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Michael T Yin,
Qiuhu Shi,
Donald R Hoover,
Kathryn Anastos,
Anjali Sharma,
Mary Young, Alexandra Levine,
Mardge H Cohen,
Elizabeth Shane,
Elizabeth T Golub,
Phyllis C Tien
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ABSTRACT: The clinical importance of the association of HIV infection and antiretroviral therapy (ART) with low bone mineral density (BMD) in premenopausal women is uncertain because BMD stabilizes on established ART and fracture data are limited.
We measured time to first new fracture at any site with median follow-up of 5.4 years in 2391 (1728 HIV-infected, 663 HIV-uninfected) participants in the Women's Interagency HIV Study (WIHS). Self-report of fracture was recorded at semiannual visits. Proportional hazard models assessed predictors of incident fracture.
At baseline, HIV-infected women were older (40 ± 9 vs. 36 ± 10 years, P < 0.0001), more likely to report postmenopausal status and be hepatitis C virus-infected, and weighed less than HIV-uninfected women. Among HIV-infected women, mean CD4(+) cell count was 482 cells/μl; 66% were taking ART. Unadjusted incidence of fracture did not differ between HIV-infected and uninfected women (1.8 vs. 1.4/100 person-years, respectively, P = 0.18). In multivariate models, white (vs. African-American) race, hepatitis C virus infection, and higher serum creatinine, but not HIV serostatus, were statistically significant predictors of incident fracture. Among HIV-infected women, older age, white race, current cigarette use, and history of AIDS-defining illness were associated with incidence of new fracture.
Among predominantly premenopausal women, there was little difference in fracture incidence rates by HIV status, rather traditional risk factors were important predictors. Further research is necessary to characterize fracture risk in HIV-infected women during and after the menopausal transition.
AIDS (London, England) 11/2010; 24(17):2679-86. · 4.91 Impact Factor
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Nancy A Hessol,
Laura A Napolitano,
Dawn Smith,
Yolanda Lie, Alexandra Levine,
Mary Young,
Mardge Cohen,
Howard Minkoff,
Kathryn Anastos,
Gypsyamber D'Souza,
Ruth M Greenblatt,
James J Goedert
[show abstract]
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ABSTRACT: During the first two decades of the U.S. AIDS epidemic, and unlike some malignancies, breast cancer risk was significantly lower for women with human immunodeficiency virus (HIV) infection compared to the general population. This deficit in HIV-associated breast cancer could not be attributed to differences in survival, immune deficiency, childbearing or other breast cancer risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection.
We conducted a breast cancer nested case-control study among women who participated in the WIHS and HERS HIV cohort studies with longitudinally collected risk factor data and plasma. Cases were HIV-infected women (mean age 46 years) who had stored plasma collected within 24 months of breast cancer diagnosis and an HIV viral load≥500 copies/mL. Three HIV-infected control women, without breast cancer, were matched to each case based on age and plasma collection date. CXCR4-tropism was determined by a phenotypic tropism assay. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer were estimated by exact conditional logistic regression. Two (9%) of 23 breast cancer cases had CXCR4-tropic HIV, compared to 19 (28%) of 69 matched controls. Breast cancer risk was significantly and independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95% CI 0.002-0.84) and with menopause (adjusted odds ratio, 0.08, 95% CI 0.001-0.83). Adjustment for CD4+ cell count, HIV viral load, and use of antiretroviral therapy did not attenuate the association between infection with CXCR4-tropic HIV and breast cancer.
Low breast cancer risk with HIV is specifically linked to CXCR4-using variants of HIV. These variants are thought to exclusively bind to and signal through a receptor that is commonly expressed on hyperplastic and neoplastic breast duct cells. Additional studies are needed to confirm these observations and to understand how CXCR4 might reduce breast cancer risk.
