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1.
Hepatol Commun ; 7(4)2023 04 01.
Article in English | MEDLINE | ID: mdl-37026760

ABSTRACT

BACKGROUND: The loss of HBV HBsAg or functional cure is a desirable goal of hepatitis B management. The relative abundances of HBsAg isoforms may offer additional diagnostic and predicting values. To evaluate the clinical utility of HBsAg isoforms, we developed novel prototype assays on the ARCHITECT automated serology platform that specifically detects total-HBsAg (T-HBsAg), large (L-HBsAg), and middle (M-HBsAg) products of the S gene to determine the isoform composition of human specimens from acute and chronic HBV infection and during long-term nucleos(t)ide analog therapy. RESULTS: In the early phase of acute HBV infection, L-HBsAg and M-HBsAg emerged within days and were in parallel to T-HBsAg during the entire course of infection. M-HBsAg levels were consistently higher than L-HBsAg levels. Patients with HBeAg(+) chronic hepatitis B had higher T-HBsAg, M-HBsAg, and L-HBsAg levels compared with HBeAg(-) patients. Correlations of M-HBsAg and L-HBsAg to T-HBsAg were similar in both. In contrast, there was no strong correlation between L-HBsAg or M-HBsAg with HBV DNA levels. During long-term nucleos(t)ide analog treatment, changes in HBsAg isoform abundance were proportional to T-HBsAg regardless of treatment responses for both HBeAg(+) and HBeAg(-) chronic hepatitis B. A larger sample size may be necessary to detect a significant difference. CONCLUSION: HBsAg isoform compositions parallel T-HBsAg levels in both acute and chronic hepatitis B infection. L-HBsAg and M-HBsAg individual biomarkers do not appear to provide an additional diagnostic benefit for staging chronic disease or monitoring response to treatment with current therapies.


Subject(s)
Hepatitis B, Chronic , Hepatitis B , Humans , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/drug therapy , Hepatitis B virus , Hepatitis B Surface Antigens , Hepatitis B e Antigens , Antiviral Agents/therapeutic use , Antigens, Surface/therapeutic use , DNA, Viral/genetics , Hepatitis B/drug therapy
2.
AIDS Res Hum Retroviruses ; 34(3): 314-318, 2018 03.
Article in English | MEDLINE | ID: mdl-29232958

ABSTRACT

Periodic evaluation of the impact of viral diversity on diagnostic tests is critical to ensure current technologies are keeping pace with viral evolution. To determine whether HIV diversity impacts the ARCHITECT HIV Combo Ag/Ab (HIV Combo) or RealTime HIV-1 (RT) assays, a set of N = 199 HIV clinical specimens from Cameroon, Senegal, Saudi Arabia, and Thailand were sequenced and tested in both assays. The panel included historical groups N and P specimens and a newly identified group N specimen. These and specimens classified as H, U (unclassified)/URF (unique recombinant form), CRF (circulating recombinant form) 01, 02, 06, 09, 11, 13, 18, 22, 37, and 43 were detected by both the RT assay (1.75-6.84 log copies/ml) and the HIV Combo assay (3.26-1121.96 sample to cutoff ratios). Sequence alignment identified 3 or fewer mismatches to the RT assay oligos in 82.4% of samples. Altogether, these data demonstrate the HIV Combo and RT assays detect diverse strains of HIV in clinical specimens.


Subject(s)
Diagnostic Tests, Routine/methods , HIV Antibodies/blood , HIV Antigens/blood , HIV Infections/diagnosis , HIV Infections/virology , HIV-1/classification , HIV-1/isolation & purification , RNA, Viral/blood , Adult , Female , Genetic Variation , HIV Core Protein p24/blood , HIV Core Protein p24/immunology , HIV Infections/genetics , HIV-1/genetics , Humans , Male , Middle Aged , Young Adult
3.
J Infect Dis ; 207(2): 223-31, 2013 Jan 15.
Article in English | MEDLINE | ID: mdl-23129758

ABSTRACT

BACKGROUND: Reliable methods for estimating the incidence of human immunodeficiency virus (HIV) infection are needed to monitor the epidemic, identify at-risk populations, and evaluate HIV prevention strategies. We used a multifaceted approach to estimate HIV incidence in the HIV Prevention Trials Network (HPTN) 064 study. METHODS: The HPTN 064 study enrolled 2067 HIV-seronegative women and 32 HIV-seropositive women with no prior HIV infection diagnosis. Women were followed for up to 12 months. HIV incidence estimates were based on (1) detection of acute HIV infection, (2) documentation of HIV seroconversion, and (3) detection of recent HIV infection, using a multiassay algorithm (MAA). RESULTS: Two women had acute HIV infection at enrollment, 4 seroconverted, and 2 were identified as recently infected at enrollment using the MAA. The annual HIV incidence estimate based on acute infection at enrollment (2.52% [95% confidence interval {CI}, .17%-9.33%], using a 14-day window period) was higher than the estimate based on seroconversion (0.24% [95% CI, .07%-.62%]; P = .027). Incidence estimates obtained using the MAA at enrollment and at the end of study were 0.25% (95% CI, .03%-.93%) and 0.13% (95% CI, .006%-.76%), respectively. CONCLUSIONS: We detected a high frequency of acute infection at enrollment. Cross-sectional HIV incidence estimates obtained using the MAA were similar to the longitudinal estimate based on HIV seroconversion. CLINICAL TRIALS REGISTRATION: NCT00995176.


