Centralized HIV Program Oversight: An Investigation of a Case Series of New HIV Infections among US Army Soldiers, 2012 to 2013.

Centralized HIV program oversight and repeal of the Department of Defense policy "Don't Ask Don't Tell" permitted characterization of HIV transmission among soldiers assigned to a large US Army base continental United States from 2012 to 2013. An investigation of a greater than expected number of new HIV infections among soldiers was initiated to characterize transmission and identify opportunities to disrupt transmission and deliver services.All soldiers who were assigned to the base at the time of their first positive HIV test and who had their first positive HIV test in 2012 or in the first 6 months of 2013 and who had a clinical genotype available for analysis were eligible for inclusion in the investigation.All patients (n = 19) were men; most were black (52%) and less than 30 years old (64%). Fifteen of the 19 patients participated in in-depth interviews. Eighty percent were men who have sex with men who reported multiple sex partners having met through social and electronic networks. All were subtype B infections. Significant knowledge gaps and barriers to accessing testing and care in the military healthcare system were identified. Most (58%) belonged to transmission networks involving other soldiers.This investigation represents an important step forward in on-going efforts to develop a comprehensive understanding of transmission networks in the Army that can inform delivery of best practices combination prevention services. The Army is developing plans to directly engage individuals in key affected populations most at risk for HIV infection to identify and address unmet needs and expand delivery and uptake of prevention services. Further investigation is underway and will determine whether these findings are generalizable to the Army.

Natural killer cell-mediated innate sieve effect on HIV-1: the impact of KIR/HLA polymorphism on HIV-1 subtype-specific acquisition in east Africa.

Here we explore the association between killer cell immunoglobulin-like receptor (KIR)/HLA and human immunodeficiency virus type 1 (HIV-1) acquisition with different viral subtypes circulating in East Africa. In the prospective Cohort Development (CODE) cohort (Mbeya, Tanzania), carriers of KIR3DS1 and its putative ligand (HLA-A or HLA-B Bw4-80Ile alleles) showed increased HIV-1 acquisition risk (odds ratio [OR] = 3.46; 95% confidence interval [CI], 1.12-10.63; P = .04) and a trend for enrichment for subtype A and A-containing recombinants (78% vs. 46%; OR = 4.05; 95% CI, .91-28.30; P = .09) at the expense of subtype C (11% vs. 43%; OR = 0.17; 95% CI, .01-.97; P = .08). In vitro, only natural killer cells from KIR3DS1(+)/HLA-Bw4-80Ile(+) healthy donors showed a 2-fold increased capacity to inhibit replication of subtype C vs subtype A viruses (P = .01). These findings suggest the presence of an innate sieve effect and may inform HIV-1 vaccine development.

An investigation of bloodborne pathogen transmission due to multipatient sharing of insulin pens.

On January 30, 2009, nursing staff at a military hospital in Texas reported that single-patient use insulin pens were used on multiple patients. An investigation was initiated to determine if patient-to-patient bloodbome transmission occurred from the practice. Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) testing was offered to patients hospitalized from August 2007 to January 2009 and prescribed insulin pen injections. Virus from HCV-infected patients' sera was sequenced and compared for relatedness. An anonymous survey was administered to nurses. Of 2,113 patients prescribed insulin pen injections, 1,501 (71%) underwent testing; 6 (0.4%) were HIV positive, 6 (0.4%) were hepatitis B surface antigen positive, and 56 (3.7%) had HCV antibody. No viral sequences from 10 of 28 patients with newly diagnosed and 12 of 28 patients with preexisting HCV infection were closely related. Of 54 nurses surveyed, 74% reported being trained on insulin pen use, but 24% believed nurses used insulin pens on more than one patient. We found no clear evidence of bloodborne pathogen transmission. Training of hospital staff on correct use of insulin pens should be prioritized and their practices evaluated. Insulin pens should be more clearly labeled for single-patient use.

