An imaging-based method of mapping multi-echo BOLD intracranial pulsatility.

PURPOSE: Cardiac-related intracranial pulsatility may relate to cerebrovascular health, and this information is contained in BOLD MRI data. There is broad interest in methods to isolate BOLD pulsatility, and the current study examines a deep learning approach. METHODS: Multi-echo BOLD images, respiratory, and cardiac recordings were measured in 55 adults. Ground truth BOLD pulsatility maps were calculated with an established method. BOLD fast Fourier transform magnitude images were used as temporal-frequency image inputs to a U-Net deep learning model. Model performance was evaluated by mean squared error (MSE), mean absolute error (MAE), structural similarity index (SSIM), and mutual information (MI). Experiments evaluated the influence of input channel size, an age group effect during training, dependence on TE, performance without the U-Net architecture, and importance of respiratory preprocessing. RESULTS: The U-Net model generated BOLD pulsatility maps with lower MSE as additional fast Fourier transform input images were used. There was no age group effect for MSE (P > 0.14). MAE and SSIM metrics did not vary across TE (P > 0.36), whereas MI showed a significant TE dependence (P < 0.05). The U-Net versus no U-Net comparison showed no significant difference for MAE (P = 0.059); however, SSIM and MI were significantly different between models (P < 0.001). Within the insula, the cross-correlation values were high (r > 0.90) when comparing the U-Net model trained with/without respiratory preprocessing. CONCLUSION: Multi-echo BOLD pulsatility maps were synthesized from a U-net model that was trained to use temporal-frequency BOLD image inputs. This work adds to the deep learning methods that characterize BOLD physiological signals.

Psychological changes in successful completers of an HIV-tailored smoking cessation program: mood, attachment and self-efficacy.

High rates of cigarette smoking is the leading contributor to the increasing risk of cardiovascular disease (CVD) among people living with HIV (PLH). Relapse rates among PLH who quit smoking are high among those receiving standard care, which may be due to several unique social and psychological challenges PLH face when they attempt to quit smoking. The purpose of the current study was to examine change in relevant psychological factors in a subgroup of participants (n = 14) who remained smoke-free at 6-months follow-up in an HIV-tailored smoking cessation counselling program (N = 50). We examined self-reported depressive symptoms, attachment style and self-efficacy across 5 time points (baseline, quite date, 4, 12 and 24 weeks). At study baseline, mean depression scores fell above the clinical cut off of 16 (M = 16.31; SD = 13.53) on the Centre for Epidemiological Studies - Depression (CES-D) scale and fell below the clinical cut off at 24 weeks post quit date (M = 13.36; SD = 10.62). Results of multi-level modeling indicated a significant linear reduction in depressive symptoms and a significant linear improvement in self-efficacy to refrain from smoking across study visits. These results suggest that positive change in mood and self-efficacy may be helpful for PLH who remain smoke-free during a quit attempt.

Transcatheter aortic valve replacement in patients with a history of cancer: Periprocedural and long-term outcomes.

BACKGROUND: A history of cancer is incorporated into the surgical risk assessment of patients undergoing surgical aortic valve replacement through the Society for Thoracic Surgeons score. However, the prognostic significance of cancer in patients treated with transcatheter aortic valve replacement (TAVR) is unclear. As the cancer survivorship population increases, it is imperative to establish the efficacy and safety of TAVR in patients with severe symptomatic aortic stenosis (AS) and a history of malignancy. OBJECTIVES: The primary goal of this study was to assess the periprocedural outcomes and long-term mortality in patients with a history of cancer undergoing TAVR. METHODS: A systematic review of PubMed, MEDLINE, and EMBASE was conducted to identify studies reporting outcomes in patients with a history of malignancy undergoing TAVR. A meta-analysis was performed using a random-effects model with a primary outcome of all-cause mortality and cardiac mortality at the longest follow-up. On secondary analyses, procedural safety was assessed. RESULTS: A total of 13 observational studies with 10,916 patients were identified in the systematic review. Seven studies including 6,323 patients were included in the quantitative analysis. Short-term mortality (relative risk [RR] 0.61, 95%CI 0.36-1.01; p = .06) and long-term all-cause mortality (RR 1.24, 95%CI 0.95-1.63; p = .11) were not significantly different when comparing patients with and without a history of cancer. No significant difference in the rate of periprocedural complications including stroke, bleeding, acute kidney injury, and pacemaker implantation was noted. CONCLUSION: In patients with severe AS undergoing TAVR, a history of cancer was not associated with adverse short or long-term survival. Based on these findings, TAVR should be considered in all patients with severe symptomatic AS, irrespective of their history of malignancy.

