PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (35)
 

Clipboard (0)
None

Select a Filter Below

Year of Publication
more »
Document Types
1.  Development of IgG Mediated Antibody Dependent Cell-mediated Cytotoxicity (ADCC) in the Serum and Genital Mucosa of HIV Seroconverters 
Background
We measured antibody-dependent cell mediated cytotoxicity (ADCC) activity in serum and genital fluids of heterosexually exposed women during HIV seroconversion.
Methods
Plasma and cervico-vaginal lavage (CVL) fluid from 11 seroconverters (SC) were analyzed biannually from one year pre- to 6 year post-seroconversion using a 51Cr-release assay to measure HIV-1 gp120 specific ADCC.
Results
No SC had significant HIV specific CVL ADCC activity before seroconversion or until 1.5 yr after seroconversion. One individual had a %Specific Release (SR) of 25.4 at 2 years, 26.7 at 3 years and 21.0 at 4 years after seroconversion in CVL. Another sample had 4.7% SR at 2 years, 5.3 at 3 years, 10.9 at 4 years, and 8.4 at 5 years after seroconversion in CVL. A third had no activity until 17% SR 5 years after seroconversion in CVL. A fourth showed activity of 36.5% SR at 6.5 years after seroconversion. Seven women had no ADCC activity in their CVL. Paired serum samples showed HIV specific ADCC activity prior to the appearance of CVL ADCC activity.
Conclusions
HIV specific ADCC activity in CVL rose 2 years after seroconversion; ADCC was present in the serum prior to this time. These data suggest that genital tract ADCC activity is not present until well after acute infection.
doi:10.4172/2155-6113.1000479
PMCID: PMC4718584  PMID: 26798561
Women; HIV; Seroconverters; Antibody dependent cellular cytotoxicity
2.  Association of Markers of Hemostasis with Death in HIV-infected Women 
In HIV-negatives, markers of hemostasis including D-dimer, Factor VIII, plasminogen activator inhibitor-1 antigen (PAI-1) and total protein S are associated with all-cause and cardiovascular disease mortality. In HIV-positives, studies of D-dimer and Factor VIII with death were limited to short follow-up; associations of PAI-1 and total protein S with death have not been examined.
In 674 HIV-infected women from the Women’s Interagency HIV Study (WIHS), markers from the first visit after enrollment were exposures of interest in multivariate analyses of death (AIDS and non-AIDS) in separate models at 5 and 16 years.
There were 87 AIDS and 44 non-AIDS deaths at 5 years, and 159 AIDS and 113 non-AIDS deaths at 16 years. An inverse association of total protein S quartiles with non-AIDS deaths was observed at 5 (p-trend=0.002) and 16 years (p-trend=0.02); there was no association with AIDS deaths. The 3rd quartile of PAI-1 was associated with AIDS deaths at 5 (hazard ratio (HR)=4.0, 95% confidence interval (CI)=1.9–8.4) and 16 years (HR=3.4, 95% CI=1.9–5.9); and with non-AIDS deaths at 5 years (HR=4.8, 95%CI=1.6,13.9). D-dimer and Factor VIII were not associated with AIDS or non-AIDS death at 5 or 16 years.
Lower total Protein S was a consistent marker of non-AIDS death. We found no association between D-dimer with AIDS or non-AIDS death, in contrast to previous studies showing increased short term (<5 years) mortality, which may represent sex differences or population heterogeneity. Given longer survival on HAART, further studies of these markers are needed to determine their prognostic value.
doi:10.1097/QAI.0000000000000306
PMCID: PMC4197808  PMID: 25314249
3.  Serum Albumin and Kidney Function Decline in HIV-Infected Women 
Background
Serum albumin concentrations are a strong predictor of mortality and cardiovascular disease in HIV-infected individuals. We studied the longitudinal associations between serum albumin levels and kidney function decline in a population of HIV-infected women.
Study Design
Retrospective cohort analysis.
Setting & Participants
The study participants were recruited from the Women’s Interagency HIV Study (WIHS), a large observational study designed to understand risk factors for the progression of HIV infection in women living in urban communities. 908 participants had baseline assessment of kidney function and two follow-up measures over an average of 8 years.
Predictor
The primary predictor was serum albumin concentration.
Outcomes
We examined annual change in kidney function. Secondary outcomes included rapid kidney function decline and incident reduced estimated glomerular filtration rate (eGFR).
Measurements
Kidney function decline was determined by cystatin C–based (eGFRcys) and creatinine-based eGFR (eGFRcr) at baseline and follow up. Each model was adjusted for kidney disease and HIV-related risk factors using linear and relative risk regression.
Results
After multivariate adjustment, each 0.5-g/dL decrement in baseline serum albumin concentration was associated with a 0.56-mL/min faster annual decline in eGFRcys (P<0.001), which was only slightly attenuated to 0.55-mL/min/1.73 m2 after adjustment for albuminuria. Results were similar whether using eGFRcys or eGFRcr. In adjusted analyses, each 0.5-g/dL lower baseline serum albumin was associated with a 1.71-fold greater risk of rapid kidney function decline (p<0.001) and a 1.72-fold greater risk of incident reduced eGFR (p<0.001).
Limitations
The cohort is composed of only female participants from urban communities within the United States.
