"The Pleasure Is Better as I've Gotten Older": Sexual Health, Sexuality, and Sexual Risk Behaviors Among Older Women Living With HIV.

There is limited research examining the sexual health and well-being of older women living with HIV (OWLH). Most studies focus on sexual dysfunction, leaving aside the richer context of sexuality and sexual health, including the effect of age-related psychosocial and interpersonal changes on sexual health behaviors. Guided by the integrative biopsychosocial model and the sexual health model, this study explored the importance of sex and sexuality among OWLH to identify their sexual health and HIV prevention needs for program planning. A purposive sample (n = 50) of OWLH was selected from a parent study (n = 2052). We conducted 8 focus groups and 41 in-depth interviews with 50 African American and Latina OWLH aged 50-69 years old in three U.S. cities. The triangulation approach was used to synthesize the data. Six salient themes emerged: sexual pleasure changes due to age, sexual freedom as women age, the role of relationships in sexual pleasure, changes in sexual ability and sexual health needs, sexual risk behaviors, and ageist assumptions about older women's sexuality. We found that sexual pleasure and the need for intimacy continue to be important for OWLH, but that changing sexual abilities and sexual health needs, such as the reduction of sexual desire, as well as increased painful intercourse due to menopause-associated vaginal drying, were persistent barriers to sexual fulfillment and satisfaction. Particular interpersonal dynamics, including low perceptions of the risk of HIV transmission as related to gender, viral suppression, and habitual condomless sex with long-term partners without HIV transmission have resulted in abandoning safer sex practices with serodiscordant partners. These findings suggest that HIV prevention for OWLH should focus on how sexual function and satisfaction intersect with sexual risk. HIV prevention for OWLH should promote ways to maintain satisfying and safe sex lives among aging women.

Cervical Precancer Risk in HIV-Infected Women Who Test Positive for Oncogenic Human Papillomavirus Despite a Normal Pap Test.

BACKGROUND: Determining cervical precancer risk among human immunodeficiency virus (HIV)-infected women who despite a normal Pap test are positive for oncogenic human papillomavirus (oncHPV) types is important for setting screening practices. METHODS: A total of 2791 HIV-infected and 975 HIV-uninfected women in the Women's Interagency HIV Study were followed semiannually with Pap tests and colposcopy. Cumulative risks of cervical intraepithelial neoplasia grade 2 or greater (CIN-2+; threshold used for CIN treatment) and grade 3 or greater (CIN-3+; threshold to set screening practices) were measured in HIV-infected and HIV-uninfected women with normal Pap tests, stratified by baseline HPV results, and also in HIV-infected women with a low-grade squamous intraepithelial lesion (LSIL; benchmark indication for colposcopy). RESULTS: At baseline, 1021 HIV-infected and 518 HIV-uninfected women had normal Pap tests, of whom 154 (15%) and 27 (5%), respectively, tested oncHPV positive. The 5-year CIN-2+ cumulative risk in the HIV-infected oncHPV-positive women was 22% (95% confidence interval [CI], 9%-34%), 12% (95% CI, 0%-22%), and 14% (95% CI, 2%-25%) among those with CD4 counts <350, 350-499, and ≥500 cells/µL, respectively, whereas it was 10% (95% CI, 0%-21%) in those without HIV. For CIN-3+, the cumulative risk averaged 4% (95% CI, 1%-8%) in HIV-infected oncHPV-positive women, and 10% (95% CI, 0%-23%) among those positive for HPV type 16. In HIV-infected women with LSIL, CIN-3+ risk was 7% (95% CI, 3%-11%). In multivariate analysis, HIV-infected HPV16-positive women had 13-fold (P = .001) greater CIN-3+ risk than oncHPV-negative women (referent), and HIV-infected women with LSIL had 9-fold (P < .0001) greater risk. CONCLUSIONS: HIV-infected women with a normal Pap result who test HPV16 positive have high precancer risk (similar to those with LSIL), possibly warranting immediate colposcopy. Repeat screening in 1 year may be appropriate if non-16 oncHPV is detected.

