HIV-1 typically infects cells via the CD4 receptor and CCR5 or CXCR4 co-receptors. Maraviroc is a CCR5-specific viral entry inhibitor; knowledge of viral co-receptor specificity is important prior to usage. We developed and validated an economical V3- Illumina-based assay to detect and quantify the frequency of viruses utilizing each co-receptor.
View Article and Find Full Text PDFSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs) are among the treatments recommended for high-risk ambulatory persons with coronavirus 2019 (COVID-19). Here, we study viral culture dynamics post-treatment in a subset of participants receiving the mAb bamlanivimab in the ACTIV-2 trial (ClinicalTrials.gov: NCT04518410).
View Article and Find Full Text PDFBackground: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectious virus isolation in outpatients with coronavirus disease 2019 (COVID-19) has been associated with viral RNA levels and symptom duration, little is known about the host, disease, and viral determinants of infectious virus detection.
Methods: COVID-19 adult outpatients were enrolled within 7 days of symptom onset. Clinical symptoms were recorded via patient diary.
Monoclonal antibodies (mAbs) are the treatment of choice for high-risk ambulatory persons with mild to moderate COVID-19. We studied viral culture dynamics post-treatment in a subset of participants receiving the mAb bamlanivimab in the ACTIV-2 trial. Viral load by qPCR and viral culture were performed from anterior nasal swabs collected on study days 0 (day of treatment), 1, 2, 3, and 7.
View Article and Find Full Text PDFResistance mutations to monoclonal antibody (mAb) therapy has been reported, but in the non-immunosuppressed population, it is unclear if emergence of SARS-CoV-2 resistance mutations alters either viral replication dynamics or therapeutic efficacy. In ACTIV-2/A5401, non-hospitalized participants with symptomatic SARS-CoV-2 infection were randomized to bamlanivimab (700mg or 7000mg) or placebo. Treatment-emergent resistance mutations were significantly more likely detected after bamlanivimab 700mg treatment than placebo (7% of 111 vs 0% of 112 participants, P=0.
View Article and Find Full Text PDFBackground: Romidepsin (RMD) is a histone deacetylase inhibitor reported to reverse HIV-1 latency. We sought to identify doses of RMD that were safe and induced HIV-1 expression.
Methods: Enrollees had HIV-1 RNA <40 copies/mL on antiretroviral therapy.
Background: While SARS-CoV-2 infectious virus isolation in outpatients with COVID-19 has been associated with viral RNA levels and symptom duration, little is known about the host, disease and viral determinants of infectious virus detection.
Methods: COVID-19 adult outpatients were enrolled within 7 days of symptom onset. Clinical symptoms were recorded via patient diary.
Background: Experimental human immunodeficiency virus (HIV)-1 vaccines frequently elicit antibodies against HIV-1 that may react with commonly used HIV diagnostic tests, a phenomenon known as vaccine-induced seropositivity/seroreactivity (VISP/VISR). We sought to determine, under clinic conditions, whether a patient-controlled HIV test, OraQuick ADVANCE Rapid HIV-1/2 Antibody Test, detected HIV-1 vaccine-induced antibodies.
Methods: Plasma assessment of HIV-1 cross-reactivity was examined in end-of-study samples from 57 healthy, HIV-uninfected participants who received a candidate vaccine that has entered Phase 2B and 3 testing.
Background: Antiretroviral therapy (ART) initiation during acute and early human immunodeficiency virus infection (AEHI) limits HIV reservoir formation and may facilitate post-ART control but is logistically challenging. We evaluated the performance of AEHI diagnostic criteria from a prospective study of early ART initiation.
Methods: AIDS Clinical Trials Group A 5354 enrolled adults at 30 sites in the Americas, Africa, and Asia who met any 1 of 6 criteria based on combinations of results of HIV RNA, HIV antibody, Western blot or Geenius assay, and/or the signal-to-cutoff (S/CO) ratio of the ARCHITECT HIV Ag/Ab Combo or GS HIV Combo Ag/Ab EIA.
Antigen (Ag)-specific immune responses to chronic infections, such as herpes simplex virus type 2 (HSV-2) in HIV/HSV-coinfected persons, may sustain HIV tissue reservoirs by promoting T-cell proliferation but are poorly studied in women on antiretroviral therapy (ART). Mixed anogenital swabs and cervical secretions were self-collected by nine HIV/HSV-2-coinfected women during ART for 28 days to establish subclinical HSV DNA shedding rates and detection of HIV RNA by real-time PCR. Typical herpes lesion site biopsy (TLSB) and cervical biopsy specimens were collected at the end of the daily sampling period.
View Article and Find Full Text PDFBackground: High-throughput assays for the SARS-CoV-2 virus are critical to increasing test capacity and slowing the spread of COVID-19. Abbott Molecular developed and received emergency use authorization (EUA) to deploy the new RealTime SARS-CoV-2 assay, run on the automated m2000sp/rt system.
Objective: To evaluate analytical and clinical performance of the RealTime SARS-CoV-2 assay compared to the SARS-CoV-2 CDC-based laboratory developed test (LDT) in clinical use by the University of Washington Clinical Virology Laboratory (UW Virology).
Background: During antiretroviral treatment (ART) with plasma HIV RNA below the limit of quantification, HIV RNA can be detected in genital or rectal secretions, termed discordant shedding (DS). We hypothesized that proliferating cells produce virions without HIV replication.