Conclusions
Lower levels of serum albumin were strongly associated with kidney function decline and incident reduced eGFR in HIV-infected women, independent of HIV disease status, BMI and albuminuria.
doi:10.1053/j.ajkd.2014.05.015
PMCID: PMC4177337  PMID: 25059222
albumin; kidney function; HIV; incident reduced eGFR; albuminuria; disease trajectory; chronic kidney disease (CKD) progression
4.  Urinary Biomarkers of Kidney Injury Are Associated with All-Cause Mortality in the Women’s Interagency HIV Study (WIHS) 
HIV medicine  2013;15(5):291-300.
Objectives
Chronic kidney disease (CKD) is common in HIV; CKD is associated with mortality. Urinary markers of tubular injury have been associated with future kidney disease risk, but associations with mortality are unknown.
Methods
We evaluated the association of urinary interleukin-18(IL-18), liver fatty acid binding protein(L-FABP), kidney injury molecule-1(KIM-1), neutrophil gelatinase-associated lipocalin(NGAL), albumin-to-creatinine ratio(ACR) with 10-year, all-cause death in 908 HIV-infected women. Kidney function was estimated using cystatin C (eGFRcys).
Results
There were 201 deaths during 9,269 person-years of follow-up. After demographic adjustment, compared to the lowest tertile, highest tertiles of IL-18 (HR 2.54,95%CI 1.75–3.68), KIM-1 (2.04,1.44–2.89), NGAL(1.50,1.05–2.14), and ACR(1.63,1.13–2.36) were associated with higher mortality. After multivariable adjustment including eGFRcys, only the highest tertiles of IL-18, (1.88,1.29–2.74) and ACR (1.46,1.01–2.12) remained independently associated with mortality. Findings with KIM-1 were borderline (1.41, 0.99–2.02). We found a J-shaped association between L-FABP and mortality. Compared to persons in the lowest tertile, HR for middle tertile of L-FABP was 0.67 (0.46–0.98) after adjustment. Findings were stronger when IL-18, ACR and L-FABP were simultaneously included in models.
Conclusions
Among HIV-infected women, some urinary markers of tubular injury are associated with mortality risk, independently of eGFRcys and ACR. These markers represent potential tools to identify early kidney injury in persons with HIV.
doi:10.1111/hiv.12113
PMCID: PMC3975680  PMID: 24313986
HIV; IL-18; KIM-1; L-FABP; NGAL; urinary biomarkers
5.  Prevalence and Long-Term Effects of Occult Hepatitis B Virus Infection in HIV-Infected Women 
Occult hepatitis B virus (HBV) infection is of concern in human immunodeficiency virus (HIV)–infected persons. We observed that 2% of 400 HIV-infected women with antibodies to hepatitis B core antigen alone had occult HBV infection (i.e., detectable HBV DNA in the absence of HBV surface antigen). CD4 cell counts of <200 cells/mm3 were more common among occult HBV-infected women than among those without occult HBV infection. Aminotransferase levels did not appear to be associated with being positive for HBV DNA.
doi:10.1086/520989
PMCID: PMC4142488  PMID: 17712758
6.  Plasma and Mucosal HIV Viral Loads Are Associated with Genital Tract Inflammation In HIV-Infected Women 
Background
Systemic and mucosal inflammation may play a role in HIV control. A cross-sectional comparison was conducted among women in the Women’s Interagency HIV Study (WIHS) to explore the hypothesis that compared to HIV-uninfected participants, women with HIV and in particular, those with high plasma viral load (PVL) have increased levels of mucosal and systemic inflammatory mediators and impaired mucosal endogenous antimicrobial activity.
Methods
19 HIV-uninfected, 40 HIV-infected on antiretroviral therapy (ART) with PVL ≤ 2600 copies/ml (low viral load) (HIV+-LVL), and 19 HIV-infected on or off ART with PVL >10,000 (high viral load) (HIV+-HVL) were evaluated. Immune mediators and viral RNA were quantified in plasma and cervicovaginal lavage (CVL). CVL antimicrobial activity was also determined.
Results
Compared to HIV-uninfected, HIV+-HVL women had higher levels of mucosal, but not systemic pro-inflammatory cytokines and chemokines, higher Nugent scores, and lower E. coli bactericidal activity. In contrast, there were no significant differences between HIV+-LVL and HIV-uninfected controls. After adjusting for PVL, HIV genital tract shedding was significantly associated with higher CVL concentrations of IL-6, IL-1β, MIP-1α, and RANTES and higher plasma concentrations of MIP-1α. High PVL was associated with higher CVL levels of IL-1β and RANTES, as well as with higher Nugent scores, lower E. coli bactericidal activity, smoking and lower CD4 counts; smoking and CD4 count retained statistical significance in a multivariate model.
Conclusion
Further study is needed to determine if the relationship between mucosal inflammation and PVL is causal and to determine if reducing mucosal inflammation is beneficial.
doi:10.1097/QAI.0b013e3182961cfc
PMCID: PMC3706034  PMID: 23591635
HIV; HSV; mucosal immunity; inflammation; female genital tract; WIHS
7.  Does HIV infection promote early kidney injury in women? 
Antiviral therapy  2013;19(1):79-87.
Background
In HIV-infected women, urine concentrations of novel tubulointerstitial injury markers, interleukin-18 (IL-18) and kidney injury marker-1 (KIM-1) are associated with kidney function decline and all-cause mortality. We hypothesized that HIV-infected individuals with preserved kidney filtration function would have more extensive kidney injury, as determined by urine injury markers, compared to the uninfected controls, and that risk factors for tubulointerstitial injury would differ from risk factors for albuminuria.
