Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer.

BACKGROUND: The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking. METHODS: We conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer. RESULTS: Of 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test). CONCLUSIONS: Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.).

Evaluating the staffing methodology model in the veterans health administration's community living centers.

PURPOSE: Program evaluation to describe nursing hours per patient day (NHPPD) within the Veterans Health Administration (VHA) and to evaluate Staffing Methodology in the VHA Community Living Centers (CLCs). METHODS: Targeted and actual NHPPD were compiled retrospectively for each VHA CLC unit over a one-year timeframe for calendar year 2019. For descriptive analyses, actual NHPPD were averaged across months for each CLC unit. RESULTS: The mean for actual hours as a percent of target was 121.6% (95% CI, 118.5 to 124.7%) indicating the units' average hours across 2019 were 21.6% significantly higher than target. The actual NHPPD significantly differed across months (p<0.001) with the 2019 months of January and October having the highest NHPPD. CONCLUSIONS: Veteran safety is a VHA priority and appropriate nurse staffing is key to providing care that improves Veteran outcomes. Further exploration is needed on the impact of nurse staffing on Veteran outcomes, safety, and satisfaction.

Design of the ANal Cancer/HSIL Outcomes Research study (ANCHOR study): A randomized study to prevent anal cancer among persons living with HIV.

It is well established that persons living with HIV (PLWH) have highly elevated rates of anal HSIL and anal cancer compared with those who are not living with HIV. The 5-year risk of anal cancer following anal HSIL has been reported to be as high as 14.1% among PLWH compared with 3.2% among those who are not living with HIV. To address these concerns, the AIDS Malignancy Consortium completed a large-scale, randomized trial to compare strategies for the prevention of anal cancer among PLWH with anal HSIL. The objective of the study was to determine whether treating anal HSIL was effective in reducing the incidence of anal cancer in PLWH compared with active monitoring. This paper describes the design of the ANal Cancer/HSIL Outcomes Research Study (ANCHOR) with respect to estimating the anal cancer event rate in this high risk population.

Rapid conversion of Tai Chi classes from face-to-face to virtual during the COVID-19 pandemic: A quality improvement project.

PURPOSE: The purpose of this quality improvement project was to examine the feasibility of rapidly converting a Tai Chi program for older Veterans from face-to-face to virtual classes. METHODS: Eighteen Veterans attending our face-to-face Tai Chi course were invited to transition to virtual classes. Feasibility was defined as the ability of program staff and participants to successfully connect and complete the initial and subsequent classes by VA Video Connect (VVC) with little to no technical difficulties, participant ability to participate in the course without safety concerns, and favorable feedback from participants and program staff. RESULTS: Nine of 18 Veterans agreed to transition to the virtual program and attended a median (interquartile range) of 11 (4-15) classes; they were younger (62.7 + 11.5 vs. 70.5 + 7.0 years, p < .05) and more likely to have the knowledge and equipment needed to participate (78% vs. 0%, p < .01) than nonparticipants. Tai Chi instructors and participating Veterans reported being able to connect to and complete the classes virtually with only minimal technical problems. No adverse events were reported. Feedback from the instructors and Veterans was positive and included comments on ease of use and enjoyability. CONCLUSION: Results suggest that virtual Tai Chi classes via VVC are feasible for some older Veterans.

Opioid Use Disorder: Treatment Outcomes in U.S. Veterans.

