Clinical Efficacy of Cefixime for the Treatment of Early Syphilis.

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.

Clinical trial protocol to evaluate the efficacy of cefixime in the treatment of early syphilis.

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.

Association of cervical precancer with human papillomavirus types other than 16 among HIV co-infected women.

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.

Tenofovir use and urinary biomarkers among HIV-infected women in the Women's Interagency HIV Study (WIHS).

BACKGROUND: Tenofovir (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. METHODS: Three urinary biomarkers of tubular impairment--neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-ß-D-glucosaminidase (NAG), and ß-2-microglobulin (ß2MG)--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. RESULTS: There were no differences between groups for NGAL or NAG, but ß2MG 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 <60 mL/minute, history of proteinuria, hepatitis C (P < 0.01 for all), and diabetes mellitus (P = 0.05). Factors associated with increased odds of elevated ß2MG were HIV RNA >100,000 copies/mL, hepatitis C, boosted protease inhibitor use, and glomerular filtration rate <60 mL/minute (P ≤ 0.01 for all). CONCLUSIONS: ß2MG levels are elevated in women on TDF, indicating probable early renal dysfunction. Biomarker elevation is additionally associated with baseline chronic kidney disease, uncontrolled viremia, and boosted protease inhibitor use. Future studies are needed to explore urinary biomarker thresholds in identifying treated HIV-infected individuals at risk for renal dysfunction.

The relationship between race and HIV-distal sensory polyneuropathy in a large cohort of US women.

INTRODUCTION: HIV-distal sensory polyneuropathy (HIV-DSPN) is a common complication of HIV infection, yet race as a potential risk factor is not known. METHODS: Between April and October 2009, as part of the NIH Women's Interagency HIV Study (WIHS), 1414 women, 973 of whom were HIV-infected, were clinically evaluated for peripheral neuropathy. Utilizing available clinical, laboratory, and sociodemographic variables, we conducted a cross-sectional analysis of factors associated with HIV-DSPN. Multivariable logistic regression was used to examine factors independently associated with HIV-DSPN. RESULTS: 36% of HIV-infected women met our definition of HIV-DSPN. 41.3% of African Americans, 34.8% of Whites and 24.7% of Hispanics had DSPN. Age, Hepatitis C-co-infection, and diabetes were each significantly associated with HIV-DSPN. After controlling for age, diabetes, Hepatitis C co-infection, alcohol use, current dideoxy-nucleoside reverse transcriptase inhibitor use, current CD4 count, and plasma HIV viral load, HIV-DSPN was significantly associated with ethnicity; the odds ratio was 1.67 (p=0.001) in African-Americans compared to other racial groups. CONCLUSION: The prevalence of HIV-DSPN in women was lower than reported in prior studies. The likelihood of HIV-DSPN was higher in African-Americans compared to other racial groups. HIV-DSPN was more common in those co-infected with Hepatitis C, older individuals, and diabetics. Further prospective studies are needed to explore the relationship between gender, race, and HIV-DSPN, and the mechanistic basis for racial differences.

Smoking cessation among women with and at risk for HIV: are they quitting?

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 < 0.001). CONCLUSIONS: HIV-infected and at-risk women in this cohort have lower smoking cessation rates than the general population. Given the high prevalence of smoking, the high risk of adverse health events from smoking, and low rates of cessation, it is imperative that we increase efforts and overcome barriers to help these women quit smoking.

Factors associated with prevalent hepatitis C infection among HIV-infected women with no reported history of injection drug use: the Women's Interagency HIV Study (WIHS).

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 < 0.0001) after controlling for blood transfusion, age, HIV infection, unemployment, birth in the United States, history of hepatitis B infection, and current smoking status. Further stratification on HIV status showed that the association was significant only for the HIV+ (OR = 1.9, 95% CI = 1.3, 2.7, p = 0.0007) compared to the HIV- women (OR = 1.1, 95% CI = 0.4, 2.7) although these odds ratios were not significantly different (p = 0.25). For HIV-positive women with no reported history of IDU, sex with an IDU male was independently associated with HCV suggesting that sexual transmission may be an important mode of HCV transmission for these high-risk women.