Methods
In this cross-sectional study, we compared urine concentrations of IL-18, KIM-1, and ACR in 908 HIV-infected and 289 HIV-uninfected women enrolled in the Women’s Interagency HIV Study, utilizing stored urine specimens from visits between 1999 and 2000.
Results
After multivariate-adjusted linear regression analysis, mean urine concentrations were higher in HIV-infected individuals by 38% for IL-18 (p<0.0001), 12% for KIM-1 (p=0.081), and 47% for ACR (p<0.0001). Higher HIV RNA level (15% per 10-fold increase, p<0.0001), lower CD4 count (8% per doubling, p=0.0025), HCV infection (30%, p=0.00018), and lower HDL (5% per 10 mg/dL, p=0.0024) were each associated with higher IL-18 concentrations. In contrast, hypertension (81%, p<0.0001) and diabetes (47%, p=0.018) were among the strongest predictors of higher ACR, though HIV RNA level (15% per 10-fold increase, p=0.0004) was also associated with higher ACR.
Conclusions
HIV-infected women had more extensive tubulointerstitial and glomerular injury than uninfected women, but the associated factors differed among the urine biomarkers. Combinations of urinary biomarkers should be investigated to further characterize early kidney injury in HIV-infected women.
doi:10.3851/IMP2677
PMCID: PMC3933452  PMID: 23970313
8.  Association Of Hepatitis C With Markers Of Hemostasis In HIV-Infected and Uninfected Women in the Women’s Interagency HIV Study (WIHS) 
Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is common. HIV infection and treatment are associated with hypercoaguability; thrombosis in HCV is under-investigated. Proposed markers of hemostasis in HIV include higher D-dimer, Factor VIII% and Plasminogen Activator Inhibitor-1 (PAI-1Ag), and lower total Protein S% (TPS), but have not been examined in HCV. We assessed the independent association of HCV with these four measures of hemostasis in a multicenter, prospective study of HIV: the Women’s Interagency HIV Study (WIHS).
We randomly selected 450 HCV-infected (anti-HCV+ with detectable plasma HCV RNA) and 450 HCV-uninfected (anti-HCV−) women. HCV was the main exposure of interest in regression models.
443 HCV+ and 425 HCV− women were included. HCV+ women had higher Factor VIII% (124.4% ±3.9 vs. 101.8% ±3.7, p <0.001) and lower TPS (75.7% ±1.1 vs. 84.3% ±1.1, <0.001) than HCV−, independent of HIV infection and viral load; there was little difference in PAI-1Ag or log10 D-dimer. After adjustment for confounders, these inferences remained. HIV infection was independently associated with higher Factor VIII% and log10 D-dimer, and lower TPS.
HCV was independently associated with higher Factor VIII% and lower TPS consistent with hypercoaguability. Higher Factor VIII % and D-dimer and lower total Protein S % were also strongly associated with HIV infection and levels of HIV viremia, independent of HCV infection. Further investigation is needed to determine if there is increased thrombotic risk from HCV. Studies examining hemostasis markers in HIV infection must also assess the contribution of HCV infection.
doi:10.1097/QAI.0b013e31827fdd61
PMCID: PMC3652915  PMID: 23221984
9.  Comparisons of creatinine and cystatin C for detection of kidney disease and prediction of all-cause mortality in HIV-infected women 
AIDS (London, England)  2013;27(14):2291-2299.
Background
Cystatin C could improve chronic kidney disease (CKD) classification in HIV-infected women relative to serum creatinine.
Design
Retrospective cohort analysis.
Methods
Cystatin C and creatinine were measured from specimens taken and stored during the 1999–2000 exam among 908 HIV-infected participants in the Women’s Interagency HIV study (WIHS). Mean follow-up was 10.2 years. The associations of baseline categories (<60, 60–90, and >90 mL/min/1.73m2) of creatinine eGFR (eGFRcr), cystatin C eGFR (eGFRcys), and combined creatinine-cystatin C eGFR (eGFRcr-cys) with all-cause mortality were evaluated using multivariable Cox regression. The net reclassification index (NRI) was calculated to evaluate the effect of cystatin C on reclassification of CKD staging.
Results
The prevalence of CKD (eGFR<60) at baseline was higher with eGFRcys (10.1%) compared to eGFRcr (6.7%, p=0.0006) and eGFRcr-cys (7.5%, p=0.011). Relative to eGFR >90, the eGFR <60 category by eGFRcys (Adjusted HR: 2.56; 95% CI: 1.63, 4.02), eGFRcr-cys (3.11; 1.94–5.00), and eGFRcr (2.34; 1.44–3.79) was associated with increased mortality risk. However, the eGFR 60–90 category was associated with increased mortality risk for eGFRcys (1.80; 1.28–2.53) and eGFRcr-cys (1.91; 1.38–2.66) but not eGFRcr (1.20; 0.85–1.67). The overall NRI for mortality was 26% when reclassifying from eGFRcr to eGFRcys (p<0.001) and was 20% when reclassifying from eGFRcr to eGFRcr-cys (p<0.001).
Conclusion
Cystatin C detected a higher prevalence of CKD relative to creatinine and improves CKD staging relative to creatinine by reclassifying individuals at the highest mortality risk to lower eGFR categories.
doi:10.1097/QAD.0b013e328362e874
PMCID: PMC3919542  PMID: 23669156
Creatinine; Cystatin C; Glomerular Filtration Rate; HIV; Mortality; Kidney; Women
10.  Urinary Markers of Kidney Injury and Kidney Function Decline in HIV-Infected Women 
Objective
HIV-infected persons have substantially higher risk of kidney failure than persons without HIV, but serum creatinine levels are insensitive for detecting declining kidney function. We hypothesized that urine markers of kidney injury would be associated with declining kidney function among HIV-infected women.
