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2.  Comparison of Lower Genital Tract Microbiota in HIV-Infected and Uninfected Women from Rwanda and the US 
PLoS ONE  2014;9(5):e96844.
Introduction
Previous studies have shown that alterations of the bacterial microbiota in the lower female genital tract influence susceptibility to HIV infection and shedding. We assessed geographic differences in types of genital microbiota between HIV-infected and uninfected women from Rwanda and the United States.
Methods
Genera of lower genital tract bacterial microbiota were identified by high-throughput pyrosequencing of the 16S rRNA gene from 46 US women (36 HIV-infected, 10 HIV-uninfected) and 40 Rwandan women (18 HIV-infected, 22 HIV-uninfected) with similar proportions of low (0–3) Nugent scores. Species of Lactobacillus were identified by assembling sequences along with reference sequences into phylogenetic trees. Prevalence of genera and Lactobacillus species were compared using Fisher's exact tests.
Results
Overall the seven most prevalent genera were Lactobacillus (74%), Prevotella (56%), Gardnerella (55%), Atopobium (42%), Sneathia (37%), Megasphaera (30%), and Parvimonas (26%), observed at similar prevalences comparing Rwandan to US women, except for Megasphaera (20% vs. 39%, p = 0.06). Additionally, Rwandan women had higher frequencies of Mycoplasma (23% vs. 7%, p = 0.06) and Eggerthella (13% vs. 0%, p = 0.02), and lower frequencies of Lachnobacterium (8% vs. 35%, p<0.01) and Allisonella (5% vs. 30%, p<0.01), compared with US women. The prevalence of Mycoplasma was highest (p<0.05) in HIV-infected Rwandan women (39%), compared to HIV-infected US women (6%), HIV-uninfected Rwandan (9%) and US (10%) women. The most prevalent lactobacillus species in both Rwandan and US women was L. iners (58% vs. 76%, p = 0.11), followed by L. crispatus (28% vs. 30%, p = 0.82), L. jensenii (20% vs. 24%, p = 0.80), L. gasseri (20% vs. 11%, p = 0.37) and L. vaginalis (20% vs. 7%, p = 0.10).
Discussion
We found similar prevalence of most major bacterial genera and Lactobacillus species in Rwandan and US women. Further work will be needed to establish whether observed differences differentially impact lower genital tract health or susceptibility to genital infections.
doi:10.1371/journal.pone.0096844
PMCID: PMC4016010  PMID: 24817204
3.  Capacity for Infectious HIV-1 Virion Capture Differs by Envelope Antibody Specificity 
Journal of Virology  2014;88(9):5165-5170.
Antibody capacity to recognize infectious virus is a prerequisite of many antiviral functions. We determined the infectious virion capture index (IVCI) of different antibody specificities. Whereas broadly neutralizing antibodies (bNAbs), except for an MPER bNAb, selectively captured infectious virions, non-bNAbs and mucosal human immunodeficiency virus type 1 (HIV-1)-positive IgG captured subsets of both infectious and noninfectious virions. Infectious virion capture was additive with a mixture of antibodies, providing proof of concept for vaccine-induced antibodies that together have improved capacity to recognize infectious virions.
doi:10.1128/JVI.03765-13
PMCID: PMC3993833  PMID: 24554654
4.  A Compositional Look at the Human Gastrointestinal Microbiome and Immune Activation Parameters in HIV Infected Subjects 
PLoS Pathogens  2014;10(2):e1003829.
HIV progression is characterized by immune activation and microbial translocation. One factor that may be contributing to HIV progression could be a dysbiotic microbiome. We therefore hypothesized that the GI mucosal microbiome is altered in HIV patients and this alteration correlates with immune activation in HIV. 121 specimens were collected from 21 HIV positive and 22 control human subjects during colonoscopy. The composition of the lower gastrointestinal tract mucosal and luminal bacterial microbiome was characterized using 16S rDNA pyrosequencing and was correlated to clinical parameters as well as immune activation and circulating bacterial products in HIV patients on ART. The composition of the HIV microbiome was significantly different than that of controls; it was less diverse in the right colon and terminal ileum, and was characterized by loss of bacterial taxa that are typically considered commensals. In HIV samples, there was a gain of some pathogenic bacterial taxa. This is the first report characterizing the terminal ileal and colonic mucosal microbiome in HIV patients with next generation sequencing. Limitations include use of HIV-infected subjects on HAART therapy.
