Factors associated with neurocognitive test performance at baseline: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES: We describe neuropsychological test performance (NP) in antiretroviral treatment (ART)-naïve HIV-positive individuals with CD4 cell counts above 500 cells/µL. METHODS: In a neurology substudy of the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) Strategic Timing of AntiRetroviral Treatment (START) study, eight neurocognitive tests were administered. The primary measure of NP was the quantitative NP z-score (QNPZ-8), the average of the z-scores for the eight tests. Associations of baseline factors with QNPZ-8 scores were assessed by multiple regression. Mild neurocognitive impairment (NCI) was defined as z-scores < -1 in at least two of six cognitive domains. RESULTS: A total of 608 participants had a median age of 34 years; 11% were women and 15% were black; the median time since HIV diagnosis was 0.9 years; the median CD4 cell count was 633 cells/µL; 19.9% had mild NCI. Better NP was independently associated with younger age, being white, higher body mass index (0.10 per 10 kg/m(2) higher), and higher haematocrit percentage (0.19 per 10% higher). Worse NP was associated with longer time since HIV diagnosis (-0.17 per 10 years), diabetes (-0.29) and higher Framingham risk score (-0.15 per 10 points higher). QNPZ-8 scores differed significantly between geographical locations, with the lowest scores in Brazil and Argentina/Chile. CONCLUSIONS: This is the largest study of NP in ART-naïve HIV-positive adults with CD4 counts > 500 cells/µL. Demographic factors and diabetes were most strongly associated with NP. Unmeasured educational/sociocultural factors may explain geographical differences. Poorer NP was independently associated with longer time since HIV diagnosis, suggesting that untreated HIV infection might deleteriously affect NP, but the effect was small.

Monitoring HPV type-specific prevalence over time through clinic-based surveillance: a perspective on vaccine effectiveness.

We investigated the feasibility of monitoring trends in prevalence of vaccine-preventable human papillomavirus (HPV) types in different clinic populations. We collected cervical specimens from women presenting to family planning, primary care, and sexually transmitted disease (STD) clinics for routine pap smears in five US cities during 2003-2005. We performed HPV genotyping and calculated annual type-specific prevalences; pre-vaccine era prevalence was highest for HPV 16 (6.0; 95% confidence interval [CI] 5.5-6.6%) and annual prevalences for vaccine-preventable types were stable, with few exceptions, after controlling for clinic type, age group, and city. With sufficient sample size and stable population characteristics, clinic-based surveillance systems can contribute to monitoring HPV vaccine impact in the cervical screening population.

Cardiovascular risk factors associated with lower baseline cognitive performance in HIV-positive persons.

OBJECTIVE: To determine factors associated with baseline neurocognitive performance in HIV-infected participants enrolled in the Strategies for Management of Antiretroviral Therapy (SMART) neurology substudy. METHODS: Participants from Australia, North America, Brazil, and Thailand were administered a 5-test neurocognitive battery. Z scores and the neurocognitive performance outcome measure, the quantitative neurocognitive performance z score (QNPZ-5), were calculated using US norms. Neurocognitive impairment was defined as z scores <-2 in two or more cognitive domains. Associations of test scores, the QNPZ-5, and impairment with baseline factors including demographics and risk factors for HIV-associated dementia (HAD) and cardiovascular disease (CVD) were determined in multiple regression. RESULTS: The 292 participants had a median CD4 cell count of 536 cells/mm(3), 88% had an HIV viral load < or =400 copies/mL, and 92% were taking antiretrovirals. Demographics, HIV, and clinical factors differed between locations. The mean QNPZ-5 score was -0.72; 14% of participants had neurocognitive impairment. For most tests, scores and z scores differed significantly between locations, with and without adjustment for age, sex, education, and race. Prior CVD was associated with neurocognitive impairment. Prior CVD, hypercholesterolemia, and hypertension were associated with poorer neurocognitive performance but conventional HAD risk factors and the CNS penetration effectiveness rank of antiretroviral regimens were not. CONCLUSIONS: In this HIV-positive population with high CD4 cell counts, neurocognitive impairment was associated with prior CVD. Lower neurocognitive performance was associated with prior CVD, hypertension, and hypercholesterolemia, but not conventional HAD risk factors. The contribution of CVD and cardiovascular risk factors to the neurocognition of HIV-positive populations warrants further investigation.