Methods
In the Women's Interagency HIV Study (WIHS), we measured concentrations of albumin-to-creatinine ratio (ACR), interleukin-18 (IL-18), kidney injury marker-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) from stored urine among 908 HIV-infected and 289 uninfected participants. Primary analyses used cystatin C based estimated glomerular filtration rate (CKD-EPI eGFRcys) as the outcome, measured at baseline and two follow-up visits over eight years; secondary analyses used creatinine (CKD-EPI eGFRcr). Each urine biomarker was categorized into tertiles, and kidney decline was modeled with both continuous and dichotomized outcomes.
Results
Compared with the lowest tertiles, the highest tertiles of ACR (−0.15ml/min/1.73m2, p<0.0001), IL-18 (−0.09ml/min/1.73m2, p<0.0001) and KIM-1 (−0.06ml/min/1.73m2, p<0.001) were independently associated with faster eGFRcys decline after multivariate adjustment including all three biomarkers among HIV-infected women. Among these biomarkers, only IL-18 was associated with each dichotomized eGFRcys outcome: ≥3% (Relative Risk 1.40; 95%CI 1.04-1.89); ≥5% (1.88; 1.30-2.71); and ≥10% (2.16; 1.20-3.88) for the highest versus lowest tertile. In alternative models using eGFRcr, the high tertile of KIM-1 had independent associations with 5% (1.71; 1.25-2.33) and 10% (1.78; 1.07-2.96) decline, and the high IL-18 tertile with 10% decline (1.97; 1.00-3.87).
Conclusions
Among HIV-infected women in the WIHS cohort, novel urine markers of kidney injury detect risk for subsequent declines in kidney function.
doi:10.1097/QAI.0b013e3182737706
PMCID: PMC3509242  PMID: 23023103
HIV; KIM-1; NGAL; IL-18; albumin-to-creatinine ratio; cystatin C; kidney injury
11.  Lower Liver-Related Death in African American Women With HIV/HCV Co-Infection Compared to Caucasian and Hispanic Women 
Hepatology (Baltimore, Md.)  2012;56(5):1699-1705.
Among individuals with and without concurrent human immunodeficiency virus (HIV), racial/ethnic differences in the natural history of hepatitis C virus (HCV) have been described. African-Americans have lower spontaneous HCV clearance than Caucasians, yet slower rates of liver fibrosis once chronically infected. It is not clear how these differences in the natural history of hepatitis C affect mortality, in either HIV positive or negative individuals. We conducted a cohort study of HIV/HCV co-infected women followed in the multicenter, NIH-funded Women’s Interagency HIV Study (WIHS) to determine the association of self-reported race/ethnicity with all-cause and liver-related mortality. Survival analyses were performed using Cox proportional hazards models. The eligible cohort (n=794) included 140 Caucasians, 159 Hispanics, and 495 African Americans. There were 438 deaths and 49 liver-related deaths during a median follow-up of 8.9 years and maximum follow-up of 16 years. African American co-infected women had significantly lower liver-related mortality compared to Caucasian (HR 0.41 95% CI 0.19–0.88, p=0.022) and Hispanic co-infected women (HR 0.38 95% CI 0.19–0.76, p=0.006). All-cause mortality was similar between racial/ethnic groups (HRs for all comparisons 0.82–1.03, logrank p=0.8).
Conclusions
African American co-infected women were much less likely to die from liver disease as compared to Caucasians and Hispanics, independent of other causes of death. Future studies are needed to investigate the reasons for this marked racial/ethnic discrepancy in liver-related mortality.
doi:10.1002/hep.25859
PMCID: PMC3440547  PMID: 22618868
race; ethnicity; viral hepatitis; mortality; gender
12.  Interleukin 10 Responses Are Associated With Sustained CD4 T-Cell Counts in Treated HIV Infection 
The Journal of Infectious Diseases  2012;206(5):780-789.
Background.Inflammation persists in treated human immunodeficiency virus (HIV) infection and may contribute to an increased risk for non–AIDS-related pathologies. We investigated the correlation of cytokine responses with changes in CD4 T-cell levels and coinfection with hepatitis C virus (HCV) during highly active antiretroviral treatment (HAART).
Methods.A total of 383 participants in the Women's Interagency HIV Study (212 with HIV monoinfection, 56 with HCV monoinfection, and 115 with HIV/HCV coinfection) were studied. HIV-infected women had <1000 HIV RNA copies/mL, 99.7% had >200 CD4 T cells/μL; 98% were receiving HAART at baseline. Changes in CD4 T-cell count between baseline and 2–4 years later were calculated. Peripheral blood mononuclear cells (PBMCs) obtained at baseline were used to measure interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 12 (IL-12), and tumor necrosis factor α (TNF-α) responses to Toll-like receptor (TLR) 3 and TLR4 stimulation.
Results.Undetectable HIV RNA (<80 copies/mL) at baseline and secretion of IL-10 by PBMCs were positively associated with gains in CD4 T-cell counts at follow-up. Inflammatory cytokines (IL-1β, IL-6, IL-12, and TNF-α) were also produced in TLR-stimulated cultures, but only IL-10 was significantly associated with sustained increases in CD4 T-cell levels. This association was significant only in women with HIV monoinfection, indicating that HCV coinfection is an important factor limiting gains in CD4 T-cell counts, possibly by contributing to unbalanced persistent inflammation.