Author Summary
Human immunodeficiency virus (HIV) infection related illness progresses despite the control of the virus itself by medications that stop the replication of the virus. This happens because the immune system gets activated. While the causes for such activation of the immune system are not exactly known, immune activation in HIV infection may be occurring as a result of bacteria or their products in the digestive tract. This study looks at the types of bacteria that reside in the lower intestinal tract in patients infected with human immunodeficiency virus, using state of the art sequencing technology, that can simultaneously look at thousands of bacteria. We have found that the bacteria at the end of the small bowel (an area also called the terminal ileum), at the right and left sides of the large intestine and in the stool is different in patients infected with the human immunodeficiency virus. HIV patients harbor more bacteria that have been linked to other human diseases and have been previously described as harmful. This finding is new and could open up a new frontier of study that could now pave the way to gain a deeper understanding of how the HIV causes illness.
doi:10.1371/journal.ppat.1003829
PMCID: PMC3930561  PMID: 24586144
5.  Vitamin D insufficiency may impair CD4 recovery among Women’s Interagency HIV Study participants with advanced disease on HAART 
AIDS (London, England)  2013;27(4):573-578.
Background
Recent studies in HIV-infected men report an association between low vitamin D (25OH-D) and CD4 recovery on HAART. We sought to test this relationship in the Women’s Interagency HIV Study (WIHS).
Methods
We examined 204 HIV-infected women with advanced disease, who started HAART after enrollment in the WIHS. We measured vitamin D (25OH-D) levels about 6 months prior to HAART initiation. The relationship between CD4 recovery (defined as increases of ≥50, 100, and 200 cells at 6, 12, and 24 months) and exposure variables was examined using logistic regression models at 6, 12 and 24 months post-HAART initiation in unadjusted and adjusted analyses, and using multivariable longitudinal Generalized Estimating Equations (GEE). Vitamin D insufficiency was defined as 25OH-D levels at least 30 ng/ml.
Results
The majority were non-Hispanic black (60%) and had insufficient vitamin D levels (89%). In adjusted analyses, at 24 months after HAART, insufficient vitamin D level (OR 0.20, 95% CI 0.05–0.83) was associated with decreased odds of CD4 recovery. The undetectable viral load (OR 11.38, 95% CI 4.31–30.05) was associated with CD4 recovery. The multivariable GEE model found that average immune reconstitution attenuated significantly (P <0.01) over time among those with insufficient vitamin D levels compared with those with sufficient vitamin D levels.
Conclusion
Vitamin D insufficiency is associated with diminished late CD4 recovery after HAART initiation among US women living with advanced HIV. The mechanism of this association on late CD4 recovery may be late vitamin D-associated production of naive CD4 cells during immune reconstitution.
doi:10.1097/QAD.0b013e32835b9ba1
PMCID: PMC3902982  PMID: 23095316
antiretroviral therapy; HIV; immune reconstitution; vitamin D; women
6.  Cause-Specific Life Expectancies After 35 Years of Age for Human Immunodeficiency Syndrome-Infected and Human Immunodeficiency Syndrome-Negative Individuals Followed Simultaneously in Long-term Cohort Studies, 1984–2008 
American Journal of Epidemiology  2013;177(2):116-125.
Parametric and semiparametric competing risks methods were used to estimate proportions, timing, and predictors of acquired immune deficiency syndrome (AIDS)-related and non-AIDS-related mortality among individuals both positive and negative for the human immunodeficiency syndrome (HIV) in the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS) from 1984 to 2008 and 1996 to 2008, respectively. Among HIV-positive MACS participants, the proportion of deaths unrelated to AIDS increased from 6% before the introduction of highly active antiretroviral therapy (HAART) (before 1996) to 53% in the HAART era (P < 0.01); the median age of persons who died from non-AIDS-related causes after age 35 years increased from 49.0 to 66.0 years (P < 0.01). In both cohorts during the HAART era, median ages at time of non-AIDS-related death were younger for HIV-positive individuals than for comparable HIV-negative individuals (8.7 years younger in MACS (P < 0.01) and 7.6 years younger in WIHS (P < 0.01)). In a multivariate proportional cause-specific hazards model, unemployment (for non-AIDS death, hazard ratio (HR) = 1.8; for AIDS death, HR = 2.3), depression (for non-AIDS death, HR = 1.4; for AIDS death, HR = 1.4), and hepatitis B or C infection (for non-AIDS death, HR = 1.8, for AIDS death; HR = 1.4) were significantly (P < 0.05) associated with higher hazards of both non-AIDS and AIDS mortality among HIV-positive individuals in the HAART era, independent of study cohort. The results illuminate the changing face of mortality among the growing population infected with HIV.
