Publications by authors named "William M Switzer"

125 Publications

The CDC HIV Outbreak Coordination Unit: Developing a Standardized, Collaborative Approach to HIV Outbreak Assessment and Response.

Public Health Rep 2021 May 28:333549211018678. Epub 2021 May 28.

1242 Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA.

The Centers for Disease Control and Prevention (CDC) and state, territorial, and local health departments have expanded efforts to detect and respond to HIV clusters and outbreaks in the United States. In July 2017, CDC created the HIV Outbreak Coordination Unit (OCU) to ensure consistent and collaborative assessment of requests from health departments for consultation or support on possible HIV clusters and outbreaks of elevated concern. The HIV OCU is a multidisciplinary, cross-organization functional unit within CDC's Division of HIV/AIDS Prevention. HIV OCU members have expertise in areas such as outbreak detection and investigation, prevention, laboratory services, surveillance and epidemiology, policy, communication, and operations. HIV OCU discussions facilitate problem solving, coordination, and situational awareness. Between HIV OCU meetings, designated CDC staff members communicate regularly with health departments to provide support and assessment. During July 2017-December 2019, the HIV OCU reviewed 31 possible HIV clusters and outbreaks (ie, events) in 22 states that were detected by CDC, health departments, or local partners; 17 events involved HIV transmission associated with injection drug use, and other events typically involved sexual transmission or overall increases in HIV diagnoses. CDC supported health departments remotely or on site with planning and prioritization; data collection, management, and analysis; communications; laboratory support; multistate coordination; and expansion of HIV prevention services. The HIV OCU has augmented CDC's support of HIV cluster and outbreak assessment and response at health departments and had important internal organizational benefits. Health departments may benefit from developing or strengthening similar units to coordinate detection and response efforts within and across public health agencies and advance the national Ending the HIV Epidemic initiative.
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http://dx.doi.org/10.1177/00333549211018678DOI Listing
May 2021

Increasing Capacity to Detect Clusters of Rapid HIV Transmission in Varied Populations-United States.

Viruses 2021 03 30;13(4). Epub 2021 Mar 30.

Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.

Molecular cluster detection analyzes HIV sequences to identify rapid HIV transmission and inform public health responses. We describe changes in the capability to detect molecular clusters and in geographic variation in transmission dynamics. We examined the reporting completeness of HIV-1 polymerase sequences in quarterly National HIV Surveillance System datasets from December 2015 to December 2019. Priority clusters were identified quarterly. To understand populations recently affected by rapid transmission, we described the transmission risk and race/ethnicity of people in clusters first detected in 2018-2019. During December 2015 to December 2019, national sequence completeness increased from 26% to 45%. Of the 1212 people in the 136 clusters first detected in 2018-2019, 69% were men who have sex with men (MSM) and 11% were people who inject drugs (PWID). State-by-state analysis showed substantial variation in transmission risk and racial/ethnic groups in clusters of rapid transmission. HIV sequence reporting has increased nationwide. Molecular cluster analysis identifies rapid transmission in varied populations and identifies emerging patterns of rapid transmission in specific population groups, such as PWID, who, in 2015-2016, comprised only 1% of people in such molecular clusters. These data can guide efforts to focus, tailor, and scale up prevention and care services for these populations.
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http://dx.doi.org/10.3390/v13040577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066706PMC
March 2021

CD4 receptor diversity represents an ancient protection mechanism against primate lentiviruses.

Proc Natl Acad Sci U S A 2021 Mar;118(13)

Lukuru Wildlife Research Foundation, Tshuapa-Lomami-Lualaba Project, BP 2012, Kinshasa, Democratic Republic of the Congo.

Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. Here, we show that within-species CD4 diversity is not unique to chimpanzees but found in many African primate species. Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. D1 domain amino acid replacements affected SIV Env-mediated cell entry in a single-round infection assay, restricting infection in a strain- and allele-specific fashion. Several identical CD4 polymorphisms, including the addition of -linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. Moreover, seven different guenons ( spp.) shared multiple distinct D1 domain variants, pointing to long-term trans-specific polymorphism. These data indicate that the HIV/SIV Env binding region of the primate CD4 protein is highly variable, both within and between species, and suggest that this diversity has been maintained by balancing selection for millions of years, at least in part to confer protection against primate lentiviruses. Although long-term SIV-infected species have evolved specific mechanisms to avoid disease progression, primate lentiviruses are intrinsically pathogenic and have left their mark on the host genome.
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http://dx.doi.org/10.1073/pnas.2025914118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020793PMC
March 2021

Broadly neutralizing HIV-1 antibody reactivity in HIV tests: implications for diagnostics.

AIDS 2021 Apr 7. Epub 2021 Apr 7.

Oak Ridge Institute for Science and Research ICF Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention.

Objective: Passive immunization with broadly neutralizing antibodies (bNAbs) is under evaluation for HIV prevention. BNAbs target gp120 or gp41, two HIV envelope antigens commonly present in diagnostic tests. Depending on bNAb type and dose administered to humans, serum levels can reach ∼1 mg/mL and wane over several weeks to months. We investigated the reactivity of bNAbs in HIV serological tests to inform diagnostic testing practices for persons treated with these products.

Design Methods: The anti-gp120 bNAbs VRCO1, PGT121, PGT145, 3BNC117, 10-1074, and N6 and anti-gp41 bNAbs 10E8 and 10E8v4 were tested with the laboratory-based Bio-Rad Ag/Ab Combo assay, the point-of-care single-use Determine Combo, OraQuick, Reveal G4, SureCheck, Uni-Gold, INSTI and DPP HIV 1/2 assays, and the supplemental Geenius and HIV-1 Western blot assays.

