"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.

Prevalence and Predictors of Hospitalizations Among HIV-Infected and At-Risk HIV-Uninfected Women.

OBJECTIVES: We evaluated the Veterans Aging Cohort Study (VACS) Index score, an index composed of age, CD4 count, viral load, hemoglobin, Hepatitis C coinfection, Fibrosis Index-4, and estimated glomerular filtration rate, and psychosocial and clinical risk factors for all-cause hospitalization among HIV-infected women on highly active antiretroviral therapy and HIV-uninfected women. METHODS: Data were collected from 2008 to 2014 from 1585 highly active antiretroviral therapy-experienced HIV infected and 692 uninfected women. Cox proportional hazards regression evaluated predictors of first hospitalization over 2 years. RESULTS: Among HIV-infected women, VACS Index score (per 5 points) [adjusted hazard ratio (aHR) 1.08; 95% confidence interval (CI): 1.06 to 1.11], Centers for Epidemiologic Studies-Depression (CESD) scores ≥16 (aHR 1.61; 95% CI: 1.30 to 1.99), smoking (aHR 1.26; 95% CI: 1.02 to 1.55), abuse history (aHR 1.52; 95% CI: 1.20 to 1.93), diabetes (aHR 1.63; 95% CI: 1.31 to 2.04), and black race (aHR 1.28; 95% CI: 1.03 to 1.59) increased risk of hospitalization. Among HIV-uninfected women, VACS Index score (aHR 1.08; 95% CI: 1.03 to 1.13), CESD scores ≥16 (aHR 1.38; 95% CI: 1.02 to 1.86), diabetes (aHR 2.15; 95% CI: 1.57 to 2.95), and black race (aHR 1.61; 95% CI: 1.15 to 2.24) predicted subsequent hospitalization. CONCLUSIONS: Psychosocial and clinical factors were associated with risk of hospitalization independently of the VACS Index score. Additional research on contextual and psychosocial influences on health outcomes among women is needed.

Trends in Nonlipid Cardiovascular Disease Risk Factor Management in the Women's Interagency HIV Study and Association with Adherence to Antiretroviral Therapy.

Cardiovascular disease (CVD) is increasingly common among women with HIV, but literature on nonlipid CVD risk factor management is lacking. We examined semiannual trends from 2006 to 2014 in hypertension treatment and control (blood pressure <140/90 mmHg), diabetes treatment and control (fasting glucose <130 mg/dL), and smoking quit rates in the Women's Interagency HIV Study. Unadjusted and adjusted Poisson regression models tested time trends and differences between HIV+ and HIV- women. Among antiretroviral therapy (ART) users, we examined the association of ART adherence and virologic suppression with each outcome. We evaluated 1636 HIV+ and 683 HIV- women, with a hypertension prevalence of 40% and 38%, respectively; diabetes prevalence of 21% and 22%; and smoking prevalence of 37% and 48%. Hypertension treatment was higher among HIV+ than HIV- women (77% vs. 67%, p < 0.001) and increased over time with no difference in trend by HIV status. Hypertension control was greater among HIV+ women (56% vs. 43%, p < 0.001) and increased over time among HIV+ but not HIV- women. Diabetes treatment was similar among HIV+ and HIV- women (48% vs. 49%) and increased over time in both groups. Diabetes control was greater among HIV+ women (73% vs. 64%, p = 0.03) and did not change over time. The percent of recent smokers who reported no longer smoking was similar between HIV+ and HIV- women (10% vs. 9%), with no differences over time. Virologic suppression was significantly associated with increased hypertension treatment and greater control. HIV+ women have better control of hypertension and diabetes than HIV- women, but many are still not at target levels.

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.

Lung cancer incidence and survival among HIV-infected and uninfected women and men.

