. A cumulative retrospective review of the period 2000 through 2007 was conducted to assess the number of patients who were provided medical care at VAMC-DC, tested for HIV, and underwent confirmatory testing. Data on demographic characteristics and risks for HIV acquisition were also collected. Results. At VAMC-DC, 3.8% to 4.9% (mean = 4.25%) of patients in care without known HIV infection underwent HIV screening annually. On average, HIV was confirmed at a yearly rate of 3.4% among those tested. During the study period, HIV prevalence ranged from 2.1% to 2.5%. Among patients receiving HIV care, 41.5% disclosed no risk factors for HIV acquisition. Conclusions. Given that the HIV prevalence observed in this study was above 2% and that 41.5% of patients in care did not disclose any acquisition risks, targeted HIV screening has not been sufficient. HIV testing must be broadened and offered as part of routine medical care