Demetre Daskalakis

Immune-driven recombination and loss of control after HIV superinfection

After acute HIV infection, CD8+ T cells are able to control viral replication to a set point. This control is often lost after superinfection, although the mechanism behind this remains unclear. In this study, we illustrate in an HLA-B27+ subject that loss of viral control after HIV superinfection coincides with rapid recombination events within two narrow regions of Gag and Env. Screening for CD8+ T cell responses revealed that each of these recombination sites (∼50 aa) encompassed distinct regions containing two immunodominant CD8 epitopes (B27-KK10 in Gag and Cw1-CL9 in Env). Viral escape and the subsequent development of variant-specific de novo CD8+ T cell responses against both epitopes were illustrative of the significant immune selection pressures exerted by both responses. Comprehensive analysis of the kinetics of CD8 responses and viral evolution indicated that the recombination events quickly facilitated viral escape from both dominant WT- and variant-specific responses. These data suggest that the ability of a superinfecting strain of HIV to overcome preexisting immune control may be related to its ability to rapidly recombine in critical regions under immune selection pressure. These data also support a role for cellular immune pressures in driving the selection of new recombinant forms of HIV.

Another Perfect Storm: Shigella Men Who Have Sex with Men, and HIV

Shigella species are a significant cause of bacterial dysentery worldwide, with -165 million cases every year, leading to 1 million deaths annually [1]. Nearly 450,000 Shigella infections, causing significant morbidity, are reported each year in the United States [2]. Many of these cases occur in children or in health care institutions or are imported through travel abroad. In the mid-1970s, outbreaks of Shigella infection among adults in New York and San Francisco raised the possibility that Shigella species may be sexually transmitted, with most infections occurring in men who have sex with men (MSM) [3, 4]. Since these early observations, Shigella infection appears to be more frequent among MSM than among other adult populations, via direct fecal-oral transmission either through accidental inoculation of contaminated stool or through direct oral-anal contact [5-9]. The efficiency of this sexual transmission is likely fueled by several elements, both biological and behavioral in nature (figure 1). A very small inoculum of Shi-

Screening Yield of HIV Antigen/Antibody Combination and Pooled HIV RNA Testing for Acute HIV Infection in a High-Prevalence Population

IMPORTANCEnAlthough acute HIV infection contributes disproportionately to onward HIV transmission, HIV testing has not routinely included screening for acute HIV infection.nnnOBJECTIVEnTo evaluate the performance of an HIV antigen/antibody (Ag/Ab) combination assay to detect acute HIV infection compared with pooled HIV RNA testing.nnnDESIGN, SETTING, AND PARTICIPANTSnMultisite, prospective, within-individual comparison study conducted between September 2011 and October 2013 in 7 sexually transmitted infection clinics and 5 community-based programs in New York, California, and North Carolina. Participants were 12 years or older and seeking HIV testing, without known HIV infection.nnnEXPOSURESnAll participants with a negative rapid HIV test result were screened for acute HIV infection with an HIV Ag/Ab combination assay (index test) and pooled human immunodeficiency virus 1 (HIV-1) RNA testing. HIV RNA testing was the reference standard, with positive reference standard result defined as detectable HIV-1 RNA on an individual RNA test.nnnMAIN OUTCOMES AND MEASURESnNumber and proportion with acute HIV infections detected.nnnRESULTSnAmong 86,836 participants with complete test results (median age, 29 years; 75.0% men; 51.8% men who have sex with men), established HIV infection was diagnosed in 1158 participants (1.33%) and acute HIV infection was diagnosed in 168 participants (0.19%). Acute HIV infection was detected in 134 participants with HIV Ag/Ab combination testing (0.15% [95% CI, 0.13%-0.18%]; sensitivity, 79.8% [95% CI, 72.9%-85.6%]; specificity, 99.9% [95% CI, 99.9%-99.9%]; positive predictive value, 59.0% [95% CI, 52.3%-65.5%]) and in 164 participants with pooled HIV RNA testing (0.19% [95% CI, 0.16%-0.22%]; sensitivity, 97.6% [95% CI, 94.0%-99.4%]; specificity, 100% [95% CI, 100%-100%]; positive predictive value, 96.5% [95% CI, 92.5%-98.7%]; sensitivity comparison, Pu2009<u2009.001). Overall HIV Ag/Ab combination testing detected 82% of acute HIV infections detectable by pooled HIV RNA testing. Compared with rapid HIV testing alone, HIV Ag/Ab combination testing increased the relative HIV diagnostic yield (both established and acute HIV infections) by 10.4% (95% CI, 8.8%-12.2%) and pooled HIV RNA testing increased the relative HIV diagnostic yield by 12.4% (95% CI, 10.7%-14.3%).nnnCONCLUSIONS AND RELEVANCEnIn a high-prevalence population, HIV screening using an HIV Ag/Ab combination assay following a negative rapid test detected 82% of acute HIV infections detectable by pooled HIV RNA testing, with a positive predictive value of 59%. Further research is needed to evaluate this strategy in lower-prevalence populations and in persons using preexposure prophylaxis for HIV prevention.

