Anal cancer screening among women with HIV: provider experiences and system-level challenges.

Women living with HIV (WLWH) are at increased risk of anal cancer compared to women without HIV, often due to persistent human papillomavirus (HPV) infections. This paper describes current practices and challenges conducting anal cancer screening for WLWH at an urban integrated safety-net system and a non-profit community-based HIV clinic. We conducted 25 semi-structured interviews with clinical and administrative stakeholders to assess knowledge, clinic practices and procedures, and experiences with anal cancer screening. Interview transcripts and fieldnotes were thematically analyzed using an iterative deductive and inductive coding scheme. Findings were organized by the Consolidated Framework for Implementation Research (CFIR) domains and constructs. Provider-level barriers to conducting anal cancer screening included limited knowledge of guidelines. System-level barriers included: structural characteristics such as lack of coordination between clinics to discern provider roles and responsibilities; and limitations in available resources such as configuration of electronic health records and infrastructure to manage referrals of abnormal anal Pap results. We conclude that anal cancer screening and follow-up for WLWH requires organization and coordination between multiple care teams, updated clinical information systems to facilitate communication and support anal Pap ordering and result documentation, and infrastructure that includes policies and protocols for management of abnormal results.Trial registration: ClinicalTrials.gov identifier: NCT02135419.

Anal Cancer and Anal Cancer Screening Knowledge, Attitudes, and Perceived Risk Among Women Living With HIV.

OBJECTIVES: The aims of the study were (1) to describe anal cancer knowledge, perceived risk, screening barriers, and acceptability of sample self-collection among women living with HIV (WLWH) at an integrated safety-net system and (2) to describe differences in demographic and psychosocial variables among a subsample of WLWH with a history of abnormal cervical cytology results versus those with normal results. MATERIALS AND METHODS: We conducted telephone surveys with English- and Spanish-speaking WLWH (N = 99) and used electronic health record data to extract insurance type, CD4+ cell count, RNA viral load, and cervical cytology results. We calculated descriptive statistics for participant demographics, HIV laboratory results, and psychosocial variables. Among the subsample of women who completed a recent cervical Pap, we used Fisher exact test to assess differences in demographic variables, CD4+ counts, RNA viral loads, knowledge, awareness, acceptability, and perceived risk by cervical cytology results. RESULTS: Most participants (70%) reported knowing nothing about anal cancer; 28% correctly responded that HIV increases one's chance of getting anal cancer. Most (68%) never heard of an anal Pap test. Forty percent would get an anal Pap if they could self-collect the sample, whereas 59% were neutral or disagreed. The 2 most commonly cited barriers to obtaining an anal Pap were "I do not know enough about it" (n = 15) and "It might hurt" (n = 9). CONCLUSIONS: This study highlights a gap in knowledge and awareness among WLWH regarding their heightened risk for anal cancer. It indicates the need for health education and suggests an opportunity for a self-collection intervention.

Lipid-Lowering Therapy in HIV-Infected Patients: Relationship with Antiretroviral Agents and Impact of Substance-Related Disorders.

BACKGROUND: The use of combination antiretroviral therapy (cART) has significantly decreased the morbidity and mortality associated with human immunodeficiency virus (HIV) infection. Lipid disorders, including lipodystrophy, hypertriglyceridemia, and hypercholesterolemia, remain the most commonly reported metabolic disorders among those treated with long-term cART. Mounting evidence suggests an association between drug abuse and poor glycemic control and diabetes complications. Substance related disorders (SRD) may increase the risk of metabolic syndrome. MATERIALS AND METHODS: The aim of this retrospective cohort study was to examine the relationship between SRD, cART, and lipid-lowering agent use in an HIV infected population. Patients received efavirenz or protease inhibitor-based cART for at least 6 months. Prescription information was retrieved from the medical records. The primary outcome was the use of lipid-lowering agents including statins, fibrates and fish oil. The impact of SRD and cART was assessed on the lipid-lowering agent use. RESULTS: A total of 276 subjects with HIV infection were included, 90 (33%) received lipid-lowering agents, and 31 (34%) had SRD. Smoking was prevalent among subjects with SRD (84 vs 15%, p<0.001). Statins were the mainstay for the management of dyslipidemia (66%), followed by the fibrates (24%), omega-3 fatty acids (5%), nicotinic acid (3%) and the cholesterol absorption inhibitors (3%). Use of statins or fibrates was significantly higher among subjects without SRD than those with (40 vs 23%, p=0.005). The type of cART, including efavirenz and protease inhibitors, appeared to have no significant impact on the use pattern of lipid-lowering agents. Lopinavir/ritonavir (lopinavir/r) was mostly prescribed for subjects with SRD (25 vs 8%, p=0.02). CONCLUSION: Among HIV-infected patients, statins remain the mainstay for the management of dyslipidemia in routine clinical care, followed by fibrates. A significant high risk of metabolic disorders among patients with SRD is implicated by heavy tobacco use and prevalent lopinavir/r-based treatment. Significantly low rate of lipid-lowering agent use in this population underscores the importance of lipid disorder scrutiny and cART treatment optimization for HIV-infected patients with SRD.