Enhanced U.S. Army HIV diagnostic algorithm used to diagnose acute HIV infection in a deployed soldier.

Antibody screening alone may fail to detect human immunodeficiency virus (HIV) in recently infected individuals. By U.S. Army regulation, HIV-infected soldiers are not permitted to deploy to areas of conflict, including Iraq and Afghanistan. We report here the first case of acute HIV infection (AHI) in a soldier in a combat area of operation detected by an enhanced U.S. Army HIV testing algorithm and discuss features of the tests which aided in clinical diagnosis. We tested the sample from the AHI case with a third generation HIV-1/HIV-2 plus O enzyme immunoassay, HIV-1 Western Blot, and a qualitative HIV-1 ribonucleic acid molecular diagnostic assay. Risk factors for HIV acquisition were elicited in an epidemiologic interview. Evaluation of the blood sample for AHI indicated an inconclusive serologic profile and a reactive HIV-1 ribonucleic acid result. The main risk factor for acquisition reported was unprotected sexual intercourse with casual strangers in the U.S. while on leave during deployment. The clinical diagnosis of AHI in a combat area of operation is important. Diagnosis of HIV is key to preventing adverse effects to the infected soldier from deployment stressors of deployment and further transmission via parenteral or sexual exposures.

Short communication: Investigation of incident HIV infections among U.S. army soldiers deployed to Afghanistan and Iraq, 2001-2007.

The U.S. Army initiated an investigation in response to observations of a possible increase in HIV incidence among soldiers deployed to combat. Human immunodeficiency virus (HIV)-infected U.S. Army soldiers are not eligible to deploy. Combat presents a health hazard to HIV-infected soldiers and they pose a threat to the safety of the battlefield blood supply and their contacts. All soldiers are routinely screened for HIV every 2 years and those who deploy are also screened both prior to and after deployment. Seroconversion rates were estimated for all soldiers who deployed to Afghanistan or Iraq in the period 2001-2007 and all active duty soldiers who did not. Seroconverters with an estimated date of infection, based on calculation of the midpoint between the last seronegative and first seropositive test date, that was either before or during deployment were eligible for inclusion. Confidential interviews and medical record reviews were conducted to determine the most likely time, geographic location, and mode of infection. Reposed predeployment samples were tested for HIV ribonucleic acid. The HIV seroconversion rate among all soldiers who deployed was less than the rate among those who did not deploy: 1.04 and 1.42 per 10,000 person-years, respectively. Among 48 cases, most were determined to have been infected in the United States or Germany and prior to deployment (n=20, 42%) or during rest and relaxation leave (n=13, 27%). Seven seronegative acute infections were identified in the predeployment period. Subtype was determined for 40 individuals; all were subtype B infections. All were acquired through sexual contact. These findings can inform development of preventive interventions and refinement of existing screening policy to further reduce HIV-infected deployed soldier person time.

Transfusion-transmissible viral infections among US military recipients of whole blood and platelets during Operation Enduring Freedom and Operation Iraqi Freedom.

BACKGROUND: Current US military clinical practice guidelines permit emergency transfusions of non-Food and Drug Administration (FDA)-compliant freshly collected blood products in theaters of war. This investigation aimed to characterize the risks of transfusion-transmitted infections (TTIs) associated with battlefield transfusions of non-FDA-compliant blood products. STUDY DESIGN AND METHODS: US Service members who received emergency transfusion products in Iraq and Afghanistan (March 1, 2002-September 30, 2007) were tested for hepatitis C virus (HCV), human immunodeficiency virus (HIV), and hepatitis B virus (HBV) infections using reposed pre- and posttransfusion sera. Selected regions of viral genomes from epidemiologically linked infected recipients and their donors were sequenced and compared. RESULTS: Of 761 US Service members who received emergency transfusion products, 475 were tested for HCV, 472 for HIV, and 469 for HBV. One transfusion-transmitted HCV infection (incidence rate of 2.1/1000 persons) was identified. The pretransfusion numbers (prevalence per 1000 persons) were HCV-four (8/1000), HIV-zero (0/1000), chronic HBV-two (4 /1000), and naturally immune (antibody to HBV core antigen)-nine (19/1000). CONCLUSION: One HCV TTI was determined to be associated with emergency blood product use. The pretransfusion HCV and HBV prevalence in transfusion recipients, themselves members of the potential donor population, indicates better characterization of the deployed force's actual donor population, and further investigations of the TTI prevalence in these donors are needed. These data will inform countermeasure development and clinical decision making.

