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Background Syphilis rates have been increasing both in the USA and internationally with incidence higher among men-who-have-sex-with-men and people living with human immunodeficiency virus (HIV) infection. Currently, benzathine penicillin is the recommended treatment for syphilis in all patients. Global shortages and cost increases in benzathine penicillin call for alternative treatment options. This study evaluates the efficacy of oral cefixime for the treatment of early syphilis. Methods We are conducting a randomized, multisite, open-label, non-comparative clinical trial in Los Angeles and Oakland, CA. Eligible participants are ≥ 18 years old, with primary, secondary, or early latent syphilis (rapid plasma reagin [RPR] titer ≥ 1:8). Patients with HIV infection must have a viral load ≤ 200 copies/mL and CD4+ T cell count ≥ 350 cells/μL during the past 6 months. Participants are randomized to receive either 2.4 M IU benzathine penicillin G intramuscularly once or cefixime 400 mg orally twice a day for 10 days. Participants return at 3, 6, and 12 months post-treatment for follow-up RPR serological testing. The primary outcome is the proportion of participants who achieve ≥ 4-fold RPR titer decrease at 3 or 6 months post-treatment. Discussion Clinical trials evaluating the efficacy of alternative antibiotics to penicillin are urgently needed. Trial registration Clinicaltrials.gov NCT03660488. Registered on 4 September 2018.

Safe and efficacious alternative treatment options for syphilis are necessary. This randomized, 2-arm, noncomparative pilot study evaluated the efficacy of oral cefixime 400 mg in achieving a ≥4-fold rapid plasma reagin titer decrease by 3 or 6 months after treatment. The proportion of cefixime arm participants treated successfully was 87% (95% confidence interval, 69%–100%; 13/15). Clinical Trials Registration. NCT03752112., The Infectious Diseases Society of America has developed 2 curricula, a core and an advanced, to prepare the next generation of clinicians in antimicrobial stewardship to meet the challenges of antimicrobial resistance, patient safety, and healthcare quality improvement.

Background Increasing incidence of syphilis in the United States and penicillin shortages internationally call for research on alternative treatment options. In this randomized, multisite, open-label, non-comparative clinical trial, we are evaluating the efficacy of cefixime as treatment of early syphilis. Methods Eligible participants are 18 years or older, have laboratory confirmed early syphilis (new Rapid Plasma Reagin [RPR] titer ≥1:8 or 4-fold titer rise in past 12 months), and no concomitant antibiotic use. Patients with HIV infection must have undetectable viral load in the past 12 months and CD4+ count ≥350 cells/μl. Participants were randomized to receive either 2.4M IU benzathine penicillin G intramuscularly once or cefixime 400 mg orally twice a day, for ten days. Participants return for follow-up at 3, 6, and 12 months post-treatment for laboratory testing. The main outcome is a 4-fold RPR titer decrease at 6 months post-treatment. Results To date, 27 participants (15 penicillin, 12 cefixime) are enrolled. The majority of the study population is men (26/27), Latino (15/27), and HIV-infected (25/27). Eight participants completed their 3-month follow up (4 cefixime/4 penicillin). In the cefixime arm, 3/4 participants had an equal or greater than four-fold decrease in the RPR titer, and 1/4 had a two-fold decrease. In the penicillin arm, 2/4 participants had an equal or greater than 4-fold decrease in the RPR titer, 1/4 had a two-fold decrease, and 1/4 is missing data. Conclusion Enrollment is still open and data collection ongoing. Initial results are encouraging. Disclosure No significant relationships.