Correction to: Assessment of stigma in patients with cystic fibrosis.

An amendment to this paper has been published and can be accessed via the original article.

Apollo-NADP(+): a spectrally tunable family of genetically encoded sensors for NADP(+).

NADPH-dependent antioxidant pathways have a critical role in scavenging hydrogen peroxide (H2O2) produced by oxidative phosphorylation. Inadequate scavenging results in H2O2 accumulation and can cause disease. To measure NADPH/NADP(+) redox states, we explored genetically encoded sensors based on steady-state fluorescence anisotropy due to FRET (fluorescence resonance energy transfer) between homologous fluorescent proteins (homoFRET); we refer to these sensors as Apollo sensors. We created an Apollo sensor for NADP(+) (Apollo-NADP(+)) that exploits NADP(+)-dependent homodimerization of enzymatically inactive glucose-6-phosphate dehydrogenase (G6PD). This sensor is reversible, responsive to glucose-stimulated metabolism and spectrally tunable for compatibility with many other sensors. We used Apollo-NADP(+) to study beta cells responding to oxidative stress and demonstrated that NADPH is significantly depleted before H2O2 accumulation by imaging a Cerulean-tagged version of Apollo-NADP(+) with the H2O2 sensor HyPer.

An HIV-tailored quit-smoking counselling pilot intervention targeting depressive symptoms plus Nicotine Replacement Therapy.

Cardiovascular disease (CVD) rates among people living with HIV/AIDS (PHAs) are high. Rates of cigarette smoking, a leading contributor to CVD among PHAs, are 40-70% (2-3 times higher than the general population). Furthermore, PHAs have high rates of depression (40-60%), a risk factor for smoking cessation relapse. The current pilot study examined the effectiveness of a specifically tailored 5-session smoking cessation counselling programme for PHAs, which addressed depression, in combination with Nicotine Replacement Therapy (NRT) in a cohort of PHA smokers (n = 50). At 6-month follow-up, 28% of participants demonstrated biochemically verified abstinence from smoking. This result compares favourably to other quit-smoking intervention studies, particularly given the high percentage of HIV+ smokers with depression. At study baseline, 52% of HIV+ smokers scored above the clinical cut-off for depression on the Centre for Epidemiological Studies - Depression (CES-D) scale. HIV+ smokers with depression at study baseline demonstrated quantitatively lower depression at 6-month follow-up with a large effect size (d = 1), though it did not reach statistical significance (p = .058). Furthermore, those with depression were no more likely to relapse than those without depression (p = .33), suggesting that our counselling programme adequately addressed this significant barrier to smoking cessation among PHAs. Our pilot study indicates the importance of tailored programmes to help PHAs quit smoking, the significance of addressing depressive symptoms, and the need for tailored counselling programmes to enhance quit rates among PHAs.

Role of P-glycoprotein in the distribution of the HIV protease inhibitor atazanavir in the brain and male genital tract.

The blood-testis barrier and blood-brain barrier are responsible for protecting the male genital tract and central nervous system from xenobiotic exposure. In HIV-infected patients, low concentrations of antiretroviral drugs in cerebrospinal fluid and seminal fluid have been reported. One mechanism that may contribute to reduced concentrations is the expression of ATP-binding cassette drug efflux transporters, such as P-glycoprotein (P-gp). The objective of this study was to investigate in vivo the tissue distribution of the HIV protease inhibitor atazanavir in wild-type (WT) mice, P-gp/breast cancer resistance protein (Bcrp)-knockout (Mdr1a-/-, Mdr1b-/-, and Abcg2-/- triple-knockout [TKO]) mice, and Cyp3a-/- (Cyp) mice. WT mice and Cyp mice were pretreated with a P-gp/Bcrp inhibitor, elacridar (5 mg/kg of body weight), and the HIV protease inhibitor and boosting agent ritonavir (2 mg/kg intravenously [i.v.]), respectively. Atazanavir (10 mg/kg) was administered i.v. Atazanavir concentrations in plasma (Cplasma), brain (Cbrain), and testes (Ctestes) were quantified at various times by liquid chromatography-tandem mass spectrometry. In TKO mice, we demonstrated a significant increase in atazanavir Cbrain/Cplasma (5.4-fold) and Ctestes/Cplasma (4.6-fold) ratios compared to those in WT mice (P<0.05). Elacridar-treated WT mice showed a significant increase in atazanavir Cbrain/Cplasma (12.3-fold) and Ctestes/Cplasma (13.5-fold) ratios compared to those in vehicle-treated WT mice. In Cyp mice pretreated with ritonavir, significant (P<0.05) increases in atazanavir Cbrain/Cplasma (1.8-fold) and Ctestes/Cplasma (9.5-fold) ratios compared to those in vehicle-treated WT mice were observed. These data suggest that drug efflux transporters, i.e., P-gp, are involved in limiting the ability of atazanavir to permeate the rodent brain and genital tract. Since these transporters are known to be expressed in humans, they could contribute to the low cerebrospinal and seminal fluid antiretroviral concentrations reported in the clinic.