doi:10.1093/aje/kws321
PMCID: PMC3590031  PMID: 23287403
acquired immunodeficiency syndrome; antiretroviral therapy, highly active; cohort studies; competing risks; HIV; mixture model; mortality; proportional hazards models
7.  Effects of highly active antiretroviral therapy and its adherence on herpes zoster incidence: a longitudinal cohort study 
Background
Herpes zoster (HZ) is common among HIV-infected individuals, but the impacts of highly active antiretroviral therapy (HAART) and HAART adherence on HZ risk have not been well studied.
Methods
The effects of HAART and HAART adherence on HZ incidence were evaluated by comparing HIV-infected women on HAART (HAART use group) with the HIV-infected women remaining HAART naïve (HAART naïve group) in the Women’s Interagency HIV Study (WIHS). A 1:1 matching with propensity score for predicting HAART initiation was conducted to balance background covariates at index visit, including HIV disease stage. Kaplan-Meier method was used to compare the risk of HZ development between the matched pairs. Cox proportional hazard models were used to assess the effects of HAART and HAART adherence on HZ incidence.
Results
Through propensity score matching, 389 pairs of participants were identified and they contributed 3,909 person years after matching. The background covariates were similar between the matched pairs at the index visit. The participants had a mean age around 39 years old, and about 61% of them were Black and 22% were Latina. No significant difference in HZ risk was observed between the HAART use group and the HAART naïve group during the first year of follow-up in any analyses. In the univariate analysis, the HAART use group had marginally lower HZ risk (Hazard Ratio (HR): 0.72; 95% Confidence Interval (CI): 0.48-1.1) over the entire follow-up period. However, women with a HAART adherence level of ≥95% had significantly lower HZ risk (HR: 0.54; 95% CI: 0.31, 0.94) compared to the HAART naïve women. The association remained significant after adjusting for quality of life score and acyclovir use, but it attenuated and was no longer statistically significant after adjusting for an intermediate variable, either CD4+ T cell counts or HIV viral load.
Conclusions
Among adult women, we observed a significant preventive effect of long-term HAART use on HZ incidence when a HAART adherence level of ≥95% was attained, and this effect was mediated through reduction of HIV viral load and improvement of CD4+ T cell counts.
doi:10.1186/1742-6405-10-34
PMCID: PMC3904465  PMID: 24373482
HAART; Adherence; Herpes zoster; Incidence; Propensity score
8.  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
9.  Assessing mortality in women with hepatitis C virus and HIV using indirect markers of fibrosis 
AIDS (London, England)  2012;26(5):599-607.
Objective
Co-infection with hepatitis C virus (HCV) is a major cause of morbidity and mortality in HIV-infected individuals. However, predictors of mortality are poorly defined and most studies have focused predominantly on co-infection in men. We evaluated whether two indirect markers of hepatic fibrosis, aspartate aminotransferase-to-platelet ratio index (APRI) and FIB-4 scores, were predictive of mortality in a well defined longitudinal cohort of HCV/HIV-co-infected women on HAART.
Methods
HCV/HIV-co-infected women on antiretroviral therapy enrolled in Women’s Interagency HIV Study (WIHS), a National Institutes of Health-funded prospective, multicenter, cohort study of women with and at risk for HIV infection were included. Using Cox regression analysis, associations between APRI and FIB-4 with all-cause mortality were assessed.