BACKGROUND: Substance use disorders are a leading cause of morbidity and mortality in the United States, with opioid use disorder representing a growing public health concern and economic burden. Veterans within the Veterans Health Administration are impacted by opioid use disorder. SIGNIFICANCE: A common medication-assisted treatment is sublingual Suboxone (buprenorphine/naloxone) used in combination with behavior modification therapy. Missed Suboxone doses may lead to withdrawal and potential drug diversion. Sublocade (buprenorphine extended-release) is an alternative once-monthly subcutaneous injection administered by a healthcare provider. The purpose of this quality improvement project was to examine the effects of Sublocade on cravings in veterans with opioid use disorder. METHODS: Veterans were considered for Sublocade monthly injections if they were enrolled in the Suboxone program, not taking Suboxone as prescribed, and disenrolled from the Suboxone program more than 2 times. Cravings were measured before and after Sublocade program enrollment. RESULTS: Fifteen veterans were enrolled in the Sublocade program over a 12-month timeframe. Most were male (93%) with a median (range) age of 42 (33-62) years. The following were the primary opioids used before enrollment in the substance use disorder program: hydrocodone (47%), oxycodone (20%), and heroin (20%). Sublocade significantly reduced cravings (p = .001). In this small group, cravings were fully eliminated. DISCUSSION: Recent studies have shown Sublocade effectively blocks the effects of other opioids and minimizes the risk of medication diversion that occurs with Suboxone. For these reasons, Sublocade is an alternative medication-assisted treatment for veterans with opioid use disorder.

Xpert HPV as a Screening Tool for Anal Histologic High-Grade Squamous Intraepithelial Lesions in Women Living With HIV.

BACKGROUND: Women living with HIV (WLWH) experience high rates of anal cancer. Screening using anal cytology, high-resolution anoscopy (HRA) with biopsies, can histologically diagnose anal cancer precursors called high-grade squamous intraepithelial lesions (HSIL). The low specificity of screening using anal cytology results in HRA referral for many WLWH without HSIL. Screening using high-risk human papillomavirus (HR-HPV) may improve specificity. METHODS: Two hundred seven WLWH (63% non-Hispanic black) were screened for anal histologic HSIL (hHSIL) using cytology, HRA-guided biopsies, and Xpert HPV. Xpert performance for predicting anal hHSIL was compared with that of cytology. Usng Xpert 5 HPV genotypic results and accompanying cycle thresholds, receiver operator characteristic curve and recursive partitioning analyses were used to create predictive models for hHSIL. RESULTS: The performance of Xpert to predict hHSIL was not different from that of cytology with a sensitivity (Sn) of 89% and specificity (Sp) of 49%. Interpretation of Xpert was modified using genotypic results and receiver operator characteristic curve analysis, which produced a screen with an Sn and Sp of 75% and 84% for hHSIL, respectively. Another reinterpretation of Xpert was created using recursive partitioning and cycle thresholds, which predicted hHSIL with an Sn and Sp of 75% and 86%, respectively. The detection of HPV-16 was highly predictive of hHSIL in all analyses. These modified screening tests would reduce HRA referral in this population by almost half compared with anal cytology. CONCLUSIONS: Xpert HPV is an alternative to anal cytology to screen for anal HSIL and can be optimized to reduce the number of unnecessary HRAs performed in WLWH.

High Prevalence of Anal High-Grade Squamous Intraepithelial Lesions, and Prevention Through Human Papillomavirus Vaccination, in Young Men Who Have Sex With Men Living With Human Immunodeficiency Virus.

BACKGROUND: Men who have sex with men (MSM) are at high risk for human papillomavirus (HPV)-related anal cancer. Little is known about the prevalence of low-grade squamous intraepithelial lesions (LSILs) and the anal cancer precursor, high-grade squamous intraepithelial lesions (HSILs), among young MSM with HIV (MSMLWH). HPV vaccination is recommended in this group, but its safety, immunogenicity, and protection against vaccine-type HPV infection and associated LSILs/HSILs have not been studied. METHODS: Two hundred and sixty MSMLWH aged 18-26 years were screened at 17 US sites for a clinical trial of the quadrivalent (HPV6,11,16,18) HPV (qHPV) vaccine. Those without HSILs were vaccinated at 0, 2, and 6 months. Cytology, high-resolution anoscopy with biopsies of lesions, serology, and HPV testing of the mouth/penis/scrotum/anus/perianus were performed at screening/month 0 and months 7, 12, and 24. RESULTS: Among 260 MSMLWH screened, the most common reason for exclusion was detection of HSILs in 88/260 (34%). 144 MSMLWH were enrolled. 47% of enrollees were previously exposed to HPV16. No incident qHPV type-associated anal LSILs/HSILs were detected among men naive to that type, compared with 11.1, 2.2, 4.5, and 2.8 cases/100 person-years for HPV6,11,16,18-associated LSILs/HSILs, respectively, among those previously exposed to that type. qHPV was immunogenic and safe with no vaccine-associated serious adverse events. CONCLUSIONS: 18-26-year-old MSMLWH naive to qHPV vaccine types were protected against incident qHPV type-associated LSILs/HSILs. Given their high prevalence of HSILs, there is an urgent need to vaccinate young MSMLWH before exposure to vaccine HPV types, before initiating sexual activity, and to perform catch-up vaccination.

