Search

Clinical trials including an analytical treatment interruption (ATI) are vital for evaluating the efficacy of novel strategies for HIV remissions. We briefly describe an interactive tool for predicting viral rebound timing in ATI trials and the impact of posttreatment controller (PTC) definitions on PTC frequency estimates. A 4-week viral load threshold of 1000 cps/ml provides both high specificity and sensitivity for PTC detection. PTC frequency varies greatly based on the definition of a PTC.

BackgroundHigh-risk anal human papillomavirus (HPV) infection is prevalent among men living with human immunodeficiency virus (HIV); the association between 9-valent (9v) high-risk HPV (HR-HPV) vaccine types and abnormal cytology has not been well characterized.MethodsWe followed a prospective cohort study of persons with HIV at 7 HIV clinics in 4 US cities from March 2004 through June 2012. Annually, providers collected separate anal swabs for HPV detection and cytopathologic examination. Among men, we examined prevalence, incidence, and clearance of 9v HR-HPV vaccine types, compared with other HR types, and associations with abnormal cytology to assess potential vaccine impact.ResultsBaseline prevalence of any anal 9v HR-HPV type among men who have sex with men (MSM) and men who have sex with women (MSW) was 74% and 25% (P < .001), respectively. Among 299 MSM, abnormal cytology was detected in 161 (54%) MSM and was associated with the presence of any 9v HR-HPV (relative risk [RR], 1.8 [95% confidence interval {CI}, 1.3-2.6]; P < .001). Among 61 MSW, abnormal anal cytology was detected in 12 (20%) and was associated with the presence of any 9v HR-HPV (RR, 4.3 [95% CI, 1.6-11.5]; P < .001).ConclusionsAmong men with HIV, the prevalence of the 7 HR-HPV types in the 9v vaccine was high and was associated with abnormal cytology. These findings indicate that men with HIV could benefit from prophylactic administration of the 9v HPV vaccine.

BackgroundHIV posttreatment controllers are rare individuals who start antiretroviral therapy (ART), but maintain HIV suppression after treatment interruption. The frequency of posttreatment control and posttreatment interruption viral dynamics have not been well characterized.MethodsPosttreatment controllers were identified from 14 studies and defined as individuals who underwent treatment interruption with viral loads ≤400 copies/mL at two-thirds or more of time points for ≥24 weeks. Viral load and CD4+ cell dynamics were compared between posttreatment controllers and noncontrollers.ResultsOf the 67 posttreatment controllers identified, 38 initiated ART during early HIV infection. Posttreatment controllers were more frequently identified in those treated during early versus chronic infection (13% vs 4%, P < .001). In posttreatment controllers with weekly viral load monitoring, 45% had a peak posttreatment interruption viral load of ≥1000 copies/mL and 33% had a peak viral load ≥10000 copies/mL. Of posttreatment controllers, 55% maintained HIV control for 2 years, with approximately 20% maintaining control for ≥5 years.ConclusionsPosttreatment control was more commonly identified amongst early treated individuals, frequently characterized by early transient viral rebound and heterogeneous durability of HIV remission. These results may provide mechanistic insights and have implications for the design of trials aimed at achieving HIV remission.

Background:Nonavalent (9v) human papilloma virus vaccine targets high-risk human papillomavirus (HR-HPV) types 16, 18, 31, 33, 45, 52, 58, and low-risk 6, 11. We examined prevalence, incidence, and clearance of anal and cervical HR-HPV in HIV-infected women. Methods:The SUN Study enrolled 167 US women in 2004-2006. Anal and cervical specimens were collected annually for cytology and identification of 37 HPV types: 14 HR included: 9v 16, 18, 31, 33, 45, 52, 58; non-9v 35, 39, 51, 56, 59, 66, 68. Results:Baseline characteristics of 126 women included: median age 38 years; 57% non-Hispanic black; 67% HIV RNA < 400 copies/mL; 90% CD4 counts ≥200 cells/mm3. HPV prevalence at anus and cervix was 90% and 83%; for 9v HR-HPV types, 67% and 51%; non-9v HR-HPV, 54% and 29%, respectively. The 9v and non-9v HR-HPV incidence rates/100 person-years were similar (10.4 vs 9.5; 8.5 vs 8.3, respectively); 9v clearance rates were 42% and 61%; non-9v 46% and 59%, in anus and cervix, respectively. Conclusions:Anal HR-HPV prevalence was higher than cervical, with lower clearance; incidence was similar. Although prevalence of non-9v HR-HPV was substantial, 9v HR-HPV types were generally more prevalent. These findings support use of nonavalent vaccine in HIV-infected women.