Results: At 1 mg/mL, all bNAbs were nonreactive in four screening tests. OraQuick, SureCheck, Reveal G4, and INSTI detected at least two bNAbs each; SureCheck exhibited reactivity to six bNAbs. Geenius was HIV-1 indeterminate (gp160+) with all bNAbs except PGT121, which was HIV antibody-negative. HIV-1 Western blot was indeterminate (gp41+/gp160+) with 10E8 and 10E8v4 and negative with the remaining bNAbs. There was no correlation between the test antigen construct(s) and bNAb reactivity.

Conclusion: We identified a laboratory-based Ag/Ab EIA and three single-use rapid HIV tests that are nonreactive against a panel of bNAbs supporting some diagnostic tests can distinguish HIV-1 infection events among persons receiving bNAb immunoprophylaxis. Evaluation of HIV diagnostic tests prior to clinical use may identify suitable serologic assays for persons administered bNAbs.
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http://dx.doi.org/10.1097/QAD.0000000000002898DOI Listing
April 2021

Human T-cell lymphotropic virus type 1 transmission dynamics in rural villages in the Democratic Republic of the Congo with high nonhuman primate exposure.

PLoS Negl Trop Dis 2021 01 28;15(1):e0008923. Epub 2021 Jan 28.

Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.

The Democratic Republic of the Congo (DRC) has a history of nonhuman primate (NHP) consumption and exposure to simian retroviruses yet little is known about the extent of zoonotic simian retroviral infections in DRC. We examined the prevalence of human T-lymphotropic viruses (HTLV), a retrovirus group of simian origin, in a large population of persons with frequent NHP exposures and a history of simian foamy virus infection. We screened plasma from 3,051 persons living in rural villages in central DRC using HTLV EIA and western blot (WB). PCR amplification of HTLV tax and LTR sequences from buffy coat DNA was used to confirm infection and to measure proviral loads (pVLs). We used phylogenetic analyses of LTR sequences to infer evolutionary histories and potential transmission clusters. Questionnaire data was analyzed in conjunction with serological and molecular data. A relatively high proportion of the study population (5.4%, n = 165) were WB seropositive: 128 HTLV-1-like, 3 HTLV-2-like, and 34 HTLV-positive but untypeable profiles. 85 persons had HTLV indeterminate WB profiles. HTLV seroreactivity was higher in females, wives, heads of households, and increased with age. HTLV-1 LTR sequences from 109 persons clustered strongly with HTLV-1 and STLV-1 subtype B from humans and simians from DRC, with most sequences more closely related to STLV-1 from Allenopithecus nigroviridis (Allen's swamp monkey). While 18 potential transmission clusters were identified, most were in different households, villages, and health zones. Three HTLV-1-infected persons were co-infected with simian foamy virus. The mean and median percentage of HTLV-1 pVLs were 5.72% and 1.53%, respectively, but were not associated with age, NHP exposure, village, or gender. We document high HTLV prevalence in DRC likely originating from STLV-1. We demonstrate regional spread of HTLV-1 in DRC with pVLs reported to be associated with HTLV disease, supporting local and national public health measures to prevent spread and morbidity.
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http://dx.doi.org/10.1371/journal.pntd.0008923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872225PMC
January 2021

Molecular Epidemiological Analysis of the Origin and Transmission Dynamics of the HIV-1 CRF01_AE Sub-Epidemic in Bulgaria.

Viruses 2021 Jan 16;13(1). Epub 2021 Jan 16.

Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.

HIV-1 subtype CRF01_AE is the second most predominant strain in Bulgaria, yet little is known about the molecular epidemiology of its origin and transmissibility. We used a phylodynamics approach to better understand this sub-epidemic by analyzing 270 HIV-1 polymerase () sequences collected from persons diagnosed with HIV/AIDS between 1995 and 2019. Using network analyses at a 1.5% genetic distance threshold (), we found a large 154-member outbreak cluster composed mostly of persons who inject drugs (PWID) that were predominantly men. At = 0.5%, which was used to identify more recent transmission, the large cluster dissociated into three clusters of 18, 12, and 7 members, respectively, five dyads, and 107 singletons. Phylogenetic analysis of the Bulgarian sequences with publicly available global sequences showed that CRF01_AE likely originated from multiple Asian countries, with Vietnam as the likely source of the outbreak cluster between 1988 and 1990. Our findings indicate that CRF01_AE was introduced into Bulgaria multiple times since 1988, and infections then rapidly spread among PWID locally with bridging to other risk groups and countries. CRF01_AE continues to spread in Bulgaria as evidenced by the more recent large clusters identified at = 0.5%, highlighting the importance of public health prevention efforts in the PWID communities.
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http://dx.doi.org/10.3390/v13010116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829743PMC
January 2021

Identification of an HIV-1 and Neurosyphilis Cluster in Vermont.

Clin Infect Dis 2020 Dec 8. Epub 2020 Dec 8.

Larner College of Medicine, Burlington, Vermont, USA.

Background: Rates of syphilis in the U.S. have more than doubled over the last several decades, largely among men who have sex with men (MSM). Our study characterizes a cluster of neurosyphilis cases among HIV-1-infected individuals in Vermont in 2017-2018.

Methods: Vermont Department of Health disease intervention specialists conduct interviews with all newly diagnosed HIV-1 cases and pursued sexual networking analyses. Phylogenetic and network analyses of available Vermont HIV-1 polymerase (pol) sequences identified clusters of infection. Fishers-exact and independent t-tests were used to compare HIV-1-infected individuals within or outside an identified cluster.