OBJECTIVES: To determine the lung cancer incidence and survival time among HIV-infected and uninfected women and men. DESIGN: Two longitudinal studies of HIV infection in the United States. METHODS: Data from 2549 women in the Women's Interagency HIV Study (WIHS) and 4274 men in the Multicenter AIDS Cohort Study (MACS), all with a history of cigarette smoking, were analyzed. Lung cancer incidence rates and incidence rate ratios were calculated using Poisson regression analyses. Survival time was assessed using Kaplan-Meier and Cox proportional-hazard analyses. RESULTS: Thirty-seven women and 23 men developed lung cancer (46 HIV-infected and 14 HIV-uninfected) during study follow-up. In multivariable analyses, the factors that were found to be independently associated with a higher lung cancer incidence rate ratios were older age, less education, 10 or more pack-years of smoking, and a prior diagnosis of AIDS pneumonia (vs. HIV-uninfected women). In an adjusted Cox model that allowed different hazard functions for each cohort, a history of injection drug use was associated with shorter survival, and a lung cancer diagnosis after 2001 was associated with longer survival. In an adjusted Cox model restricted to HIV-infected participants, nadir CD4 lymphocyte cell count less than 200 was associated with shorter survival time. CONCLUSIONS: Our data suggest that pulmonary damage and inflammation associated with HIV infection may be causative for the increased risk of lung cancer. Encouraging and assisting younger HIV-infected smokers to quit and to sustain cessation of smoking is imperative to reduce the lung cancer burden in this population.

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.

Long-term cumulative detection of human papillomavirus among HIV seropositive women.

OBJECTIVE: To estimate the effects of infection by HIV on the type-specific cumulative detection of cervicovaginal infection by human papillomavirus (HPV). DESIGN: Retrospective assessment of prospectively collected data in a multicenter US cohort. METHODS: HIV-seropositive and at-risk seronegative participants in the Women's Interagency HIV Study were followed semiannually for up to 11 years. HPV typing was determined from cervicovaginal lavage specimens by PCR; types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68 were considered carcinogenic. RESULTS: Among the 3438 women enrolled (2543 HIV-seropositive, 895 seronegative), the cumulative detection of any HPV infection rose among HIV-seropositive women from 53% at baseline to 92% at 8 years, and among seronegative women from 22 to 66% (P < 0.0001 for HIV-seropositive vs. seronegative women). The 8-year cumulative detection of carcinogenic and noncarcinogenic HPV was 67 and 89% among HIV-seropositive, and 36 and 56% among seronegative women (P = 0.001 for both carcinogenic and noncarcinogenic HPV). The 8-year cumulative detection of HPV16 and HPV18 was 15.2 and 15.0% in HIV-seropositive, and 6.7 and 6.1% in HIV-seronegative women (P < 0.0001 for both). In multivariable regression analyses, lower CD4(+) cell count, age under 30 years, and smoking, but not number of lifetime sexual partners, were significant correlates of cumulative HPV detection. CONCLUSION: More than 90% of the HIV-seropositive women have HPV detected during a long follow-up. The rates are lower among at-risk HIV-seronegative women, though most also develop HPV infections.

Genital tract HIV RNA levels and their associations with human papillomavirus infection and risk of cervical precancer.

OBJECTIVE: Plasma HIV RNA levels have been associated with the risk of human papillomavirus (HPV) and cervical neoplasia in HIV-seropositive women. However, little is known regarding local genital tract HIV RNA levels and their relation with cervical HPV and neoplasia. DESIGN/METHODS: In an HIV-seropositive women's cohort with semiannual follow-up, we conducted a nested case-control study of genital tract HIV RNA levels and their relation with incident high-grade squamous intraepithelial lesions (HSIL) subclassified as severe (severe HSIL), as provided for under the Bethesda 2001 classification system. Specifically, 66 incidents of severe HSIL were matched to 130 controls by age, CD4 count, highly active antiretroviral therapy use, and other factors. We also studied HPV prevalence, incident detection, and persistence in a random sample of 250 subjects. RESULTS: Risk of severe HSIL was associated with genital tract HIV RNA levels (odds ratio comparing HIV RNA ≥ the median among women with detectable levels versus undetectable, 2.96; 95% confidence interval: 0.99 to 8.84; Ptrend = 0.03). However, this association became nonsignificant (Ptrend = 0.51) after adjustment for plasma HIV RNA levels. There was also no association between genital tract HIV RNA levels and the prevalence of any HPV or oncogenic HPV. However, the incident detection of any HPV (Ptrend = 0.02) and persistence of oncogenic HPV (Ptrend = 0.04) were associated with genital tract HIV RNA levels, after controlling plasma HIV RNA levels. CONCLUSIONS: These prospective data suggest that genital tract HIV RNA levels are not a significant independent risk factor for cervical precancer in HIV-seropositive women, but they leave open the possibility that they may modestly influence HPV infection, an early stage of cervical tumorigenesis.