Treatment of Male Sexual Partners of Women With Bacterial Vaginosis: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: We aimed to determine if treatment of male sexual partners of women with recurrent bacterial vaginosis (BV) with oral metronidazole 2×/day for 7 days (ie, multidose metronidazole) significantly decreased BV recurrence rates in the female. METHODS: This was a multicenter, 2-arm, double-blind, placebo-controlled study. Women with recurrent BV and current diagnosis of BV by Amsel and Nugent were enrolled. Multidose metronidazole for 7 days was dispensed to women. Male partners were randomized to placebo versus multidose metronidazole for 7 days and asked to refrain from unprotected sex for 14 days. Female follow-up visits were conducted at day 21 and 8 and 16 weeks. Male follow-up visits occurred at days 14-21. BV cure was defined as 0-2 Amsel criteria and Nugent score 0-6 in the female partner with the primary endpoint at 16 weeks. RESULTS: 214 couples were enrolled. In the intent-to-treat population, there was no significant difference between treatment arms for the primary outcome. BV treatment failure occurred in 81% and 80% of women in the metronidazole and placebo arms through the third follow-up visit, respectively (P > .999). However, women whose male partners adhered to study medication were less likely to fail treatment (adjusted relative risk, .85; 95% CI, .73-.99; P = .035). This finding persisted in post hoc comparisons in the metronidazole arm. CONCLUSIONS: Overall, this study did not find that male partner treatment with multidose metronidazole significantly reduces BV recurrence in female partners, although women whose partners adhered to multidose metronidazole were less likely to fail treatment. CLINICAL TRIALS REGISTRATION: (NCT02209519).

Factors Influencing the Commitment of Students to Radiology as a Career Choice During Medical School Education.

RATIONALE AND OBJECTIVES: The purpose of this study is to analyze the significance of specific factors in choosing radiology as a specialty compared to switching to/from a different specialty as reported in the Graduation Questionnaire (GQ) and Matriculating Student Questionnaire (MSQ) data provided by Association of American Medical Colleges. METHOD AND MATERIALS: The study cohort included students who completed both the MSQ and GQ questionnaires in the span of 3-5 years. The cohort was divided into three groups-"Committed" (students who chose radiology in both the first and final year of medical school), "Switched Away" (students who chose radiology on the MSQ but later switched to a different specialty, and "Switched-To" (students who chose radiology on GQ after initially selecting an alternate specialty on the MSQ). RESULTS: Of 1965 students who chose radiology between the years 2013 and 2016, 281 were Committed, 625 Switched-Away, and 1059 Switched-To. There were significant differences among the groups for salary, length of residency, and work-life balance factors. In the Switched-Away group, more students were influenced by length of residency (18% vs. 5%, p < 0.001) and fewer were influenced by salary (21% vs. 30%, p=0.004) or work-life balance (54% vs. 66%, p = 0.001) when compared to the Committed group. The Switched-To group did not significantly differ from the Committed group (all p > 0.05) for length of residency (6% vs. 5%), salary (30% vs. 30%) and work-life balance (69% vs. 66%). CONCLUSION: The data provide insight into factors that influence medical students to initially commit to, switch away from, and switch to radiology during medical school. Understanding these dynamics can inform mentors to guide medical students who are interested in a radiology career.