Results: Between January 1, 2017 and December 31, 2018, 38 Vermont residents were newly diagnosed with HIV-1 infection. The mean age was 35.5 years, 79% were male and 82% were white. Risk factors for HIV-1 acquisition included MSM status (79%) and methamphetamine use (21%). Eighteen cases (49%) had HIV-1 viral loads (VLs) >100,000 copies/mL and 47% had CD4 cell counts <200/mm 3. Eleven of the 38 (29%) cases had positive syphilis serology, including four (36%) with neurosyphilis. Sexual networking analysis revealed a ten-person cluster with higher VLs at diagnosis (90% with VLs > 100,000 copies/mL vs. 33%, p=0.015). Phylogenetic analysis of pol sequences showed a cluster of 14 cases with sequences that shared 98-100% HIV-1 nucleotide identity.

Conclusions: This investigation of newly infected HIV-1 cases in Vermont led to identification of a cluster that appeared more likely to have advanced HIV-1 disease and neurosyphilis. Identification of a cluster was strongly supported by both phylogenetic and network analyses of HIV-1 pol sequences.
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http://dx.doi.org/10.1093/cid/ciaa1834DOI Listing
December 2020

Koala retrovirus diversity, transmissibility, and disease associations.

Retrovirology 2020 10 2;17(1):34. Epub 2020 Oct 2.

Laboratory Branch, Division of HIV/AIDS Prevention, Center for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA, MS G4530329, USA.

Background: Koalas are infected with the koala retrovirus (KoRV) that exists as exogenous or endogenous viruses. KoRV is genetically diverse with co-infection with up to ten envelope subtypes (A-J) possible; KoRV-A is the prototype endogenous form. KoRV-B, first found in a small number of koalas with an increased leukemia prevalence at one US zoo, has been associated with other cancers and increased chlamydial disease. To better understand the molecular epidemiology of KoRV variants and the effect of increased viral loads (VLs) on transmissibility and pathogenicity we developed subtype-specific quantitative PCR (qPCR) assays and tested blood and tissue samples from koalas at US zoos (n = 78), two Australian zoos (n = 27) and wild-caught (n = 21) in Australia. We analyzed PCR results with available clinical, demographic, and pedigree data.

Results: All koalas were KoRV-A-infected. A small number of koalas (10.3%) at one US zoo were also infected with non-A subtypes, while a higher non-A subtype prevalence (59.3%) was found in koalas at Australian zoos. Wild koalas from one location were only infected with KoRV-A. We observed a significant association of infection and plasma VLs of non-A subtypes in koalas that died of leukemia/lymphoma and other neoplasias and report cancer diagnoses in KoRV-A-positive animals. Infection and VLs of non-A subtypes was not associated with age or sex. Transmission of non-A subtypes occurred from dam-to-offspring and likely following adult-to-adult contact, but associations with contact type were not evaluated. Brief antiretroviral treatment of one leukemic koala infected with high plasma levels of KoRV-A, -B, and -F did not affect VL or disease progression.

Conclusions: Our results show a significant association of non-A KoRV infection and plasma VLs with leukemia and other cancers. Although we confirm dam-to-offspring transmission of these variants, we also show other routes are possible. Our validated qPCR assays will be useful to further understand KoRV epidemiology and its zoonotic transmission potential for humans exposed to koalas because KoRV can infect human cells.
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http://dx.doi.org/10.1186/s12977-020-00541-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530975PMC
October 2020

Human Immunodeficiency Virus (HIV) Outbreak Investigation Among Persons Who Inject Drugs in Massachusetts Enhanced by HIV Sequence Data.

J Infect Dis 2020 09;222(Suppl 5):S259-S267

Massachusetts Department of Public Health, Bureau of Infectious Disease and Laboratory Sciences, Jamaica Plain, Massachusetts, USA.

Background: The Massachusetts Department of Public Health and the Centers for Disease Control and Prevention collaborated to characterize a human immunodeficiency virus (HIV) outbreak in northeastern Massachusetts and prevent further transmission. We determined the contributions of HIV sequence data to defining the outbreak.

Methods: Human immunodeficiency virus surveillance and partner services data were analyzed to understand social and molecular links within the outbreak. Cases were defined as HIV infections diagnosed during 2015-2018 among people who inject drugs with connections to northeastern Massachusetts or HIV infections among other persons named as partners of a case or whose HIV polymerase sequence linked to another case, regardless of diagnosis date or geography.

Results: Of 184 cases, 65 (35%) were first identified as part of the outbreak through molecular analysis. Twenty-nine cases outside of northeastern Massachusetts were molecularly linked to the outbreak. Large molecular clusters (75, 28, and 11 persons) were identified. Among 161 named partners, 106 had HIV; of those, 40 (38%) diagnoses occurred through partner services.

Conclusions: Human immunodeficiency virus sequence data increased the case count by 55% and expanded the geographic scope of the outbreak. Human immunodeficiency virus sequence and partner services data each identified cases that the other method would not have, maximizing prevention and care opportunities for HIV-infected persons and their partners.
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http://dx.doi.org/10.1093/infdis/jiaa053DOI Listing
September 2020

Employing Molecular Phylodynamic Methods to Identify and Forecast HIV Transmission Clusters in Public Health Settings: A Qualitative Study.

Viruses 2020 08 22;12(9). Epub 2020 Aug 22.

Department of Epidemiology, College of Public Health and Health Professions & College of Medicine, University of Florida, Gainesville, FL 32610, USA.

