The antibiotic resistance epidemic should lead to immediate replication of this study in a larger more generalizable population. If inaccurate physician perceptions of parent desires for antimicrobials for viral infections are confirmed, then an intervention to change the way physicians acquire this set of perceptions should be undertaken.
Concern has been raised that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be transmitted to infants by breastfeeding. A number of organizations advise that women infected with SARS-CoV-2 may choose to breastfeed with protections to prevent transmission of the virus through respiratory droplets. Of 24 case reports on breast milk samples from women infected with SARS-CoV-2, viral RNA was detected in 10 samples from 4 women. 1-6 In some cases, environmental contamination or retrograde flow from an infected infant could not be ruled out. Detection of viral RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) does not equate with infectivity. To date, SARS-CoV-2 has not been isolated from breast milk, and there are no documented cases of transmission of infectious virus to the infant through breast milk. However, potential for viral transmission through breast milk remains a critical question for women infected with SARS-CoV-2 who wish to breastfeed.
We describe an antiviral small molecule, LJ001, effective against numerous enveloped viruses including Influenza A, filoviruses, poxviruses, arenaviruses, bunyaviruses, paramyxoviruses, flaviviruses, and HIV-1. In sharp contrast, the compound had no effect on the infection of nonenveloped viruses. In vitro and in vivo assays showed no overt toxicity. LJ001 specifically intercalated into viral membranes, irreversibly inactivated virions while leaving functionally intact envelope proteins, and inhibited viral entry at a step after virus binding but before virus-cell fusion. LJ001 pretreatment also prevented virus-induced mortality from Ebola and Rift Valley fever viruses. Structure-activity relationship analyses of LJ001, a rhodanine derivative, implicated both the polar and nonpolar ends of LJ001 in its antiviral activity. LJ001 specifically inhibited virus-cell but not cell-cell fusion, and further studies with lipid biosynthesis inhibitors indicated that LJ001 exploits the therapeutic window that exists between static viral membranes and biogenic cellular membranes with reparative capacity. In sum, our data reveal a class of broad-spectrum antivirals effective against enveloped viruses that target the viral lipid membrane and compromises its ability to mediate virus-cell fusion.virology | viral entry | fusion inhibitor | small molecule | lipid membrane
ABSTRACT. Objective. The complexity of highly active antiretroviral therapy (HAART), with multiple medications, formulations, and dosing intervals, makes adherence challenging. Little is known about the adherence of children to HAART. The objective of this study was to identify correlates of adherence to HAART and the relationship between adherence and study outcomes in a pediatric clinical trial.Methods. Pediatric AIDS Clinical Trials Group 377 is a phase I/II randomized trial of 4 HAART regimens in antiretroviral-experienced, clinically stable children aged 4 months to 17 years. The 4 treatment arms include various 3-or 4-drug combinations of d4T, 3TC, nevirapine, ritonavir, and nelfinavir. After informed consent was obtained, 193 children were enrolled between December 1997 and September 1998. Questionnaires were developed to collect subject-or caregiver-reported adherence to study medications and to identify problems associated with medication administration. Every 3 months, the number of doses of each medication missed during the 3 days preceding the study visit was recorded. Full adherence (FA) and non-full adherence were defined as missing no doses and missing at least 1 dose, respectively.Results. Adherence data from study week 48 or the most recent study visit were available for 125 children (week 48 for 109 children). Overall, 70% of children reported FA and 30% reported non-full adherence. Adherence did not differ by treatment arm, age, or the child's knowledge of his or her human immunodeficiency virus infection status. There was a suggestion that adherence was less for white than nonwhite children (40% vs 73% FA) and did not differ between black and Hispanic children. Rates of FA were 82% for d4T, 79% for 3TC, 83% for nevirapine, 84% for ritonavir, and 68% for nelfinavir. Despite the similar rates of FA, difficulties with taking specific medications were reported most frequently for ritonavir and nelfinavir. These included poor taste, patient refusal, and scheduling problems. Adherence was associated with the virologic response: FA was seen in 92% of children with >2 log 10 drop in viral load and in 64% with <2 log 10 drop in viral load.Conclusion. In children, reported adherence predicts the virologic response to HAART therapy and is a useful measure of adherence. Interventions and regimens to increase adherence to HAART should result in an improved outcome. Pediatrics 2002;109(4). URL: http:// www.pediatrics.org/cgi/content/full/109/4/e61; adherence, compliance, HIV, antiretroviral therapy, protease inhibitors.ABBREVIATIONS. HAART, highly active antiretroviral therapy; HIV, human immunodeficiency virus; PACTG, Pediatric AIDS Clinical Trials Group; RT, reverse transcriptase; BID, twice-daily; TID, 3 times a day; FA, full adherence; NFA, non-full adherence.H ighly active combination antiretroviral therapy (HAART) is effective in suppressing human immunodeficiency virus (HIV) replication, preventing opportunistic infections, reducing mortality, and improving the well-being of children and adults with...
Using a quantitative polymerase chain reaction (PCR) method, we have previously shown that a molecularly cloned isolate of human immunodeficiency virus type 1 (HIV-1) can efficiently enter quiescent primary lymphocytes; however, the reverse transcription process is not completed in these cells. In this study, we further characterized the reverse transcription of HIV-1 in quiescent cells, and our results indicate that while initiation of reverse transcription occurs simultaneously in both activated and quiescent lymphocytes, it not only ends prematurely but also proceeds more slowly in quiescent cells. We also performed experiments to address the role of partial reverse transcripts as intermediates in the viral life cycle. We used azidothymidine either before or after infection with HIV-1 to prevent formation of and further DNA synthesis by partial reverse transcripts, respectively. Decreases in virus production from these cells following mitogenic stimulation indicated that partial reverse transcripts can contribute significantly to virus rescue from infected quiescent cells stimulated subsequent to infection. Furthermore, we established that mitogenic stimulation of infected quiescent cells induces reinitiation of DNA synthesis from partial reverse transcripts. However, the virus rescue is inefficient relative to the initial multiplicity of infection, and this is explained by inefficient completion of DNA synthesis from the partial reverse transcript. Thus, the arrest of reverse transcription in quiescent cells may play an important role in HIV-1 pathogenesis by contributing to the inefficient infection of potential target cells in the peripheral blood of HIV-1-infected individuals.
, "Combination treatment with zidovudine, didanosine, and nevirapine in infants with human immunodeficiency virus type 1 infection" (1997). Open Access Articles. 1686.
Most HIV-1 infections of children result from mother-to-infant transmission, which may occur perinatally or postnatally, as a consequence of breast feeding. In this study, the influence of maternal viral load on transmission of infection to infants from non-breast-feeding mothers was examined using samples of plasma and peripheral blood mononuclear cells (PBMCs) collected at several time points during pregnancy and the 6-month period after delivery. These samples were analyzed by several quantitative methods, including virus cultures of PBMCs and polymerase chain reaction (PCR) assays for HIV-1 RNA in plasma and DNA in PBMCs. The risk of transmission increased slightly with a higher viral load, but transmission and nontransmission occurred over the entire range of values for each assay. No threshold value of virus load was identified which discriminated between transmitters and nontransmitters. We also noted a significant rise in viral load and a decline in CD4+ lymphocytes in the six months after delivery. These findings suggest that a high maternal viral load is insufficient to fully explain vertical transmission of HIV-1. Additional studies are needed to examine the post-partum increase in viremia.
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