Results
Four hundred and fifty HCV/HIV-co-infected women, of whom 191 women died, had a median follow-up of 6.6 years and 5739 WIHS visits. Compared with women with low APRI or FIB-4 levels, severe fibrosis was significantly associated with an increased risk of all-cause mortality {APRI: hazard ratio 2.78 [95% confidence interval (CI) 1.87, 4.12]; FIB-4: hazard ratio 2.58 (95% CI 1.68, 3.95)}. Crude death rates per 1000 patient-years increased with increasing liver fibrosis: 34.8 for mild, 51.3 for moderate and 167.9 for severe fibrosis as measured by FIB-4. Importantly, both APRI and FIB-4 increased during the 5 years prior to death for all women: the slope of increase was greater for women dying a liver-related death compared with nonliver-related death.
Conclusion
Both APRI and FIB-4 are independently associated with all-cause mortality in HCV/HIV-co-infected women and may have clinical prognostic utility among women with HIV and HCV.
doi:10.1097/QAD.0b013e32834fa121
PMCID: PMC3698040  PMID: 22156972
fibrosis markers; hepatitis C virus; HIV; longitudinal study; mortality
10.  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
11.  The insulin-like growth factor axis and risk of liver disease in hepatitis C virus/HIV-co-infected women 
AIDS (London, England)  2008;22(4):527-531.
Objective
Insulin-like growth factor (IGF) I stimulates the proliferation of hepatic stellate cells (HSC), the primary source of extracellular matrix accumulation in liver fibrosis. In contrast, insulin-like growth factor binding protein (IGFBP) 3, the most abundant IGFBP in circulation, negatively modulates HSC mitogenesis. To investigate the role of the IGF axis in hepatitis C virus (HCV)-related liver disease among high-risk patients, we prospectively evaluated HCV-viremic/HIV-positive women.
Design
A cohort investigation.
Methods
Total IGF-I and IGFBP-3 were measured in baseline serum specimens obtained from 472 HCV-viremic/HIV-positive subjects enrolled in the Women's Inter-agency HIV Study, a large multi-institutional cohort. The aspartate aminotransferase to platelet ratio index (APRI), a marker of liver fibrosis, was assessed annually.
Results
Normal APRI levels (< 1.0) at baseline were detected in 374 of the 472 HCV-viremic/HIV-positive subjects tested, of whom 302 had complete liver function test data and were studied. IGF-I was positively associated [adjusted odds ratio comparing the highest and lowest quartiles (AORq4–q1), 5.83; 95% confidence interval (CI) 1.17–29.1; Ptrend = 0.03], and IGFBP-3 was inversely associated (AORq4–q1, 0.13; 95% CI 0.02–0.76; Ptrend = 0.04), with subsequent (incident) detection of an elevated APRI level(> 1.5), after adjustment for the CD4 T-cell count, alcohol consumption, and other risk factors.
Conclusion
High IGF-I may be associated with increased risk and high IGFBP-3 with reduced risk of liver disease among HCV-viremic/HIV-positive women.
doi:10.1097/QAD.0b013e3282f22cdf
PMCID: PMC3507535  PMID: 18301066
aspartate aminotransferase to platelet ratio index; APRI; hepatitis C virus (HCV); HIV; IGFBP-3; IGF; liver disease
12.  Factors associated with hepatitis C viremia in a large cohort of HIV-infected and - uninfected women 
Background
Coinfection with hepatitis C virus (HCV) is common among HIV-infected women.
Objective
To further our understanding of the risk factors for HCV viremia and the predictors of HCV viral load among women.
Study design
We investigated sociodemographic, immunologic, and virologic factors associated with presence and level of HCV viremia among 882 HIV-infected and 167 HIV-uninfected HCV-seropositive women at entry into the Women's Interagency HIV Study.
Results
Plasma HCV RNA was detected in 852 (81%) of these 1,049 women (range: 1.2–7.8 log10 copies/ml). HCV-viremic women were more likely to have an HIV RNA level >100,000 copies/ml (P =0.0004), have reported smoking (P =0.01), or to be Black (P =0.005). They were less likely to have current or resolved hepatitis B infection. HCV RNA levels were higher in women who were >35 years old, or HIV-infected. Current smoking and history of drug use (crack/freebase cocaine, marijuana, amphetamines, or heroin) were each associated with both presence and level of viremia.