The relation of plasmacytoid dendritic cells (pDCs) and regulatory T-cells (Tregs) with HPV persistence in HIV-infected and HIV-uninfected women.

Other than CD4+ count, the immunologic factors that underlie the relationship of HIV/AIDS with persistent oncogenic HPV (oncHPV) and cervical cancer are not well understood. Plasmacytoid dendritic cells (pDCs) and regulatory T-cells (Tregs) are of particular interest. pDCs have both effector and antigen presenting activity and, in HIV-positive patients, low pDC levels are associated with opportunistic infections. Tregs downregulate immune responses, and are present at high levels in HIV-positives. The current pilot study shows for the first time that low pDC and high Treg levels may be significantly associated with oncHPV persistence in both HIV-positive and HIV-negative women. Larger studies are now warranted.

Increase in single-tablet regimen use and associated improvements in adherence-related outcomes in HIV-infected women.

INTRODUCTION: The use of single-tablet antiretroviral therapy (ART) regimens and its implications on adherence among HIV-infected women have not been well described. METHODS: Participants were enrolled in the Women's Interagency HIV Study, a longitudinal study of HIV infection in US women. We examined semiannual trends in single-tablet regimen use and ART adherence, defined as self-reported 95% adherence in the past 6 months, during 2006-2013. In a nested cohort study, we assessed the comparative effectiveness of a single-tablet versus a multiple-tablet regimen with respect to adherence, virologic suppression, quality of life, and AIDS-defining events, using propensity score matching to account for demographic, behavioral, and clinical confounders. We also examined these outcomes in a subset of women switching from a multiple- to single-tablet regimen using a case-crossover design. RESULTS: We included 15,523 person-visits, representing 1727 women (53% black, 29% Hispanic, 25% IDU, median age 47). Use of single-tablet regimens among ART users increased from 7% in 2006% to 27% in 2013; adherence increased from 78% to 85% during the same period (both P < 0.001). Single-tablet regimen use was significantly associated with increased adherence (adjusted risk ratio: 1.05; 95% confidence interval: 1.03 to 1.08) and virologic suppression (risk ratio: 1.06; 95% confidence interval: 1.01 to 1.11), while associations with improved quality of life and fewer AIDS-defining events did not achieve statistical significance. Similar findings were observed among the subset of switchers. CONCLUSIONS: Single-tablet regimen use was associated with increased adherence and virologic suppression. Despite this, 15% of women prescribed ART were still not optimally adherent; additional interventions are needed to maximize therapeutic benefits.

An effective reinduction regimen for first relapse of adult acute lymphoblastic leukemia.