Identifying Effective Approaches for Dissemination of Clinical Evidence--Correlation Analyses on Promotional Activities and Usage of a Guideline-Driven Interactive Case Simulation Tool in a Statewide HIV-HCV-STD Clinical Education Program.

Dissemination of the latest clinical evidence to community-based healthcare providers is a critical step to translate biomedical knowledge into clinical practice. We performed a study to analyze the correlations between the promotional activities and the usage of a guideline-driven interactive case simulation tool (ICST) for insomnia screening and treatment in a statewide HIV-HCV-STD clinical education program. For this purpose, we tracked users' interactions with the ICST and the sending of promotional email newsletters during a study period of 44 weeks. Results showed that promotional activities were strongly correlated with the number of audience as well as the intensity of use of the target resource. The strength of correlation varied in specific use contexts. Strong correlations were found between the sending of email newsletters and the intensity of resource use by promotion recipients, by new users, and through the most convenient access channel associated with the promotion. Selection of approaches for resource dissemination should consider the potentials and limitations of use contexts to make them more effective.

Depot medroxyprogesterone acetate in combination with a twice-daily lopinavir-ritonavir-based regimen in HIV-infected women showed effective contraception and a lack of clinically significant interactions, with good safety and tolerability: results of the ACTG 5283 study.

We conducted an open-label, steady-state pharmacokinetic (PK) study of drug-drug interactions between depot medroxyprogesterone acetate (DMPA) and twice-daily lopinavir (LPV) plus low-dose ritonavir (RTV) (LPV/r) among 24 HIV-infected women and compared the results to those for HIV-infected women receiving DMPA while on no antiretroviral therapy or on nucleosides only (n = 14 subjects from the control arm of AIDS Clinical Trials Group [ACTG] study 5093). The objectives of the study were to address the effect of LPV/r on DMPA and to address the effect of DMPA on LPV/r therapy. PK parameters were estimated using noncompartmental analysis with between-group comparisons of medroxyprogesterone acetate (MPA) PKs and within-subject comparisons of LPV and RTV PKs before and 4 weeks after DMPA dosing. Plasma progesterone concentrations were measured every 2 weeks after DMPA dosing through week 12. Although the MPA area under the concentration-time curve and maximum concentration of drug in plasma were statistically significantly increased in the study women on LPV/r compared to those in the historical controls, these increases were not considered clinically significant. There were no changes in LPV or RTV exposure after DMPA. DMPA was well tolerated, and suppression of ovulation was maintained. (This study has been registered at ClinicalTrials.gov under registration no. NCT01296152.).

The impact of age on the prognostic capacity of CD8+ T-cell activation during suppressive antiretroviral therapy.

OBJECTIVE: To assess whether CD8 T-cell activation predicts risk of AIDS and non-AIDS morbidity during suppressive antiretroviral treatment (ART). DESIGN: Post-hoc analyses of ART-naive participants in prospective ART studies. Participants with HIV-RNA levels 200 copies/ml or less and CD8 T-cell activation data (%CD38HLA-DR) at year-1 of ART were selected to determine years 2-5 incidence of AIDS and non-AIDS events. METHODS: We censored data at time of ART interruption or virologic failure. Inverse probability of censoring-weighted logistic regression was used to correct for informative censoring. RESULTS: We included 1025 participants; 82% were men, median age 38 years, pre-ART CD4 cell count 255 cells/µl, and year-1-activated CD8 T cells 24%. Of these, 752 had 5 years of follow-up; 379 remained on ART and had no confirmed plasma HIV-RNA more than 200 copies/ml. The overall probability of an AIDS or non-AIDS event in years 2-5 was estimated at 13% [95% confidence interval (CI) 10-15%] had everyone remained on suppressive ART. Higher year-1-activated CD8 T-cell percentage increased the probability of subsequent events [odds ratio 1.22 per 10% higher (95% CI 1.04-1.44)]; this effect was not significant after adjusting for age. Among those age 50 years at least (n=108 at year 1), the probability of an event in years 2-5 was 37% and the effect of CD8 T-cell activation was more apparent (odds ratio=1.42, P=0.02 unadjusted and adjusted for age). CONCLUSION: CD8 T-cell activation is prognostic of clinical events during suppressive ART, although this association is confounded by age. The consequences of HIV-associated immune activation may be more important in patients 50 years and older.

Assessing the usage of a guideline-driven interactive case simulation tool for insomnia screening and treatment in an HIV clinical education program.