Longitudinal Trends in Sexual Behaviors with Advancing Age and Menopause Among Women With and Without HIV-1 Infection.

We assessed changes in self-reported sexual activity (SA) over 13 years among HIV-infected and uninfected women. The impact of aging and menopause on SA and unprotected anal or vaginal intercourse (UAVI) was examined among women in the Women's Interagency HIV Study (WIHS), stratifying by HIV status and detectable viral load among HIV-infected women. Generalized mixed linear models were fitted for each outcome, adjusted for relevant covariates. HIV-uninfected women evidenced higher levels of SA and UAVI than HIV-infected. The odds of SA declined by 62-64 % per decade of age. The odds of SA in a 6-month interval for women aged 40-57 declined by 18-22 % post-menopause (controlling for age). Among HIV+/detectable women only, the odds of any UAVI decreased by 17 % per decade of age; the odds of UAVI were unchanged pre-menopause, and then decreased by 28 % post-menopause. Elucidating the factors accounting for ongoing unprotected sex among older women should inform interventions.

Interleukin 10 responses are associated with sustained CD4 T-cell counts in treated HIV infection.

BACKGROUND: Inflammation persists in treated human immunodeficiency virus (HIV) infection and may contribute to an increased risk for non-AIDS-related pathologies. We investigated the correlation of cytokine responses with changes in CD4 T-cell levels and coinfection with hepatitis C virus (HCV) during highly active antiretroviral treatment (HAART). METHODS: A total of 383 participants in the Women's Interagency HIV Study (212 with HIV monoinfection, 56 with HCV monoinfection, and 115 with HIV/HCV coinfection) were studied. HIV-infected women had <1000 HIV RNA copies/mL, 99.7% had >200 CD4 T cells/µL; 98% were receiving HAART at baseline. Changes in CD4 T-cell count between baseline and 2-4 years later were calculated. Peripheral blood mononuclear cells (PBMCs) obtained at baseline were used to measure interleukin 1ß (IL-1ß), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 12 (IL-12), and tumor necrosis factor α (TNF-α) responses to Toll-like receptor (TLR) 3 and TLR4 stimulation. RESULTS: Undetectable HIV RNA (<80 copies/mL) at baseline and secretion of IL-10 by PBMCs were positively associated with gains in CD4 T-cell counts at follow-up. Inflammatory cytokines (IL-1ß, IL-6, IL-12, and TNF-α) were also produced in TLR-stimulated cultures, but only IL-10 was significantly associated with sustained increases in CD4 T-cell levels. This association was significant only in women with HIV monoinfection, indicating that HCV coinfection is an important factor limiting gains in CD4 T-cell counts, possibly by contributing to unbalanced persistent inflammation. CONCLUSIONS: Secreted IL-10 from PBMCs may balance the inflammatory environment of HIV, resulting in CD4 T-cell stability.

Cervicovaginal human papillomavirus (HPV)-infection before and after hysterectomy: evidence of different tissue tropism for oncogenic and nononcogenic HPV types in a cohort of HIV-positive and HIV-negative women.

Human papillomavirus (HPV) is detected in nearly all cervical cancers and approximately half of vaginal cancers. However, vaginal cancer is an order of magnitude less common than cervical cancer, not only in the general population but also among women with HIV/AIDS. It is interesting therefore that recent studies found that HPV was common in both normal vaginal and cervical tissue, with higher prevalence of nononcogenic HPV types in the vagina. In our investigation, we prospectively examined HPV infection in 86 HIV-positive and 17 HIV-negative women who underwent hysterectomy during follow-up in a longitudinal cohort. Cervicovaginal lavage specimens were obtained semi-annually and tested for HPV DNA by polymerase chain reaction. To address possible selection biases associated with having a hysterectomy, subjects acted as their own comparison group--before versus after hysterectomy. The average HPV prevalence was higher in HIV-positive than HIV-negative women both before (59% vs. 12%; p < 0.001) and after hysterectomy (56% vs. 6%; p < 0.001). Multivariate random effects models (within-individual comparisons) demonstrated significantly lower HPV prevalence [odds ratio (OR) = 0.71; 95% confidence interval (CI) = 0.59-0.85) after hysterectomy. The association of HPV prevalence with hysterectomy was similar among HIV-positive and HIV-negative women. However, hysterectomy had greater effects on oncogenic (OR = 0.48; 95% CI = 0.35-0.66) than nononcogenic HPV types (OR = 0.89; 95% CI = 0.71-1.11; P(interaction) = 0.002). Overall, we observed greater reductions in oncogenic than nononcogenic HPV prevalence after hysterectomy. If correct, these data could suggest that oncogenic HPV have greater tropism for cervical compared to vaginal epithelium, consistent with the lower incidence of vaginal than cervical cancer.