Background:The natural history of anal human papilloma virus (HPV) infection among human immunodeficiency virus (HIV)-infected men is unknown. Methods:Annually, from 2004 to 2012, we examined baseline prevalence, incidence, and clearance of anal HPV infection at 48 months, and associated factors among HIV-infected men. Results:We examined 403 men who have sex with men (MSM) and 96 men who have sex with women (MSW) (median age 42 years for both, 78% versus 81% prescribed cART, median CD4+ T-lymphocyte cell count 454 versus 379 cells/mm3, and 74% versus 75% had undetectable viral load, respectively). Type 16 prevalence among MSM and MSW was 38% versus 14% (P < .001), and incidence 24% versus 7% (P = .001). Type 18 prevalence was 24% versus 8% (P < .001), and incidence 13% versus 4% (P = .027). Among MSM and MSW, clearance of prevalent HPV 16 and HPV 18 was 31% and 60% (P = .392), and 47% and 25% (P = .297), respectively. Among MSM, receptive anal sex (with or without a condom) was associated with persistent HPV 16 (OR 2.24, P < .001). Conclusions:MSM had higher prevalence and incidence of HPV than MSW, but similar clearance. Receptive anal sex may predict cancer risk among HIV-infected MSM.

BackgroundThere are few recent data on the rates of AIDS-defining opportunistic infections (OIs) among human immunodeficiency virus (HIV)-infected patients in care in the United States and Canada.MethodsWe studied HIV-infected participants in 16 cohorts in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) during 2000-2010. After excluding 16 737 (21%) with any AIDS-defining clinical events documented before NA-ACCORD enrollment, we analyzed incident OIs among the remaining 63 541 persons, most of whom received antiretroviral therapy during the observation. We calculated incidence rates per 100 person-years of observation (hereafter, "person-years") with 95% confidence intervals (CIs) for the first occurrence of any OI and select individual OIs during 2000-2003, 2004-2007, and 2008-2010.ResultsA total of 63 541 persons contributed 261 573 person-years, of whom 5836 (9%) developed at least 1 OI. The incidence rate of any first OI decreased over the 3 observation periods, with 3.0 cases, 2.4 cases, and 1.5 cases per 100 person-years of observation during 2000-2003, 2004-2007, and 2008-2010, respectively (Ptrend

BACKGROUND: Anal cancer rates are higher for human immunodeficiency virus (HIV)-infected adults than for uninfected adults. Limited published data exist characterizing the incidence of precursor lesions detected by anal cytology. METHODS: The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy was a prospective cohort of 700 HIV-infected participants in 4 US cities. At baseline and annually thereafter, each participant completed a behavioral questionnaire, and healthcare professionals collected anorectal swabs for cytologic examination and human papillomavirus (HPV) detection and genotyping. RESULTS: Among 243 participants with negative baseline results of anal cytology, 37% developed abnormal cytology findings (incidence rate, 13.9 cases/100 person-years of follow-up; 95% confidence interval [CI], 11.3-16.9) over a median follow-up duration of 2.1 years. Rates among men having sex with men, among women, and among men having sex with women were 17.9 cases/person-years of follow-up (95% CI, 13.9-22.7), 9.4 cases/person-years of follow-up (95% CI, 5.6-14.9), and 8.9 cases/person-years of follow-up (95% CI, 4.8-15.6), respectively. In multivariable analysis, the number of persistent high-risk HPV types (adjusted hazard ratio [aHR], 1.17; 95% CI, 1.01-1.36), persistent high-risk HPV types except 16 or 18 (aHR, 2.46; 95% CI, 1.31-4.60), and persistent types 16 or 18 (aHR, 3.90; 95% CI, 1.78-8.54) remained associated with incident abnormalities. CONCLUSIONS: The incidence of abnormal anal cytology findings was high and more likely to develop among persons with persistent high-risk HPV.