Current salvage regimens achieve complete remission (CR) in about a third of adults with relapsed/refractory acute lymphoblastic leukemia (ALL), and this represents a major barrier for performing allogeneic hematopoietic stem cell transplant (HSCT), the only potentially curative treatment. We conducted in adults with first relapse of ALL, a prospective clinical trial with intensive regimen derived from the pediatric Berlin-Frankfurt-Muenster-85 protocol, with addition of a continuous infusional multi-agent chemotherapy in phase II induction followed by consolidation with alternating monthly cycles. Objectives of this study included CR rate, leukemia-free survival (LFS) and toxicity of the regimen in adults. We report the outcome of 19 patients (19-51 years of age) treated prospectively on the study, as well as a subsequent cohort of 31 patients (18-53 years of age) treated off the study. Thirteen of 19 (68%) patients from the initial prospective study achieved CR, and the median overall survival (OS) of these 13 CR patients was 10.3 months. The median OS and LFS of all 19 patients were 5.6 and 4.3 months, respectively. The regimen was well tolerated, and no grade 4 non-hematological toxicity was observed. Of the 31 patients treated off the study and analyzed retrospectively, 16 (52%) achieved CR. After including all 50 patients, the CR rate was 58%. The regimen used in this trial appears to be feasible and effective salvage therapy option for adult patients younger than age 55 with relapsed ALL, produced a high CR rate and could facilitate subsequent allogeneic HSCT.

Serum biomarkers of immune activation and subsequent risk of non-hodgkin B-cell lymphoma among HIV-infected women.

BACKGROUND: There is increasing evidence that chronic immune activation predisposes to non-Hodgkin lymphoma (NHL). Whether this association exists among women representative of the current HIV epidemic in the United States who are at high risk of HIV-associated NHL (AIDS-NHL), remains to be determined. METHODS: We conducted a nested case-control study within the Women's Interagency HIV Study with longitudinally collected risk factor data and sera. Cases were HIV-infected women with stored sera collected at three time-windows 3 to 5 years, 1 to 3 years, and 0 to 1 year before AIDS-NHL diagnosis (n = 22). Three to six HIV-infected controls, without AIDS-NHL, were matched to each case on age, race, CD4(+) T-cell count, and study follow-up time (n = 78). ORs and 95% confidence intervals (CI) for the association between one unit increase in log-transformed biomarker levels and AIDS-NHL were computed using random effect multivariate logistic regression models. RESULTS: Elevated levels of sCD27 (OR = 7.21; 95% CI, 2.62-19.88), sCD30 (OR = 2.64; 95% CI, 1.24-5.64), and CXCL13 (OR = 2.56; 95% CI, 1.32-4.96) were associated with subsequent diagnosis of AIDS-NHL overall. Elevated sCD23 was associated with a two to three-fold increased risk of AIDS-NHL in certain subgroups, whereas elevated interleukin 6 was associated with a two-fold increased risk in the 0 to 1 year time-window, only. CONCLUSIONS: These findings support the hypothesis that chronic B-cell activation contributes to the development of AIDS-NHL in women. IMPACT: Soluble CD23 (sCD23), sCD27, sCD30, and CXCL13 may serve as biomarkers for AIDS-NHL.

Changing patterns of anal canal carcinoma in the United States.

PURPOSE: Persistent human papillomavirus infection is associated with squamous cell carcinoma of the anal canal (SCCA). With changing sexual behaviors, SCCA incidence and patient demographics may also have changed in recent years. METHODS: The Surveillance, Epidemiology, and End Results public-use data set from 1973 to 2009 was analyzed to determine incidence trends for and demographic factors characterizing SCCA. Joinpoint analyses identified time points when incidence rates changed. For comparison, similar analyses were conducted for anal adenocarcinoma. RESULTS: Joinpoint analyses identified 1997 as the single inflection point among 11,231 patients with SCCA, at which the slope of incidence rates statistically increased (1997 to 2009 v 1973 to 1996: risk ratio [RR], 2.2; 95% CI, 2.1 to 2.3). Annual percent change (APC) increased for all SCCA stages and was the greatest for anal carcinoma in situ (CIS; APC, 14.2; 95% CI, 10.2 to 18.4). Demographic changes characterizing later versus earlier time period included younger age at diagnosis and rising incidence rates in all stage, sex, and racial groups. During 1997 to 2009, women were less likely to present with CIS (RR, 0.3; 95% CI, 0.3 to 0.3) but more likely to present with localized (RR, 1.2; 95% CI, 1.1 to 1.3) and regional SCCA (RR, 1.5; 95% CI, 1.4 to 1.7). In contrast, adenocarcinoma APCs among 1,791 patients remained stable during this time period. CONCLUSION: CIS and SCCA incidence increased dramatically after 1997 for men and women, although men were more likely to be diagnosed with CIS. These changes likely resulted from available screening in men and argue for efforts to identify high-risk individuals who may benefit from screening.