Rituximab plus concurrent infusional EPOCH chemotherapy is highly effective in HIV-associated B-cell non-Hodgkin lymphoma.

Rituximab plus intravenous bolus chemotherapy is a standard treatment for immunocompetent patients with B-cell non-Hodgkin lymphoma (NHL). Some studies have suggested that rituximab is associated with excessive toxicity in HIV-associated NHL, and that infusional chemotherapy may be more effective. We performed a randomized phase 2 trial of rituximab (375 mg/m(2)) given either concurrently before each infusional etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone (EPOCH) chemotherapy cycle or sequentially (weekly for 6 weeks) after completion of all chemotherapy in HIV-associated NHL. EPOCH consisted of a 96-hour intravenous infusion of etoposide, doxorubicin, and vincristine plus oral prednisone followed by intravenous bolus cyclophosphamide given every 21 days for 4 to 6 cycles. In the concurrent arm, 35 of 48 evaluable patients (73%; 95% confidence interval, 58%-85%) had a complete response. In the sequential arm, 29 of 53 evaluable patients (55%; 95% confidence interval, 41%-68%) had a complete response. The primary efficacy endpoint was met for the concurrent arm only. Toxicity was comparable in the 2 arms, although patients with a baseline CD4 count less than 50/microL had a high infectious death rate in the concurrent arm. We conclude that concurrent rituximab plus infusional EPOCH is an effective regimen for HIV-associated lymphoma.

Short-term garlic supplementation and highly active antiretroviral treatment adherence, CD4+ cell counts, and human immunodeficiency virus viral load.

CONTEXT: Human immunodeficiency virus (HIV)-infected individuals frequently have consumed garlic, a popular complementary supplement. Researchers rarely have studied garlic's association with antiretroviral therapies, however, even though that association is very relevant clinically. OBJECTIVE: To examine associations of supplemental use of garlic with highly active antiretroviral treatment (HAART) adherence level and HAART effectiveness (HIV viral load and CD4+ cell counts) in HIV-infected women. DESIGN: The research team carried out a self-controlled, longitudinal study nested within the Women's Interagency HIV Study (WIHS). The team used a paired study design that allowed participants to serve as their own controls. The team first identified all of the studies visits in which the participant self-reported the use of a garlic supplement since her last visit (index visit). Then for each index visit, the team identified a matching visit (a control visit) using the following criteria: (a) the visit must be one for the same participant in which that participant reported no garlic supplementation; (b) the visit must immediately precede the index visit (less than 1 year apart); and (c) at the time of the control visit, the participant must have been using antiretroviral therapy identical to that used at the time of the index visit. PARTICIPANTS: Participants were persons using garlic supplementation who already were participants in the WIHS. OUTCOME MEASURES: The research team used a logistic regression model to examine the association between garlic supplementation and HAART adherence level. The team used a mixed linear model to examine the association of garlic supplementation with HIV viral load and CD4+ cell counts. RESULTS: From October 1994 to April 2009, 390 HIV-infected women in the WIHS made 1112 visits at which they reported using garlic supplements. Seventy-seven HIV-infected women using HAART met the research teams selection criteria and contributed 99 pairs of visits for the study. Among the women who used garlic supplements, 22% were 50 years and older; 58% were black and non-Hispanic; and 23% had less than a high-school education. Neither use of garlic supplementation nor reasons for using garlic supplements were significantly associated with the HAART adherence level, HIV viral load, or CD4+ cell counts; however, use garlic as needed, a potential marker of a disease state, was significantly associated with higher viral load (P=.0003). CONCLUSION: Short-term garlic supplementation did not impact HAART adherence level, HIV viral load, and CD4+ cell counts.