Background HIV-seropositive women face high risk for infection with oncogenic human papillomavirus (oncHPV) types, abnormal Pap test results, and precancer, but cervical cancer risk is only modestly increased. Human papillomavirus (HPV)16 is highly oncogenic but only weakly associated with HIV status and immunosuppression, suggesting HPV16 may have a greater innate ability to evade host immune surveillance than other oncHPV types, which in turn should result in a greater relative increase in the prevalence of other oncHPV types among women with cervical precancer. Objective We sought to assess whether the underrepresentation of HPV16 among HIV-seropositive relative to HIV-seronegative women remains among those with cervical precancers. Study Design HIV-seropositive and HIV-seronegative women in the Women's Interagency HIV Study were screened for cervical intraepithelial neoplasia (CIN) grade ≥3 (CIN3 + ). DNA from >40 HPV types was detected by polymerase chain reaction in cervicovaginal lavage specimens obtained at the visit at which CIN3 + was diagnosed. Results HPV16 was detected in 13 (62%) of 21 HIV-seronegative women with CIN3 + but only 44 (29%) of 154 HIV-seropositive women with CIN3 + ( P = .01). The lower prevalence of HPV16 in CIN3 + among HIV-seropositive women persisted after controlling for covariates (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.08–0.78). The prevalence of other members of the HPV16-related alpha-9 oncHPV clade as a group was similar in HIV-infected and uninfected women with CIN3 + (OR, 1.02; 95% CI, 0.53–1.94). The prevalence of non-alpha-9 oncHPV types was increased in HIV-seropositive vs HIV-seronegative women with CIN3 + (OR, 3.9; 95% CI, 1.3–11.8). Conclusion The previously demonstrated increase in CIN3 + incidence among HIV-seropositive women is associated with lower HPV16 and higher non-alpha-9 oncHPV prevalence. This is consistent with prior reports that HIV has a weak effect on infection by HPV16 relative to other oncHPV and supports use of nonavalent HPV vaccine in HIV-seropositive women.

Although the primary mode of hepatitis C virus (HCV) transmission is exposure to blood products or injection drug use (IDU), studies have found varying independent risk factors for HCV infection among persons with no history of IDU or exposure to blood products. For HIV-infected women, sexual transmission may be another potential source of HCV infection. HIV-infected and HIV-negative women at risk for HIV enrolled in the Women's Interagency HIV Study (WIHS) during October 1994 to November 1995 and again between October 2001 and November 2002 were studied. Clinical and demographic factors associated with HCV seroprevalence were assessed in multivariate logistic regression models controlling for history of blood transfusion and IDU. Among 3636 women with HCV results, 31.5% were HCV antibody positive (HCV+) including 13.5% with no reported history of IDU or blood transfusions. Multivariate logistic regression analyses stratified on IDU showed that among women with no history of IDU, sex with an IDU male was independently associated with HCV positivity (odds ratio [OR] = 2.8, 95% confidence [CI] = 2.1, 3.8, p

BackgroundTenofovir (TDF) has been associated with renal tubular injury. Biomarkers that signal early tubular dysfunction are needed because creatinine rise lags behind TDF-associated kidney dysfunction. We examined several urinary biomarkers to determine if rises accompanying TDF initiation preceded creatinine changes.MethodsThree urinary biomarkers of tubular impairment--neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG), and β-2-microglobulin (β2MG)--were measured across 3 time points (one pre-TDF visit and 2 post-TDF visits) in 132 HIV-positive women from the Women's Interagency HIV Study. Women initiating highly active antiretroviral therapy (HAART) containing TDF were propensity score matched to women initiating HAART without TDF and women not on HAART.ResultsThere were no differences between groups for NGAL or NAG, but β2MG was 19 times more likely to be elevated among TDF users at the second post-TDF visit compared with non-TDF users at the pre-TDF visit (P < 0.01). History of proteinuria was associated with elevated NGAL (P < 0.01). Factors associated with elevated NAG were glomerular filtration rate 100,000 copies/mL, hepatitis C, boosted protease inhibitor use, and glomerular filtration rate