Prediction of cervical intraepithelial neoplasia grade 2-3 using risk assessment and human papillomavirus testing in women with atypia on papanicolaou smears.

OBJECTIVE: To determine whether human papillomavirus (HPV) DNA testing and risk assessment can predict cervical intraepithelial neoplasia (CIN) 2-3 on biopsies in women with atypia on Papanicolaou smears. METHODS: One hundred ninety-five consenting women were referred for colposcopy because of atypia on Papanicolaou smears between September 1997 and April 1999. Before colposcopy, women completed risk assessments and had cervical swabs collected for HPV testing using the Hybrid Capture-II assay (Digene Corporation, Silver Spring, MD). Associations of demographic and clinical variables were assessed by chi(2) analysis, and logistic regression was used to assess factors associated with CIN 2-3. The cost-effectiveness of routine colposcopy versus reflex HPV testing by either conventional or liquid-based Papanicolaou smear media was compared. RESULTS: Cervical intraepithelial neoplasia was diagnosed in 70 of 195 women (35.9%), 55 (28.2%) with CIN 1 and 15 (7.7%) with CIN 2-3. High-risk HPV types were detected in 31.3% of all subjects, 36.4% of those with CIN 1, and 93.3% of those with CIN 2-3. By logistic regression, CIN 2-3 was associated only with detection of high-risk HPV (odds ratio 110.08, 95% confidence interval 8.35, 999. 00). The sensitivity of high-risk HPV for detecting CIN 2-3 was 93. 3%, specificity 73.9%, positive predictive value 23.0%, and negative predictive value 99.3%. The cost of reflex HPV testing using conventional smear or liquid-based media was less than routine colposcopy ($4809 and $4308, respectively, versus $4875 per case detected). CONCLUSIONS: Triage based on HPV testing would result in referral of approximately 31% of patients to colposcopy and appears to be a sensitive and cost-effective alternative to colposcopy.

Pap smear screening in an urban STD clinic. Yield of screening and predictors of abnormalities.

BACKGROUND: Pap smear screening studies in STD clinics have reported high rates of squamous intraepithelial lesions (SIL); however, there are limited data on levels of unsatisfactory smears of characteristics associated with cytologic abnormalities. GOAL: To assess the yield to Pap smear screening in an STD clinic and to evaluate the rates of and risk factors for atypia, low-grade SIL (LSIL), and high-grade SIL (HSIL). STUDY DESIGN: A chart review of the clinic records of women undergoing Pap smear screening between 1991 and 1994 was conducted. Results were assessed from two different screening protocols, the first using a Dacron swab to obtain the endocervical sample and the second using a cytobrush. RESULTS: Of 2034 Pap smears, 1313 (64.6%) were negative, 202 (9.9%) were unsatisfactory, 257 (12.6%) were atypical, 211 (10.4%) had LSIL, and 51 (2.5%) had HSIL. With the change to the cytobrush protocol, the rate of unsatisfactory smears decreased from 14.4% to 3% (p < 0.001), atypia increased from 10% to 16.7% (p < 0.001), and HSIL rose from 1.7% to 3.7% (p < 0.001). By multivariate analysis, atypia was associated with genital warts (odds ratio (OR) 1.53, 95% confidence interval (CI): 1.16-2.02); LSIL with younger age (p < 0.001, for trend), black race (OR 1.51, 95% CI: 1.08-2.10), genital warts (OR 1.81, 95% CI: 1.33-2.47), and an abnormal appearance of the cervix on examination (OR 2.49, 95% CI: 1.85-3.35); and HSIL with a previous abnormal Pap smear (OR 2.48, 95% CI: 1.08-2.10). Overall, abnormality rates were significantly higher in adolescents (35.5%) than older women (21.7%) (p < 0.01). CONCLUSIONS: Obtaining satisfactory Pap smears among women undergoing screening in an STD clinic is feasible and cytologic abnormalities are common. These results continue to support the need for Pap smear screening in STD clinics, but the high rates in adolescents, a group in whom the natural history of cytologic abnormalities has not been well-defined, raise questions about the need to develop age-appropriate screening and management strategies.