Methods: ART-naive Peruvians initiating ART were observed for DS over 2 years.
Background: Measurements of HIV exposure could help identify subpopulations at highest risk of acquisition and improve the design of HIV prevention efficacy trials and public health interventions. The HVTN 915 study evaluated the feasibility of self-administered vaginal swabs for detection of HIV virions to assess exposure.
Methods: Fifty 18- to 25-year-old sexually active HIV-seronegative women using contraception were enrolled in Soweto, South Africa.
Background: Adults living with human immunodeficiency virus (HIV) are at increased risk for anal and oropharyngeal cancer caused by human papillomavirus (HPV). The efficacy of HPV vaccines in this population is unknown.
Methods: In this phase 3, double-blind, randomized, controlled trial, we assigned HIV-infected adults aged ≥27 years to the quadrivalent HPV (types 6, 11, 16, 18) vaccine or placebo (1:1) stratified by sex and presence of anal high-grade squamous intraepithelial lesions on biopsy (bHSIL).
Background: The quadrivalent human papillomavirus (HPV) vaccine (qHPV; types 6, 11, 16, 18) is indicated for men and women aged 9 to 26 years to prevent HPV associated anogenital high-grade squamous intraepithelial lesions (HSIL) and cancer. ACTG 5298 was a randomized placebo controlled Phase 3 study in human immunodeficiency virus (HIV)-infected men who have sex with men, and women of qHPV to prevent persistent anal HPV infection. Baseline data are presented here.
View Article and Find Full Text PDFObjective: To investigate whether oral preexposure prophylaxis (PrEP) alters timing and patterns of seroconversion when PrEP use continues after HIV-1 infection.
Design: Retrospective testing of the timing of Fiebig stage HIV-1 seroconversion in the Partners PrEP Study, a randomized placebo-controlled clinical trial of PrEP conducted in Kenya and Uganda.
Methods: Specimens from 138 seroconverters were collected every 3 months and when HIV-1 infection was suspected based on monthly rapid HIV-1 tests.
: We evaluated detection of HIV-1 RNA from dried blood spots (DBS) and oral fluid specimens. Between February 2010 and August 2014, HIV-1 was newly diagnosed in eight (2.6%) study participants who had median blood HIV-1 RNA of 61 500 copies/ml (interquartile range 7500-146 000).
View Article and Find Full Text PDFBackground. To improve clinical and public health outcomes through early human immunodeficiency virus (HIV) detection, fourth-generation antigen/antibody immunoassay (4IA) and supplemental testing results must be returned rapidly. Methods.
View Article and Find Full Text PDFBackground And Objective: The rapid test study was a real-time comparison of point-of-care (POC) HIV tests to determine their abilities to detect early HIV infection.
Study Design: Men and transgender persons reporting sex with men in the prior year were recruited at the Public Health-Seattle & King County STD Clinic, Gay City Health Project, and University of Washington Primary Infection Clinic. Study tests included the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test performed on oral fluids and tests performed on fingerstick whole blood specimens including OraQuick, Uni-Gold Recombigen HIV test, Determine HIV-1/2 Ag/Ab Combo, and INSTI HIV-1 Rapid Antibody Test.
Background: Point-of-care (POC) rapid HIV tests have sensitivity during the "window period" comparable only to earliest generation EIAs. To date, it is unclear whether any POC test performs significantly better than others.
Objective: Compare abilities of POC tests to detect early infection in real time.
Background: An accurate and rapid serologic method to differentiate HIV-2 from HIV-1 infection is required since the confirmatory HIV-1 Western Blot (WB) may demonstrate cross-reactivity with HIV-2 antibodies.
Objectives: To evaluate the performance of the Bio-Rad Multispot HIV-1/HIV-2 rapid assay as a supplemental test to correctly identify HIV-2 infection and identify HIV-1 WB cross-reactivity with HIV-2 in clinical samples tested at an academic medical center.
Study Design: Between August 2008 and July 2012, clinical samples were screened for HIV using either 3rd- or 4th-generation HIV-1/2 antibody or combination antibody and HIV-1 p24 antigen assays, respectively.
Background: The ARCHITECT HIV Ag/Ab Combo assay has a wide dynamic range for determining the sample-to-cutoff ratio (S/CO) values compared to other diagnostic HIV antibody assays.
Objectives: Determine the performance of an HIV testing algorithm that uses the ARCHITECT combo assay in the clinical setting and explore the utility of the signal-to-cutoff (S/CO) ratio to predict acute HIV-1 infection status.
Study Design: A retrospective analysis of clinical samples from a hospital and referral population screened for HIV-1 infection between May 2011 and March 2013.
Background: Combination antiretroviral therapy (cART) reduces genital tract human immunodeficiency virus type 1 (HIV-1) load and reduces the risk of sexual transmission, but little is known about the efficacy of cART for decreasing genital tract viral load (GTVL) and differences in sex or HIV-1 subtype.
Methods: HIV-1 RNA from blood plasma, seminal plasma, or cervical wicks was quantified at baseline and at weeks 48 and 96 after entry in a randomized clinical trial of 3 cART regimens.
Results: One hundred fifty-eight men and 170 women from 7 countries were studied (men: 55% subtype B and 45% subtype C; women: 24% subtype B and 76% subtype C).