An outpatient Tai Chi program: Effects on veterans' functional outcomes.

PURPOSE: To evaluate the effectiveness of an evidence-based 12-week Tai Chi course designed to improve balance and physical function in a population of older veterans. METHODS: Community dwelling veterans of all ages with gait and balance problems were invited to participate in the Tai Chi program. Participants completed the Berg Balance Scale (BBS), the Timed Up and Go (TUG) test, and the Falls Efficacy Scale-International (FES-I) at baseline and again at the end of the program. Descriptive statistics were used to summarize study participants' characteristics. The change from baseline to the end of the 12-week program was calculated for each of the three primary outcome variables (BBS, TUG, FES-I). RESULTS: Twenty-two veterans, aged 58 years and above, with perceived gait and/or balance issues were enrolled in the program with completion by 11 veterans. Veterans who completed their final assessments showed the BBS, improved significantly (p = 0.004) from baseline to the 12-week assessment. The TUG scores improved by a median of 1.3 s (p = 0.022). There was not a significant change in the FES-I. CONCLUSIONS: Preliminary findings provide evidence of the effectiveness of a 12-week Tai Chi program to improve functional outcomes for older veterans with mild to moderate gait and balance problems.

An Interdisciplinary Approach to Educating Medical Students About Dementia Assessment and Treatment Planning.

BACKGROUND: Many general practitioners consider dementia care beyond their clinical domain and feel that dementia assessment and treatment should be addressed by specialists, such as geriatricians, geriatric psychiatrists, or neurologists. An urgent need exists to educate all medical trainees in dementia care, regardless of their specialization interests. OBSERVATIONS: We developed a multicomponent, experiential, brief curriculum using team-based learning to expose senior medical students who rotated through the US Department of Veterans Affairs Memory Disorders Clinic at the Central Arkansas Veterans Healthcare System in Little Rock to an interdisciplinary assessment of dementia. The curriculum included didactics, clinical experience, and team-based learning. In pre- and postevaluation, students rated their perception of the role of interdisciplinary team members in assessing and managing dementia, their personal abilities to assess cognition, behavioral problems, caregiver burden, and their perception of the impact of behavioral problems on dementia care. CONCLUSIONS: Dementia knowledge gaps were prevalent in this cohort of senior medical students. Providing interdisciplinary geriatric educational experience improved students perception of their ability to assess for dementia and their recognition of the roles of interdisciplinary team members. Plans are in place to continue and expand the program to other complex geriatric syndromes.

Screening strategies for the detection of anal high-grade squamous intraepithelial lesions in women living with HIV.

OBJECTIVE: HIV-infected women (WLHIV) have more than 10-fold higher risk for squamous cell cancer of the anus. Experts suggest cytology-based strategies developed for cervical cancer screening may prevent anal cancer by detecting anal cytologic or histological high-grade squamous intraepithelial lesion (hHSIL) for treatment. Currently, there is no consensus on anal-hHSIL screening strategies for WLHIV. DESIGN: Between 2014 and 2016, 276 WLHIV were recruited at 12 US AIDS Malignancy Consortium clinical trials sites to evaluate hHSIL prevalence and (test) screening strategies. METHODS: Participants completed detailed questionnaire, underwent anal assessments including high-risk human papillomavirus (hrHPV) testing using hrHPV-Hybrid Capture 2 (HC2) and hrHPV-APTIMA, anal cytology, and concurrent high-resolution anoscopy. Screening test characteristics for predicting hHSIL validated by central review of histologic diagnosis were estimated sensitivity, specificity, positive predictive value, and false-omission rate. Paired analyses compared sensitivity and specificity for hrHPV single tests to anal cytology alone. RESULTS: 83% (229/276) of enrolled WLHIV had complete anal assessment data and were included in this analysis. Mean age was 50, 62% black and 60 (26%) had hHSIL. Anal cyotology (>atypical squamous cells of undetermined significance), hrHPV-HC2, and hrHPV-APTIMA sensitivity estimates were similarly high (83, 77, and 75%, respectively, P values > 0.2). Specificity was higher for both hrHPV-APTIMA and hrHPV-HC2 compared with anal cytology (67 vs. 50%, P < 0.001) and (61 vs. 50%, P = 0.020), respectively. CONCLUSION: Anal hrHPV testing demonstrated similar sensitivity for anal cytology (>atypical squamous cells of undetermined significance) to predict anal hHSIL. Among tests with similar sensitivity, the specificity was significantly higher for hrHPV-APTIMA and hrHPV-HC2. Thus, anal hrHPV testing may be an important alternative strategy to anal cytology for anal hHSIL screening among WLHIV.