Acupuncture and amitriptyline for pain due to HIV-related peripheral neuropathy: a randomized controlled trial. Terry Beirn Community Programs for Clinical Research on AIDS.

CONTEXT: Peripheral neuropathy is common in persons infected with the human immunodeficiency virus (HIV) but few data on symptomatic treatment are available. OBJECTIVE: To evaluate the efficacy of a standardized acupuncture regimen (SAR) and amitriptyline hydrochloride for the relief of pain due to HIV-related peripheral neuropathy in HIV-infected patients. DESIGN: Randomized, placebo-controlled, multicenter clinical trial. Each site enrolled patients into 1 of the following 3 options: (1) a modified double-blind 2 x 2 factorial design of SAR, amitriptyline, or the combination compared with placebo, (2) a modified double-blind design of an SAR vs control points, or (3) a double-blind design of amitriptyline vs placebo. SETTING: Terry Beirn Community Programs for Clinical Research on AIDS (HIV primary care providers) in 10 US cities. PATIENTS: Patients with HIV-associated, symptomatic, lower-extremity peripheral neuropathy. Of 250 patients enrolled, 239 were in the acupuncture comparison (125 in the factorial option and 114 in the SAR option vs control points option), and 136 patients were in the amitriptyline comparison (125 in the factorial option and 11 in amitriptyline option vs placebo option). INTERVENTIONS: Standardized acupuncture regimen vs control points, amitriptyline (75 mg/d) vs placebo, or both for 14 weeks. MAIN OUTCOME MEASURE: Changes in mean pain scores at 6 and 14 weeks, using a pain scale ranging from 0.0 (no pain) to 1.75 (extremely intense), recorded daily. RESULTS: Patients in all 4 groups showed reduction in mean pain scores at 6 and 14 weeks compared with baseline values. For both the acupuncture and amitriptyline comparisons, changes in pain score were not significantly different between the 2 groups. At 6 weeks, the estimated difference in pain reduction for patients in the SAR group compared with those in the control points group (a negative value indicates a greater reduction for the "active" treatment) was 0.01 (95% confidence interval [CI], -0.11 to 0.12; P=.88) and for patients in the amitriptyline group vs those in the placebo group was -0.07 (95% CI, -0.22 to 0.08; P=.38). At 14 weeks, the difference for those in the SAR group compared with those in the control points group was -0.08 (95% CI, -0.21 to 0.06; P=.26) and for amitriptyline compared with placebo was 0.00 (95% CI, -0.18 to 0.19; P=.99). CONCLUSIONS: In this study, neither acupuncture nor amitriptyline was more effective than placebo in relieving pain caused by HIV-related peripheral neuropathy.

Human immunodeficiency virus seroprevalence and risk assessment of a homeless population in Denver.

OBJECTIVE: TO determine the prevalence of human immunodeficiency virus (HIV) infection among the homeless of Denver and to describe behaviors in the homeless that may be associated with HIV infection. DESIGN: A cross-sectional cohort study. METHODS: From July 1990 through June 1994, the authors conducted an unlinked survey collecting demographic and risk exposure data, and from August 1990 through June 1992, a more detailed risk behavior survey was completed on persons who attended the largest homeless clinic in Denver. RESULTS: For the combined survey years, the overall seroprevalence rate in the unlinked survey was 0.9%. Men were more likely to be seropositive than women (1.3% versus 0.1%) (P < 0.001). Black and Hispanic men had higher seroprevalence rates than white men (3.1% and 2.2% versus 0.5%) (P < 0.001). Gay and bisexual men, men who were injection drug users, and men with partners at risk had a nearly fivefold higher seroprevalence rate compared to other risk groups (3.1% versus 0.7%, P < 0.001). During the 4 study years, 14% of homeless persons tested positive for tuberculosis. In the risk behavior survey, 41% of the clients reported previous injection drug use (since 1978), and 22% reported recent use (past 12 months); of this 22%, 16% reported sharing their works (needles and paraphernalia). Seventy percent of the study participants stated that they changed their sexual behavior, and 39% reported using condoms in the past 12 months. CONCLUSIONS: In this homeless Denver population, there is a low seroprevalence of HIV but a high rate of HIV risk behavior. Certain groups of homeless persons are at high risk for HIV infection, and targeted interventions are necessary.