Molecular HIV surveillance is a promising public health strategy for curbing the HIV epidemic. Clustering technologies used by health departments to date are limited in their ability to infer/forecast cluster growth trajectories. Resolution of the spatiotemporal dynamics of clusters, through phylodynamic and phylogeographic modelling, is one potential strategy to develop a forecasting tool; however, the projected utility of this approach needs assessment. Prior to incorporating novel phylodynamic-based molecular surveillance tools, we sought to identify possible issues related to their feasibility, acceptability, interpretation, and utility. Qualitative data were collected via focus groups among field experts ( = 17, 52.9% female) using semi-structured, open-ended questions. Data were coded using an iterative process, first through the development of provisional themes and subthemes, followed by independent line-by-line coding by two coders. Most participants routinely used molecular methods for HIV surveillance. All agreed that linking molecular sequences to epidemiological data is important for improving HIV surveillance. We found that, in addition to methodological challenges, a variety of implementation barriers are expected in relation to the uptake of phylodynamic methods for HIV surveillance. The participants identified several opportunities to enhance current methods, as well as increase the usability and utility of promising works-in-progress.
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http://dx.doi.org/10.3390/v12090921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551766PMC
August 2020

Complete Genome Sequence of a Baboon Simian Foamy Virus Isolated from an Infected Human.

Microbiol Resour Announc 2020 Jul 2;9(27). Epub 2020 Jul 2.

Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA

We obtained the full-length genome of a simian foamy virus (SFV) from an infected human. This virus originated from a baboon ( species, strain SFVpxx_hu9406). The genome is 13,113 nucleotides long with the canonical SFV genome structure. Phylogenetically, SFVpxx_hu9406 clustered closely with SFVpan_V909/03F from a captive baboon and other Cercopithecidae SFVs.
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http://dx.doi.org/10.1128/MRA.00522-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330242PMC
July 2020

Molecular Epidemiology of the HIV-1 Subtype B Sub-Epidemic in Bulgaria.

Viruses 2020 04 14;12(4). Epub 2020 Apr 14.

Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30303, USA.

HIV-1 subtype B is the predominant strain in Bulgaria, yet little is known about the molecular epidemiology of these infections, including its origin and transmissibility. We used a phylodynamics approach by combining and analyzing 663 HIV-1 polymerase () sequences collected from persons diagnosed with HIV/AIDS between 1988-2018 and associated epidemiologic data to better understand this sub-epidemic in Bulgaria. Using network analyses at a 1.5% genetic distance threshold ( we found several large phylogenetic clusters composed mostly of men who have sex with men (MSM) and male heterosexuals (HET). However, at d = 0.5%, used to identify more recent transmission, the largest clusters dissociated to become smaller in size. The majority of female HET and persons with other transmission risks were singletons or pairs in the network. Phylogenetic analysis of the Bulgarian sequences with publicly available global sequences showed that subtype B was likely introduced into Bulgaria from multiple countries, including Israel and several European countries. Our findings indicate that subtype B was introduced into Bulgaria multiple times since 1988 and then infections rapidly spread among MSM and non-disclosed MSM. These high-risk behaviors continue to spread subtype B infection in Bulgaria as evidenced by the large clusters at = 0.5%. Relatively low levels of antiretroviral drug resistance were observed in our study. Prevention strategies should continue to include increased testing and linkage to care and treatment, as well as expanded outreach to the MSM communities.
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http://dx.doi.org/10.3390/v12040441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232140PMC
April 2020

Using an Established Outbreak Response Plan and Molecular Epidemiology Methods in an HIV Transmission Cluster Investigation, Tennessee, January-June 2017.

Public Health Rep 2020 May/Jun;135(3):329-333. Epub 2020 Mar 30.

5719 Division of Communicable Environmental Diseases and Emergency Preparedness, Tennessee Department of Health, Nashville, TN, USA.

Introduction: In April 2017, the Tennessee Department of Health (TDH) was notified of an increase in the number of persons newly diagnosed with HIV in eastern Tennessee in the same month. Two were identified as persons with a history of injection drug use (IDU) and named each other as syringe-sharing partners, prompting an investigation into a possible HIV cluster among persons with a history of IDU.

Materials And Methods: TDH and public health staff members in eastern Tennessee collaborated to implement procedures outlined in TDH's HIV/hepatitis C virus (HCV) Outbreak Response Plan, including conducting enhanced interviewing and using a preestablished database for data collection and management. To complement contact tracing and enhanced interviewing, TDH partnered with the Centers for Disease Control and Prevention to conduct molecular HIV analyses.

Results: By June 27, 2017, the investigation had identified 31 persons newly diagnosed with HIV infection; 8 (26%) self-reported IDU, 4 of whom were also men who have sex with men (MSM). Of the remaining 23 persons newly diagnosed with HIV infection, 10 were MSM who did not report IDU, 9 reported high-risk heterosexual contact, and 4 had other or unknown risk factors. Molecular analysis of the 14 HIV-1 polymerase genes (including 7 of the 8 persons self-reporting IDU) revealed 3 distinct molecular clusters, one of which included 3 persons self-reporting IDU.

Practice Implications: This investigation highlights the importance of implementing an established Outbreak Response Plan and using HIV molecular analyses in the event of a transmission cluster or outbreak investigations. Future HIV outbreak surveillance will include using Global Hepatitis Outbreak Surveillance Technology to identify HCV gene sequences as a potential harbinger for HIV transmission networks.
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http://dx.doi.org/10.1177/0033354920915445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238710PMC
July 2020

Investigation of Presumptive HIV Transmission Associated with Hospitalization Using Nucleotide Sequence Analysis - New York, 2017.

MMWR Morb Mortal Wkly Rep 2020 Mar 13;69(10):260-264. Epub 2020 Mar 13.