Conclusions
Substance abuse counseling aimed at eliminating ongoing use of illicit drugs and tobacco may reduce clinical progression, improve response to treatment, and decrease HCV transmission by lowering levels of HCV viremia in women.
doi:10.1016/j.jcv.2007.08.021
PMCID: PMC3493623  PMID: 18243785
Hepatitis C; Hepatitis C RNA levels; Hepatitis C viremia; HIV/hepatitis C virus coinfection
13.  LOWER LEVELS OF INTERLEUKIN-12 PRECEDE THE DEVELOPMENT OF TUBERCULOSIS AMONG HIV-INFECTED WOMEN 
Cytokine  2011;56(2):325-331.
Tuberculosis (TB) is the worldwide leading cause of death among HIV-infected individuals, accounting for more than half of AIDS-related deaths. A high risk of tuberculosis (TB) has been shown in early stages of the HIV disease, even in the presence of normal CD4+ cell counts. Moreover, the factors that determine protective immunity vs. susceptibility to M. tuberculosis cannot be fully explained by simple changes in IFNγ levels or a shift from Th1 to Th2 cytokines. This work investigated the relationship between cytokine expression profiles in peripheral blood mononuclear cells (PBMC) and susceptibility to M. tuberculosis in ten HIV+ women who went on to develop TB. RNA transcripts for IL-4, IL-4δ2, IL-10, IL-12(p35), IL-13, IL-17A, IFNγ and TNFα were measured by real-time quantitative PCR in unstimulated or TB peptide antigen-stimulated PBMCs from ten HIV+ women with positive tuberculin skin tests (TST) and compared with HIV-seropositive and seronegative women without previous TB and negative TST. Stimulated PBMC cultures showed significantly lower expression of IL-12p35 (p=0.004) and IL-10 (p=0.026) in the HIV+TB+ group six to twelve months before onset of TB compared to HIV+TB− women. Unstimulated PBMC from HIV+TB+ women also had lower expression of Th2 cytokines [IL-4 (p=0.056) and IL-13 (p=0.050)] compared to HIV+TB− women. These results suggest that lower IL-12 production by PBMC in response to TB antigens and lower levels of both Th1 and Th2 cytokines by PBMC correlate with future development of TB in HIV-infected women and may be responsible for their increased susceptibility.
doi:10.1016/j.cyto.2011.08.018
PMCID: PMC3466167  PMID: 21880503
Interferon-γ(IFNγ); Interleukin-4 (IL-4); Interleukin-12 (IL-12); Human Immunodeficiency Virus (HIV); Tuberculosis (TB)
14.  The Association of HIV Status with Bacterial Vaginosis and Vitamin D in the United States 
Journal of Women's Health  2011;20(10):1497-1503.
Abstract
Objective
To estimate the association between vitamin D deficiency and bacterial vaginosis (BV) among nonpregnant HIV-infected and uninfected women.
Methods
In a substudy of the Women's Interagency HIV Study, including women from Chicago and New York, the association between BV and vitamin D deficiency, demographics, and disease characteristics was tested using generalized estimating equations. Deficiency was defined as <20 ng/mL 25 (OH) vitamin D and insufficiency as >20 and ≤30 ng/mL. BV was defined by the Amsel criteria.
Results
Among 602 observations of nonpregnant women (480 HIV infected and 122 uninfected), BV was found in 19%. Vitamin D deficiency was found in 59.4%, and insufficiency was found in 24.4%. In multivariable analysis, black race was the most significant predictor of BV (adjusted odds ratio [AOR] 5.90, (95% confidence interval [CI] 2.52-13.8). Vitamin D deficiency was independently associated with BV among HIV-infected women (AOR 3.12, 95% CI 1.16-8.38) but not among HIV-uninfected women. There was a negative linear correlation between vitamin D concentration and prevalence of BV in HIV-infected women (r=−0.15, p=0.001).
Conclusions
Vitamin D deficiency was very common in this cohort and significantly associated with BV among HIV-infected women. These preliminary findings suggest that further epidemiologic and mechanistic exploration of the relationship between vitamin D and BV in HIV-infected women is warranted.
doi:10.1089/jwh.2010.2685
PMCID: PMC3233211  PMID: 21875343
15.  Risk Factors for Tuberculosis After Highly Active Antiretroviral Therapy Initiation in the United States and Canada: Implications for Tuberculosis Screening 
The Journal of Infectious Diseases  2011;204(6):893-901.