Neuromodulation for Apathy in Alzheimer's Disease: A Double-Blind, Randomized, Sham-Controlled Pilot Study.

BACKGROUND: Apathy, a profound loss of motivation, initiation, and goal directed cognition, is a common comorbidity of Alzheimer's disease (AD). The presence of apathy is associated with rapid progression of AD, long-term impairment, disability, and higher mortality. Pharmacological treatments of apathy are limited. OBJECTIVE: The primary objective was to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) for apathy in AD. METHODS: A randomized, double-blind, parallel-arm, sham-controlled pilot study was conducted in subjects with AD and apathy (N = 20). Subjects were randomized to rTMS or sham treatment (5 days/week) for four weeks. Primary outcome, apathy evaluation scale-clinician version (AES-C), and secondary outcome measures, modified-Mini Mental State Examination (3MS), instrumental activities of daily living (IADL), and clinical global impression (CGI), were assessed at baseline and four weeks. Follow-up visits were conducted at 8 and 12 weeks to test the durability of effects of intervention. RESULTS: Mean age was 77.3 (±7.2) years, 80% were Caucasians and 10% were females. After adjusting for baseline, there was a significantly greater improvement in the AES-C with rTMS compared to sham treatment (-10.1 (-15.9 to -4.3); t (16) â€Š= -3.69; p = 0.002) at 4 weeks. There was also significantly greater improvement in 3MS (6.9 (1.7 to 12.0); t (15) â€Š= 2.85; p = 0.012), IADL (3.4 (1.0 to 5.9); χ21 = 7.72; p = 0.006), CGI-S (1.4 (0.5 to 2.3), t (16) â€Š= 3.29; p = 0.005), and CGI-I (-2.56 (-3.5 to -1.6), t (17) â€Š= -5.72; p < 0.001) for rTMS compared to the sham at 4 weeks. The effects of rTMS were durable at 12 weeks. CONCLUSION: rTMS may be safely used in subjects with AD and may improve apathy, function, and some aspects of cognition.

Sustained fetal hematopoiesis causes juvenile death from leukemia: evidence from a dual-age-specific mouse model.

It is not clear whether disrupted age-specific hematopoiesis contributes to the complex manifestations in leukemia patients who carry identical mutations, particularly in pediatric and adult patients with similar clinical characteristics. By studying a dual-age-specific mouse model, we demonstrate that (1) loss of Pten during the fetal-to-adult hematopoiesis switch (hematopoiesis switch) causes sustained fetal hematopoiesis, resulting in death in juvenile leukemia; (2) myeloid-biased hematopoiesis in juvenile mice is associated with the sustained fetal properties of hematopoietic stem cells (HSCs); (3) the age specificity of juvenile myelomonocytic leukemia depends on the copy number of Pten and Nf1; (4) single-allelic Pten deletion during the hematopoiesis switch causes constitutive activation of MAPK in juvenile mice with Nf1 loss of heterozygosity (LOH); and (5) Nf1 LOH causes monocytosis in juvenile mice with Pten haploinsufficiency but does not cause lethality until adulthood. Our data suggest that 1 copy of Pten is sufficient to maintain an intact negative-feedback loop of the Akt pathway and HSC function in reconstitution, despite MAPK being constitutively activated in juvenile Pten+/ΔNf1LOH mice. However, 2 copies of Pten are required to maintain the integrity of the MAPK pathway in juvenile mice with Nf1 haploinsufficiency. Our data indicate that previous investigations of Pten function in wild-type mice may not reflect the impact of Pten loss in mice with Nf1 mutations or other genetic defects. We provide a proof of concept that disassociated age-specific hematopoiesis contributes to leukemogenesis and pediatric demise.