Since implementation of Standard Precautions* for the prevention of bloodborne pathogen transmission in 1985, health care-associated transmission of human immunodeficiency virus (HIV) in the United States has been rare (1). In October 2017, the New York City Department of Health and Mental Hygiene (NYCDOHMH) and the New York State Department of Health (NYSDOH) were notified by a clinician of a diagnosis of acute HIV infection in a young adult male (patient A) without recognized risk factors (i.e., he was monogamous, had an HIV-negative partner, and had no injection drug use) who had recently been hospitalized for a chronic medical condition. The low risk coupled with the recent hospitalization and medical procedures prompted NYSDOH, NYCDOHMH, and CDC to investigate this case as possible health care-associated transmission of HIV. Among persons with known HIV infection who had hospitalization dates overlapping those of patient A, one person (patient B) had an HIV strain highly similar to patient A's strain by nucleotide sequence analysis. The sequence relatedness, combined with other investigation findings, indicated a likely health care-associated transmission. Nucleotide sequence analysis, which is increasingly used for detecting HIV clusters (i.e., persons with closely related HIV strains) and to inform public health response (2,3), might also be used to identify possible health care-associated transmission of HIV to someone with health care exposure and no known HIV risk factors (4).
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http://dx.doi.org/10.15585/mmwr.mm6910a2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075254PMC
March 2020

Phylodynamic Analysis Complements Partner Services by Identifying Acute and Unreported HIV Transmission.

Viruses 2020 01 27;12(2). Epub 2020 Jan 27.

Centers for Disease Control and Prevention, Atlanta, GA 30322, USA.

Tailoring public health responses to growing HIV transmission clusters depends on accurately mapping the risk network through which it spreads and identifying acute infections that represent the leading edge of cluster growth. HIV transmission links, especially those involving persons with acute HIV infection (AHI), can be difficult to uncover, or confirm during partner services investigations. We integrated molecular, epidemiologic, serologic and behavioral data to infer and evaluate transmission linkages between participants of a prospective study of AHI conducted in North Carolina, New York City and San Francisco from 2011-2013. Among the 547 participants with newly diagnosed HIV with polymerase sequences, 465 sex partners were reported, of whom only 35 (7.5%) had HIV sequences. Among these 35 contacts, 23 (65.7%) links were genetically supported and 12 (34.3%) were not. Only five links were reported between participants with AHI but none were genetically supported. In contrast, phylodynamic inference identified 102 unreported transmission links, including 12 between persons with AHI. Importantly, all putative transmission links between persons with AHI were found among large clusters with more than five members. Taken together, the presence of putative links between acute participants who did not name each other as contacts that are found only among large clusters underscores the potential for unobserved or undiagnosed intermediaries. Phylodynamics identified many more links than partner services alone and, if routinely and rapidly integrated, can illuminate transmission patterns not readily captured by partner services investigations.
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http://dx.doi.org/10.3390/v12020145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077189PMC
January 2020

Trends in HIV-2 Diagnoses and Use of the HIV-1/HIV-2 Differentiation Test - United States, 2010-2017.

MMWR Morb Mortal Wkly Rep 2020 Jan 24;69(3):63-66. Epub 2020 Jan 24.

Since 2014, the recommended laboratory testing algorithm for diagnosing human immunodeficiency virus (HIV) infection has included a supplemental HIV-1/HIV-2 differentiation test to confirm infection type on the basis of the presence of type-specific antibodies (1). Correctly identifying HIV-1 and HIV-2 infections is vital because their epidemiology and clinical management differ. To describe the percentage of diagnoses for which an HIV-1/HIV-2 differentiation test result was reported and to categorize HIV type based on laboratory test results, 2010-2017 data from CDC's National HIV Surveillance System (NHSS) were analyzed. During 2010-2017, a substantial increase in the number of HIV-1/HIV-2 differentiation test results were reported to NHSS, consistent with implementation of the HIV laboratory-based testing algorithm recommended in 2014. However, >99.9% of all HIV infections identified in the United States were categorized as HIV-1, and the number of HIV-2 diagnoses (mono-infection or dual-infection) remained extremely low (<0.03% of all HIV infections). In addition, the overall number of false positive HIV-2 test results produced by the HIV-1/HIV-2 differentiation increased. The diagnostic value of a confirmatory antibody differentiation test in a setting with sensitive and specific screening tests and few HIV-2 infections might be limited. Evaluation and consideration of other HIV tests approved by the Food and Drug Administration (FDA) that might increase efficiencies in the CDC and Association of Public Health Laboratories-recommended HIV testing algorithm are warranted.
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http://dx.doi.org/10.15585/mmwr.mm6903a2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367036PMC
January 2020

Seroreactivity against Marburg or related filoviruses in West and Central Africa.

Emerg Microbes Infect 2020 8;9(1):124-128. Epub 2020 Jan 8.

Vitalant Research Institute, San Francisco, CA, USA.

A serological survey of 2,430 archived serum samples collected between 1997 and 2012 was conducted to retrospectively determine the prevalence of Marburg virus in five African countries. Serum samples were screened for neutralizing antibodies in a pseudotype micro-neutralization assay and confirmed by enzyme-linked immunosorbent assay (ELISA). Surprisingly, a seroprevalence for Marburg virus of 7.5 and 6.3% was found in Cameroon and Ghana, respectively, suggesting the circulation of filoviruses or related viruses outside of known endemic areas that remain undetected by current surveillance efforts. However, due to the lack of validated assays and appropriate positive controls, these results must be considered preliminary.
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http://dx.doi.org/10.1080/22221751.2019.1709563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968259PMC
September 2020

Natural selection favoring more transmissible HIV detected in United States molecular transmission network.