Background: Anemia is common in patients (pts) infected with the Human Immunodeficiency Virus (HIV). In these pts, anemia is associated with diminished quality of life (QoL) and is an independent prognostic factor for mortality. Aranesp® (darbepoetin-alfa) is a recombinant erythropoiesis-stimulating protein with extended serum half-life allowing for less frequent dosing than conventional recombinant erythropoietin. We studied Aranesp® in anemic HIV-positive pts to evaluate safety, hemoglobin (Hgb) response, and quality of life (QoL). Methods: Entry criteria included HIV infection, Hgb < 11.5 g/dL, and adequate renal and liver function. Patients with anemia due to bleeding, malignancy, B12, folate, or iron deficiency were excluded. Aranesp® 3.0 mg/kg was given sc every 2 weeks (Q2W) for 24 weeks. Treatment response was defined as Hgb increase of ≥ 1.5 g/dL from baseline sustained for ≥ 4 weeks duration at any time during the study. If no response by wk 8, Aranesp® was escalated to 5.0 μg/kg. Results: Thirteen female and 10 male pts have been enrolled to date. Median age was 43 years (range 27–67), median entry Hgb was 10.6 g/dL (range 8.6–11.5), and median CD4 count was 197 cells/mm3 (range 29–821). Nine (39%) pts had a prior clinical AIDS-defining illness or opportunistic infection, 19 (87%) pts received concurrent HAART therapy; 11 (58%) were receiving a zidovudine- containing regimen with either combivir (n=6) or trizivir (n=5). Aranesp® was well tolerated. The only treatment-associated side effect was mild pain at the injection site. Pts who received ≥ 8 wks of Aranesp® were analyzed (n=20). 17 of the 20 pts (85%) had a Hgb response (median duration 12+ weeks [range 4+ to 22+]). One of these pts required a dose escalation. Evaluation of change in QoL using a Linear Analog Scale in 20 evaluable patients showed a mean improvement in energy level (+23.2 mm), activity level (+19.8 mm) and overall QoL (+15.5 mm) over the first 8 wks of treatment. Conclusions: In HIV-infected pts with anemia, Aranesp® at a dose of 3.0 mg/kg Q2W is well tolerated, is associated with a Hgb response in the majority of pts, effectively maintains Hgb levels, and improves QoL. Further work is on-going.

BACKGROUND Cigarette smoking is an important risk factor for adverse health events in HIV-infected populations. While recent US population-wide surveys report annual sustained smoking cessation rates of 3.4–8.5%, prospective data are lacking on cessation rates for HIV-infected smokers. OBJECTIVE To determine the sustained tobacco cessation rate and predictors of cessation among women with or at risk for HIV infection. DESIGN Prospective cohort study. PARTICIPANTS A total of 747 women (537 HIV-infected and 210 HIV-uninfected) who reported smoking at enrollment (1994–1995) in the Women’s Interagency HIV Study (WIHS) and remained in follow-up after 10 years. The participants were mostly minority (61% non-Hispanic Blacks and 22% Hispanics) and low income (68% with reported annual incomes of less than or equal to $12,000). MEASUREMENTS AND MAIN RESULTS The primary outcome was defined as greater than 12 months continuous cessation at year 10. Multivariate logistic regression was used to identify independent baseline predictors of subsequent tobacco cessation. A total of 121 (16%) women reported tobacco cessation at year 10 (annual sustained cessation rate of 1.8%, 95% CI 1.6–2.1%). Annual sustained cessation rates were 1.8% among both HIV-positive and HIV-negative women (p = 0.82). In multivariate analysis, the odds of tobacco cessation were significantly higher in women with more years of education (p trend = 0.02) and of Hispanic origin (OR = 1.87, 95% CI = 1.4–2.9) compared to Black women. Cessation was significantly lower in current or former illicit drug users (OR = 0.42 95% CI = 0.24–0.74 and OR = 0.65, 95% CI = 0.49–0.86, respectively, p trend = 0.03) and women reporting a higher number of cigarettes per day at baseline (p trend