PLoS ONE 01/2010; 5(12):e14349. · 4.09 Impact Factor
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Chenglong Liu,
Yang Yang,
Stephen J Gange,
Kathleen Weber,
Gerald B Sharp,
Tracey E Wilson, Alexandra Levine,
Esther Robison,
Lakshmi Goparaju,
Monica Gandhi,
Monica Ganhdi,
Dan Merenstein
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ABSTRACT: To determine prevalence and predictors of complementary and alternative medicine (CAM) use disclosure to health care providers and whether CAM use disclosure is associated with highly active antiretroviral therapy (HAART) adherence among HIV-infected women, we analyzed longitudinal data collected between October 1994 and March 2002 from HIV-infected CAM-using women enrolled in the Women's Interagency HIV Study. Repeated measures Poisson regression models were constructed to evaluate associations of selected predictors with CAM use disclosure and association between CAM use disclosure and HAART adherence. A total of 1,377 HIV-infected women reported CAM use during study follow-up and contributed a total of 4,689 CAM-using person visits. The overall prevalence of CAM use disclosure to health care providers was 36% across study visits. Women over 45 years old, with a college education, or with health insurance coverage were more likely to disclose their CAM use to health care providers, whereas women identified as non-Hispanic Black or other ethnicities were less likely to communicate their CAM usage. More health care provider visits, more CAM domains used, and higher health care satisfaction scores had significant relationships with increased levels of CAM use disclosure. Restricting analysis to use of herbal or nonherbal medications only, similar results were obtained. Compared to other CAM domains, mind-body practice had the lowest prevalence of CAM use disclosure. Additionally, CAM use disclosure was significantly associated with higher HAART adherence. From this study, we showed that a high percentage of HIV-infected women did not discuss their CAM use with health care providers. Interventions targeted towards both physicians and patients may enhance communication of CAM use, avoid potential adverse events and drug interactions, and enhance HAART adherence.
AIDS patient care and STDs 10/2009; 23(11):965-71. · 2.68 Impact Factor
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ABSTRACT: Hepatitis C virus (HCV) infection is associated with the development of hepatocellular carcinoma and probably also non-Hodgkin's B-cell lymphoma. The molecular mechanisms of HCV-associated carcinogenesis are unknown. Here we demonstrated that peripheral blood mononuclear cells obtained from hepatitis C patients and hepatocytes infected with HCV in vitro showed frequent chromosomal polyploidy. HCV infection or the expression of viral core protein alone in hepatocyte culture or transgenic mice inhibited mitotic spindle checkpoint function because of reduced Rb transcription and enhanced E2F-1 and Mad2 expression. The silencing of E2F-1 by RNA interference technology restored the function of mitotic checkpoint in core-expressing cells. Taken together, these data suggest that HCV infection may inhibit the mitotic checkpoint to induce polyploidy, which likely contributes to neoplastic transformation.
Journal of Virology 09/2009; 83(23):12590-600. · 5.40 Impact Factor
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ABSTRACT: To assess trends in mortality and cause of death for women with HIV, we studied deaths over a 10-year period among participants in the Women's Interagency HIV Study, a representative US cohort.
Deaths were ascertained by National Death Index Plus match, and causes of death determined by death certificate.
From 1995 through 2004, 710 of 2792 HIV-infected participants died. During this interval, the standardized mortality ratio fell from a high of 24.7 in 1996 to a plateau with a mean of 10.3 from 2001 to 2004. Over the decade, deaths from non-AIDS causes increased and accounted for the majority of deaths by 2001-2004. The most common non-AIDS causes of death were trauma or overdose, liver disease, cardiovascular disease, and malignancy. Independent predictors of mortality besides HIV-associated variables were depressive symptoms and active hepatitis B or C. Women who were overweight or obese were significantly less likely to die of AIDS than women of normal weight.
In the Women's Interagency HIV Study, the death rate has plateaued in recent years. Although HIV-associated factors predicted AIDS and non-AIDS deaths, other treatable conditions predicted mortality. Further gains in reducing mortality among HIV-infected women may require broader access to therapies for depression, viral hepatitis, and HIV itself.