Subject(s)
HIV Infections/diagnosis , HIV Infections/epidemiology , HIV-1/immunology , Adolescent , Adult , Algorithms , Cohort Studies , Female , HIV Antibodies/blood , HIV Infections/prevention & control , HIV Infections/virology , HIV Seropositivity/diagnosis , HIV Seropositivity/epidemiology , Humans , Incidence , Young Adult
4.
AIDS Res Hum Retroviruses ; 20(9): 944-57, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15585082

ABSTRACT

HIV-1 strain diversity was examined in a study population that consisted of hospital and clinic patients from seven cities and villages located in the northwestern regions of Cameroon. Specimens were screened using a serological algorithm designed to identify HIV-1 group M, N, and O, and SIVcpz-like infections followed by RT-PCR amplification to characterize the infecting virus. The results show that the HIV epidemic in northwest Cameroon is dominated by HIV-1 group M CRF02_AG infections (57%). Additional group M subtypes present include A, D, F2, G, and CRF01_AE. Based on discordant subtype classification between gag and env sequences, a high percentage (23%) of viral strains appear to be unique intersubtype recombinants with the majority (88%) involving recombination with CRF02_AG. Group O prevalence is low accounting for only 0.4% of HIV infections. However, group O strain diversity is high; isolates from clades I, IV, and V, as well as unclassified and recombinant strains, were found. Three dual infections by HIV-1 group M and group O were identified and characterized. In two specimens, both group M and O sequences were amplified in gag, pol, and env suggesting the presence of both viruses. Analysis of the third specimen shows the presence of a group O virus and an intergroup M/O recombinant virus. Finally, no infections due to HIV-1 group N or SIVcpz-like strains were found in the study population.


Subject(s)
HIV Infections/epidemiology , HIV Infections/virology , HIV-1/classification , HIV-1/genetics , Recombination, Genetic , Amino Acid Sequence , Animals , Cameroon/epidemiology , Genetic Variation , HIV Envelope Protein gp120/chemistry , HIV Infections/complications , HIV-1/chemistry , HIV-2/chemistry , HIV-2/classification , HIV-2/genetics , Humans , Immunodominant Epitopes/chemistry , Immunodominant Epitopes/immunology , Molecular Sequence Data , Pan troglodytes , Peptide Fragments/chemistry , Peptides/chemistry , Peptides/immunology , Sequence Analysis, DNA , Serotyping , Simian Immunodeficiency Virus/chemistry , Simian Immunodeficiency Virus/classification , Simian Immunodeficiency Virus/genetics
5.
AIDS Res Hum Retroviruses ; 18(4): 269-82, 2002 Mar 01.
Article in English | MEDLINE | ID: mdl-11860674

ABSTRACT

HIV-1 group O strains have a level of genetic diversity similar to that of strains in group M; however, group O has not been readily classified into genetic subtypes. Phylogenetic classification of group O has been hindered by the limited sequence information available. To facilitate phylogenetic analysis, we sequenced the gag p24 (693 nt), pol p32 (864 nt), and env gp160 (approximately 2700 nt) genes from 39 group O-infected specimens. These specimens include 32 plasma samples collected in Cameroon between 1996 and 1999, 2 specimens collected in the United States, and 5 infections previously isolated in Equatorial Guinea. Phylogenetic analysis of HIV-1 group O sequences resulted in the identification of five clusters that are maintained across gag, pol, and env, generally supported by high bootstrap values, and approximately equidistant from each other. In addition to the group O clusters, several isolates branch independently and are equidistant from the other group O isolates. Cluster I comprises greater than 50% of the group O isolates and is a diverse set of isolates that is subdivided into subclusters. The average intra-, sub-, and intercluster distances for group O are similar to the corresponding distances for group M subtypes. The five group O clusters have characteristics similar to those of group M subtypes. Thus the data presented may form the basis for classification of group O into subtypes. However, full-length genomes representing each group O cluster will be required to formalize a group O subtype classification.


Subject(s)
HIV Infections/virology , HIV-1/isolation & purification , Phylogeny , Amino Acid Sequence , Cameroon , Genes, env , Genes, gag , Genes, pol , Guinea , HIV Envelope Protein gp120/chemistry , HIV-1/classification , HIV-1/genetics , Humans , Molecular Sequence Data , Peptide Fragments/chemistry , Polymerase Chain Reaction , Sequence Homology, Amino Acid , United States
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