Conclusions.Secreted IL-10 from PBMCs may balance the inflammatory environment of HIV, resulting in CD4 T-cell stability.
doi:10.1093/infdis/jis380
PMCID: PMC3491747  PMID: 22693231
13.  Racial/Ethnic Differences in Spontaneous HCV Clearance in HIV Infected and Uninfected Women 
Digestive diseases and sciences  2012;58(5):1341-1348.
Background/Aims
Among individuals without human immunodeficiency virus (HIV), African Americans have lower spontaneous clearance of hepatitis C virus (HCV) than Caucasians, and women have higher clearance than men. Few studies report racial/ethnic differences in acute HCV in HIV infected, or Hispanic women. We examined racial/ethnic differences in spontaneous HCV clearance in a population of HCV mono- and co-infected women.
Methods
We conducted a cross sectional study of HCV seropositive women (897 HIV infected and 168 HIV uninfected) followed in the US multicenter, NIH-funded Women's Interagency HIV Study (WIHS), to determine the association of race/ethnicity with spontaneous HCV clearance, as defined by undetectable HCV RNA at study entry.
Results
Among HIV and HCV seropositive women, 18.7 % were HCV RNA negative, 60.9 % were African American, 19.3 % Hispanic and 17.7 % Caucasian. HIV infected African American women were less likely to spontaneously clear HCV than Hispanic (OR 0.59, 95 % CI 0.38–0.93, p = 0.022) or Caucasian women (OR 0.57, 95 % CI 0.36–0.93, p = 0.023). Among HIV uninfected women, African Americans had less HCV clearance than Hispanics (OR 0.18, 95 % CI 0.07–0.48, p = 0.001) or Caucasians (OR 0.26, 95 % CI 0.09–0.79, p = 0.017). There were no significant differences in HCV clearance between Hispanics and Caucasians, among either HIV infected (OR 0.97, 95 % CI 0.57–1.66, p = 0.91) or uninfected (OR 1.45, 95 % CI 0.56–3.8, p = 0.45) women.
Conclusions
African Americans were less likely to spontaneously clear HCV than Hispanics or Caucasians, regardless of HIV status. No significant differences in spontaneous HCV clearance were observed between Caucasian and Hispanic women. Future studies incorporating IL28B genotype may further explain these observed racial/ethnic differences in spontaneous HCV clearance.
doi:10.1007/s10620-012-2486-8
PMCID: PMC3663918  PMID: 23179159
African American; Hispanic; Acute hepatitis C; Female
15.  Hepatitis C Viremia Is Associated with Cytomegalovirus IgG Antibody Levels in HIV-Infected Women 
PLoS ONE  2013;8(4):e61973.
Background
Individuals with HIV infection exhibit high cytomegalovirus (CMV) IgG levels, but there are few data regarding the association of hepatitis C virus (HCV) with the immune response against CMV.
Methods
Associations of HCV with CMV seropositivity and CMV IgG levels were studied in 635 HIV-infected women, 187 of whom were HCV-seropositive, with adjustment in multivariable models for age, race/ethnicity, and HIV disease characteristics. Eighty one percent of the women reported receipt of highly active antiretroviral therapy (HAART) prior to or at CMV testing.
Results
In adjusted models women with chronic HCV had higher CMV IgG levels than those without HCV RNA (β = 2.86, 95% CI:0.89 – 4.83; P = 0.004). The association of HCV RNA with CMV IgG differed by age (Pinteraction = 0.0007), with a strong association observed among women in the low and middle age tertiles (≤45.3 years of age; β = 6.21, 95% CI:3.30 – 9.11, P<0.0001) but not among women in the high age tertile. CMV IgG levels were not associated with non-invasive measures of liver disease, APRI and FIB-4, or with HCV RNA level and adjustment for Epstein-Barr virus (EBV) IgG levels did not affect the association between HCV and CMV.
Conclusions
CMV IgG levels are higher in HCV/HIV co-infected women than in HIV mono-infected women. Further research on the association of HCV with CMV IgG is indicated because prior studies have found CMV IgG to be associated with morbidity and mortality in the general population and subclinical carotid artery disease in HIV-infected patients.
doi:10.1371/journal.pone.0061973
PMCID: PMC3629158  PMID: 23613990
16.  Absence of reproducibly detectable low-level HIV viremia in highly exposed seronegative men and women. 
AIDS (London, England)  2011;25(5):619-623.
Objective
Transient HIV infections have been invoked to account for the cellular immune responses detected in highly virus-exposed individuals who have remained HIV seronegative. We tested for very low levels of HIV RNA in 524 seronegative plasma samples from 311 highly exposed women and men from 3 longitudinal HIV cohorts.
Design
2073 transcription mediated amplification (TMA) HIV RNA tests were performed for an average of 3.95 TMA assays per plasma sample. Quadruplicate TMA assays, analyzing a total of 2 ml of plasma, provided an estimated sensitivity of 3.5 HIV RNA copies/ml.
Results
Four samples from subjects who did not sero-convert within the following six months were positive for HIV RNA. For one sample, human polymorphism DNA analysis indicated a sample mix up. Borderline HIV RNA detection signals were detected for the other three positive samples and further replicate TMA testing yielded no positive results. Nested PCR assays (n=254) for HIV proviral DNA on PBMC from these 3 subjects were negative.