Correlating knowledge of cervical cancer prevention and human papillomavirus with compliance after colposcopy referral.

OBJECTIVE: This study aimed to assess the impact of knowledge of cervical cancer biology and prevention as well as noncognitive measures on compliance with colposcopy referral in a high-risk population. METHODS: Participants in a US cohort of women with human immunodeficiency virus (HIV) infection and at-risk comparison women completed behavior questionnaires and instruments measuring knowledge of cervical cancer prevention, depressive symptoms, trust in physicians, and perceived stress. Examinations including Pap tests also were conducted. Associations with compliance with resulting indicated colposcopy were assessed in multivariable models. RESULTS: Of 326 women with indicated colposcopy, 222 (68%) were compliant with colposcopy referral and 104 (32%) were noncompliant. In multivariable analysis, better colposcopy compliance was associated with less education (odds ratio [OR] for compliance = 2.24, 95% confidence interval = 1.12-4.51 vs more than high school), previous abnormal Pap result (OR per previous abnormal Pap result = 1.08, 95% CI = 1.01-1.15), study site (OR for site with best vs worst compliance = 16.1, 95% CI = 2.91-88.6), and higher stress (OR for perceived stress scale 10 score >16 vs lower 3.25, 95% CI = 1.45-7.26). CONCLUSIONS: Noncognitive factors and how sites manage abnormal Pap testing affect colposcopy compliance. Educational interventions alone are unlikely to improve colposcopy compliance in similar high-risk populations.

Risk of cervical precancer and cancer among HIV-infected women with normal cervical cytology and no evidence of oncogenic HPV infection.

CONTEXT: US cervical cancer screening guidelines for human immunodeficiency virus (HIV)-uninfected women 30 years or older have recently been revised, increasing the suggested interval between Papanicolaou (Pap) tests from 3 years to 5 years among those with normal cervical cytology (Pap test) results who test negative for oncogenic human papillomavirus (HPV). Whether a 3-year or 5-year screening interval could be used in HIV-infected women who are cytologically normal and oncogenic HPV-negative is unknown. OBJECTIVE: To determine the risk of cervical precancer or cancer defined cytologically (high-grade squamous intraepithelial lesions or greater [HSIL+]) or histologically (cervical intraepithelial neoplasia 2 or greater [CIN-2+]), as 2 separate end points, in HIV-infected women and HIV-uninfected women who at baseline had a normal Pap test result and were negative for oncogenic HPV. DESIGN, SETTING, AND PARTICIPANTS: Participants included 420 HIV-infected women and 279 HIV-uninfected women with normal cervical cytology at their enrollment in a multi-institutional US cohort of the Women's Interagency HIV Study, between October 1, 2001, and September 30, 2002, with follow-up through April 30, 2011. Semiannual visits at 6 clinical sites included Pap testing and, if indicated, cervical biopsy. Cervicovaginal lavage specimens from enrollment were tested for HPV DNA using polymerase chain reaction. The primary analysis was truncated at 5 years of follow-up. MAIN OUTCOME MEASURE: Five-year cumulative incidence of cervical precancer and cancer. RESULTS: No oncogenic HPV was detected in 369 (88% [95% CI, 84%-91%]) HIV-infected women and 255 (91% [95% CI, 88%-94%]) HIV-uninfected women with normal cervical cytology at enrollment. Among these oncogenic HPV-negative women, 2 cases of HSIL+ were observed; an HIV-uninfected woman and an HIV-infected woman with a CD4 cell count of 500 cells/µL or greater. Histologic data were obtained from 4 of the 6 clinical sites. There were 6 cases of CIN-2+ in 145 HIV-uninfected women (cumulative incidence, 5% [95% CI, 1%-8%]) and 9 cases in 219 HIV-infected women (cumulative incidence, 5% [95% CI, 2%-8%]). This included 1 case of CIN-2+ in 44 oncogenic HPV-negative HIV-infected women with CD4 cell count less than 350 cells/µL (cumulative incidence, 2% [95% CI, 0%-7%]), 1 case in 47 women with CD4 cell count of 350 to 499 cells/µL (cumulative incidence, 2% [95% CI, 0%-7%]), and 7 cases in 128 women with CD4 cell count of 500 cells/µL or greater (cumulative incidence, 6% [95% CI, 2%-10%]). One HIV-infected and 1 HIV-uninfected woman had CIN-3, but none had cancer. CONCLUSION: The 5-year cumulative incidence of HSIL+ and CIN-2+ was similar in HIV-infected women and HIV-uninfected women who were cytologically normal and oncogenic HPV-negative at enrollment.

