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Annals of internal medicine 11/2002; 137(8):696-7. · 16.73 Impact Factor
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Kathryn Anastos,
Yolanda Barrón,
Paolo Miotti,
Barbara Weiser,
Mary Young,
Nancy Hessol, Ruth M Greenblatt,
Mardge Cohen,
Michael Augenbraun,
Alexandra Levine,
Alvaro Muñoz
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ABSTRACT: The optimal virologic and immunologic stage at which to initiate antiretroviral therapy in individuals infected with human immunodeficiency virus type 1 (HIV-1) is undefined.
Among 1054 HIV-1-infected women in a prospective cohort study, we determined the time from initiation of highly active antiretroviral treatment (HAART) to acquired immunodeficiency syndrome (AIDS) and death.
Median follow-up was 3.4 years. Of 553 women without AIDS at HAART initiation, 62 (11%) developed AIDS. Compared with women with CD4(+) cell counts greater than 350/microL at HAART initiation, women with cell counts of 200 to 350/microL and less than 200/microL had relative hazards (RHs) for progression to AIDS of 0.93 (95% confidence interval [CI], 0.46-1.86) and 2.48 (95% CI, 1.39-4.42), respectively. Compared with those with HIV-1 RNA values less than 5000 copies/mL, women with 5000 to 50,000 copies/mL and greater than 50,000 copies/mL had RHs of 1.39 (95% CI, 0.74-2.64) and 2.09 (95% CI, 1.09-3.99), respectively. Among women with AIDS at HAART initiation (n = 501), RHs of death were 1.97 (95% CI, 0.84-4.66) and 3.35 (95% CI, 1.59-7.08) with CD4(+) cell counts of 200 to 350/microL and less than 200/microL, respectively, relative to those with greater than 350/microL, and 1.90 (95% CI, 0.84-4.30) and 3.70 (95% CI, 1.81-7.54) for those with HIV-1 RNA values of 5000 to 50,000 and greater than 50,000 copies/mL, respectively, relative to those with less than 5000 copies/mL.
Progression to AIDS and death was predicted by pre-HAART values of less than 200/microL for CD4(+) cells and greater than 50,000 HIV-1 RNA copies/mL, indicating that deferral of HAART until the CD4(+) cell count is between 350 and 200/microL is a valid strategy in the clinical management of HIV-1 infection.
Archives of Internal Medicine 10/2002; 162(17):1973-80. · 11.46 Impact Factor
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ABSTRACT: We undertook a critical epidemiological review of the available evidence concerning whether women have lower levels of human immunodeficiency virus (HIV) RNA than do men at similar stages of HIV infection. The 13 studies included in this analysis reported viral load measurements in HIV-infected men and women at a single point in time (cross-sectional studies) or over time (longitudinal studies). Seven of the 9 cross-sectional studies demonstrated that women had 0.13-0.35 log(10) ( approximately 2-fold) lower levels of HIV RNA than do men, despite controlling for CD4(+) cell count. Four longitudinal studies revealed that women had 0.33-0.78 log(10) (2- to 6-fold) lower levels of HIV RNA than do men, even when controlling for time since seroconversion. Adjustment for possible confounders of the relationship between sex and viral load, including age, race, mode of virus transmission, and antiretroviral therapy use, did not change this outcome. This finding is significant, because viral loads are frequently used to guide the initiation and modification of antiretroviral therapy.
Clinical Infectious Diseases 09/2002; 35(3):313-22. · 9.15 Impact Factor
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Michael J Silverberg,
Linda Ahdieh,
Alvaro Munoz,
Kathryn Anastos,
Robert D Burk,
Susan Cu-Uvin,
Ann Duerr, Ruth M Greenblatt,
Robert S Klein,
Stewart Massad,
Howard Minkoff,
Laila Muderspach,
Joel Palefsky,
Eva Piessens,
Paula Schuman,
Heather Watts,
Keerti V Shah
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ABSTRACT: HIV infection and associated immunodeficiency are known to alter the course of human papillomavirus (HPV) infections and of associated diseases.
This study investigated the association between HIV and HPV and genital warts.
HPV testing and physical examinations were performed in two large prospective studies: the Women's Interagency HIV Study (WIHS) and the HIV Epidemiology Research Study (HERS). Statistical methods incorporating dependencies of longitudinal data were used to examine the relationship between HIV and HPV and genital warts.