JAIDS Journal of Acquired Immune Deficiency Syndromes 06/2009; 51(4):399-406. · 4.43 Impact Factor
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Monica Gandhi,
Niloufar Ameli,
Peter Bacchetti,
Stephen J Gange,
Kathryn Anastos, Alexandra Levine,
Charles L Hyman,
Mardge Cohen,
Mary Young,
Yong Huang,
Ruth M Greenblatt
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ABSTRACT: Antiretroviral (ARV) therapies fail when behavioral or biologic factors lead to inadequate medication exposure. The currently available methods to assess ARV exposure are limited. Levels of ARVs in hair reflect plasma concentrations over weeks to months, and may provide a novel method for predicting therapeutic responses.
The Women's Interagency HIV Study, a prospective cohort of HIV-infected women, provided the basis for developing and assessing methods to measure commonly prescribed protease inhibitors (lopinavir/ritonavir and atazanavir) in small hair samples. We examined the association between hair protease inhibitor levels and initial virologic responses to therapy in multivariate logistic regression models.
ARV concentrations in hair were strongly and independently associated with treatment response for 224 women starting a new protease inhibitor-based regimen. For participants initiating lopinavir/ritonavir, the odds ratio (OR) for virologic suppression was 39.8 [95% confidence interval (CI) = 2.8-564] for those with lopinavir hair levels in the top tertile (>1.9 ng/mg) compared to the bottom (</=0.41 ng/mg) when controlling for self-reported adherence, age, race, starting viral load and CD4 cell count, and prior experience with protease inhibitors. For women starting atazanavir, the adjusted OR for virologic success was 7.7 (95% CI = 2.0-29.7) for those with hair concentrations in the top tertile (>3.4 ng/mg) compared to the lowest (</=1.2 ng/mg).
Protease inhibitor levels in small hair samples were the strongest independent predictor of virologic success in a diverse group of HIV-infected adults. This non-invasive method for determining ARV exposure may have particular relevance for the epidemic in resource-poor settings due to the ease of collecting and storing hair.
AIDS (London, England) 01/2009; 23(4):471-8. · 4.91 Impact Factor
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ABSTRACT: BACKGROUND:: Evidence suggesting an increased risk of cardiovascular disease in HIV-infected individuals has heightened the need to understand the relation of HIV infection, antiretroviral therapy use, and non-HIV-related factors with insulin resistance (IR). METHODS:: Prospective study of 1614 HIV-infected and 604 HIV-uninfected participants from the Women's Interagency HIV Study between October 2000 and March 2007. Homeostasis model assessment (HOMA)-estimated IR at 11,019 semiannual visits. RESULTS:: HIV-infected women reporting highly active antiretroviral therapy (HAART) had higher median HOMA than HIV-uninfected women {1.20 [95% confidence interval (CI): 1.11 to 1.30] times higher for those reporting protease inhibitor-containing HAART; 1.10 (95% CI: 1.01 to 1.20) times higher for those reporting non-protease inhibitor-containing HAART}. Among HIV-infected, cumulative exposure to nucleoside reverse transcriptase inhibitors (NRTIs) of >3 years was associated with HOMA 1.13 (95% CI: 1.02 to 1.25) times higher than the HOMA without any cumulative NRTI exposure. Cumulative exposure to the NRTI stavudine of >1 year was associated with HOMA 1.15 (95% CI: 1.05 to 1.27) times higher than the HOMA without any cumulative stavudine use. Family history of diabetes, hepatitis C virus seropositivity, higher body mass index, or reporting menopause was associated with higher HOMA. CONCLUSIONS:: Longer cumulative exposure to NRTI; in particular, stavudine is associated with greater IR in HIV-infected women.
