ABSTRACT
OBJECTIVE: A novel algorithm to identify fetal microdeletion events in maternal plasma has been developed and used in clinical laboratory-based noninvasive prenatal testing. We used this approach to identify the subchromosomal events 5pdel, 22q11del, 15qdel, 1p36del, 4pdel, 11qdel, and 8qdel in routine testing. We describe the clinical outcomes of those samples identified with these subchromosomal events. METHODS: Blood samples from high-risk pregnant women submitted for noninvasive prenatal testing were analyzed using low coverage whole genome massively parallel sequencing. Sequencing data were analyzed using a novel algorithm to detect trisomies and microdeletions. RESULTS: In testing 175,393 samples, 55 subchromosomal deletions were reported. The overall positive predictive value for each subchromosomal aberration ranged from 60% to 100% for cases with diagnostic and clinical follow-up information. The total false positive rate was 0.0017% for confirmed false positives results; false negative rate and sensitivity were not conclusively determined. CONCLUSION: Noninvasive testing can be expanded into the detection of subchromosomal copy number variations, while maintaining overall high test specificity. In the current setting, our results demonstrate high positive predictive values for testing of rare subchromosomal deletions.
Subject(s)
Gene Deletion , Genome, Human , Maternal Serum Screening Tests , Female , Humans , PregnancyABSTRACT
BACKGROUND: Although influenza vaccination is recommended in persons infected with HIV-1, its efficacy is unknown. OBJECTIVE: To assess the immunogenicity, efficacy, and risks associated with influenza vaccination in persons infected with HIV-1. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Outpatient military clinic. PATIENTS: 102 patients with HIV-1 infection. INTERVENTION: Influenza vaccine (n = 55) or saline placebo (n = 47). MEASUREMENTS: Influenza antibody titers, CD4+ cell counts, and plasma HIV-1 RNA levels at baseline, 1 month after immunization, and 3 months after immunization; viral cultures from persons presenting with respiratory illness; and respiratory symptom interview. RESULTS: Twenty-three placebo recipients (49%) and 16 vaccine recipients (29%) reported respiratory symptoms (P = 0.04). Ten placebo recipients but no vaccine recipients had laboratory-confirmed symptomatic influenza (P < 0.001) (protective efficacy, 100% [95% CI, 73% to 100%]). No effect on plasma HIV-1 RNA levels or CD4+ cell counts was noted. CONCLUSION: Influenza vaccination is highly effective in HIV-1-infected persons and does not seem to be associated with substantial changes in viral load or CD4 cell count.
Subject(s)
HIV Infections/immunology , Immunocompromised Host , Influenza A virus , Influenza Vaccines , Influenza, Human/prevention & control , Vaccination , CD4 Lymphocyte Count , Double-Blind Method , HIV Infections/virology , HIV-1/genetics , Humans , RNA, Viral/blood , Viral LoadABSTRACT
The natural variability of quantitative virologic measures among human immunodeficiency virus (HIV) type 1-infected persons was prospectively studied in 29 untreated persons with >600 CD4 cells/microL and in 15 persons receiving zidovudine monotherapy who had 400-550 CD4 cells/microL at study entry. Cell- and plasma-associated infectious HIV-1, provirus, and virion RNA were determined monthly as were numbers of CD4 and CD8 cells. HIV-1 replication varied widely among subjects with similar CD4 cell counts. The within-individual variability was significantly less than the variability between subjects for all virologic measures. Plasma virion HIV-1 RNA levels had the least variability. A mathematical model was devised to assess whether a potential therapeutic intervention significantly alters peripheral HIV-1 load. The model indicated that three measurements of plasma RNA would be outside the 95th percentile for the expected change in an individual due to natural variability. This approach can be used to accurately assess a therapeutic intervention among persons with low plasma HIV-1 titers.
Subject(s)
HIV Infections/immunology , HIV Infections/therapy , HIV-1/growth & development , Immunotherapy , Viral Load , Adult , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , DNA, Viral/genetics , Female , HIV Infections/blood , HIV-1/genetics , Humans , Longitudinal Studies , Lymphocyte Count , Male , Middle Aged , Polymerase Chain Reaction , Proviruses/growth & development , RNA, Viral/analysis , Vaccines, Synthetic/immunologyABSTRACT
AIDS: HIV viral markers, such as p24 antigen and viral RNA, measure how much virus is present. Studies are showing a relationship between RNA levels and clinical outcomes, which can help doctors evaluate the efficacy of drug therapy. Eventually, it is believed, RNA will replace T-cell counts as the marker of choice. The challenge is to interpret what the results of a viral load test mean for a specific patient. Currently, the two main viral load tests commercially available do not have a one-to-one linear relationship, so tests should not be switched. Doctors are advised not to over-interpret minor changes because of the ten to thirty percent variation in individual test results. These tests are not FDA-approved but are available at commercial reference labs.^ieng