A total of 1008 HIV-seronegative and 2930 HIV-seropositive women were enrolled in the two studies. The prevalence of HPV 6 or 11 was 5.6 times higher in HIV-seropositive women in the WIHS and 3.6 times higher in the HERS. Genital wart prevalence increased by a factor of 3.2 in the WIHS and 2.7 in the HERS in HIV-seropositive women. In the WIHS, infection with HPV type 6 or 11, in comparison with no HPV infection, was associated with odds of genital wart prevalence of 5.1 (95% CI: 2.9-8.8), 8.8 (95% CI: 6.1-12.8), and 12.8 (95% CI: 8.8-18.8) in HIV-seronegative women, HIV-seropositive women with > or =201 CD4 cells/microl, and HIV-seropositive women with < or =200 CD4 cells/microl, respectively. In the HERS, infection with HPV type 6 or 11 was associated with odds of 2.7 (95% CI: 1.6-4.6), 4.9 (95% CI: 3.2-7.7), and 5.3 (95% CI: 3.3-8.5) in these same groups. Other HPV types showed a similar dose-response relation, but of substantially lower magnitude and statistical significance.
HIV infection and immunodeficiency synergistically modified the relation between HPV 6 or 11 infection and genital wart prevalence.
Sex Transm Dis 08/2002; 29(8):427-35. · 2.87 Impact Factor
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ABSTRACT: The purpose of this study was to describe the variability in highly active antiretroviral therapy (HAART) regimens over time, the extent to which individuals switch, and the characteristics of those who are switching.
We evaluated data collected between 1994 and 2000 from 1056 HIV-positive women enrolled in the Women's Interagency HIV Study (WIHS) who reported initiating HAART. We described the variability and prevalence of changes in HAART regimens between semiannual visits, estimated time to switch using Kaplan-Meier methods, investigated factors associated with a first switch using Cox proportional hazards models, and compared disease markers among women switching or remaining on unchanged HAART regimens.
We demonstrated a 13-fold increase in the number of unique HAART regimens reported since mid-1996 and showed that the amount of time spent on the first, second, or third regimen is similar, with an 8-month median time to switching or discontinuing the initial HAART regimen. Women who switched had a lower mean CD4 cell count and were more likely to have HIV RNA levels greater than 400 copies/mL. Overall, the percentage of women switching decreased over the course of follow-up (to 37% in September 2000), although the percentage discontinuing therapy altogether increased 2-fold.
Our findings on the relatively high rate of HAART switching emphasize the complexity of managing and evaluating these therapies.
JAIDS Journal of Acquired Immune Deficiency Syndromes 05/2002; 29(5):495-503. · 4.43 Impact Factor
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ABSTRACT: Objective: The purpose of this study was to describe the variability in highly active antiretroviral therapy (HAART) regimens over time, the extent to which individuals switch, and the characteristics of those who are switching.
Methods: We evaluated data collected between 1994 and 2000 from 1056 HIV-positive women enrolled in the Women's Interagency HIV Study (WIHS) who reported initiating HAART. We described the variability and prevalence of changes in HAART regimens between semiannual visits, estimated time to switch using Kaplan-Meier methods, investigated factors associated with a first switch using Cox proportional hazards models, and compared disease markers among women switching or remaining on unchanged HAART regimens.
Results: We demonstrated a 13-fold increase in the number of unique HAART regimens reported since mid-1996 and showed that the amount of time spent on the first, second, or third regimen is similar, with an 8-month median time to switching or discontinuing the initial HAART regimen. Women who switched had a lower mean CD4 cell count and were more likely to have HIV RNA levels greater than 400 copies/mL. Overall, the percentage of women switching decreased over the course of follow-up (to 37% in September 2000), although the percentage discontinuing therapy altogether increased 2-fold.
Conclusion: Our findings on the relatively high rate of HAART switching emphasize the complexity of managing and evaluating these therapies.
(C) 2002 Lippincott Williams & Wilkins, Inc.
JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2002; 29(5). · 4.43 Impact Factor
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Kathryn Anastos,
Stephen J. Gange,
Bryan Lau,
Barbara Weiser,
Roger Detels,
Janis V. Giorgi,
Joseph B. Margolick,
Mardge Cohen,
John Phair,
Sandra Melnick,
Charles R. Rinaldo,
Andrea Kovacs,
Alexandra Levine,
Sheldon Landesman,
Mary Young,
Alvaro Muñoz, Ruth M. Greenblatt,
for the Women’s Interagency HIV Study
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ABSTRACT: Context: HIV-1 RNA and lymphocyte subset levels are the principal indications for antiretroviral treatment. Past reports have differed with regard to the effect of gender and race on these measures and in measures of disease progression.
Objective: To assess racial and gender differences in HIV-1 RNA levels and CD4+ lymphocyte decline.
Design: A longitudinal study based in the two largest HIV natural history cohort studies conducted in 7 metropolitan areas of the United States.
Results: In all, 1256 adult women and 1603 adult men for whom multiple data points were available prior to initiation of antiretroviral therapy were included. Women were more likely to be nonwhite, to have a history of injection drug use, and to have HIV-associated symptoms. After adjustment for differences in measurement method, baseline CD4+ cell count, age, and clinical symptoms, HIV-1 RNA levels were 32% to 50% lower in women than in men at CD4+ counts >200 cells/mm3 (p < .001) but not at CD4+ cell counts <200 cells/mm3. HIV-1 RNA levels were also 41% lower in nonwhites than in whites (p < .001) and 21% lower in persons reporting a prior history of injection drug use (p < .001). Women had more rapid declines in CD4+ cell counts over time than men (difference in slope of 46 cells/year) and nonwhite individuals had slower decline in CD4 cell counts than whites (difference of 39 cells/year).
Conclusions: Both race and gender influence the values of HIV-1 RNA and the rate of HIV-1 disease progression as indicated by decline in CD4 cell counts over time. These effects could provide clues regarding the factors that influence HIV-disease progression and may indicate that guidelines for therapy should be adjusted for demographic characteristics.
(C) 2000 Lippincott Williams & Wilkins, Inc.
JAIDS Journal of Acquired Immune Deficiency Syndromes 06/2000; 24(3). · 4.43 Impact Factor
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ABSTRACT: Background: Cervical neoplasia occurs with increased frequency among women infected with HIV-1.
Objective: To characterize prevalence of and risk factors for abnormal cervical cytology among women with HIV and to compare them to uninfected women.
Methods: Baseline cervical cytology was obtained from 1713 women seropositive for HIV and 482 at-risk control women who were enrolled in the Women's Interagency HIV Study, a multicenter prospective cohort study conducted in six U.S. cities. Associations with sociodemographic, medical, and sexual variables were assessed by Fisher's exact test, Mantel extension test, and logistic regression analysis.
Results: Cervical cytology was abnormal in 38.3% of HIV-infected women (atypical squamous cells of uncertain significance [ASCUS] 20.9%, low-grade squamous cells of uncertain significance [LSIL] 14.9%, high-grade squamous cells of uncertain significance [HSIL] 2.3%, cancer 0.2%) and 16.2% of HIV-uninfected women (ASCUS 12.7%, LSIL 2.3%, HSIL 1.2%, cancer 0.0%). Risk factors for any abnormal cytology in multivariate analysis included HIV infection, CD4 cell count, HIV RNA level, detection of human papillomavirus (HPV), a prior history of abnormal cytology, employment, and number of male sex partners within 6 months of enrollment. Prior abortion was associated with a decreased risk of cytologic abnormality.
Conclusions: Cervical cytologic abnormalities were frequent among women infected with HIV, although high-grade changes were found in only 2.5%. Factors linked to sexual and reproductive history, HPV infection, and HIV disease all influenced risk.
(C) 1999 Lippincott Williams & Wilkins, Inc.
JAIDS Journal of Acquired Immune Deficiency Syndromes 04/1999; 21(1). · 4.43 Impact Factor
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Edward E. Telzak,
Ronald Hershow,
Leslie A. Kalish,
William D. Jr. Hardy,
Evelyn Zuckerman,
Alexandra Levine,
Robert Delapenha,
Jack DeHovitz, Ruth M. Greenblatt,
Kathryn Anastos,
for the Women's Interagency HIV Study
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ABSTRACT: Objectives: To determine the seroprevalence of, and risk factors for, HTLV-I and HTLV-II infection among HIV-infected women and women at high risk for HIV infection.