JAIDS Journal of Acquired Immune Deficiency Syndromes 10/2008; · 4.43 Impact Factor
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The Journal of Alternative and Complementary Medicine 01/2008; 13(10):1053-6. · 1.59 Impact Factor
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Victor R Gordeuk,
Gladys Onojobi,
Michael F Schneider,
Fitzroy W Dawkins,
Robert Delapenha,
Yaroslav Voloshin,
Victor von Wyl,
Melanie Bacon,
Howard Minkoff, Alexandra Levine,
Mardge Cohen,
Ruth M Greenblatt
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ABSTRACT: Whether degree of iron stores influences progression of human immunodeficiency virus (HIV) disease is controversial. We studied the relationship of indirect measures of iron stores with mortality in highly active antiretroviral therapy (HAART)-naive participants from the Women's Interagency HIV Study.
One hundred and fifty-eight HIV-infected women who died before July 1996 were individually matched by CD4+ cell count (within +/- 50 cells/mL) and HIV RNA level (within +/- 0.50 log10 copies/mL) to 154 controls. Serum ferritin and transferrin receptor concentrations were measured in 151 pairs of women. Results. Using multivariable conditional logistic regression models that were adjusted for self-reported antiretroviral therapy use, age, smoking status, ethnicity, hemoglobin concentration, C-reactive protein and aspartate amino transferase, a log10 increase in baseline serum ferritin concentration was associated with a 1.67-fold increase in the odds of death (95% CI: 0.98, 2.86) and a one-unit decrease in transferrin receptor to log10 ferritin ratio was associated with a 1.12-fold (95% CI: 1.01, 1.23) increase in the odds of death.
In this study, higher indirect measures of iron status were associated with reduced survival among HAART-naive HIV-infected women. Additional prospective studies with data on direct measures of iron status along with randomized trials are needed to elucidate the current equipoise over whether iron supplementation is beneficial by preventing anemia or harmful by increasing iron stores in HIV-infected women.
Haematologica 07/2006; 91(6):739-43. · 6.42 Impact Factor
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Monica Gandhi,
Niloufar Ameli,
Peter Bacchetti,
Gerald B Sharp,
Audrey L French,
Mary Young,
Stephen J Gange,
Kathryn Anastos,
Susan Holman, Alexandra Levine,
Ruth M Greenblatt
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ABSTRACT: Applicability of randomized controlled clinical trial (RCT) results to 'real world' situations is dependent on the comparability of trial participants to general patient populations. A full disclosure of criteria employed for trial enrollment is necessary for clinicians to assess generalizability. We sought to assess both the impact on generalizability and the disclosure rate of enrollment criteria for 32 major HIV RCTs in the AIDS Clinical Trial Group (ACTG) and Community Programs for Clinical Research on AIDS (CPCRA) trial networks.
Eligibility criteria were compared in complete protocols to criteria listed in publications from these 32 NIH-funded HIV RCTs. We then applied these criteria to the Women's Interagency HIV Study (WIHS), the largest cohort study of HIV-infected women in the US.
When applied to WIHS, eligibility criteria from protocols excluded 0-67.6% (median 42%) of WIHS participants (50.6% excluded from ACTG trials). Eligibility criteria in publications excluded 0-62% (median 19.6%) of WIHS (21.2% excluded from ACTG trials). The number of women in WIHS seemingly ineligible for trial participation per enrollment criteria listed in publications averaged only 60% of those actually excluded based on the protocols.
We found that HIV RCT eligibility criteria excluded a large proportion of a representative cohort of HIV-infected women from trial participation. Furthermore, trial publications are not fully reflective of protocols in terms of disclosing eligibility criteria. Standardization and full disclosure of trial methodology will allow clinicians and researchers to more fully assess the generalizability of findings to their patient populations.
AIDS 12/2005; 19(16):1885-96. · 6.24 Impact Factor
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L Stewart Massad,
Charlesnika T Evans,
Howard D Strickler,
Robert D Burk,
D Heather Watts,
Lorraine Cashin,
Teresa Darragh,
Stephen Gange,
Yi-Chun Lee,
Michael Moxley, Alexandra Levine,
Douglas J Passaro
[show abstract]
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ABSTRACT: To estimate the risk of and risk factors for progression among human immunodeficiency virus (HIV)-seropositive women with abnormal cervical cytology but negative colposcopy.
