Anna Person

Pre-exposure prophylaxis--one more tool for HIV prevention.

The 30 years of the human immunodeficiency virus (HIV) epidemic have been marked by many triumphs. Today, thanks to life-saving anti-retroviral medications, patients are living longer than ever. However, despite scientific advances in the field of HIV treatment, HIV prevention has had less success. Despite efforts on several fronts, the number of new HIV diagnoses each year in the United States is unchanged. In this review, we will give a brief overview of the ups and downs of the field of HIV prevention, focusing on pre-exposure prophylaxis (PrEP). CAPRISA 004, iPrEx, FEMPREP, the VOICE trial and HPTN 052, among other prevention trials, are discussed. The CAPRISA 004 and iPrEx studies suggest optimism regarding the use of PrEP for those at risk for HIV infection, but the recent early termination of FEM-PREP and of one arm of VOICE has led to tempered enthusiasm. Many questions remain: Who should get PrEP? How long is it safe to take PrEP? What role will adherence play, and will there be problems with acquired resistance to the drugs with larger numbers using it daily? What is the best method of administering PrEP? Pre-exposure prophylaxis alone is unlikely to be the magic bullet- instead, this strategy will likely need to be part of a broader test-and-treat effort, ongoing education, treatment of sexually transmitted infections, and condom use.

Diagnosis and treatment of latent tuberculosis infection: an update

It is estimated that more than two billion people have latent M. tuberculosis infection, and this population serves as an important reservoir for future tuberculosis cases. Prevalence estimates are limited by difficulties in diagnosing the infection, including the lack of an ideal test, and an incomplete understanding of latency. Current tests include the tuberculin skin test and two interferon-γ release assays: QuantiFERON Gold In-Tube and T-SPOT.TB. This update focuses on recent publications regarding the ability of these tests to predict tuberculosis disease, their reproducibility over serial tests, and discordance between tests. We also discuss recent advances in the treatment of latent M. tuberculosis infection, including the three-month regimen of once-weekly rifapentine plus isoniazid, and prolonged isoniazid therapy for HIV-infected persons living in high-tuberculosis-incidence settings. We provide an update on the tolerability of the three-month regimen.

Risk Prediction Tool for Medical Appointment Attendance Among HIV-Infected Persons with Unsuppressed Viremia

Successful treatment of HIV infection requires regular clinical follow-up. A previously published risk-prediction tool (RPT) utilizing data from the electronic health record (EHR) including medication adherence, previous appointment attendance, substance abuse, recent CD4+ count, prior antiretroviral therapy (ART) exposure, prior treatment failure, and recent HIV-1 viral load (VL) has been shown to predict virologic failure at 1 year. If this same tool could be used to predict the more immediate event of appointment attendance, high-risk patients could be identified and interventions could be targeted to improve this outcome. We conducted an observational cohort study at the Vanderbilt Comprehensive Care Clinic from August 2013 through March 2014. Patients with routine medical appointments and most recent HIV-1 VL >200 copies/mL were included. Risk scores for a modified RPT were calculated based on data from the EHR. Odds ratios (OR) for missing the next appointment were estimated using multivariable logistic regression. Among 510 persons included, median age was 39 years, 74% were male, 55% were black, median CD4+ count was 327 cells/mm(3) [Interquartile Range (IQR): 142-560], and median HIV-1 VL was 21,818 copies/mL (IQR: 2,030-69,597). Medium [OR 3.95, 95% confidence interval (CI) 2.08-7.50, p-value<0.01] and high (OR 9.55, 95% CI 4.31-21.16, p-value<0.01) vs. low RPT risk scores were independently associated with missing the next appointment. RPT scores, constructed using readily available data, allow for risk-stratification of HIV medical appointment non-attendance and could support targeting limited resources to improve appointment adherence in groups most at-risk of poor HIV outcomes.

Outcomes of HIV-positive patients with cryptococcal meningitis in the Americas

BACKGROUND Cryptococcal meningitis (CM) is associated with substantial mortality in HIV-infected patients. Optimal timing of antiretroviral therapy (ART) in persons with CM represents a clinical challenge, and the burden of CM in Latin America has not been well described. Studies suggest that early ART initiation is associated with higher mortality, but data from the Americas are scarce. METHODS HIV-infected adults in care between 1985-2014 at participating sites in the Latin America (the Caribbean, Central and South America network (CCASAnet)) and the Vanderbilt Comprehensive Care Clinic (VCCC) and who had CM were included. Survival probabilities were estimated. Risk of death when initiating ART within the first 2 weeks after CM diagnosis versus initiating between 2-8 weeks was assessed using dynamic marginal structural models adjusting for site, age, sex, year of CM, CD4 count, and route of HIV transmission. FINDINGS 340 patients were included (Argentina 58, Brazil 138, Chile 28, Honduras 27, Mexico 34, VCCC 55) and 142 (42%) died during the observation period. Among 151 patients with CM prior to ART 56 (37%) patients died compared to 86 (45%) of 189 with CM after ART initiation (p=0.14). Patients diagnosed with CM after ART had a higher risk of death (p=0.03, log-rank test). The probability of survival was not statistically different between patients who started ART within 2 weeks of CM (7/24, 29%) vs. those initiating between 2-8 weeks (14/53, 26%) (p=0.96), potentially due to lack of power. INTERPRETATION In this large Latin-American cohort, patients with CM had very high mortality rates, especially those diagnosed after ART initiation. This study reflects the overwhelming burden of CM in HIV-infected patients in Latin America.