Background. Screening for tuberculosis prior to highly active antiretroviral therapy (HAART) initiation is not routinely performed in low-incidence settings. Identifying factors associated with developing tuberculosis after HAART initiation could focus screening efforts.
Methods. Sixteen cohorts in the United States and Canada contributed data on persons infected with human immunodeficiency virus (HIV) who initiated HAART December 1995–August 2009. Parametric survival models identified factors associated with tuberculosis occurrence.
Results. Of 37845 persons in the study, 145 were diagnosed with tuberculosis after HAART initiation. Tuberculosis risk was highest in the first 3 months of HAART (20 cases; 215 cases per 100000 person-years; 95% confidence interval [CI]: 131–333 per 100000 person-years). In a multivariate Weibull proportional hazards model, baseline CD4+ lymphocyte count <200, black race, other nonwhite race, Hispanic ethnicity, and history of injection drug use were independently associated with tuberculosis risk. In addition, in a piece-wise Weibull model, increased baseline HIV-1 RNA was associated with increased tuberculosis risk in the first 3 months; male sex tended to be associated with increased risk.
Conclusions. Screening for active tuberculosis prior to HAART initiation should be targeted to persons with baseline CD4 <200 lymphocytes/mm3 or increased HIV-1 RNA, persons of nonwhite race or Hispanic ethnicity, history of injection drug use, and possibly male sex.
doi:10.1093/infdis/jir421
PMCID: PMC3156918  PMID: 21849286
16.  Seroincidence of 2009 H1N1 infection in HIV-infected and HIV-uninfected women prior to vaccine availability 
AIDS (London, England)  2011;25(9):1229-1232.
The 2009 H1N1 pandemic was a unique opportunity to investigate differences in influenza infection using serology by HIV status. Using serial serum specimens collected from 1 April to 30 September 2009 and the prior 2 years from Women’s Interagency HIV study participants, there was no difference in serologic evidence of 2009 H1N1 infection among HIV-infected women with a CD4 cell count at least 350 cells/µl compared with HIV-uninfected women. Owing to evidence showing a greater risk of influenza-related complications, HIV-infected individuals should continue to be a priority group for vaccination.
doi:10.1097/QAD.0b013e3283471cf2
PMCID: PMC3442364  PMID: 21505313
17.  Vitamin D deficiency in HIV-infected and un-infected women in the US 
Background
Vitamin D deficiency is of increasing concern in HIV-infected persons, because of its reported association with a number of negative health outcomes that are common in HIV. We undertook this study to determine the prevalence and predictors of vitamin D deficiency among a nationally representative cohort of middle-aged, ethnically diverse HIV-infected and uninfected women enrolled in the Women’s Interagency HIV study (WIHS).
Methods
Vitamin D testing was performed by Quest Diagnostics on frozen sera using the liquid chromatography/mass spectroscopy (LC-MS) method. Vitamin D deficiency was defined as 25 (OH) D ≤20 ng/ml. Comparisons of continuous and categorical characteristics among HIV-infected and HIV-uninfected women were made by Wilcoxon tests and Pearson chi-squared tests, respectively.
Results
1778 women (1268 HIV+) were studied. 63% had vitamin D deficiency (60% HIV +vs. 72% HIV−; p<0.001). Multivariable predictors of Vitamin D Deficiency were being African American (AOR 3.02), Hispanic (AOR 1.40), Body mass index (AOR 1.43), Age (AOR 0.84), HIV+ (AOR 0.76), Glomerular filtration rate <90/ml/min (AOR 0.94) and WIHS site; Los Angeles (AOR 0.66), Chicago (AOR 0.63). In the HIV+ women multivariate predictors were; undetectable HIVRNA (AOR 0.69), CD4 50–200 cells/mm3 (AOR 1.60), CD4 <50 cells/mm3 (AOR 1.94) and recent Protease Inhibitor use (AOR 0.67).
Conclusions
In this study of over 1700 women in the US, most women with or without HIV infection had low vitamin D levels and African American women had the highest rates of Vitamin D deficiency. An understanding of the role that vitamin D deficiency plays in non-AIDS related morbidities is planned for investigation in WIHS.
doi:10.1097/QAI.0b013e31821ae418
PMCID: PMC3431159  PMID: 21471818
Vitamin D; Vitamin D Deficiency; HIV infected; HIV uninfected
18.  Lack of Increased Hepatotoxicity in HIV-infected Pregnant Women Receiving Nevirapine Compared to Other Antiretrovirals 
AIDS (London, England)  2010;24(1):109-114.