In a prospective cohort study, 391 HIV-seropositive and 103 seronegative women with cervical cytology read as atypical squamous cells (ASC) or low-grade squamous intraepithelial lesion (LSIL) but negative colposcopy were followed up for a mean of 4.0 years with cytology at 6-month intervals. Colposcopy was prescribed for any epithelial abnormality.
Progression to CIN2, CIN3, high-grade SIL/severe dysplasia, or cancer occurred in 47 (12%) HIV-seropositive women and 4 (4%) HIV-seronegative women (P = .02). Progression to CIN1 was seen in an additional 12 HIV-seropositive women and 1 seronegative woman. In multivariate analysis, high-risk but not low-risk HPV detection (hazard ratio [HR] 2.46-95% confidence interval [CI] 1.18-5.12, P = .02 for high risk, HR 1.41, 95% CI 0.62-3.21, P = .42 for low risk), satisfactory colposcopy (HR 2.01, 95% CI 1.11-3.65, P = .02), and non-Hispanic African-American ethnicity (HR 5.08, 95% CI 1.72-14.98, P = .003) were the only factors associated with progression, while HIV serostatus was marginally significant (HR 2.53, 95% CI 0.85-7.50, P = .09).
Human immunodeficiency virus-seropositive women with negative colposcopy after borderline cytology face a higher risk of progression than seronegative women, but the absolute risk is low and becomes nonsignificant after controlling for HPV risk type, ethnicity, and colposcopic findings. Observation is appropriate.
II-2.
Obstetrics and Gynecology 10/2005; 106(3):525-32. · 4.73 Impact Factor
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ABSTRACT: To determine the association of race with clinical and laboratory outcomes after initiation of highly active antiretroviral therapy (HAART) in HIV-1-infected women in the United States.
Prospective cohort study.
A total of 961 HIV-1-infected women participating in the Women's Interagency HIV Study initiating HAART between July 1, 1995 and September 30, 2003.
Over a median of 5.1 years of follow-up, in univariate Cox regression analyses, white women were more likely than African American women to attain a virologic response (relative hazard [RH]=1.34, P=0.005), less likely to experience viral rebound (RH=0.76, P=0.051), and less likely to die (RH=0.63, P=0.040). There were no significant differences, however, among racial groups in outcomes after adjustment for pre-HAART CD4, HIV-1 RNA, history of AIDS-defining illness, age, antiretroviral therapy use, baseline HIV-1 exposure category, and post-HAART behavioral and clinical variables associated with poorer response (discontinuation of HAART, lower income, smoking, current drug use, and depression). Continuous HAART use and lack of depression differed by race and were the strongest predictors of favorable outcomes.
No significant differences by race were found in virologic, immunologic, or clinical outcomes after adjustment for continued HAART use and depression. These findings suggest that strategies to enhance HAART continuation, including assessing pharmacogenetic influences that may result in greater toxicity and discontinuation rates, and treating depression can improve individual and population-based effects of treatment and potentially mitigate racial disparities in AIDS-related outcomes.
JAIDS Journal of Acquired Immune Deficiency Syndromes 09/2005; 39(5):537-44. · 4.43 Impact Factor
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ABSTRACT: With fewer patients now succumbing to infectious complications of AIDS, other HIV-related morbidities such as malignancies have become increasingly important. Apart from Kaposi's sarcoma, non-Hodgkin's lymphoma, and cervical cancer, which are considered as AIDS-defining, several additional cancers, referred to as non-AIDS-defining cancers, are also statistically increased in HIV-infected persons. These include Hodgkin's disease, anal carcinoma, lung cancer, nonmelanomatous skin cancer, and testicular germ cell tumors, among others. However, the types of cancer observed at an increased frequency and the relative risks reported vary widely among studies. Although immunosuppression is consistently associated with an increased risk of AIDS-related malignancies, the role of immunosuppression in the pathogenesis of non-AIDS- defining cancers is controversial. Although data regarding the optimal management of these cancers are lacking, current studies suggest that patients with HIV-associated malignancies should be treated with similar approaches to those of their counterparts in the general population.