Effect of stress and depression on the frequency of squamous intraepithelial lesions.

OBJECTIVE: To explore the previously reported associations between cervical squamous lesions and psychologic measures of stress and depression. METHODS: In a multicenter cohort study, women with HIV and HIV-seronegative women had Pap tests and completed self-report questionnaires including the Perceived Stress Scale-10 (PSS), which measures perceived stress, the Posttraumatic Stress Disorder (PTSD) Checklist-Civilian Version (PCL-C), which measures symptoms of PTSD, and the Center for Epidemiologic Studies Depression (CES-D) scale, which measures depressive symptoms. RESULTS: Median scores were 13 (range = 0-38) for the PSS, 24 (range = 17-85) for the PCL-C, and 8 (range = 0-57) for the CES-D, indicating moderate stress and minimal depression. For PSS, compared with women in the lowest tertile of reported stress, the odds ratios (ORs) for squamous intraepithelial lesions (SIL) were 0.88 (95% confidence interval [CI] = 0.50-1.54) for women in the middle tertile and 0.96 (95% CI = 0.54-1.68) for women in the highest tertile. For PCL-C, compared with women in the lowest tertile of PTSD symptoms, ORs for SIL were 0.79 (95% CI = 0.43-1.41) for women in the middle tertile and 1.17 (95% CI = 0.68-2.01) for women in the highest tertile. Rates of SIL were similar for CES-D scores 16 or higher (compared with women with lower scores; OR = 1.41, 95% CI = 0.88-2.26) and 23 or higher (OR = 1.39, 95% CI = 0.81-2.40). In the multivariable analysis including the number of sexual partners, age, income, ethnicity, and serostatus, stress as measured by PSS and PCL-C and depressive symptoms as measured by CES-D remained unassociated with SIL. CONCLUSIONS: We found no evidence that stress and depression affect the prevalence of cervical squamous lesions.

Influence of adherent and effective antiretroviral therapy use on human papillomavirus infection and squamous intraepithelial lesions in human immunodeficiency virus-positive women.

BACKGROUND: The impact of highly active antiretroviral therapy (HAART) on the natural history of human papillomavirus (HPV) remains uncertain following conflicting reports. Prior studies, however, did not consider patients' adherence to their regimens or HAART effectiveness (viral suppression). METHODS: Human immunodeficiency virus (HIV)-positive women (N = 286) who initiated HAART during follow-up in a prospective cohort were assessed semiannually for HPV infection (by polymerase chain reaction) and squamous intraepithelial lesions (SILs). Adherence was defined as use of HAART as prescribed > or = 95% of the time, and effective HAART was defined as suppression of HIV replication. The prevalence, incident detection, and clearance of HPV infection and/or SILs before versus after HAART initiation were compared (using women as their own comparison group). RESULTS: HAART initiation among adherent women was associated with a significant reduction in prevalence (odds ratio, 0.60 [95% confidence interval {CI}, 0.44-0.81]; P = .001), incident detection of oncogenic HPV infection (hazard ratio [HR], 0.49 [95% CI, 0.30-0.82]; P = .006), and decreased prevalence and more rapid clearance of oncogenic HPV-positive SILs (HR, 2.35 [95% CI, 1.07-5.18]; P = .03). Effects were smaller among nonadherent women. The associations of HPV infection and/or SILs with HAART effectiveness were fairly similar to those with HAART adherence. CONCLUSION: Effective and adherent HAART use is associated with a significantly reduced burden of HPV infection and SILs; this may help explain why rates of cervical cancer have not increased during the HAART era, despite greater longevity.

