Combination antiretroviral therapy (cART) reduces HIV-associated morbidities and mortalities but cannot cure the infection. Given the difficulty of eradicating HIV-1, a functional cure for HIV-infected patients appears to be a more reachable short-term goal. We identified 14 HIV patients (post-treatment controllers [PTCs]) whose viremia remained controlled for several years after the interruption of prolonged cART initiated during the primary infection. Most PTCs lacked the protective HLA B alleles that are overrepresented in spontaneous HIV controllers (HICs); instead, they carried risk-associated HLA alleles that were largely absent among the HICs. Accordingly, the PTCs had poorer CD8+ T cell responses and more severe primary infections than the HICs did. Moreover, the incidence of viral control after the interruption of early antiretroviral therapy was higher among the PTCs than has been reported for spontaneous control. Off therapy, the PTCs were able to maintain and, in some cases, further reduce an extremely low viral reservoir. We found that long-lived HIV-infected CD4+ T cells contributed poorly to the total resting HIV reservoir in the PTCs because of a low rate of infection of naïve T cells and a skewed distribution of resting memory CD4+ T cell subsets. Our results show that early and prolonged cART may allow some individuals with a rather unfavorable background to achieve long-term infection control and may have important implications in the search for a functional HIV cure. There is a renewed scientific interest in developing strategies allowing long-term remission in HIV-1-infected individuals. Very rare (<1%) patients are able to spontaneously control viremia to undetectable levels (HIV controllers, HICs). However, the possibility to translate their mechanisms of control to other patients is uncertain. Starting antiretroviral therapy during primary infection may provide significant benefits to HIV-infected patients (i.e. reduction of viral reservoirs, preservation of immune responses, protection from chronic immune activation). Indeed, we have observed that some HIV-infected patients interrupting a prolonged antiretroviral therapy initiated close to primary infection are able to control viremia afterwards. We present here 14 of such post-treatment controllers (PTCs). We show that PTCs have achieved control of infection through mechanisms that are, at least in part, different from those commonly observed in HICs and that their capacity to control is likely related to early therapeutic intervention. We found that PTCs were able, after therapy interruption, to keep, and in some cases further reduce, a weak viral reservoir. This might be related to the low contribution of long-lived cells to the HIV-reservoir in these patients. Finally, we estimated the probability of maintaining viral control at 24 months post-early treatment interruption to be ∼15%, which is much higher than the one expected for spontaneous control.

Background— The diagnostic performance of the latest 64-slice CT scanner, with increased temporal (165 ms) and spatial (0.4 mm ³ ) resolution, to detect significant stenoses in the clinically relevant coronary tree is unknown. Methods and Results— We studied 52 patients (34 men; mean age, 59.6±12.1 years) with atypical chest pain, stable or unstable angina pectoris, or non–ST-segment elevation myocardial infarction scheduled for diagnostic conventional coronary angiography. All patients had stable sinus rhythm. Patients with initial heart rates ≥70 bpm received β-blockers. Mean scan time was 13.3±0.9 seconds. The CT scans were analyzed by 2 observers unaware of the results of invasive coronary angiography, which was used as the standard of reference. All available coronary segments, regardless of size, were included in the evaluation. Lesions with ≥50 luminal narrowing were considered significant stenoses. Invasive coronary angiography demonstrated the absence of significant disease in 25% (13 of 52), single-vessel disease in 31% (16 of 52), and multivessel disease in 45% (23 of 52) of patients. One unsuccessful CT scan was classified as inconclusive. Ninety-four significant stenoses were present in the remaining 51 patients. Sensitivity, specificity, and positive and negative predictive values of CT for detecting significant stenoses on a segment-by-segment analysis were 99% (93 of 94; 95% CI, 94 to 99), 95% (601 of 631; 95% CI, 93 to 96), 76% (93 of 123; 95% CI, 67 to 89), and 99% (601 of 602; 95% CI, 99 to 100), respectively. Conclusions— Noninvasive 64-slice CT coronary angiography accurately detects coronary stenoses in patients in sinus rhythm and presenting with atypical chest pain, stable or unstable angina, or non–ST-segment elevation myocardial infarction.

Background— Multislice spiral computed tomography (MSCT) is a promising technique for noninvasive coronary angiography, although clinical application has remained limited because of frequently incomplete interpretability, caused by motion artifacts and calcifications. Methods and Results— In 59 patients (53 male, aged 58±12 years) with suspected obstructive coronary artery disease, ECG-gated MSCT angiography was performed with a 16-slice MSCT scanner (0.42-s rotation time, 12×0.75-mm detector collimation). Thirty-four patients were given additional β-blockers (average heart rate: 56±6 min ⁻¹ ). After contrast injection, all data were acquired during an approximately 20-s breath hold. The left main (LM), left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA), including ≥2.0-mm side branches, were independently evaluated by two blinded observers and screened for ≥50% stenoses. The consensus reading was compared with quantitative coronary angiography. MSCT was successful in 58 patients. Eighty-six of the 231 evaluated branches were significantly diseased. Without exclusion of branches, the sensitivity, specificity and positive and negative predictive value to identify ≥50% obstructed branches was 95% (82/86), 86% (125/145), 80% (82/102), and 97% (125/129), respectively. The overall accuracy for the LM, LAD, RCA, and LCX was 100%, 91%, 86%, and 81%, respectively. No obstructed LM, LAD, or RCA branches remained undetected. Classification of patients as having no, single, or multivessel disease was accurate in 78% (45/58) of patients and no patients with significant obstructions were incorrectly excluded. Conclusions— Improvements in MSCT technology, combined with heart rate control, allow reliable noninvasive detection of obstructive coronary artery disease.

The key attributes of CD8+ T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that CD8+ T cell responses specific for Gag and, in particular, the immunodominant p24 epitope KK10 correlate with control of HIV-1 replication in human histocompatibility leukocyte antigen (HLA)–B27 patients. To understand further the nature of CD8+ T cell–mediated antiviral efficacy, we performed a comprehensive study of CD8+ T cells specific for the HLA-B27–restricted epitope KK10 in chronic HIV-1 infection based on the use of multiparametric flow cytometry together with molecular clonotypic analysis and viral sequencing. We show that B27-KK10–specific CD8+ T cells are characterized by polyfunctional capabilities, increased clonal turnover, and superior functional avidity. Such attributes are interlinked and constitute the basis for effective control of HIV-1 replication. These data on the features of effective CD8+ T cells in HIV infection may aid in the development of successful T cell vaccines.