Conclusions
Transient viremia was not reproducibly detected in highly HIV exposed seronegative men and women. If transient infections do occur, plasma HIV RNA levels may remain below the detection limits of the sensitive assay used here, be of very short duration, or viral replication may be restricted to mucosal surfaces or their draining lymphoid tissues.
doi:10.1097/QAD.0b013e3283440269
PMCID: PMC3458706  PMID: 21297421
17.  The effect of HIV infection and HAART on inflammatory biomarkers in a population-based cohort of US women 
AIDS (London, England)  2011;25(15):1823-1832.
Objective
HIV causes inflammation that can be at least partially corrected by HAART. To determine the qualitative and quantitative nature of cytokine perturbation, we compared cytokine patterns in three HIV clinical groups including HAART responders (HAART), untreated HIV non-controllers (NC), and HIV-uninfected (NEG).
Methods
Multiplex assays were used to measure 32 cytokines in a cross-sectional study of participants in the Women's Interagency HIV Study (WIHS). Participants from 3 groups were included: HAART (n=17), NC (n=14), and HIV NEG (n=17).
Results
Several cytokines and chemokines showed significant differences between NC and NEG participants, including elevated IP-10 and TNF-α and decreased IL-12(p40), IL-15, and FGF-2 in NC participants. Biomarker levels among HAART women more closely resembled the NEG, with the exception of TNF-α and FGF-2. Secondary analyses of the combined HAART and NC groups revealed that IP-10 showed a strong, positive correlation with viral load and negative correlation with CD4+ T cell counts. The growth factors VEGF, EGF, and FGF-2 all showed a positive correlation with increased CD4+ T cell counts.
Conclusion
Untreated, progressive HIV infection was associated with decreased serum levels of cytokines important in T cell homeostasis (IL-15) and T cell phenotype determination (IL-12), and increased levels of innate inflammatory mediators such as IP-10 and TNF-α. HAART was associated with cytokine profiles that more closely resembled those of HIV uninfected women. The distinctive pattern of cytokine levels in the 3 study groups may provide insights into HIV pathogenesis, and responses to therapy.
doi:10.1097/QAD.0b013e3283489d1f
PMCID: PMC3314300  PMID: 21572306
HIV; CD4+ T cells; cytokines; chemokines; HAART
18.  Sexual Serosorting among Women with or at Risk of HIV Infection 
AIDS and behavior  2011;15(1):9-15.
Serosorting, the practice of selectively engaging in unprotected sex with partners of the same HIV serostatus, has been proposed as a strategy for reducing HIV transmission risk among men who have sex with men (MSM). However, there is a paucity of scientific evidence regarding whether women engage in serosorting. We analyzed longitudinal data on women’s sexual behavior with male partners collected in the Women’s Interagency HIV Study from 2001 to 2005. Serosorting was defined as an increasing trend of unprotected anal or vaginal sex (UAVI) within seroconcordant partnerships over time, more frequent UAVI within seroconcordant partnerships compared to non-concordant partnerships, or having UAVI only with seroconcordant partners. Repeated measures Poisson regression models were used to examine the associations between serostatus partnerships and UAVI among HIV-infected and HIV-uninfected women. The study sample consisted of 1,602 HIV-infected and 664 HIV-uninfected women. Over the follow-up period, the frequency of seroconcordant partnerships increased for HIV-uninfected women but the prevalence of UAVI within seroconcordant partnerships remained stable. UAVI was reported more frequently within HIV seroconcordant partnerships than among serodiscordant or unknown serostatus partnerships, regardless of the participant’s HIV status or types of partners. Among women with both HIV-infected and HIV-uninfected partners, 41% (63 HIV-infected and 9 HIV-uninfected) were having UAVI only with seroconcordant partners. Our analyses suggest that serosorting is occurring among both HIV-infected and HIV-uninfected women in this cohort.
doi:10.1007/s10461-010-9710-3
PMCID: PMC2987377  PMID: 20490909
HIV; Unprotected sex; Serosorting; Risk reduction; Condom use
19.  Correlates of Immune Activation Marker Changes in Human Immunodeficiency Virus (HIV)–Seropositive and High-Risk HIV-Seronegative Women Who Use Illicit Drugs 
The Journal of infectious diseases  2003;188(2):209-218.
The majority of natural history studies of human immunodeficiency virus (HIV) infection have immune and viral parameters in men. Data demonstrating that women have lower HIV-1 RNA levels than men at the same CD4 cell counts have raised the question of immunologic differences in HIV-seropositive women. This study describes levels and changes in phenotypic markers of immune maturity, function, and activation in the CD4 and CD8 cell subsets in HIV-seropositive and high-risk HIV-seronegative women. Our primary hypothesis was that activation levels would be significantly higher among illicit drug users. However, results showed that HIV-1 RNA level was the strongest predictor of marker level and that both HIV-1 RNA level and CD4 cell count were independently associated with CD4 activation, but illicit drug use was not. In summary, this study demonstrated that immune activation was a significant pathogenic feature in women and that activation was driven by HIV infection and not illicit drug use.
doi:10.1086/376509
PMCID: PMC3164115  PMID: 12854075
20.  Presence of Hepatitis C Virus (HCV) RNA in the Genital Tracts of HCV/HIV-1–Coinfected Women 
The Journal of infectious diseases  2005;192(9):1557-1565.
Background
Hepatitis C virus (HCV)–infected women—in particular, those coinfected with human immunodeficiency virus type 1 (HIV-1)—can transmit infection to their children and sex partners.