Advancing global health and strengthening the HIV response in the era of the Sustainable Development Goals: the International AIDS Society—Lancet Commission

Author(s): Bekker, Linda-Gail; Alleyne, George; Baral, Stefan; Cepeda, Javier; Daskalakis, Demetre; Dowdy, David; Dybul, Mark; Eholie, Serge; Esom, Kene; Garnett, Geoff; Grimsrud, Anna; Hakim, James; Havlir, Diane; Isbell, Michael T; Johnson, Leigh; Kamarulzaman, Adeeba; Kasaie, Parastu; Kazatchkine, Michel; Kilonzo, Nduku; Klag, Michael; Klein, Marina; Lewin, Sharon R; Luo, Chewe; Makofane, Keletso; Martin, Natasha K; Mayer, Kenneth; Millett, Gregorio; Ntusi, Ntobeko; Pace, Loyce; Pike, Carey; Piot, Peter; Pozniak, Anton; Quinn, Thomas C; Rockstroh, Jurgen; Ratevosian, Jirair; Ryan, Owen; Sippel, Serra; Spire, Bruno; Soucat, Agnes; Starrs, Ann; Strathdee, Steffanie A; Thomson, Nicholas; Vella, Stefano; Schechter, Mauro; Vickerman, Peter; Weir, Brian; Beyrer, Chris

Hospitalization Rates Among People With HIV/AIDS in New York City, 2013

BackgroundnHospitalizations are an important indicator of healthcare quality and access for people with human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS). This study assesses hospitalization rates among people with HIV/AIDS in New York City.nnnMethodsnWe performed a deterministic match between people in the New York City HIV surveillance registry alive as of 1 January 2013 and diagnosed with HIV as of 31 December 2013 and patient-level inpatient hospitalization records during 2013. Event-level data were analyzed to determine characteristics of and reasons for hospitalizations. Primary diagnoses were classified using the International Classification of Diseases, Ninth Revision, Clinical Modification. We estimated hospitalization rates as the number of hospitalizations per 100 person-years for all causes, AIDS-defining illnesses, and non-AIDS-defining infections.nnnResultsnNearly one-fifth of hospitalizations were attributed to non-AIDS-defining infections, whereas AIDS-defining illness diagnoses were infrequent (3.6% of hospitalizations). Other common causes were cardiovascular (10.9%) and substance use (9.8%). The estimated all-cause hospitalization rate was 36.7 per 100 person-years. Higher all-cause hospitalization rates were observed among females (46.8 per 100 person-years), Black and Latino/Hispanic people (41.8 and 39.5 per 100 person-years, respectively), people living in high-poverty neighborhoods (47.4 per 100 person-years), and people with a history of injection drug use (74.9 per 100 person-years). The estimated AIDS-defining illness and non-AIDS-defining infection hospitalization rates were 1.3 and 7.2 per 100 person-years, respectively.nnnConclusionsnPeople with HIV in New York City were frequently hospitalized. While AIDS-defining illnesses were relatively rare, non-AIDS-defining infection hospitalizations were more common. Disparities in hospitalization rates indicate a need for targeted improved primary care and comorbid disease management.

