HIV-1 Drug Resistance Emergence among Breastfeeding Infants Born to HIV-Infected Mothers during a Single-Arm Trial of Triple-Antiretroviral Prophylaxis for Prevention of Mother-To-Child Transmission: A Secondary Analysis

Analysis of a substudy of the Kisumu breastfeeding trial by Clement Zeh and colleagues reveals the emergence of HIV drug resistance in HIV-positive infants born to HIV-infected mothers treated with antiretroviral drugs

Nucleotide and Predicted Amino Acid Sequence-Based Analysis of the Avian Metapneumovirus Type C Cell Attachment Glycoprotein Gene: Phylogenetic Analysis and Molecular Epidemiology of U.S. Pneumoviruses

A serologically distinct avian metapneumovirus (aMPV) was isolated in the United States after an outbreak of turkey rhinotracheitis (TRT) in February 1997. The newly recognized U.S. virus was subsequently demonstrated to be genetically distinct from European subtypes and was designated aMPV serotype C (aMPV/C). We have determined the nucleotide sequence of the gene encoding the cell attachment glycoprotein (G) of aMPV/C (Colorado strain and three Minnesota isolates) and predicted amino acid sequence by sequencing cloned cDNAs synthesized from intracellular RNA of aMPV/C-infected cells. The nucleotide sequence comprised 1,321 nucleotides with only one predicted open reading frame encoding a protein of 435 amino acids, with a predicted M(r) of 48,840. The structural characteristics of the predicted G protein of aMPV/C were similar to those of the human respiratory syncytial virus (hRSV) attachment G protein, including two mucin-like regions (heparin-binding domains) flanking both sides of a CX3C chemokine motif present in a conserved hydrophobic pocket. Comparison of the deduced G-protein amino acid sequence of aMPV/C with those of aMPV serotypes A, B, and D, as well as hRSV revealed overall predicted amino acid sequence identities ranging from 4 to 16.5%, suggesting a distant relationship. However, G-protein sequence identities ranged from 72 to 97% when aMPV/C was compared to other members within the aMPV/C subtype or 21% for the recently identified human MPV (hMPV) G protein. Ratios of nonsynonymous to synonymous nucleotide changes were greater than one in the G gene when comparing the more recent Minnesota isolates to the original Colorado isolate. Epidemiologically, this indicates positive selection among U.S. isolates since the first outbreak of TRT in the United States

Anemia and Red Blood Cell Abnormalities in HIV-Infected and HIV-Exposed Breastfed Infants: A Secondary Analysis of the Kisumu Breastfeeding Study.

Anemia results in increased morbidity and mortality, underscoring the need to better understand its pathophysiology amongst HIV-exposed and infected children in sub-Saharan Africa, the region where most infant HIV exposure and infections occur.This analysis used samples obtained from children in the Kisumu Breastfeeding Study (KiBS). KiBS was a longitudinal phase IIB, open-label, one-arm clinical trial, designed to investigate the safety, tolerability and effectiveness of a maternal triple-antiretroviral (ARV) regimen for prevention of mother-to-child transmission (PMTCT) of HIV, during late pregnancy and early infancy while breastfeeding. Blood samples from 482 children were obtained at birth, 2, 6, 10 and 14 weeks and 6, 9, 12, 18 and 24 months. Severity of anemia was graded using the NIH Division of AIDS (DAIDS) toxicity tables. We describe the proportion of children with anemia and anomalies in red blood cell parameters at various time points over 24 months and compare rates of anemia between HIV-infected and HIV-uninfected children and by mothers' ARV regimen and infant malaria infection.The proportion of children with anemia significantly increased after the breastfeeding period in both HIV-infected and HIV-uninfected children with higher proportion among HIV-infected children compared to HIV-uninfected children (RR: 1.72; CI: 1.22-2.44, p = 0.002). Maternal triple-antiretroviral regimen was not associated with infant anemia (p = 0.11). There was no significant difference in mean hemoglobin between HIV-uninfected children with and without malaria at each time point except at 24 months.A relatively lower proportion of children with severe anemia during the breastfeeding period suggest that exposure to mother's triple antiretroviral combinations through breast milk, posed minimal risk of hematologic toxicity

Percent of HIV-uninfected and HIV-infected infants with normal and abnormal hemoglobin, Kisumu Breastfeeding study, Kisumu, Kenya, July 2003- February, 2009.

<p>Percent of HIV-uninfected and HIV-infected infants with normal and abnormal hemoglobin, Kisumu Breastfeeding study, Kisumu, Kenya, July 2003- February, 2009.</p

Comparison of mean A) hemoglobin concentration and B) RBC count by treatment status in HIV-1 infected children, Kisumu Breastfeeding Study, Kisumu, Kenya, July 2003- February 2009.

<p>(* p<0.05).</p

HIV and Malaria co-morbidity among children, Kisumu Breastfeeding study, Kisumu, Kenya, July 2003- February, 2009.

<p>HIV and Malaria co-morbidity among children, Kisumu Breastfeeding study, Kisumu, Kenya, July 2003- February, 2009.</p

Comparison of mean A) hemoglobin concentration and B) RBC count by malaria infection status and mean C) hemoglobin concentration and D) RBC count by mother’s triple-antiretroviral prophylaxis regimen in children, Kisumu Breastfeeding Study, Kisumu, Kenya, July 2003- February 2009.

<p>(* p<0.05). HIV+ Malaria + omitted from graphs (2A and 2B) because of small sample size.</p

Comparison of mean A) hemoglobin concentration, B) RBC count, C) hematocrit, D) corpuscular volume, E) corpuscular hemoglobin and F) red cell distribution width by HIV-1 status in children, Kisumu Breastfeeding Study, Kisumu, Kenya, July 2003- February 2009.

<p>Dotted line represents the lower limit of normal for each parameter. (*p<0.05 between HIV-infected and HIV-uninfected children).</p