Use of a Novel Couples' Verification Tool in a Male Partner Treatment Study of Women With Recurrent Bacterial Vaginosis.

Verification of relationship status beyond self-report is an important aspect in sexually transmitted infection research, including partner treatment studies where primary sexual partners are targeted for enrollment. This exploratory study describes the use of a novel couples' verification tool in a male partner treatment study of women with recurrent bacterial vaginosis.

Prevalence of and Risk Factors for Anal High-grade Squamous Intraepithelial Lesions in Women Living with Human Immunodeficiency Virus.

BACKGROUND: Women living with human immunodeficiency virus (WLHIV) have disproportionately high rates of squamous cell carcinoma of the anus compared with the general population of women. Anal high-grade squamous intraepithelial lesions (HSILs) precede anal cancer, and accurate studies of HSIL prevalence among WLHIV in the United States are lacking. METHODS: The AIDS Malignancy Consortium 084 study was a multicenter national trial to evaluate the prevalence of and risk factors for anal HSIL in a US cohort. Eligible participants were WLHIV aged ≥18 years with no history of anal HSIL. Study participants had an examination including collection of cervical/vaginal and anal specimens, followed by high-resolution anoscopy with biopsy. RESULTS: We enrolled 256 women with evaluable anal pathology. The mean age was 49.4 years, 64% women were non-Hispanic black, 67% were former or current smokers, and 56% reported ever having anal sex with a man. The median CD4 T-cell count was 664 cells/µL. The prevalence of anal histologic HSIL (hHSIL) was 27% (95% confidence interval [CI], 22%-33%). There was a strong concordance (240/254) between local and consensus pathologists for hHSIL vs less than hHSIL (κ = 0.86 [95% CI, .79-.93]). Current CD4 count of ≤200 cells/µL was the strongest predictor of consensus anal hHSIL diagnosis (adjusted odds ratio [aOR], 10.34 [95% CI, 3.47-30.87]). History of anoreceptive intercourse was also associated with hHSIL (aOR, 2.44 [95% CI, 1.22-4.76]). CONCLUSIONS: The prevalence of anal hHSIL in WLHIV in the United States was 27% in this study where all participants received high-resolution anoscopy and biopsy.

Increasing the availability of Tai Chi to veterans through a training of trainers course.

PURPOSE: The purpose of this nurse-led project was to increase the number of interprofessional Tai Chi instructors for veterans through a 5-week (32 hours) training of trainers (ToT) course led by a Tai Chi master trainer. METHODS: This project was designed to evaluate the effectiveness of using the ToT model to increase the availability of Tai Chi to veterans. To understand how well the ToT course met learners' needs, a two-phase course evaluation was conducted. RESULTS: Fifteen interprofessional employees enrolled in and completed the course. Most learners were white (67%) females (67%) with a median age of 50 years. All agreed that the training provided the skills, materials, and confidence to lead Tai Chi classes. Most (93%) indicated experiencing positive health benefits from the training and none experienced any negative effects. The 3-month follow-up evaluation indicated that 10 (67%) were teaching veterans in individual or group classes with two others assisting. Twelve instructors taught more than 150 veterans. CONCLUSIONS: Overall, learners evaluated this ToT course positively and indicated their needs were met and felt prepared to teach Tai Chi despite being inexperienced. The course was a success with 80% of new instructors teaching or coteaching Tai Chi to veterans.