Nat Commun 2019 12 19;10(1):5788. Epub 2019 Dec 19.

Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA.

HIV molecular epidemiology can identify clusters of individuals with elevated rates of HIV transmission. These variable transmission rates are primarily driven by host risk behavior; however, the effect of viral traits on variable transmission rates is poorly understood. Viral load, the concentration of HIV in blood, is a heritable viral trait that influences HIV infectiousness and disease progression. Here, we reconstruct HIV genetic transmission clusters using data from the United States National HIV Surveillance System and report that viruses in clusters, inferred to be frequently transmitted, have higher viral loads at diagnosis. Further, viral load is higher in people in larger clusters and with increased network connectivity, suggesting that HIV in the United States is experiencing natural selection to be more infectious and virulent. We also observe a concurrent increase in viral load at diagnosis over the last decade. This evolutionary trajectory may be slowed by prevention strategies prioritized toward rapidly growing transmission clusters.
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http://dx.doi.org/10.1038/s41467-019-13723-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923435PMC
December 2019

Evaluation of the performance of the Cepheid Xpert HIV-1 Viral Load Assay for quantitative and diagnostic uses.

J Clin Virol 2020 01 15;122:104214. Epub 2019 Nov 15.

National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address:

Background: Cepheid's Xpert HIV-1 Viral Load (Xpert VL), a simplified, automated, single-use quantitative assay used with the GeneXpert System, is not FDA approved.

Objectives: Using stored plasma, we conducted a study to assess the ability of Xpert VL to quantify viral load relative to the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 (Cobas VL) and to examine the use of the Xpert VL as a qualitative diagnostic test.

Study Design: Following HIV-1 viral stock dilutions, we conducted a probit analysis to identify the concentration where 95 % of specimens had quantified VLs. We also examined Xpert and Cobas log VL correlation in linearity panels; compared the proportion of 220 seroconverter specimens with virus detected using McNemar's test; and tested specimens from persons with untreated, established HIV-1 infection (n=149) and uninfected persons (n=497). Furthermore, we examined Xpert VL as a qualitative test in seroconverter specimens with early (n=20) and later (n=68) acute infections.

Results: At 1.80 log10 copies/mL, 95 % of specimens had quantifiable virus using Xpert VL. Xpert and Cobas VLs were highly correlated (R=0.994). The proportion of seroconverter specimens with virus detected using Cobas and with Xpert VL was not statistically different (p=0.0578). Xpert VL detected 97.9 % of established infections, and specificity was 99.80 % (95 % CI 98.87%-99.99%). Xpert VL detected 90 % and 98.5 % of early and later acute infections, respectively.

Conclusions: If approved, Xpert VL could allow U.S. laboratories that cannot bring on large, complex testing platforms to conduct HIV monitoring. An approval for diagnostic use may provide timely identification of HIV infections.
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http://dx.doi.org/10.1016/j.jcv.2019.104214DOI Listing
January 2020

Opioid Use Fueling HIV Transmission in an Urban Setting: An Outbreak of HIV Infection Among People Who Inject Drugs-Massachusetts, 2015-2018.

Am J Public Health 2020 01 14;110(1):37-44. Epub 2019 Nov 14.

Charles Alpren and Amanda Burrage are with the Epidemic Intelligence Service, Division of Scientific Education and Professional Development, Center for Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention (CDC), Atlanta, GA. Philip J. Peters, Sheryl B. Lyss, William M. Switzer, Ashley Murray, Christine Agnew-Brune, Erica L. Dawson, Nivedha Panneer, Paul McClung, Ellsworth M. Campbell, Sharoda Dasgupta, Kischa Hampton, William Adih, Susie P. Danner, Hongwei Jia, and Kate Buchacz are with the Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), CDC. Betsey John, Kevin Cranston, H. Dawn Fukuda, Kathleen Roosevelt, R. Monina Klevens, Janice Bryant, Tracy Stiles, Courtney Breen, Liisa M. Randall, Shauna Onofrey, Katherine K. Hsu, Barry Callis, Linda R. Goldman, Matthew Tumpney, Catherine Brown, and Alfred DeMaria Jr are with the Bureau of Infectious Disease and Laboratory Sciences, Massachusetts Department of Public Health, Boston, MA. Danae Bixler is with the Division of Viral Hepatitis, NCHHSTP, CDC. Jenifer Leaf Jaeger is with the Infectious Disease Bureau, Boston Public Health Commission, Boston. Amy Board is with the Oak Ridge Institute of Science and Education, Oak Ridge, TN.

To describe and control an outbreak of HIV infection among people who inject drugs (PWID). The investigation included people diagnosed with HIV infection during 2015 to 2018 linked to 2 cities in northeastern Massachusetts epidemiologically or through molecular analysis. Field activities included qualitative interviews regarding service availability and HIV risk behaviors. We identified 129 people meeting the case definition; 116 (90%) reported injection drug use. Molecular surveillance added 36 cases to the outbreak not otherwise linked. The 2 largest molecular groups contained 56 and 23 cases. Most interviewed PWID were homeless. Control measures, including enhanced field epidemiology, syringe services programming, and community outreach, resulted in a significant decline in new HIV diagnoses. We illustrate difficulties with identification and characterization of an outbreak of HIV infection among a population of PWID and the value of an intensive response. Responding to and preventing outbreaks requires ongoing surveillance, with timely detection of increases in HIV diagnoses, community partnerships, and coordinated services, all critical to achieving the goal of the national Ending the HIV Epidemic initiative.
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http://dx.doi.org/10.2105/AJPH.2019.305366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893347PMC
January 2020

Simian Foamy Viruses in Central and South America: A New World of Discovery.