Time to HAART Initiation after Diagnosis and Treatment of Opportunistic Infections in Patients with AIDS in Latin America

Background Since 2009, earlier initiation of highly active antiretroviral therapy (HAART) after an opportunistic infection (OI) has been recommended based on lower risks of death and AIDS-related progression found in clinical trials. Delay in HAART initiation after OIs may be an important barrier for successful outcomes in patients with advanced disease. Timing of HAART initiation after an OI in “real life” settings in Latin America has not been evaluated. Methods Patients in the Caribbean, Central and South America network for HIV Epidemiology (CCASAnet) ≥18 years of age at enrolment, from 2001–2012 who had an OI before HAART initiation were included. Patients were divided in an early HAART (EH) group (those initiating within 4 weeks of an OI) and a delayed HAART (DH) group (those initiating more than 4 weeks after an OI). All patients with an AIDS-defining OI were included. In patients with more than one OI the first event reported was considered. Calendar trends in the proportion of patients in the EH group (before and after 2009) were estimated by site and for the whole cohort. Factors associated with EH were estimated using multivariable logistic regression models. Results A total of 1457 patients had an OI before HAART initiation and were included in the analysis: 213 from Argentina, 686 from Brazil, 283 from Chile, 119 from Honduras and 156 from Mexico. Most prevalent OI were Tuberculosis (31%), followed by Pneumocystis pneumonia (24%), Invasive Candidiasis (16%) and Toxoplasmosis (9%). Median time from OI to HAART initiation decreased significantly from 5.7 (interquartile range [IQR] 2.8–12.1) weeks before 2009 to 4.3 (IQR 2.0–7.1) after 2009 (p<0.01). Factors associated with starting HAART within 4 weeks of OI diagnosis were lower CD4 count at enrolment (p-<0.001), having a non-tuberculosis OI (p<0.001), study site (p<0.001), and more recent years of OI diagnosis (p<0.001). Discussion The time from diagnosis of an OI to HAART initiation has decreased in Latin America coinciding with the publication of evidence of its benefit. We found important heterogeneity between sites which may reflect differences in clinical practices, local guidelines, and access to HAART. The impact of the timing of HAART initiation after OI on patient survival in this “real life” context needs further evaluation.

New Faces of HIV Infection: Age, Race, and Timing of Entry into HIV Care in the Southeastern United States

Among younger men who have sex with men (MSM), the incidence of HIV is rising nationally. Of the 281 persons who entered into care at a large HIV clinic in the southeastern United States in 2010 to 2012, 78 (27.8%) were <25 years old at the time of diagnosis. Those in the younger group were more likely than those aged ≥25 to be black (59.0% versus 37.4%), MSM (78.2% versus 55.2%), and to have a longer median time from diagnosis to entry into care (71 versus 53 days; P < .05 each). In adjusted survival analysis, persons of black race were less likely to enter care after diagnosis than those of nonblack race (hazard ratio = 0.75, P = .02). Young MSM represent an important target population for prevention and HIV testing interventions, and there is a need to shorten the time from diagnosis to linkage to care, particularly in persons aged <25 and of black race.

Health Literacy and Demographic Disparities in HIV Care Continuum Outcomes

Studies evaluating the association between human immunodeficiency virus (HIV) infection continuum of care outcomes [antiretroviral (ART) adherence, retention in care, viral suppression] and health literacy have yielded conflicting results. Moreover, studies from the southern United States, a region of the country disproportionately affected by the HIV epidemic and low health literacy, are lacking. We conducted an observational cohort study among 575 people living with HIV (PLWH) at the Vanderbilt Comprehensive Care Clinic (Nashville, Tennessee). Health literacy was measured using the brief health literacy screen, a short tool which can be administered verbally by trained clinical personnel. Low health literacy was associated with a lack of viral suppression, but not with poor ART adherence or poor retention. Age and racial disparities in continuum of care outcomes persisted after accounting for health literacy, suggesting that factors in addition to health literacy must be addressed in order to improve outcomes for PLWH.