Design: Cross-sectional analysis of baseline data for women enrolled in the prospective Women's Interagency HIV Study (WIHS).
Methods: From October 1994 through November 1995, 2657 women from five metropolitan areas in the United States (Chicago, Los Angeles, New York City [two sites], Northern California, and Washington DC) were enrolled in WIHS. An interview-based survey collected data on demographics, behavior, and medical history. HTLV-I and HTLV-II determinations were made using a combined HTLV-I/HTLV-II indirect immunofluorescent antibody (IFA) screening test, an IFA titration specificity test, and individual HTLV-I and HTLV-II confirmatory Western blots. Fisher's exact tests and logistic regression were used to determine univariate and multivariate independent predictors for HTLV-II infection.
Results: Of 2625 women enrolled in WIHS with confirmed HIV results, 2487 (95%) were tested for HTLV-I and HTLV-II. Of these, 241 (10%) were HTLV-II-seropositive and 13 (0.5%) were HTLV-I-seropositive. On multivariate analysis, independent predictors of HTLV-II infection included injection drug use (OR = 5.2; p < .001), black race (OR = 3.6; p < 0.001), age >35 years (OR = 3.3; p < .001) and a history of sex with a male injecting drug user (OR = 1.9; p < .001). Among women infected with HIV, the seroprevalence of HTLV-II was 11% compared with 6% for women at risk for HIV but not infected (p < .001). However, HIV was not an independent predictor of HTLV-II infection in multivariate analysis.
Conclusions: This cross-sectional analysis confirms that HTLV-II is found commonly in HIV-infected women and uninfected women at risk for HIV in major urban areas throughout the United States and that HTLV-II is far more common than HTLV-I in these populations. Although injecting drug use is most strongly associated with HTLV-II infection, sexual transmission likely contributes to the high HTLV-II seroprevalence in this cohort.
JAIDS Journal of Acquired Immune Deficiency Syndromes 12/1998; 19(5):513-518. · 4.43 Impact Factor
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ABSTRACT: The AIDS (Acquired Immunodeficiency Syndrome) epidemic has brought increased attention to the problems investigators face in collecting highly sensitive information. In this context, literature on response bias in sex research is reviewed with particular attention to test-retest reliability and nonresponse issues. The influence of various task, interviewer, and respondent motivation variables on response bias in sex surveys is discussed. Recommendations for decreasing response bias are made. These recommendations are limited in that there is need for additional methodological studies among low socioeconomic class respondents, ethnic minorities, non-English speaking people, and other subpopulations of interest to AIDS investigators (e.g., IVDUs, prostitutes). Suggestions for accomplishing this goal are made.
Evaluation and Program Planning. 02/1990;
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Kathryn Anastos,
Yolanda Barrón,
Paolo Miotti,
Barbara Weiser,
Mary Young,
Nancy Hessol, Ruth M. Greenblatt,
Mardge Cohen,
Michael Augenbraun,
Alexandra Levine,
Alvaro Muñoz
[show abstract]
[hide abstract]
ABSTRACT: Background
The optimal virologic and immunologic stage at which to initiate antiretroviral therapy in individuals infected with human immunodeficiency virus type 1 (HIV-1) is undefined.Methods
Among 1054 HIV-1–infected women in a prospective cohort study, we determined the time from initiation of highly active antiretroviral treatment (HAART) to acquired immunodeficiency syndrome (AIDS) and death.Results
Median follow-up was 3.4 years. Of 553 women without AIDS at HAART initiation, 62 (11%) developed AIDS. Compared with women with CD4+ cell counts greater than 350/µL at HAART initiation, women with cell counts of 200 to 350/µL and less than 200/µL had relative hazards (RHs) for progression to AIDS of 0.93 (95% confidence interval [CI], 0.46-1.86) and 2.48 (95% CI, 1.39-4.42), respectively. Compared with those with HIV-1 RNA values less than 5000 copies/mL, women with 5000 to 50 000 copies/mL and greater than 50 000 copies/mL had RHs of 1.39 (95% CI, 0.74-2.64) and 2.09 (95% CI, 1.09-3.99), respectively. Among women with AIDS at HAART initiation (n = 501), RHs of death were 1.97 (95% CI, 0.84-4.66) and 3.35 (95% CI, 1.59-7.08) with CD4+ cell counts of 200 to 350/µL and less than 200/µL, respectively, relative to those with greater than 350/µL, and 1.90 (95% CI, 0.84-4.30) and 3.70 (95% CI, 1.81-7.54) for those with HIV-1 RNA values of 5000 to 50 000 and greater than 50 000 copies/mL, respectively, relative to those with less than 5000 copies/mL.Conclusions
Progression to AIDS and death was predicted by pre-HAART values of less than 200/µL for CD4+ cells and greater than 50 000 HIV-1 RNA copies/mL, indicating that deferral of HAART until the CD4+ cell count is between 350 and 200/µL is a valid strategy in the clinical management of HIV-1 infection.