Viruses 2019 10 20;11(10). Epub 2019 Oct 20.

Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-617, RJ, Brazil.

Foamy viruses (FVs) are the only exogenous retrovirus to date known to infect neotropical primates (NPs). In the last decade, an increasing number of strains have been completely or partially sequenced, and molecular evolution analyses have identified an ancient co-speciation with their hosts. In this review, the improvement of diagnostic techniques that allowed the determination of a more accurate prevalence of simian FVs (SFVs) in captive and free-living NPs is discussed. Determination of DNA viral load in American primates indicates that oral tissues are the viral replicative site and that buccal swab collection can be an alternative to diagnose SFV infection in NPs. Finally, the transmission potential of NP SFVs to primate workers in zoos and primate centers of the Americas is examined.
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http://dx.doi.org/10.3390/v11100967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832937PMC
October 2019

Molecular Analysis of the Complete Genome of a Simian Foamy Virus Infecting (pileated gibbon) Reveals Ancient Co-Evolution with Lesser Apes.

Viruses 2019 07 3;11(7). Epub 2019 Jul 3.

Laboratory Branch, Division of HIV/AIDS Prevention, Center for Disease Control and Prevention, Atlanta, GA 30329, USA.

Foamy viruses (FVs) are complex retroviruses present in many mammals, including nonhuman primates, where they are called simian foamy viruses (SFVs). SFVs can zoonotically infect humans, but very few complete SFV genomes are available, hampering the design of diagnostic assays. Gibbons are lesser apes widespread across Southeast Asia that can be infected with SFV, but only two partial SFV sequences are currently available. We used a metagenomics approach with next-generation sequencing of nucleic acid extracted from the cell culture of a blood specimen from a lesser ape, the pileated gibbon (), to obtain the complete SFVhpi_SAM106 genome. We used Bayesian analysis to co-infer phylogenetic relationships and divergence dates. SFVhpi_SAM106 is ancestral to other ape SFVs with a divergence date of ~20.6 million years ago, reflecting ancient co-evolution of the host and SFVhpi_SAM106. Analysis of the complete SFVhpi_SAM106 genome shows that it has the same genetic architecture as other SFVs but has the longest recorded genome (13,885-nt) due to a longer long terminal repeat region (2,071 bp). The complete sequence of the SFVhpi_SAM106 genome fills an important knowledge gap in SFV genetics and will facilitate future studies of FV infection, transmission, and evolutionary history.
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http://dx.doi.org/10.3390/v11070605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669568PMC
July 2019

Genome-Wide Patterns of Gene Expression in a Wild Primate Indicate Species-Specific Mechanisms Associated with Tolerance to Natural Simian Immunodeficiency Virus Infection.

Genome Biol Evol 2019 06;11(6):1630-1643

Department of Anthropology, University of Oregon.

Over 40 species of nonhuman primates host simian immunodeficiency viruses (SIVs). In natural hosts, infection is generally assumed to be nonpathogenic due to a long coevolutionary history between host and virus, although pathogenicity is difficult to study in wild nonhuman primates. We used whole-blood RNA-seq and SIV prevalence from 29 wild Ugandan red colobus (Piliocolobus tephrosceles) to assess the effects of SIV infection on host gene expression in wild, naturally SIV-infected primates. We found no evidence for chronic immune activation in infected individuals, suggesting that SIV is not immunocompromising in this species, in contrast to human immunodeficiency virus in humans. Notably, an immunosuppressive gene, CD101, was upregulated in infected individuals. This gene has not been previously described in the context of nonpathogenic SIV infection. This expands the known variation associated with SIV infection in natural hosts and may suggest a novel mechanism for tolerance of SIV infection in the Ugandan red colobus.
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http://dx.doi.org/10.1093/gbe/evz099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561381PMC
June 2019

Serologic Prevalence of Ebola Virus in Equatorial Africa.

Emerg Infect Dis 2019 05;25(5):911-918

We conducted a serologic survey of 2,430 serum samples collected during 1997-2012 for various studies to determine the prevalence of the hemorrhagic fever virus Ebola virus (EBOV) in equatorial Africa. We screened serum samples for neutralizing antibodies by using a pseudotype microneutralization assay and a newly developed luciferase immunoprecipitation system assay. Specimens seroreactive for EBOV were confirmed by using an ELISA. Our results suggest a serologic prevalence of 2%-3.5% in the Republic of the Congo and the Democratic Republic of the Congo, which have reported outbreaks of infection with EBOV. In addition we detected a seroprevalence of 1.3% in southern Cameroon, which indicated a low risk for exposure in this region.
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http://dx.doi.org/10.3201/eid2505.180115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478206PMC
May 2019

Undisclosed HIV infection among MSM in a behavioral surveillance study.

AIDS 2019 04;33(5):913-918

Division of HIV/AIDS Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Objective: As a proxy for undiagnosed HIV, the Centers for Disease Control and Prevention's National HIV Behavioral Surveillance (NHBS) monitors participants who report being unaware of their infection, defined as self-reporting an HIV-negative or unknown status during the interview but testing positive for HIV infection. We validated the NHBS measure of awareness among MSM in 2014.

Design: We tested dried blood spots from MSM who reported being unaware of their infection for seven antiretrovirals (ARVs). MSM unaware with at least one ARV detected were defined as misreporters.

Methods: Weighted percentages and 95% confidence intervals were calculated to compare characteristics among misreporters, nonmisreporters, and those who self-reported as HIV-positive. Viral load was quantified with a validated assay using dried blood spots.