Pilot Trial AMC-063: Safety and Efficacy of Bortezomib in AIDS-associated Kaposi Sarcoma.

PURPOSE: AIDS-related Kaposi sarcoma is often incompletely controlled, requiring serial therapies. Kaposi sarcoma herpesvirus (KSHV) induces transformation of endothelial cells, where it resides in a predominately latent state. We hypothesized proteasome inhibition would have direct antitumor activity, induce lytic activation of KSHV, and inhibit HIV infectivity, improving control of both Kaposi sarcoma and HIV. The primary objective was determining the MTD of bortezomib in AIDS-Kaposi sarcoma. Secondary objectives included estimating the impact of bortezomib on Kaposi sarcoma response, KSHV plasma DNA copy number (PDCN), and HIV viral loads (VL). PATIENTS AND METHODS: A 3+3 dose escalation design was employed evaluating four dose levels of bortezomib (0.75, 1, 1.2, or 1.6 mg/m2) administered intravenously on days 1, 8, and 15 of 28-day cycles in patients with relapsed/refractory (r/r) AIDS-Kaposi sarcoma taking antiretroviral therapy. RESULTS: Seventeen patients enrolled. No dose-limiting toxicities occurred and the MTD was not reached. The most common adverse events included diarrhea, fatigue and nausea. Among 15 evaluable patients, partial response (PR) occurred in nine (60%), with a PR rate of 83% in the 1.6 mg/m2 cohort; the remainder had stable disease (SD). Median time to response was 2.1 months. Median change in KSHV PDCN was significantly different between those with PR versus SD. During cycle 1, seven of 11 evaluable patients had decreases in HIV VL. CONCLUSIONS: Bortezomib is well-tolerated and active in AIDS-Kaposi sarcoma. The 60% PR rate is notable given the dose-finding nature of the study in a r/r population. Changes in KSHV PDCN and HIV VL trended as hypothesized.

Incubation period and risk factors support sexual transmission of bacterial vaginosis in women who have sex with women.

OBJECTIVE: The epidemiology of bacterial vaginosis (BV) favours sexual transmission of BV-associated bacteria. We examined incubation period and risk factors for incident BV (iBV) in a prospective study of women who have sex with women (WSW). METHODS: Using daily self-collected vaginal swabs, WSW with normal vaginal microbiota (no Amsel criteria and a Nugent score of 0-3) were followed for 90 days or until iBV (Nugent score 7-10 on at least 2-3 consecutive days). Daily diaries of sexual activity and menses were completed. Time to iBV was estimated. Accounting for differing lengths of follow-up and age, rates of sexual activities (per 100 person-days (pd)) were compared according to iBV status. The relationship between menses and iBV was also investigated. RESULTS: Of the 36 WSW, the mean age was 30 years (SD 8) and 92% were African American. The probability of iBV at 30 and 60 days was 20% (SD 7%) and 36% (SD 8%), respectively; 14 (39%) developed iBV by 90 days. In WSW with iBV versus those without iBV, the relative rate of any sexual activity prior to iBV was 40% higher (20.4 vs 14.6 per 100 pd; p=0.010), sex with a woman was 38% higher (14.3 vs 10.3 per 100 pd; p=0.038), digital-vaginal sex was 57% higher (14.3 vs 9.1 per 100 pd; p=0.005) and digital-anal sex was 5.6 times higher (2.9 vs 0.5 per 100 pd; p<0.001). iBV was more likely for those WSW with menses in the prior 2 days as compared with those without recent menses (HR 3.4; p=0.029). Sexual activity occurred in 93% WSW at a median of 4 days (95% CI 2 to 6) prior to iBV. CONCLUSION: iBV was common and associated with sexual activity in this cohort of predominantly African American WSW. An incubation period of 4 days is consistent with other bacterial STIs.