Knowledge of cervical cancer prevention and human papillomavirus among women with HIV.

OBJECTIVE: To assess knowledge of and attitudes towards human papillomavirus (HPV), Pap testing, and the HPV vaccine. METHODS: In a multicenter U.S. cohort study, women with the human immunodeficiency virus (HIV) and at-risk comparison women completed 44-item standardized self-report questionnaires exploring their knowledge of cervical cancer prevention, HPV, and HPV vaccination. Results were correlated with demographic variables, measures of education and attention, and medical factors. Data were clustered using principal component analysis. Significant associations were assessed in multivariable models. RESULTS: Among 1588 women, HIV seropositive women better understood facts about cervical cancer prevention and HPV than seronegative women, but both had substantial knowledge deficits. Almost all women considered Pap testing important, although 53% of HIV seropositive and 48% of seronegative women considered cervical cancer not preventable (P=0.21). Only 44% of HIV seropositive women knew Paps assess the cervix, versus 42% of HIV seronegative women (P=0.57). Both groups understood that HPV causes genital warts and cervical cancer (67% of HIV seropositive vs. 55% of seronegative women, P=0.002). About half of both groups considered HPV vaccination extremely important for cervical cancer prevention. HIV seronegative women were more likely to report learning of HPV vaccination through advertising than from clinicians (81% vs. 64%, P<0.0001). CONCLUSION: High risk women need effective education about cervical cancer prevention, HPV, and HPV vaccination.

Management of T-cell and natural-killer-cell neoplasms in Asia: consensus statement from the Asian Oncology Summit 2009.

T-cell and natural-killer (NK)-cell lymphomas are neoplasms with geographical variations in frequencies. T-cell lymphomas are more prevalent in Asia than in Europe and North America, and NK-cell lymphomas occur almost exclusively in Asia and South America. These low frequencies mean that the diagnosis and optimum treatment of patients with T-cell and NK-cell lymphomas have not been studied prospectively in randomised controlled trials. Because T-cell and NK-cell lymphomas are more prevalent in Asia, the establishment of management recommendations by Asian oncologists in collaboration with international experts is pertinent. This review outlines guidelines commensurate with different levels of health-care resources and expertise. Consensus statements were formulated for diagnosis, staging, follow-up, and treatment approaches in patients with T-cell and NK-cell lymphomas--aimed at unifying the design of studies and interpretation of results. For patients not in clinical trials, consensus opinions offer useful guidelines on optimum management.

Insulin-like growth factor axis and oncogenic human papillomavirus natural history.

High serum levels of insulin-like growth factor-I (IGF-I) are reported to be a risk factor for several common cancers, and recent cross-sectional data suggest a possible additional association of IGF-I with cervical neoplasia. To prospectively assess whether circulating IGF-I levels influence the natural history of oncogenic human papillomavirus (HPV), the viral cause of cervical cancer, we conducted a pilot investigation of 137 women who underwent semiannual type-specific HPV DNA PCR testing and cervical cytology. Total IGF-I and IGF binding protein-3 (IGFBP-3), the most abundant IGFBP in circulation, were measured using baseline serum specimens. Having a high IGF-I/IGFBP-3 ratio was associated with increased persistence of oncogenic HPV infection [that is, a lower rate of clearance; adjusted hazard ratio (AHR), 0.14; 95% confidence interval (95% CI), 0.04-0.57], whereas IGFBP-3 was inversely associated with both the incident detection of oncogenic HPV (AHR, 0.35; 95% CI, 0.13-0.93) and the incidence of oncogenic HPV-positive cervical neoplasia (that is, squamous intraepithelial lesions at risk of progression; AHR, 0.07; 95% CI, 0.01-0.66). These prospective data provide initial evidence that the IGF axis may influence the natural history of oncogenic HPV.