Results: Of 1818 HIV-positive MSM, 299 (16%) self-reported as HIV-negative or unknown infection status. Of these 299, 145 (49%) were considered misreporters based on ARV detection. Among the unaware, misreporters were more likely than nonmisreporters to be older and have health insurance. Compared with self-reported HIV-positive MSM, misreporters were more likely to be black, be bisexual, and have perceived discrimination. Of 138 misreporters with viral load data, 116 (84%) had an undetectable viral load.

Conclusion: ARV testing revealed that half of MSM classified as unaware of their infection misreported their status. Although off-label preexposure prophylaxis use might explain the presence of ARVs, it is unlikely as many misreporters were virally suppressed, suggesting they were on HIV therapy. Biomarker validation of behavioral data can improve data quality and usefulness in NHBS and other studies.
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http://dx.doi.org/10.1097/QAD.0000000000002147DOI Listing
April 2019

A Multiplex HIV Incidence Assay for Inferring Recent HIV-1 Transmission and Time of Infection.

J Acquir Immune Defic Syndr 2019 04;80(4):454-460

Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA.

Background: Laboratory assays for determining recent HIV-1 infection are an important public health tool for aiding in the estimation of HIV incidence. Some incidence assay analytes are remarkably predictive of time since seroconversion and may be useful for additional applications, such as predicting recent transmission events during HIV outbreaks and informing prevention strategies.

Methods: Plasma samples (n = 154) from a recent HIV-1 outbreak in a rural community in Indiana were tested with the customized HIV-1 Multiplex assay, based on the Bio-Rad Bio-Plex platform, which measures antibody response to HIV envelope antigens, gp120, gp160, and gp41. Assay cutoffs for each analyte were established to determine whether an individual seroconverted within 30, 60, or 90 days of the sample collection date. In addition, a novel bioinformatics method was implemented to infer infection dates of persons newly diagnosed with HIV during the outbreak.

Results: Sensitivity/specificity of the HIV-1 Multiplex assay for predicting seroconversion within 30, 60, and 90 days, based on a training data set, was 90.5%/95.4%, 94.1%/90%, and 89.4%/82.9%, respectively. Of 154 new diagnoses in Indiana between December 2014 and August 2016, the majority (71%) of recent infections (≤3 months since seroconversion) were identified between February and May 2016. The epidemiologic curve derived from the bioinformatics analysis indicated HIV transmission began as early as 2010, grew exponentially in 2014, and leveled off in April 2015.

Conclusions: The HIV-1 Multiplex assay has the potential to identify and monitor trends in recent infection during an epidemic to assess the efficacy of programmatic or treatment interventions.
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http://dx.doi.org/10.1097/QAI.0000000000001937DOI Listing
April 2019

A Strategy for PrEP Clinicians to Manage Ambiguous HIV Test Results During Follow-up Visits.

Open Forum Infect Dis 2018 Aug 21;5(8):ofy180. Epub 2018 Jul 21.

Division of HIV/AIDS Prevention, National Center for HIV, Viral Hepatitis, STD, Atlanta, Georgia.

Prompt determination of HIV infection status is critical during follow-up visits for patients taking pre-exposure prophylaxis (PrEP) medication. Those who are uninfected can then continue safely taking PrEP, and those few who have acquired HIV infection can initiate an effective treatment regimen. However, a few recent cases have been reported of ambiguous HIV test results using common testing algorithms in PrEP patients. We review published reports of such cases and testing options that can be used to clarify true HIV status in these situations. In addition, we review the benefits and risks of 3 antiretroviral management options in these patients: (1) continue PrEP while conducting additional HIV tests, (2) initiate antiretroviral therapy for presumptive HIV infection while conducting confirmatory tests, or (3) discontinue PrEP to reassess HIV status after a brief antiretroviral-free interval. A clinical consultation resource is also provided.
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http://dx.doi.org/10.1093/ofid/ofy180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105113PMC
August 2018

Clinical and Molecular Features of Feline Foamy Virus and Feline Leukemia Virus Co-Infection in Naturally-Infected Cats.

Viruses 2018 12 11;10(12). Epub 2018 Dec 11.

Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil.

Feline foamy virus (FFV) and feline leukemia virus (FeLV) belong to the family. While disease has not been reported for FFV infection, FeLV infection can cause anemia and immunosuppression (progressive infection). Co-infection with FFV/FeLV allows evaluation of the pathogenic potential and epidemiology of FFV infection in cats with FeLV pathology. Blood and buccal swab samples from 81 cats were collected in Rio de Janeiro. Plasma was serologically tested for FeLV. DNA extracted from peripheral blood mononuclear cells and buccal swabs was used to PCR detect FFV and FeLV. A qPCR was developed to detect and measure FFV proviral loads (pVLs) in cats. FeLV qPCR was performed using previous methods. The median log10 pVL of FFV mono-infected individuals was lower than found in FFV/FeLV co-infected cats in buccal swabs ( = 0.003). We found 78% of cats had detectable buccal FFV DNA in FFV mono-infected and FFV co-infected FeLV-progressive cats, while in FeLV-regressive cats (those without signs of disease) 22% of cats had detectable buccal FFV DNA ( = 0.004). Our results suggest that regressive FeLV infection may reduce FFV saliva transmission, the main mode of FV transmission. We did not find evidence of differences in pathogenicity in FFV mono- and -dually infected cats. In summary, we show that FVs may interact with FeLV within the same host. Our study supports the utility of cats naturally co-infected with retroviruses as a model to investigate the impact of FV on immunocompromised mammalian hosts.
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http://dx.doi.org/10.3390/v10120702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315984PMC
December 2018