Figures in this Article
THE INTRODUCTION in 1996 of highly active antiretroviral treatment (HAART) regimens1 for individuals infected with the human immunodeficiency virus (HIV) type 1 (HIV-1) has resulted in marked decreases in HIV-related morbidity and mortality in the United States and Europe.2- 4 It has been documented that individuals at more severe stages of disease are more likely to receive HAART.5 Despite this selection by indication, cohort studies have clearly shown that the disease burden (incidence of acquired immunodeficiency syndrome [AIDS] and mortality) has been drastically reduced at the population level.2,6 However, the heterogeneity of response among those individuals who are treated remains uncharacterized. Because of the paucity of data on long-term clinical outcomes among individuals initiating therapy at different clinical, virologic, and immunologic stages of disease, the optimal time at which to initiate HAART remains undefined. The guidelines for treatment developed and implemented in different countries thus vary in the levels of immunosuppression at which to initiate therapy7- 10 and are changed frequently.10 Although it has been suggested that HIV should be "hit early and hit hard" with antiretroviral therapy,11 recent reconsideration has led some to suggest that we "hit HIV-1 hard, but only when necessary."12
Before the availability of HAART, studies of disease progression investigated the natural (untreated) course of HIV-1 infection. However, optimal clinical decision making with regard to initiation of HAART is best guided by characterization of the treated course of HIV-1 infection. Cohort studies of HIV-1–infected individuals have characterized the risk of progression to AIDS while receiving HAART according to disease stage defined by CD4+ cell count and HIV-1 RNA. Such studies have identified the stages at which disease progression is low, making deferral of therapy an option.10 The significant toxicity associated with HAART also makes it imperative to determine the optimal time at which to initiate treatment. The primary objective of this report is to describe the factors associated with clinical progression after HAART initiation in a large cohort study conducted in 5 metropolitan areas of the United States.
Simple and direct comparisons of survival after HAART is initiated at different stages of disease do not suffice to allow conclusions regarding when to start: those who initiate treatment at a later stage had an unmeasured survival benefit before HAART was started. This lead time survival needs to be considered in analyses of data from cohort studies. If the survival is equal among those initiating HAART at different stages, deferral of treatment to a more advanced stage should be considered. This is because the addition of the lead time to the group treated later would result in survival at least equal to that among individuals receiving earlier treatment. On the other hand, if the survival of those initiating treatment at a later stage is worse, then adjustment for lead time (transition time between stages of disease) is necessary13 to ensure a valid comparison. To help guide strategic clinical decision making on when to initiate HAART, we provide herein data from a large cohort study of HIV-1–infected women followed up for more than 6 years. Our inferences are presented in the context of strengths and limitations (eg, lead time bias, for which we adjust) of observational studies.
Archives of Internal Medicine 162(17):1973-1980. · 11.46 Impact Factor
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Sheila M Keating,
Elizabeth T Golub,
Marek Nowicki,
Mary Young,
Kathryn Anastos,
Howard Crystal,
Mardge H Cohen,
Jinbing Zhang, Ruth M Greenblatt,
Seema Desai,
Shiquan Wu,
Alan L Landay,
Stephen J Gange,
Philip J Norris
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ABSTRACT: d and the Women's Interagency HIV Study 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 ¼ 17), NC (n ¼ 14), and HIV NEG (n ¼ 17). Results: Several cytokines and chemokines showed significant differences between NC and NEG participants, including elevated IP-10 and TNF-a 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-a 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 CD4þ T cell counts. The growth factors VEGF, EGF, and FGF-2 all showed a positive correlation with increased CD4þ T cell counts. Conclusion: Untreated, progress 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-a. 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.