Objective
To estimate whether HIV-infected pregnant women were at increased risk of hepatotoxicity when taking nevirapine (NVP) containing regimens compared to HIV-infected pregnant women taking antiretroviral therapy (ART) not containing NVP.
Methods
This analysis included HIV-infected pregnant women on ART from two multicenter, prospective cohorts: The Women and Infants Transmission Study (WITS) and the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) protocol P1025. Multivariate Cox proportional hazards regression models were used to investigate the association between NVP use and hepatotoxicity. NVP use was dichotomized as use or no use and further categorized according to ART exposure history. We investigated two outcomes: any liver enzyme elevation (LEE) (grade 1-4) and severe LEE (grade 3-4).
Results
A total of 1229 women with ART use during pregnancy were studied, 218 (17.7%) of whom received NVP. Among the women receiving NVP, 137 (62.8%) were NVP naïve. Twenty-nine women (13.3%) who received NVP developed any LEE and one (0.5%) developed severe LEE. Of the 1011 women on non-NVP regimens, 145 (14.3%) developed any LEE and 14 (1.4%) developed severe LEE. There were no maternal deaths. In univariate models, LEE was not significantly associated with CD4+ count > 250 cells/μL or NVP use. In adjusted multivariate models, no significant increased risk of LEE (any or severe) in women taking NVP was detected as compared to those taking other ART regardless of prior exposure history.
Conclusions
We did not observe an increased risk of hepatotoxicity among HIV-infected pregnant women on NVP versus other ART, including women who were ART naïve.
doi:10.1097/QAD.0b013e3283323941
PMCID: PMC3388940  PMID: 19926957
AIDS; antiretroviral therapy; hepatotoxicity; HIV; nevirapine; pregnancy; women
19.  A Novel Expression of Exercise Induced Pulmonary Hypertension in Human Immunodeficiency Virus Patients: A Pilot Study 
Background:
Patients with the human immunodeficiency virus (HIV) are at risk for multiple pulmonary complications including pulmonary hypertension. Exercise induced pulmonary hypertension (EIPH) has been previously described in patients with scleroderma, sickle cell disease and chronic obstructive pulmonary disease, yet has not been associated with the HIV population.
Methods:
A prospective case-control study design was implemented. Four HIV patients with unexplained dyspnea and four healthy controls underwent symptom-limited stationary bicycle exercise. Transthoracic Doppler Echocardiography was used to measure tricuspid regurgitation velocity which was used to calculate the right ventricular to right atrial pressure (RV-RA) gradient at rest and at peak exercise using the simplified Bernoulli’s equation. Change in RV-RA gradient between rest and peak exercise was calculated and considered to represent change in pulmonary arterial systolic pressure.
Results:
The mean age was 41.25 years (±8.7) for patients and 33.5 years (±6.0) for controls. The mean CD4 count of patients was 191.5 cells/μL (±136.2). Patients had a significantly higher increase in RV-RA gradient as compared to controls (180.2% vs. 27.5%, p = 0.03).
Discussion:
This pilot study suggests that it is feasible to use recumbent bicycle and transthoracic Doppler echocardiography for the evaluation of EIPH among HIV patients with dyspnea of unknown etiology. The study is too small to draw any broad conclusion. Further evaluation of this concept with a larger study is warranted.
doi:10.2174/1874192401206010044
PMCID: PMC3339433  PMID: 22550549
Human immunodeficiency virus (HIV); pulmonary hypertension; exercises induced pulmonary hypertension.
20.  Comparison of the Diversity of the Vaginal Microbiota in HIV-infected and -uninfected women with and without Bacterial Vaginosis 
The Journal of infectious diseases  2008;198(8):1131-1140.
Background
This study investigated whether HIV-infection is associated with a change in diversity of genital microbiota in women.
Methods
Amplicon length heterogeneity PCR (LH-PCR) and pyrosequencing of the 16S rRNA gene were used to analyze diversity of the microbiota from HIV-positive (HIV+) and HIV-negative (HIV-) women with or without bacterial vaginosis (BV).