Interactive case simulation tools (ICSTs) are important vehicles to disseminate medical knowledge. We conducted a study to examine the usage of an insomnia screening and treatment case simulation tool in an HIV clinical education program. Using system usage diagrams (SUDs) as an instrument, we quantified visit frequency and length of stay for different types of system resources. Preliminary results have shown that both recommendations and interactive decision diagrams were frequently used, with the former having a longer length of stay but fewer visits. Case simulation functions seemed to be able to engage users. Future research is required to verify the generalizability of the identified usage patterns, to investigate issues in usability design, and to perform correlation analyses on system usage and context parameters.

Polypharmacy in the HIV-infected older adult population.

The prevalence of human immunodeficiency virus (HIV) infection among people older than 50 years is increasing. Older HIV-infected patients are particularly at risk for polypharmacy because they often have multiple comorbidities that require pharmacotherapy. Overall, there is not much known with respect to both the impact of aging on medication use in HIV-infected individuals, and the potential for interactions with highly active antiretroviral therapy (HAART) and coadministered medications and its clinical consequences. In this review, we aim to provide an overview of polypharmacy with a focus on its impact on the HIV-infected older adult population and to also provide some clinical considerations in this high-risk population.

Effect of highly active antiretroviral therapy (HAART) and menopause on risk of progression of cervical dysplasia in human immune-deficiency virus- (HIV-) infected women.

BACKGROUND: More HIV-infected women are reaching older age and menopause, but there is limited information on cervical squamous intraepithelial lesions (SILs) on these women. METHODS: To assess the effect of HAART and menopause on SILs in HIV-infected women, we reviewed the results of Papanicolaou (Pap) tests obtained between 1991 and 2011 on 245 women. Progression to SILs was determined by comparing Pap test results. The association of HAART and transition to menopause on SILs was assessed using survival analysis. RESULTS: Women receiving HAART had a 52% reduced risk in the progression to SILs compared to women receiving any other antiretroviral regimen or no regimen (CI: 0.33-0.70, P = 0.0001). A greater increase of CD4(+) cell counts was associated with a greater reduction on the risk of progression to SILs. Menopausal women had a 70% higher risk of progression to SILs than premenopausal women (CI: 1.11-2.62, P < 0.0001), adjusting for HIV medications, CD4(+) count, duration of HIV infection, moderation effect of menopause by age, prior IV drug use, and smoking. CONCLUSION: HAART had a positive long-term effect on the progression to SILs. However, being younger and menopausal increases the risk of progression.

Anal cancer screening in HIV-infected patients: is it time to screen them all?

BACKGROUND: Annual screening for anal cancer is recommended only for HIV patients at increased risk: men who have sex with men, individuals with a history of anogenital warts, and women with cervical dysplasia. OBJECTIVE: The aim of this study was to examine the screening outcomes between HIV populations with and without these risk factors. METHODS: We reviewed the records of all HIV patients referred for anal cytology and high-resolution anoscopy from June 2009 to June 2010. Patients were stratified into an increased-risk group or a standard-risk group. MAIN OUTCOME: Of the 329 evaluable patients, 285 (89.8% men, 10.2% women, mean age 46 ± 10 years) were classified to the increased-risk group, whereas 44 (72.7% men, 27.3% women, mean age 52 ± 8 years) were included in the standard-risk group. Male sex, white race, sexual orientation, past and current receptive anal intercourse, noncompliance with condom use, and absence of a new sexual partner were significantly different in the increased-risk group in comparison with the standard-risk group. In the increased-risk group, 187 (66.5%) patients had biopsy-proven dysplasia of which 118 (42.0%) had high-grade disease. In the standard-risk group, 15 (34.9%) patients had biopsy-proven dysplasia of which 7 (16.3%) had high-grade disease. Cytology detected biopsy-confirmed high-grade dysplasia only in 23 of 118 (19.5%) patients in the increased-risk group and in 2 of 7 (28.6%) patients in the standard-risk group. Kappa agreement in detecting high-grade disease was low for both increased-risk and standard-risk groups: 0.16 (95% CI 0.07-0.23) and 0.40 (95% CI 0.02-0.40). LIMITATIONS: Our study is a chart-based retrospective review of data with a small female population. Histology reports came from 2 different laboratories. CONCLUSION: High-grade anal dysplasia was prevalent even among HIV patients who only have standard risk factors. Anal cytology and high-resolution anoscopy have poor agreement. We suggest considering annual screening by using high-resolution anoscopy in addition to cytology for all HIV patients regardless of risk factors.

Therapeutic drug monitoring of protease inhibitors and efavirenz in HIV-infected individuals with active substance-related disorders.