RecDraw: a software package for the representation of HIV-1 recombinant structures.

The crucial role of recombination in HIV-1 biology is being increasingly recognized. In vitro studies have shown that up to 30 strand-transfer events may occur per viral replication cycle. Thus, recombination may surpass mutation as a major mechanism driving HIV-1 evolution. Currently, recombinant strains comprise 37% of the full-genome HIV-1 sequence database, including sequences representing 47 Circulating Recombinant Forms (CRFs) and more than 250 different Unique Recombinant Forms (URFs). Mapping of recombination breakpoints helps establish relationships among strains that are related by descent, such as CRF07_BC and CRF08_BC in China, and sheds light on their origin and epidemic spread. Additionally, unrelated recombinants sharing common breakpoints may reflect recombination hotspots within the viral genome. Here we present a software tool, RecDraw, for the graphical representation and efficient comparison of recombinant HIV-1 structures and breakpoints. RecDraw is a platform-flexible, Java stand-alone application available through http://www.hivresearch.org/research.php?ServiceID = 5&SubServiceID = 6 .

High-throughput high-resolution class I HLA genotyping in East Africa.

HLA, the most genetically diverse loci in the human genome, play a crucial role in host-pathogen interaction by mediating innate and adaptive cellular immune responses. A vast number of infectious diseases affect East Africa, including HIV/AIDS, malaria, and tuberculosis, but the HLA genetic diversity in this region remains incompletely described. This is a major obstacle for the design and evaluation of preventive vaccines. Available HLA typing techniques, that provide the 4-digit level resolution needed to interpret immune responses, lack sufficient throughput for large immunoepidemiological studies. Here we present a novel HLA typing assay bridging the gap between high resolution and high throughput. The assay is based on real-time PCR using sequence-specific primers (SSP) and can genotype carriers of the 49 most common East African class I HLA-A, -B, and -C alleles, at the 4-digit level. Using a validation panel of 175 samples from Kampala, Uganda, previously defined by sequence-based typing, the new assay performed with 100% sensitivity and specificity. The assay was also implemented to define the HLA genetic complexity of a previously uncharacterized Tanzanian population, demonstrating its inclusion in the major East African genetic cluster. The availability of genotyping tools with this capacity will be extremely useful in the identification of correlates of immune protection and the evaluation of candidate vaccine efficacy.

HyperPack: a software package for the study of levels, contexts, and patterns of APOBEC-mediated hypermutation in HIV.

G-to-A hypermutation, a massive substitution of G for A, was first observed in HIV genomes 15 years ago. Initially ascribed to fluctuating nucleotide pools or PCR errors, it has now been recognized as the result of an important host-defense mechanism mediated by APOBECs, a family of sequence-specific cytidine deaminases. Levels of hypermutation vary, and APOBECs have different preferences for the sequence context of cytidines targeted for deamination; analysis of hypermutation provides important information about the host-virus interaction during viral replication. Here we present HyperPack, a software package to support systematic characterization of hypermutated sequences. Users can define the context of substitution for independent study of the effects of different APOBECs. The SubstrateScan and HyperScan modules are overlapping sliding-window strategies to analyze the distribution of targeted motifs and their substitution levels, respectively, across the viral genome. HyperPack is a platform-flexible, Java stand-alone application available through http://www.hivresearch.org/hyperpack/.