BackgroundAnal cancer rates are higher for human immunodeficiency virus (HIV)-infected adults than for uninfected adults. Limited published data exist characterizing the incidence of precursor lesions detected by anal cytology.MethodsThe Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy was a prospective cohort of 700 HIV-infected participants in 4 US cities. At baseline and annually thereafter, each participant completed a behavioral questionnaire, and healthcare professionals collected anorectal swabs for cytologic examination and human papillomavirus (HPV) detection and genotyping.ResultsAmong 243 participants with negative baseline results of anal cytology, 37% developed abnormal cytology findings (incidence rate, 13.9 cases/100 person-years of follow-up; 95% confidence interval [CI], 11.3-16.9) over a median follow-up duration of 2.1 years. Rates among men having sex with men, among women, and among men having sex with women were 17.9 cases/person-years of follow-up (95% CI, 13.9-22.7), 9.4 cases/person-years of follow-up (95% CI, 5.6-14.9), and 8.9 cases/person-years of follow-up (95% CI, 4.8-15.6), respectively. In multivariable analysis, the number of persistent high-risk HPV types (adjusted hazard ratio [aHR], 1.17; 95% CI, 1.01-1.36), persistent high-risk HPV types except 16 or 18 (aHR, 2.46; 95% CI, 1.31-4.60), and persistent types 16 or 18 (aHR, 3.90; 95% CI, 1.78-8.54) remained associated with incident abnormalities.ConclusionsThe incidence of abnormal anal cytology findings was high and more likely to develop among persons with persistent high-risk HPV.

BackgroundIdentifying immunologic mechanisms that contribute to premature cardiovascular disease (CVD) among HIV-positive patients will inform prevention strategies.MethodsCoronary artery calcium (CAC) progression was studied in an HIV cohort. Immunophenotypes were measured on baseline cryopreserved peripheral blood mononuclear cells using multicolor flow cytometry. Logistic regression identified predictors of CAC progression after adjusting for traditional and HIV-related risk factors.ResultsBaseline characteristics for the analysis cohort (n=436) were median age 42 years, median CD4 cell count 481 cells/μl, and 78% receiving antiretroviral therapy. Higher frequencies of CD16 monocytes were associated with greater likelihood of CAC progression, after adjusting for traditional and HIV risk factors [odds ratio per doubling was 1.66 for CD14/CD16 (P=0.02), 1.36 for CD14/CD16 (P=0.06), and 1.69 for CD14/CD16 (P=0.01)]. Associations for CD16 monocytes persisted when restricted to participants with viral suppression. We found no significant associations for CAC progression with other cellular phenotypes, including T-cell activation and senescence markers.ConclusionCirculating CD16 monocytes, potentially reflecting a more pro-atherogenic subpopulation, independently predicted greater CAC progression among HIV-infected persons at low risk for AIDS. In contrast to T-cell abnormalities classically associated with AIDS-related disease progression, these data highlight the potential role of monocyte activation in HIV-related CVD risk.

A rotational version of the fluid-mechanical sewing machine (FMSM) is investigated experimentally. A thin thread of silicon oil was dispensed at a constant flow rate Q from a height H and fell on a table rotating at an angular speed ω, at a distance R from the axis. In all experimental runs, the values of Q and H were kept constant while the radius R was changed manually after each full rotation. Preliminary results show that the usual stitching patterns ensue as the local linear speed V=ωR approaches the critical transition speeds seen in the FMSM scenario but with subtle asymmetries introduced by rotational (centrifugal) effects. In some instances, arcs and loops of the traces were noticeably more pronounced when directed outward compared to those pointing toward the axis of rotation. Moreover, we observed stitching patterns not reported before. Overall, the symmetry-breaking features, while clearly visible, were rather subtle. Their morphological characteristics, such as differences in local curvature of traces relative to those in FMSM, are estimated to be below 10% in most cases.