Outbreak of Influenza A(H7N2) Among Cats in an Animal Shelter With Cat-to-Human Transmission—New York City, 2016

We describe the first case of cat-to-human transmission of influenza A(H7N2), an avian-lineage influenza A virus, that occurred during an outbreak among cats in New York City animal shelters. We describe the public health response and investigation.

Proposing a New Indicator for the National Human Immunodeficiency Virus/AIDS Strategy: Percentage of Newly Diagnosed Persons Achieving Viral Suppression Within 3 Months of Diagnosis

We propose an outcome indicator, the percentage of newly diagnosed persons achieving viral suppression within 3 months of diagnosis, to be included in the US National HIV/AIDS Strategy to monitor the progress in human immunodeficiency virus (HIV) care among persons newly diagnosed with HIV. Using HIV registry data, we reported that the percentage in New York City increased from 9% in 2007 to 37% in 2016. We recommend that the Centers for Disease Control and Prevention and local health agencies use this new indicator to monitor the progress in HIV care among persons newly diagnosed with HIV in the United States.

Pneumonia-Associated Hospitalizations, New York City, 2001-2014

Objectives: Death certificate data indicate that the age-adjusted death rate for pneumonia and influenza is higher in New York City than in the United States. Most pneumonia and influenza deaths are attributed to pneumonia rather than influenza. Because most pneumonia deaths occur in hospitals, we analyzed hospital discharge data to provide insight into the burden of pneumonia in New York City. Methods: We analyzed data for New York City residents discharged from New York State hospitals with a principal diagnosis of pneumonia, or a secondary diagnosis of pneumonia if the principal diagnosis was respiratory failure or sepsis, during 2001-2014. We calculated mean annual age-adjusted pneumonia-associated hospitalization rates per 100u2009000 population and 95% confidence intervals (CIs). We examined data on pneumonia-associated hospitalizations by sociodemographic characteristics and colisted conditions. Results: During 2001-2014, a total of 495u2009225 patients residing in New York City were hospitalized for pneumonia, corresponding to a mean annual age-adjusted pneumonia-associated hospitalization rate of 433.8 per 100u2009000 population (95% CI, 429.3-438.3). The proportion of pneumonia-associated hospitalizations with in-hospital death was 12.0%. The mean annual age-adjusted pneumonia-associated hospitalization rate per 100u2009000 population increased as area-based poverty level increased, whereas the percentage of pneumonia-associated hospitalizations with in-hospital deaths decreased with increasing area-based poverty level. The proportion of pneumonia-associated hospitalizations that colisted an immunocompromising condition increased from 18.7% in 2001 to 33.1% in 2014. Conclusion: Sociodemographic factors and immune status appear to play a role in the epidemiology of pneumonia-associated hospitalizations in New York City. Further study of pneumonia-associated hospitalizations in at-risk populations may lead to targeted interventions.

Redefining Prevention and Care: A Status-Neutral Approach to HIV

Abstract Recent biomedical advances inspire hope that an end to the epidemic of HIV is in sight. Adopting new approaches and paradigms for treatment and prevention in terms of both messaging and programming is a priority to accelerate progress. Defining the key sequential steps that comprise engagement in HIV care has provided a useful framework for clinical programs and motivated quality improvement initiatives. Recently, the same approach has been applied to use of pre-exposure prophylaxis for HIV prevention. Building on the various prevention and care continua previously proposed, we present a novel schematic that incorporates both people living with HIV and people at risk, making it effectively “status-neutral” in that it proposes the same approach for engagement, regardless of one’s HIV status. This multidirectional continuum begins with an HIV test and offers 2 divergent paths depending on the results; these paths end at a common final state. To illustrate how this continuum can be utilized for program planning as well as for monitoring, we provide an example using data for New York City men who have sex with men, a population with high HIV incidence and prevalence.

Public Health Detailing for Human Immunodeficiency Virus Pre-exposure Prophylaxis

Despite the promise of human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP), PrEP remains underutilized, often due to clinician factors. Academic or public health detailing is a process by which university and/or government groups employ the marketing practices of pharmaceutical companies to improve clinical practice. We describe the novel application of detailing to increase PrEP prescribing and related care in New York City and New England. Detailing can play a crucial role in PrEP implementation.