Management of AIDS-related lymphoma.

PURPOSE OF REVIEW: With the advent of highly active antiretroviral therapy, the epidemiology of AIDS-lymphoma has changed, and prognosis has improved. Paradigms of therapy have changed. Although the incidence of AIDS-lymphoma has decreased, the incidence of HIV-associated Hodgkin's lymphoma has increased; mechanisms for these changes in epidemiology will be discussed. RECENT FINDINGS: Use of highly active antiretroviral therapy, either concomitantly or immediately after completion of chemotherapy, has resulted in rates of complete remission and survival that are similar to those in HIV-negative patients. The use of rituximab, while initially controversial because of reports of increased risk of infectious death, is associated with improved outcome; the increased risk of infectious death has not been confirmed. The infusional etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin regimen is associated with excellent results. High-dose chemotherapy with autologous stem cell transplant is associated with long-term, disease-free survival in approximately 50-80% of patients with relapsed/refractory AIDS-lymphoma. SUMMARY: Highly active antiretroviral therapy should be used with chemotherapy. Addition of rituximab is associated with improved response rates, without an increase in infections. Infusional etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin is associated with excellent results among patients with either diffuse large B cell lymphoma or Burkitt's lymphoma. Optimal therapy for patients with HIV-Hodgkin's lymphoma has not yet been defined.

Efficacy of epoetin alfa administered every 2 weeks to maintain hemoglobin and quality of life in anemic HIV-infected patients.

Anemia, a common hematological abnormality in HIV, contributes to decreased quality of life (QOL). This study assessed once-every-2-week epoetin alfa on maintaining QOL and hemoglobin (Hb) in anemic HIV-infected patients in a 24-week, open-label, multicenter study. HIV-infected patients (Hb < or =12 g/dl) received epoetin alfa 40,000 units subcutaneously once weekly, until reaching Hb > or =13 g/dl. Patients then entered a maintenance phase (MP), in which epoetin alfa was administered every other week or at longer intervals. The trial objectives were to determine if QOL, as measured by the Medical Outcomes Study-HIV (MOS-HIV) general health perceptions (GHP) domain and Hb, was maintained. Safety was also assessed. A total of 292 patients were enrolled (72% on HAART). Mean baseline laboratory values were Hb = 10.8 g/dl, CD4(+) count = 280 cells/microl, and HIV RNA = 51,867 copies/ml. In all, 81% of patients reached Hb > or =13 g/dl and 92% reached Hb > or =12 g/dl. QOL was maintained from the beginning (GHP = 44.2 points) to the end of MP (GHP = 43.4 points) with every other week or longer dosing. Mean Hb at the beginning of MP was 13.4 +/- 0.5 g/dl and was 12.8 +/- 1.4 g/dl at study end. Epoetin alfa was well tolerated; adverse events were consistent with those reported in previous studies of epoetin alfa in HIV-infected patients. Although the clinical approach tested in this study is not consistent with current prescribing recommendations, the results confirm the efficacy of prolonged dosing intervals (every 2-4 weeks) in maintaining optimal Hb levels and QOL in anemic HIV-infected patients.

Association of cells with natural killer (NK) and NKT immunophenotype with incident cancers in HIV-infected women.

Evidence indicates that immunosupression is associated with the development of certain cancers. The pathogenesis of HIV disease includes an alteration in innate immunity, mediated through NK and NKT cells. The evaluation of innate immune status in HIV patients prior to cancer diagnosis may identify the specific immunological events preceding the development of malignant disease. We evaluated the association between immunophenotypically defined NK, NKT, and CD8(+) cell percentages and incident malignancies in 1817 HIV(+) women in the Women's Interagency HIV Study (WIHS) who were followed for a median of 7.5 years. A total of 52 incident cancers of 20 different sites were identified. Compared to cancer-free women, cancer cases were older (p < 0.01), more likely to be anti-HCV(+) (p = 0.02), and had higher baseline median HIV RNA levels than controls. The CD8(+), NK, and NKT percents at baseline were not related to cancer risk. However, when time-dependent values for NKT cells were used, higher levels of NKT cells were associated with a reduced risk of cancer (adjusted hazard ratio = 0.67, 95% CI = 0.50, 0.89 per NKT percentage point). In addition to the loss of CD4(+) lymphocytes and an increased risk of opportunistic infections, HCV coinfected individuals may also experience alterations in innate immunity, including reduced NKT and NK cell number and possibly their function. In time-dependent analyses, increased numbers of NKT cells were associated with a reduced risk of cancer. HIV-induced innate immune dysfunction may contribute to the eventual emergence of cancer in the setting of existing coinfections and altered immunosurveillance.