Methods
The present study was conducted to analyze the presence of HCV RNA in cervicovaginal lavage (CVL) fluid from 71 women (58 HCV/HIV-1–coinfected women and 13 HCV-infected, HIV-1–uninfected women) enrolled in the Women’s Interagency HIV Study.
Results
HCV RNA was detected (by a commercial polymerase chain reaction assay) in CVL fluid from 18 (29%) of the HIV-1–infected women and from none of the HIV-1–uninfected women (P < .05). Multivariate analysis revealed that risk factors for the presence of HCV RNA in CVL fluid were HCV viremia (odds ratio [OR], 16.81; P = .02) and HIV-1 RNA in CVL fluid (OR, 19.87; P = .02). This observation suggests local interactions between HIV-1 and HCV in the genital tract compartment. There was no correlation between HCV RNA in CVL fluid and CD4, CD8, or CD3 cell counts, HIV-1 RNA viremia, the number of leukocytes in CVL fluid, or HIV-1 therapy. Furthermore, in 3 of 5 analyzed patients who had a detectable CVL HCV RNA load, we found viral variants differing in the 5′ untranslated region that were present neither in plasma nor in peripheral-blood mononuclear cells.
Conclusions
Our observations point to the importance of the genital tract compartment, in which local HCV replication could be facilitated by local HIV-1 replication.
doi:10.1086/491742
PMCID: PMC3164119  PMID: 16206070
21.  Evaluating the Impact of Hepatitis C Virus (HCV) on Highly Active Antiretroviral Therapy–Mediated Immune Responses in HCV/HIV-Coinfected Women: Role of HCV on Expression of Primed/Memory T Cells 
The Journal of infectious diseases  2006;193(9):1202-1210.
Objective
To evaluate the impact of hepatitis C virus (HCV) on the immune system before receipt of highly active antiretroviral therapy (HAART) and on immune recovery after receipt of HAART among human immunodeficiency virus (HIV)/HCV–coinfected women enrolled in the Women’s Interagency HIV Study.
Methods
The study included 294 HIV-infected women who initiated HAART and attended 2 follow-up visits. The women were grouped on the basis of positive HCV antibody and HCV RNA tests. There were 148 women who were HCV antibody negative, 34 who were HCV antibody positive but RNA negative, and 112 who were HCV antibody and RNA positive. Immune recovery was measured by flow-cytometric assessment for markers of activation and maturation on CD4+ and CD8+ T cells. Data analysis used repeated measures of variance.
Results
HIV/HCV coinfection is associated with an increased number of CD4+ and CD8+ primed/memory T cells. HIV/HCV coinfection, however, did not affect any further decreases in CD4+ or CD4+ and CD8+ naive/memory T cell counts or enhanced T cell activation. HIV/HCV coinfection also did not affect HAART responses in the CD4+ and CD8+ T cell compartment.
Conclusions
HCV does not affect immune responses to HAART in HIV/HCV–coinfected individuals but is associated with an expansion of CD4+ and CD8+ memory T cell subsets. Functional impairment in the CD4+ and CD8+ T cell compartments still needs to be assessed in coinfected patients.
doi:10.1086/500843
PMCID: PMC3126663  PMID: 16586355
22.  HCV viremia is associated with drug use in young HIV-1 and HCV coinfected pregnant and non-pregnant women* 
Addiction (Abingdon, England)  2005;100(5):626-635.
Aims
Vertical transmission of HCV is increased among HIV-1/HCV coinfected women and is related to HCV viral load. In this study we assessed clinical and demographic factors associated with HCV viremia in a cohort of young pregnant and non-pregnant mothers coinfected with HIV-1.
Design
A cross-sectional clinic-based study nested within a prospective cohort study.
Methods
From 1988 to 2000, HIV-1 + pregnant and non-pregnant women with children followed in a large maternal, child and adolescent HIV-1 clinic were evaluated for HCV infection using EIA 3.0. HCV RNA levels were determined for HCV antibody + women using polymerase chain reaction. Demographic and clinical characteristics between HCV-RNA(+) and HCV-RNA(−) women and between pregnant and non-pregnant HIV-1/HCV coinfected women were compared using univariate and multivariate analyses.
Findings
Among 359 HIV-1(+) women, 84 (23%) were HCV-ab + and 49/84 (58%) had detectable HCV-RNA in plasma. Median age was 31. CD4 counts, HIV-1 RNA levels and demographic characteristics were similar for viremic and non-viremic women and pregnant and non-pregnant women. However, viremic women were more likely to report a history of (88% versus 43%; P < 0.001) or active injection drug use (AIDU) (83% versus 29%; P < 0.001). Logistic regression analysis showed that HCV viremia was associated significantly with AIDU (adjusted OR: 15.17; 95% CI: 3.56, 64.56) after adjusting for age, race, number of sexual partners, pregnancy status, CD4 counts and HIV-1 viral load.
Conclusion
In this cohort of young HIV-1 and HCV coinfected women, HCV viremia was associated strongly with active injection drug use, perhaps due to reinfection or reactivation of HCV. Thus, careful evaluation for HCV infection and counseling related to drug use may be necessary.
doi:10.1111/j.1360-0443.2005.01054.x
PMCID: PMC3118993  PMID: 15847620
HCV; HIV-1 infection; HCV viremia; intravenous drug use; pregnancy
23.  Glycated Hemoglobin in Diabetic Women with and Without HIV Infection: Data from the Women's Interagency HIV Study 
Antiviral therapy  2010;15(4):571-577.
