Risk factors for antiretroviral therapy (ART) discontinuation in a large multinational trial of early ART initiators.

OBJECTIVE: We aimed to investigate potential causes of higher risk of treatment interruptions within the multicountry Strategic Timing of AntiRetroviral Treatment (START) trial in 2015. METHODS: We defined baseline as the date of starting antiretroviral therapy (ART) and a treatment interruption as discontinuing ART for at least 2 weeks. Participants were stratified by randomization arm and followed from baseline to earliest end date of the initial phase of START, death, date of consent withdrawn or date of first treatment interruption. Cox regression was used to calculate hazard ratios and 95% confidence intervals for factors that may predict treatment interruptions in each arm. RESULTS: Of the 3438 participants who started ART, 2286 were in the immediate arm and 1152 in the deferred arm. 12.9% of people in the immediate arm and 10.5% of people in the deferred arm experienced at least one treatment interruption by 3 years after starting ART. In adjusted analyses, age [hazard ratio for 35-50 years: 0.75 (95% confidence interval: 0.59-0.97) and >50 years: 0.53 (0.33-0.80) vs. <35 years], education status [hazard ratio for postgraduate education vs. less than high-school education (0.23 (0.10-0.50))] and region [hazard ratio for United States vs. Europe/Israel (3.16 (2.09-4.77))] were significantly associated with treatment interruptions in the immediate arm. In the deferred arm, age and education status were significantly associated with treatment interruptions. CONCLUSION: Within START, we identified younger age and lower educational attainment as potential causes of ART interruption. There is a need to strengthen adherence advice and wider social support in younger people and those of lower education status.

Treatment of high-grade anal intraepithelial neoplasia with infrared coagulation in a primary care population of HIV-infected men and women.

BACKGROUND: High-grade anal intraepithelial neoplasia, the putative anal carcinoma precursor, is more common in HIV-infected persons. The ideal treatment for these lesions has not been established. OBJECTIVE: The aim of this study was to evaluate the effectiveness of infrared coagulation treatment for high-grade anal intraepithelial neoplasia. DESIGN: This is a prospective cohort study. Patients with high-grade anal intraepithelial neoplasia either received infrared coagulation treatment or voluntarily did not receive treatment and were reevaluated at a subsequent time point. SETTING: This investigation was performed at a Ryan White-funded clinic located in the United States. PATIENTS: HIV-infected men and women with biopsy-confirmed high-grade anal intraepithelial neoplasia were included. MAIN OUTCOME MEASURES: The primary outcome measured was the histology collected by high-resolution anoscopy-directed biopsy. RESULTS: The study included 124 patients. Of 42 patients who either delayed treatment or were not treated, 37 (88%; 95% CI = 74%-96%) still had high-grade anal intraepithelial neoplasia on reevaluation and 2 (5%; 95%CI = 1%-16%) had squamous-cell carcinoma. Of 98 patients who received infrared coagulation treatment, 73 (74%; 95% CI = 65%-83%) patients had no evidence of high-grade anal intraepithelial neoplasia on their first posttreatment evaluation, and none had progressed to squamous-cell carcinoma (p < 0.0001 in comparison with untreated). Upon completing all initial and, if necessary, follow-up treatment, 85 (87%; 95% CI = 78%-93%) patients treated by infrared coagulation had no evidence of high-grade anal intraepithelial neoplasia and none had progressed to squamous-cell carcinoma. LIMITATIONS: The study population may not be representative of the general population, the study environment was uncontrolled, and patients were not randomly assigned to treatment. CONCLUSIONS: Infrared coagulation is an effective treatment for high-grade anal intraepithelial neoplasia.

Prevalence of anal intraepithelial neoplasia defined by anal cytology screening and high-resolution anoscopy in a primary care population of HIV-infected men and women.

BACKGROUND: Prevalence of high-grade anal intraepithelial neoplasia, the human papillomavirus-associated putative anal cancer precursor, is high in HIV-infected men who have sex with men, but less is known about its prevalence in other HIV-infected subgroups. Similarly, the prevalence of abnormal cytology, used as a screen, is not well-defined in these subgroups. OBJECTIVE: This study aimed to estimate the prevalence of abnormal cytology and anal intraepithelial neoplasia in a primary care HIV-infected population. DESIGN: This investigation was designed as a cross-sectional study. SETTING: This study took place at a Ryan White-funded clinic. PATIENTS: Included in the study were all (n = 779) HIV-infected patients receiving primary care services between March 2006 and March 2008. MAIN OUTCOME MEASURES: The main outcome measures were anal cytology and high-resolution anoscopy results. RESULTS: The prevalence of abnormal cytology was 43%: 62% in men who reported receptive anal intercourse, 39% in women who reported receptive anal intercourse, and 25% in all others (P trend <.0001). High-grade anal intraepithelial neoplasia prevalence was 27%: 44% in men who reported receptive anal intercourse, 26% in women who reported receptive anal intercourse, and 10% in all others (P trend <.0001). Two patients had squamous-cell cancer. Independent predictors of dysplasia were CD4 at screening, receptive anal intercourse, sexual orientation, and history of human papillomavirus disease. Anal cytology and histology findings were not well correlated. LIMITATIONS: The study population may not be representative of the general HIV-infected population, there were differences between screened and unscreened patients and between patients with abnormal cytology who had high-resolution anoscopy and those who did not, only patients with abnormal cytology had high-resolution anoscopy, and there were possible misclassification errors and uncontrolled possible confounders. CONCLUSIONS: High-grade anal intraepithelial neoplasia is relatively common in HIV-infected patients regardless of sexual practice. Although risk increases with receptive anal intercourse, patient-provided information on this sexual practice should not be used as a determining factor for screening. Strategies to prevent anal cancer are necessary for all HIV-infected patients.

General health status and adherence to antiretroviral therapy.

UNLABELLED: Highly active antiretroviral therapy (HAART) adherence is crucial in lowering HIV/AIDS-related mortality. General health status is known to predict mortality, but no study has assessed its association with HAART adherence. A total of 103 whites, African Americans, and Hispanic/Latinos with HIV/AIDS underwent an interview using validated measures. Regression analyses assessed the relationship between general health status and HAART adherence while controlling for social support, sense of control, depression, stress, HIV stigma, substance abuse, and unfair treatment because of race. Those rating their general health as fair/poor were 4 times more likely to be nonadherent (odds ratio [OR], 4.34; 95% confidence interval [CI], 1.19-15.79). This association dramatically strengthened in the multivariate regression model (OR, 10.96; 95% CI, 1.46-82.36) after controlling for the covariates. CONCLUSION: General health status was the strongest predictor of HAART nonadherence, and future research is needed to assess whether this 1-question general health measure can be clinically used to influence adherence.