Association of complementary and alternative medicine use with highly active antiretroviral therapy initiation.

OBJECTIVE: To assess whether complementary and alternative medicine (CAM) use is associated with the timing of highly active antiretroviral therapy (HAART) initiation among human immunodeficiency virus (HIV)-infected participants of the Women's Interagency HIV Study. STUDY METHODS: Prospective cohort study between January 1996 and March 2002. Differences in the cumulative incidence of HAART initiation were compared between CAM users and non-CAM users using a logrank test. Cox regression model was used to assess associations of CAM exposures with time to HAART initiation. MAIN OUTCOME AND EXPOSURES: Study outcome was time from January 1996 to initiation of HAART. Primary exposure was use of any CAM modality before January 1996, and secondary exposures included the number and type of CAM modalities used (ingestible CAM medication, body practice, or spiritual healing) during the same period. RESULTS: One thousand thirty-four HIV-infected women contributed a total of 4987 person-visits during follow-up. At any time point, the cumulative incidence of HAART initiation among CAM users was higher than that among non-CAM users. After adjustment for potential confounders, those reporting CAM use were 1.34 times (95% confidence interval: 1.09, 1.64) more likely to initiate HAART than non-CAM users. CONCLUSION: Female CAM users initiated HAART regimens earlier than non-CAM users. Initiation of HAART is an important clinical marker, but more research is needed to elucidate the role specific CAM modalities play in HIV disease progression.

The relationship between cocaine use and human papillomavirus infections in HIV-seropositive and HIV-seronegative women.

OBJECTIVE: Animal data suggest that cocaine has an immunosuppressive effect, but no human studies have been conducted to assess the relation of cocaine use with human papillomavirus (HPV) infection, the viral cause of cervical cancer. Since both cocaine use and HPV infection are common among HIV-positive women, we sought to determine whether use of cocaine and/or crack influences the natural history of HPV among women with or at high risk of HIV. METHODS: Women enrolled in the Women's Interagency HIV Study (2278 HIV-seropositive and 826 high-risk seronegative women) were examined every six months for up to 9.5 years with Pap smear, collection of cervicovaginal lavage (CVL) samples, and detailed questionnaires regarding health and behavior, including use of crack and cocaine (crack/cocaine). CVLs were tested for HPV DNA by PCR, with genotyping for over forty HPV types. RESULTS: In multivariate logistic regression models, censoring women treated for cervical neoplasia, crack/cocaine use within the last six months was associated with prevalent detection of oncogenic HPV DNA (odds ratio [OR] = 1.30 (1.09-1.55)), and with oncogenic HPV-positive squamous intraepithelial lesions (SIL) (OR = 1.70 (1.27-2.27)), following adjustment for age, race, HIV-serostatus, and CD4+ T-cell count, the number of sexual partners in the past six months, and smoking. In multivariate Cox models crack/cocaine use was also associated with a trend that approached significance in regard to incident detection of oncogenic HPV-positive SIL (HR = 1.51, 95% CI 0.99-2.30), and while the rate of oncogenic HPV clearance was not related to cocaine use, the clearance of any SIL was significantly lower in those with versus those without recent crack/cocaine use (HR = 0.57, 95% CI 0.34-0.97). CONCLUSIONS: Cocaine use is associated with an increased risk of detection of both prevalent and incident oncogenic HPV infection, as well as an increased risk of HPV-positive SIL over time.