Current Infectious Disease Reports 06/2005; 7(3):227-234.
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ABSTRACT: The role of hormonal contraceptive use in the effectiveness of highly active antiretroviral therapy (HAART) was examined among participants in the Women's Interagency HIV Study who were followed from HAART initiation to 2001. Propensity score selection was used to match 77 hormonal contraceptive users with 77 nonusers on age, race, and pre-HAART CD4-positive T-lymphocyte (CD4+ cell) count and viral load. The authors compared hormonal contraceptive users and nonusers with regard to the CD4+ cell count and viral load responses to HAART upon initiation. Proportional hazards analyses were used to assess the effect of hormonal contraceptive use on times to increases in CD4+ cell count of 50 cells/mm(3) and 100 cells/mm(3) and achievement of an undetectable viral load. There were no statistically significant differences in CD4+ cell counts and log viral load responses by hormone use after HAART initiation, except in log viral load at the third visit after initiation (p = 0.047). Time-dependent hormonal contraceptive use was not a statistically significant predictor of achieving increases in CD4+ cell count of 50 cells/mm(3) and 100 cells/mm(3) or an undetectable viral load (p = 0.517, p = 0.751, and p = 0.218, respectively) after HAART initiation. In conclusion, the authors did not find substantial evidence that use of hormonal contraceptives strongly affected responses to HAART.
American Journal of Epidemiology 06/2005; 161(9):881-90. · 5.22 Impact Factor
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ABSTRACT: We sought to estimate rates of progression and regression of grade 1 cervical intraepithelial neoplasia (CIN 1) among women with human immunodeficiency virus (HIV).
In a multicenter prospective cohort study, HIV-seropositive and HIV-seronegative women were evaluated colposcopically after receiving an abnormal cytology test result between November 1994 and September 2002. Women with CIN 1 were included, except those who had undergone hysterectomy, cervical therapy, or had CIN 2-3 or cervical cancer. Those women who were included were followed cytologically twice yearly, with colposcopy repeated for atypia or worse.
We followed 223 women with CIN 1 (202 HIV seropositive and 21 HIV seronegative) for a mean of 3.3 person-years. Progression occurred in 8 HIV-seropositive women (incidence density, 1.2/100 person-years; 95% confidence interval [CI] 0.5-2.4/100 person-years) and in no HIV seronegative women. Regression occurred in 66 (33%) HIV-seropositive women (13/100 person-years, 95% CI 10-16/100 person-years) versus 14 (67%) seronegative women (32/100 person-years, relative risk 0.40, 95% CI 0.25-0.66; P < .001). In multivariate analysis, regression was associated with human papillomavirus (HPV) detection (hazard ratio [HR] for low risk 0.28, 95% CI 0.13-0.61, P = .001; and for high-risk 0.34, 95% CI 0.20-0.55, P < .001 versus no HPV detected) and Hispanic ethnicity (HR 0.48, 95% CI 0.230.98; P = .04); HIV serostatus was only marginally linked to regression (HR 0.52, 95% CI 0.27-1.03; P = .06), but seropositive women were less likely to regress when analysis was limited to 146 women with HPV detected at CIN 1 diagnosis (HR 0.18, 95% CI 0.05-0.62; P = .006).
Grade 1 cervical intraepithelial neoplasia infrequently progresses in women with HIV. Thus, observation appears safe absent other indications for treatment.
II-1.
Obstetrics and Gynecology 12/2004; 104(5 Pt 1):1077-85. · 4.73 Impact Factor
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ABSTRACT: We assessed the association between initiation of highly active antiretroviral treatment (HAART) regimens and sexual risk behaviors among HIVinfected women.