BACKGROUND: Achieving targeted antiretroviral (ARV) plasma concentrations during long-term treatment in human immunodeficiency virus (HIV)-infected patients with substance-related disorders (SRDs) may be challenging due to a number of factors, including medication adherence, coinfection with hepatitis B or C virus, medication intolerance, and drug interactions. One approach to investigate these factors is to conduct therapeutic drug monitoring to measure ARV exposure during treatment. The objective of this study was to utilize therapeutic drug monitoring to compare efavirenz (EFV) and protease inhibitor pharmacokinetics in patients with and without SRDs. METHODS: This was a multicenter, cross-sectional open-label study in patients with HIV-1 infection receiving antiretroviral therapy (ART), with active (n=129) or without (n=146) SRD according to National Institute on Drug Abuse criteria. Two hundred seventy-five subjects who were receiving either protease inhibitor-based or EFV-based ART regimens for >6 months were enrolled at 4 HIV treatment centers with an equal distribution of SRD and non-SRD at each site. The patients were instructed during enrollment visits with regard to the importance of adherence before and after study visits. Demographics and routine clinical laboratory tests were recorded. RESULTS: Among the 275 patients, 47% had SRD with at least 1 substance. There were no significant differences between SRD and non-SRD groups for race, gender, age, or CD4 count at entry. A significantly higher proportion of patients with SRD had an entry HIV RNA plasma concentration>75 copies per milliliter compared with patients without SRD (40% vs 28%, P=0.044). Logistic regression modeling revealed an association between HIV RNA plasma concentration and African American race (P=0.017). A significantly higher proportion of SRDs also had an EFV or protease inhibitor trough concentration below the desired range (23% vs 9%, P=0.048). Significantly lower trough concentrations were noted in patients with SRDs receiving atazanavir (0.290 vs 0.976 µg/mL) or lopinavir (3.75 vs 5.30 µg/mL). CONCLUSIONS: The pharmacokinetic data indicate differences between HIV-infected patients with and without SRDs that may influence viral load suppression during long-term ART. These findings require additional investigation in a randomized design with more intensive pharmacokinetic assessment to identify individual factors that are contributing to suboptimal ARV exposure in patients with SRDs.

Prevalence of human papillomavirus genotypes in HIV-1-infected women in Seattle, USA and Nairobi, Kenya: results from the Women's HIV Interdisciplinary Network (WHIN).

BACKGROUND: HIV-infected women have a high prevalence of human papillomavirus (HPV) infection and are more likely to be infected with HPV genotypes that are considered high-risk and have the potential for progressing to cervical cancer. The currently available HPV vaccines protect against specific HPV genotypes that may not be the most important causes of dysplasia and potentially of cervical cancer in HIV-1-infected women. African women have been underrepresented in the studies of global prevalence of HPV genotypes. METHODS: We compared the HPV genotype distribution in HIV-1-infected women from Seattle, Washington, USA and Nairobi, Kenya. The reverse line blot assay and DNA sequencing on cervicovaginal lavage (CVL) specimens were carried out. RESULTS: The most commonly detected HPV types among the women from Seattle were HPV 56, 66, MM8, and 81; in contrast HPV 53, 33, and 58 were the most common HPV genotypes detected in the CVL specimens from the women in the Nairobi cohort. The HPV types associated with low-grade squamous intraepithelial lesions (LSIL) were HPV 53 and HPV 56. HPV types 58, 52, and 16 were associated with high-grade squamous intraepithelial lesions (HSIL). CONCLUSIONS: A better understanding of HPV genotype distribution in the most affected regions of the world is essential to planning effective vaccine strategies if we are unable to demonstrate cross-protection between HPV genotypes included in the present vaccines and those prevalent in the different populations.

Prevalence of human papillomavirus genotypes and related abnormalities of cervical cytological results among HIV-1-infected women in Rochester, New York.

Women with human immunodeficiency virus (HIV) infection have higher rates of concurrent human papillomavirus (HPV) infection and cervical dysplasia than do HIV-uninfected women. They are also more commonly infected with multiple HPV types simultaneously. To determine the prevalence of different HPV genotypes in a group of HIV-infected women and to correlate these findings with cervical cytological results, we studied a group of 229 women attending a university-based HIV clinic during a 7-year period. When cervicovaginal lavage specimens, the reverse line-blot assay, and DNA sequencing were used, the most commonly detected HPV types (in decreasing order of frequency) were 56, 53, 16, 58, 52, MM7, MM8, and 33. These results contrast sharply with similar studies of HIV-uninfected women, in whom HPV-16 and -18 generally predominate. In our study, the HPV types most commonly associated with low-grade squamous intraepithelial lesions (SILs) were 56 and 53. Types most commonly associated with high-grade SILs were 52 and 58. High-risk HPV types other than 16 and 18 are often found in HIV-infected women and are frequently associated with abnormal cervical cytological results in this setting. These observations have implications for the design of future HPV vaccines.