Pegylated liposomal doxorubicin, rituximab, cyclophosphamide, vincristine, and prednisone in AIDS-related lymphoma: AIDS Malignancy Consortium Study 047.

PURPOSE: Infusional chemotherapy is efficacious in patients with AIDS-related lymphoma, but it may be difficult to administer. We studied standard agents with rituximab plus pegylated liposomal doxorubicin (DR-COP) in an attempt to provide a more practical approach to therapy while ascertaining rates of response, potential infectious complications, and prognostic role of biologic markers. PATIENTS AND METHODS: We conducted a prospective, multi-institutional phase II trial, employing (day 1) pegylated liposomal doxorubicin 40 mg/m(2), rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2), vincristine 1.4 mg/m(2) (not > 2 mg), and prednisone 100 mg orally on days 1 through 5, with concomitant antiretroviral therapy. RESULTS: In 40 evaluable patients, median CD4 cells was 114/µL (range, 5 to 1,026/µL), and median HIV-1 viral load (VL) was 25,000 copies/mL. High or intermediate/high age-adjusted International Prognostic Index was present in 28%. Overall response was 67.5%, with complete remission in 47.5% (95% CI, 31.5 to 63.9). Of 19 complete responders, 84% had extranodal disease, 47% had CD4 < 100/µL, and 47% had VL > 50,000 copies/mL; one relapsed. With 25.5-month median follow-up, 62% (95% CI, 44 to 75) of patients remain alive. Sixteen patients (40%) experienced 22 infections, with grade 4 in only two (5%). No patient died as a result of infection during treatment; one had opportunistic infection. CONCLUSION: Profound immunodeficiency and high HIV-1 viral load do not preclude attainment of complete response after DR-COP with highly active antiretroviral therapy. The regimen is tolerable, and use of rituximab was not associated with death as a result of infection during treatment. This approach may be useful in patients in whom the more intensive infusional regimens are impractical.

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.

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.

An investigation of the possible interaction between the use of Vitamin C and highly active antiretroviral therapy (HAART) adherence and effectiveness in treated HIV+ women.

OBJECTIVES: Our goal in this study was to examine how Vitamin C interacts with antiretroviral therapy in individuals with HIV. We specifically evaluated how Vitamin C impacts highly active antiretroviral therapy (HAART) adherence and HAART effectiveness as adjudicated by HIV viral loads and CD4 cell counts. Women served as their own controls, comparing periods of Vitamin C usage with periods of non-usage. DESIGN: An intra-individual, cross-sectional comparative study 'nested' in the WIHS observational cohort study. SUBJECTS: Women in the Women's Interagency HIV Study (WIHS). OUTCOME MEASURES: Adherence, CD4 count and viral load. RESULTS: Our study population was drawn from 2813 HIV+ participants who contributed 44,588 visits in WIHS from October, 1994 to April, 2009. Among them, there were 1122 Vitamin C users with 4954 total visits where use was reported. In the multivariate model adjusting for age, education, race, income, drug use, Vitamin C use order and depression score, there was a 44% increase in the odds of ≥ 95% HAART adherence among participants during their period of Vitamin C use compared to when they were not using Vitamin C (OR=1.44; 95% CI=1.1-1.9; P-value=0.0179). There was an association with Vitamin C usage and CD4 counts on viral loads. CONCLUSION: Vitamin C usage appears to be associated with improved adherence. Future Vitamin C studies should target specific HAART drugs, and prospective clinical outcomes.