Results
LH-PCR analysis showed significantly more diversity in BV-positive (BV+) women than in BV-negative (BV-) women, but no significant difference between HIV+ women and HIV- women. Pyrosequencing revealed that Lactobacillus constituted a median of 96% of the bacteria in BV- women. BV+ women had a significantly higher number of taxa found at ≥ 1% of the microbiota (median of 11). Common taxa in BV were Prevotella, Megasphaera, Gardnerella, Coriobacterineae, Lachnospira, and Sneathia. There was a trend (p=0.07) toward a higher number of taxa in HIV+BV+ compared to HIV-BV+ women. Propionibacterineae, Citrobacter and Anaerococcus were found only in HIV+ women (p<0.05).
Conclusions
This study showed that both LH-PCR and pyrosequencing differentiated BV+ from BV- microbiota and that pyrosequencing indicated a trend toward increased diversity in BV+HIV+ suggesting that HIV-infection is associated with changes in diversity of genital microbiota.
doi:10.1086/591942
PMCID: PMC2800037  PMID: 18717638
HIV infection; Microbiota; Bacteria; Pyrosequencing; Diversity; Bacterial Vaginosis; Lactobacillus
21.  Positive association between HIV RNA and IL-6 in the genital tract of Rwandan Women 
Infections and inflammation in the genital tract can influence HIV expression or HIV susceptibility. The goal of this study was to determine if significant relationships exist between cytokines and HIV in genital tract secretions from 57 HIV-seropositive Rwandan women. Genital tract secretions were obtained by cervicovaginal lavage (CVL). Ten different cytokines in CVL were measured by multiplex Cytometric Bead Arrays. HIV RNA in CVL and plasma were measured by quantitative PCR. In univariate analysis, genital tract HIV RNA was significantly associated with plasma HIV RNA and several of the cytokines, while in multivariate analysis, genital tract HIV RNA was only significantly associated with plasma HIV RNA and IL-6. This association of IL-6 with HIV RNA levels suggests that IL-6 is an indicator for conditions that induce HIV expression and that IL-6 may contribute to induction of HIV expression in the genital tract.
doi:10.1089/aid.2008.0004
PMCID: PMC2792594  PMID: 18671479
22.  Awareness of Hepatitis C Infection Among Women With and At Risk for HIV 
Journal of General Internal Medicine  2007;22(12):1689-1694.
BACKGROUND
Treatment guidelines recommend all HIV/HCV-co-infected persons be considered for hepatitis C virus (HCV) treatment, yet obstacles to testing and accessing treatment for HCV continue for women.
OBJECTIVE
To assess awareness of HCV, and describe diagnostic referrals and HCV treatment among women in the Women’s Interagency HIV Study (WIHS).
DESIGN
Prospective epidemiologic cohort.
PARTICIPANTS
Of 3,768 HIV-infected and uninfected women in WIHS, 1,166 (31%) were HCV antibody positive.
MEASUREMENTS AND MAIN RESULTS
Awareness of HCV infection and probability of referrals for diagnostic evaluations and treatment using logistic regression. Follow-up HCV information was available for 681 (390 died, 15 withdrew, 80 missed visit) in 2004. Of these 681, 522 (76.7%) reported knowing their HCV diagnosis. Of these, 247 of 522 (47.3%) stated their providers recommended a liver biopsy, whereas 139 of 247 or 56.3% reported having a liver biopsy. A total of 170 of 522 (32.6%) reported being offered treatment and 74.1% (n = 126 of 170) reported receiving HCV treatment. In multivariate regression analyses, African-American race, Hispanic/Latina ethnicity, poverty, and current crack/cocaine/heroin use were negatively associated with treatment referrals, whereas elevated alanine aminotransferase (ALT) was associated with increased likelihood of referral and increased likelihood of treatment.
CONCLUSION
One quarter of women with HCV in this cohort were not aware of their diagnosis. Among those aware of their HCV, 1 in 4 received liver biopsy and treatment for HCV. Both provider and patient education interventions regarding HCV testing and HCV treatment options and guidelines are needed to enhance HCV awareness and participation in HCV evaluation and treatment.
doi:10.1007/s11606-007-0395-x
PMCID: PMC2219830  PMID: 17924170
women; hepatitis C; HIV; race; drug use; therapy

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