We analyzed data from 724 women who initiated HAART between January 1996 and January 2001 and who had pre-HAART viral loads at or above 400 copies per milliliter.
Sexually active women were less likely (odds ratio [OR] = 0.79) to report 2 or more partners during a 6-month period after HAART initiation than before HAART initiation. However, the risk for unprotected sex was higher after HAART initiation than before HAART initiation among all sexually active women (both those who reported 2 or more partners [OR = 1.84] and those who reported 1 partner [OR = 1.22]).
Sexual risk behaviors are associated with receipt of therapy but not with therapeutic response, indicating a risk for transmission among female HAART recipients.
American Journal of Public Health 08/2004; 94(7):1141-6. · 3.93 Impact Factor
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ABSTRACT: Background. Smoking may increase the risk of cervical cancer, a disease that is related to human papillomavirus (HPV) infection. However, the effects of smoking on the natural history of HPV are poorly understood, especially in women coinfected with human immunodeficiency virus (HIV).Methods. HIV-infected (n=1797) and HIV-uninfected (n=496) women were assessed every 6 months for type-specific HPV DNA. Smoking status was self-reported. Covariates included age, parity, sexual behavior, HIV load, CD4(+) T cell count, and antiretroviral therapy.Results. Smoking was positively associated with HPV prevalence at baseline in HIV-infected women (P=.002) and was significantly associated with type-specific HPV detection (e.g., type 18, odds ratio [OR], 2.45; 95% confidence interval [CI], 1.86-3.22). In Cox models, detection of HPV was significantly associated with smoking in HIV-infected women (relative hazard [RH], 1.33; 95% CI, 1.10-1.60; P=.003), but HPV persistence was not (RH, 0.97; 95% CI, 80-1.16; P=.72). The overall likelihood of acquiring persistent HPV was higher in smokers (OR, 1.39; 95% CI, 1.05-1.86; P=.023) because of greater incidence.Conclusions. Among HIV-infected women, smoking is associated with a significantly higher prevalence and incidence of HPV infection. Smoking during HIV infection may alter the natural history of HPV infection and increase the risk of cervical disease.
The Journal of Infectious Diseases 06/2004; 189(10):1821-8. · 6.41 Impact Factor
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ABSTRACT: Total lymphocyte count (TLC) and hemoglobin level have been suggested as useful and inexpensive parameters to indicate need for HAART in settings in which CD4 cell counts are unavailable. If delayed-type hypersensitivity (DTH) response predicts clinical response in persons using highly active antiretroviral therapy (HAART), it may also prove useful in resource-poor settings.
To examine whether TLC, hemoglobin, and DTH response observed prior to initiation of HAART predict post-HAART clinical response.
Prospective cohort study.
873 women in the Women's Interagency HIV Study.
TLC, hemoglobin, CD4 cell counts, and DTH testing using mumps, candida, and tetanus toxoid antigens, performed within 1 year prior to HAART initiation; death; self-report of initiation of HAART use and AIDS-defining illness (ADI).
Three different multivariate analyses were performed: 2 models that excluded CD4 cell count and assessed TLC at either < 850 or < 1250 cells/microL, and 1 model that excluded TLC and included CD4 < 200 cells/microL. TLC < 850, TLC < 1250, CD4 < 200 cells/microL, anergy to DTH testing, hemoglobin < 10.6 g/dL, and a pre-HAART report of ADI were each consistently independently associated both with death and with incident ADI. Log likelihood chi2 values suggested similar power among the 3 models in predicting both death and incident ADI.
Pre-HAART TLC, hemoglobin level, anergy to DTH testing, and clinical disease each independently predicted morbidity and death after HAART initiation. These findings support the use of TLC to guide decision-making for HAART initiation and suggest that further study of TLC, hemoglobin level, and DTH responses as an indication to provide HAART may be useful in resource-limited settings.
