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1.  Breast Milk α-Defensins Are Associated with HIV Type 1 RNA and CC Chemokines in Breast Milk But Not Vertical HIV Type 1 Transmission 
α-Defensins are proteins exhibiting in vitro anti-HIV-1 activity that may protect against mother-to-child transmission of HIV-1 via breast milk. Correlates of α-defensins in breast milk and transmission risk were determined in a cohort of HIV-1-infected pregnant women in Nairobi followed for 12 months postpartum with their infants. Maternal blood was collected antenatally and at delivery for HIV-1 viral load and infant HIV-1 infection status was determined <48 h after birth and at months 1, 3, 6, 9, and 12. Breast milk specimens collected at month 1 were assayed for α-defensins, HIV-1 RNA, subclinical mastitis, and CC and CXC chemokines. We detected α-defensins in breast milk specimens from 108 (42%) of 260 HIV-1-infected women. Women with detectable α-defensins (≥50 pg/ml) had a median concentration of 320 pg/ml and significantly higher mean breast milk HIV-1 RNA levels than women with undetectable α-defensins (2.9 log10 copies/ml versus 2.5 log10 copies/ml, p = 0.003). Increased α-defensins concentrations in breast milk were also associated with subclinical mastitis (Na+/K+ ratio > 1) and increased breast milk chemokine levels. Overall, 40 (15%) infants were HIV-1 uninfected at birth and subsequently acquired HIV-1. There was no significant association between month 1 α-defensins and risk of HIV-1 transmission. In conclusion, α-defensins were associated with breast milk HIV-1 viral load, chemokine levels, and subclinical mastitis, all of which may alter risk of infant HIV-1 acquisition. Despite these associations there was no significant relationship between breast milk α-defensins and mother-to-child transmission, suggesting a complex interplay between breast milk HIV-1, inflammation, and antiinfective factors.
doi:10.1089/aid.2006.0125
PMCID: PMC3382116  PMID: 17331027
2.  A Decrease in Albumin in Early SIV Infection Is Related to Viral Pathogenicity 
Abstract
A decrease in circulating albumin levels after seroconversion has been reported as a predictor of disease progression in HIV-infected adults. We hypothesized that a similar decrease would be seen in pig-tailed macaques in early SIV infection, and that the degree of this decrease would be related to the pathogenicity of the infecting viral strain. Ten juvenile pig-tailed macaques were previously inoculated with virus derived from molecular clones representing different stages of infection: early (SIVMneCL8, n = 2), intermediate (SIVMne35wkSU, n = 2), late blood (SIVMne170, n = 3), or late lymph node (SIVMne027, n = 3). Albumin was measured in stored samples. Changes from baseline were evaluated by paired sample t tests and by linear regression with generalized estimating equations (GEE). Albumin levels decreased in the week after SIV inoculation (p = 0.02), increased above baseline at week 5, then fell, returning below baseline by week 16 (p = 0.03). In GEE modeling, albumin decreased significantly in both early and chronic infection (weeks 0–3, p < 0.001; weeks 5–16, p = 0.004) and this change differed significantly between infections caused by late versus early or intermediate virus variants (weeks 0–3, p = 0.002; weeks 5–16, p = 0.001). A decrease in albumin levels occurs in both early and chronic SIV infection, and is more marked in macaques infected with more pathogenic virus variants. These results suggest that both early and late events in SIV pathogenesis are influenced by properties of the infecting viral strain.
doi:10.1089/aid.2008.0267
PMCID: PMC2768648  PMID: 19320603
3.  A Decrease in Albumin in Early SIV Infection Is Related to Viral Pathogenicity 
A decrease in circulating albumin levels after seroconversion has been reported as a predictor of disease progression in HIV-infected adults. We hypothesized that a similar decrease would be seen in pig-tailed macaques in early SIV infection, and that the degree of this decrease would be related to the pathogenicity of the infecting viral strain. Ten juvenile pig-tailed macaques were previously inoculated with virus derived from molecular clones representing different stages of infection: early (SIVMneCL8, n = 2), intermediate (SIVMne35wkSU, n = 2), late blood (SIVMne170, n = 3), or late lymph node (SIVMne027, n = 3). Albumin was measured in stored samples. Changes from baseline were evaluated by paired sample t tests and by linear regression with generalized estimating equations (GEE). Albumin levels decreased in the week after SIV inoculation (p = 0.02), increased above baseline at week 5, then fell, returning below baseline by week 16 (p = 0.03). In GEE modeling, albumin decreased significantly in both early and chronic infection (weeks 0–3, p < 0.001; weeks 5–16, p = 0.004) and this change differed significantly between infections caused by late versus early or intermediate virus variants (weeks 0–3, p = 0.002; weeks 5–16, p = 0.001).A decrease in albumin levels occurs in both early and chronic SIV infection, and is more marked in macaques infected with more pathogenic virus variants. These results suggest that both early and late events in SIV pathogenesis are influenced by properties of the infecting viral strain.
doi:10.1089/aid.2008.0267
PMCID: PMC2768648  PMID: 19320603
4.  Examination of a Second Region of the HIV Type 1 Genome Reveals Additional Cases of Superinfection 
HIV-1 superinfection may occur at a rate similar to that of initial infection, raising concerns for HIV-1 vaccine strategies predicated on eliciting immune responses similar to those in natural infection. Because of the high rate of recombination during HIV-1 replication, studies examining only one region of the HIV-1 genome are likely to miss cases of HIV-1 superinfection. We examined HIV-1 gag sequences from 14 high-risk Kenyan women in whom superinfection was not detected in a previous study of env sequences. We detected two additional cases of HIV-1 superinfection: one intersubtype superinfection that occurred between 1046 and 1487 days postinfection (DPI) and one intrasubtype superinfection that occurred between 341 and 440 DPI. Our results suggest that studies that examine only small genome regions may lead to underestimates of the risk of superinfection, highlighting the need for more extensive studies examining multiple regions of the HIV-1 genome.
doi:10.1089/aid.2008.0100
PMCID: PMC2743231  PMID: 18729772
5.  Examination of a Second Region of the HIV Type 1 Genome Reveals Additional Cases of Superinfection 
AIDS Research and Human Retroviruses  2008;24(9):1221-1224.
Abstract
HIV-1 superinfection may occur at a rate similar to that of initial infection, raising concerns for HIV-1 vaccine strategies predicated on eliciting immune responses similar to those in natural infection. Because of the high rate of recombination during HIV-1 replication, studies examining only one region of the HIV-1 genome are likely to miss cases of HIV-1 superinfection. We examined HIV-1 gag sequences from 14 high-risk Kenyan women in whom superinfection was not detected in a previous study of env sequences. We detected two additional cases of HIV-1 superinfection: one intersubtype superinfection that occurred between 1046 and 1487 days postinfection (DPI) and one intrasubtype superinfection that occurred between 341 and 440 DPI. Our results suggest that studies that examine only small genome regions may lead to underestimates of the risk of superinfection, highlighting the need for more extensive studies examining multiple regions of the HIV-1 genome.
doi:10.1089/aid.2008.0100
PMCID: PMC2743231  PMID: 18729772

Results 1-5 (5)