Background
Limited data suggest that glycated hemoglobin (hemoglobin A1c; A1C) values may not reflect glycemic control accurately in HIV-infected individuals with diabetes.
Methods
We evaluated repeated measures of paired fasting glucose and A1C values in 315 HIV-infected and 109 HIV-uninfected diabetic participants in the Women's Interagency HIV Study. Generalized estimating equations used log A1C as the outcome variable, with adjustment for log fasting glucose concentration in all models.
Results
An HIV-infected woman on average had 0.9868 times as much A1C (that is, 1.32% lower; 95% confidence interval 0.9734-0.9904) as an HIV-uninfected woman with the same log fasting glucose concentration. In multivariate analysis, HIV serostatus was not associated, but white, other non-black race, and higher red blood cell mean corpuscular volume (MCV) were statistically associated with lower A1C values. Use of diabetic medication was associated with higher A1C values. In multivariate analysis restricted to HIV-infected women, white and other race, higher MCV, and HCV viremia were associated with lower A1C values whereas older age, use of diabetic medications and higher CD4 cell count were associated with higher A1C values. Use of combination antiretroviral therapy, protease inhibitors, zidovudine, stavudine, or abacavir was not associated with A1C values.
Conclusions
We conclude that A1C values were modestly lower in HIV-infected diabetic women relative to HIV-uninfected diabetic women after adjustment for fasting glucose concentration. The difference was abrogated by adjustment for MCV, race, and diabetic medication use. Our data suggest that in clinical practice A1C gives a reasonably accurate refection of glycemic control in HIV-infected diabetic women.
doi:10.3851/IMP1557
PMCID: PMC2943237  PMID: 20587850
24.  Hepatitis C Seropositivity and Kidney Function Decline Among Women With HIV: Data From the Women's Interagency HIV Study 
Background
How co-infection with hepatitis C virus (HCV) impacts on the trajectory of kidney function among HIV-infected patients is unclear. This study examined the effect of HCV on kidney function over time among women infected with HIV.
Study Design
Retrospective observational cohort
Setting and Participants
Study sample included participants from the Women's Interagency HIV Study who were HIV-infected and had received HCV antibody testing and serum creatinine measurement at baseline.
Predictor
HCV seropositivity
Outcomes and Measurement
Estimated glomerular filtration rate (eGFR) calculated from semi-annual serum creatinine measurements using the 4-variable Modification of Diet in Renal Diseases (MDRD) Study equation. Linear mixed models were used to evaluate the independent effect of being HCV seropositive on eGFR over time, adjusting for demographic factors, co-morbid conditions, illicit drug use, measures of HIV disease status, use of medications, and interactions with baseline low eGFR (<60 mL/min/1.73m2).
Results
Of the 2,684 HIV-infected women, 952 (35%) were found to be HCV seropositive. For 180 women with CKD at baseline (eGFR <60 mL/min/1.73m2), being HCV seropositive was independently associated with a fully-adjusted net decline in eGFR of about 5% per year (95% CI: 3.2 to 7.2%), relative to women who were seronegative. In contrast, HCV was not independently associated with decline in eGFR among women without low eGFR at baseline (p<0.001 for interaction).
Limitations
The MDRD Study equation has not been validated as a measure of GFR among persons with HIV or HCV. Proteinuria was not included in the study analysis. Because the study is observational, the effects of residual confounding cannot be excluded.
Conclusions
Among HIV-infected women with CKD, co-infection with HCV is associated with a modest, but statistically significant decline in eGFR over time. More careful monitoring of kidney function may be warranted for HIV-infected patients with CKD who are also co-infected with HCV.
doi:10.1053/j.ajkd.2009.02.009
PMCID: PMC2997705  PMID: 19394735
hepatitis C virus; HIV; kidney diseases; women
25.  Genital herpes evaluation by quantitative TaqMan PCR: correlating single detection and quantity of HSV-2 DNA in cervicovaginal lavage fluids with cross-sectional and longitudinal clinical data 
Virology Journal  2010;7:328.
Objective
To evaluate the utility of a single quantitative PCR (qPCR) measurement of HSV (HSV-1&2) DNA in cervicovaginal lavage (CVL) specimens collected from women with predominantly chronic HSV-2 infection in assessing genital HSV shedding and the clinical course of genital herpes (GH) within a cohort with semiannual schedule of follow up and collection of specimens.
Methods
Two previously described methods used for detection of HSV DNA in mucocutaneous swab samples were adapted for quantification of HSV DNA in CVLs. Single CVL specimens from 509 women were tested. Presence and quantity of CVL HSV DNA were explored in relation to observed cross-sectional and longitudinal clinical data.
Results
The PCR assay was sensitive and reproducible with a limit of quantification of ~50 copies per milliliter of CVL. Overall, 7% of the samples were positive for HSV-2 DNA with median log10 HSV-2 DNA copy number of 3.9 (IQR: 2.6-5.7). No HSV-1 was detected. Presence and quantity of HSV-2 DNA in CVL directly correlated with the clinical signs and symptoms of presence of active symptomatic disease with frequent recurrences.
Conclusion
Single qPCR measurement of HSV DNA in CVL fluids of women with chronic HSV-2 infection provided useful information for assessing GH in the setting of infrequent sampling of specimens. Observed positive correlation of the presence and quantity of HSV-2 DNA with the presence of active and more severe course of HSV-2 infection may have clinical significance in the evaluation and management of HSV-2 infected patients.
doi:10.1186/1743-422X-7-328
PMCID: PMC3000844  PMID: 21087488

Results 1-25 (35)