JAIDS Journal of Acquired Immune Deficiency Syndromes 05/2004; 35(4):383-92. · 4.43 Impact Factor
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ABSTRACT: The prognostic value of CD4+ cell counts and HIV-1 RNA levels attained after the initiation of highly active antiretroviral therapy (HAART) compared with before the initiation of HAART has not been well defined.
To determine the prognostic value for clinical outcomes of CD4+ cell counts and HIV-1 RNA levels attained after initiating therapy.
Prospective cohort study.
Women's Interagency HIV Study.
1132 participants in the Women's Interagency HIV Study.
HIV-1 RNA level, CD+ cell counts, AIDS-defining illness, and death.
In multivariate analyses with a median follow-up of 3.9 years, women with CD4+ cell counts of less than 0.200 x 10(9) cells/L compared with women with CD4+ cell counts of greater than 0.350 x 10(9) cells/L after HAART initiation had a relative hazard of death from all causes of 2.66 (95% CI, 1.42 to 4.99) and a relative hazard of death from AIDS of 47.61 (CI, 5.69 to 398.40). The relative hazard of all-cause death was 3.44 (CI, 1.67 to 7.09) in women with RNA levels of more than 10 000 copies/mL compared with women with attained RNA levels of less than 80 copies/mL. The relative hazard of AIDS-related or all-cause death did not increase for women with post-HAART CD4+ cell counts between 0.200 and 0.350 x 10(9) cells/L compared with women with CD4+ cell counts of greater than 0.350 x 10(9) cells/L. Also, the relative hazard did not increase in women with post-HAART HIV-1 RNA levels between 80 and 10 000 copies/mL compared with women with post-HAART HIV-1 RNA levels of less than 80 copies/mL. Of the laboratory markers, only the post-HAART CD4+ cell count and HIV-1 RNA level were predictive of new AIDS-defining illness.
Post-HAART laboratory markers predicted death and new AIDS-defining illness. Pre-HAART CD4+ cell count and HIV-1 RNA level were not predictive of clinical outcomes if adjusted for values attained after HAART initiation, suggesting that even advanced immune suppression can be overcome with HAART that results in CD4+ cell counts of greater than 0.200 x 10(9) cells/L and RNA levels of less than 10 000 copies/mL.
Annals of internal medicine 03/2004; 140(4):256-64. · 16.73 Impact Factor
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Raphael P Viscidi,
Linda Ahdieh-Grant,
Michael F Schneider,
Barbara Clayman,
L Stewart Massad,
Kathryn M Anastos,
Robert D Burk,
Howard Minkoff,
Joel Palefsky, Alexandra Levine,
Howard Strickler
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ABSTRACT: Serum samples from 2008 human immunodeficiency virus (HIV)-positive and 551 HIV-negative women were tested for immunoglobulin A (IgA) to human papillomavirus (HPV) type 16 capsids. IgA seropositivity was lower than previously reported IgG seropositivity (7% vs. 51%), but, like IgG antibodies, HPV 16 IgA was associated with sexual behavior, cervicovaginal HPV 16 DNA, and cytological abnormalities. IgA seropositivity was higher in HIV-positive women than in HIV-negative women (7.7% vs. 4.9%; P=.02), but the association was lost after adjustment for HPV 16 cervicovaginal infection. IgA, but not IgG, seropositivity was associated with progression to high-grade cytological abnormalities (relative hazard [RH], 2.2 [95% confidence interval, 1.2-4.2]), raising the possibility that an IgA response to HPV 16, as described for other DNA viruses, may be a marker of persistent viral replication. The risk of incident infection with non-16-related HPV types was increased in IgA seropositive women (RH, 1.8 [95% confidence interval, 1.3-2.6]), compared with seronegative women (RH, 2.2 [95% confidence interval, 0.9-5.4]), but there was no difference in the risk of incident HPV 16 or HPV 16-related infections. This may be evidence of partial type-specific or clade-specific immunity conferred by seropositivity to HPV 16 capsids.
The Journal of Infectious Diseases 01/2004; 188(12):1834-44. · 6.41 Impact Factor