Development and psychometric validation of a cystic fibrosis knowledge scale.

BACKGROUND AND OBJECTIVE: Well-developed and validated measures of cystic fibrosis (CF) knowledge are scarce. The purpose of the present study is to develop and validate a CF knowledge scale that is brief, easy to use, self-administered and demonstrates clinical utility. METHODS: A comprehensive literature search generated a pool of scale items; an expert panel of CF team members reviewed and provided recommendations for item inclusion. A focus group of CF patients and family members (n = 12) then reviewed the items for face validity and reading clarity. To evaluate the validity and reliability of the newly developed CF knowledge scale, it was administered to several different samples including CF patients (n = 45), respirology patients (n = 100), health-care providers (n = 74) and university student samples (psychology students, n = 71; medical students, n = 36). RESULTS: Internal consistency of the scale was high, with an alpha coefficient for the overall sample of .95 (n = 326). The scale also demonstrated excellent construct validity. CONCLUSIONS: This study is an important first step in a line of research that aims to develop and empirically validate a psycho-educational adherence intervention for improving quality of life and treatment outcomes among adult CF patients. The CF knowledge scale has potential applications as a clinical teaching tool with patients and health-care providers and could be used as an outcome measure in CF educational intervention studies aimed at optimizing CF treatment knowledge, adherence and quality of life among CF patients.

Assessment of stigma in patients with cystic fibrosis.

BACKGROUND: Research that explores stigma in Cystic Fibrosis (CF) is limited. Productive cough, repeated lung infections, and periods of serious illness requiring hospitalizations are among common symptoms of CF. These symptoms may cause a negative perception by others. We developed a CF-specific Stigma Scale and tested its psychometric properties. METHODS: We conducted a focus group with 11 participants including adult patients with CF (n = 5) and their informal caregivers (n = 6). The thematic content of the focus group was analyzed to find key themes. We developed a CF-specific Stigma Scale and assessed its psychometric properties in a 3-month prospective cohort study of adult CF outpatients (n = 45). RESULTS: Stigma emerged as consistent concern for people living and caring for those with CF, affecting both patients' lives and health through the focus group. Using the newly developed CF Stigma scale, the mean baseline score was 16.6 (SD = 4.5, Range = 10-25). The CF Stigma Scale demonstrated robust psychometric properties: 1) Internal consistency: α = 0.79; 2) Mean inter-item correlation: 0.30 with good test-retest reliability; 3) Convergent validity: Positive associations with depression, severity of CF symptoms and anxiety; negative associations with validated quality of life scores were observed. CONCLUSIONS: Stigma is measurable and significantly impacts the lives of CF patients. Further research should investigate the role of stigma in patients living with CF.

HIV prevention in action on the football field: the WhizzKids United program in South Africa.

The Africaid Trust is a grassroots South African non-profit organization that engages youth in HIV prevention by harnessing the popularity of football (i.e. soccer). WhizzKids United, the organization's primary program, operates a 12-week program in elementary schools in Pietermaritzburg, South Africa, which aims to impart knowledge and life skills critical to HIV prevention. The goal of this research was to compare elementary school youth who received the program to youth who only received traditional classroom-based HIV education on health behaviors and HIV-related knowledge and stigma. A secondary objective was to evaluate HIV knowledge, sexual behaviors, attitudes towards HIV and health care seeking behaviors among South African youth in grades 9-12. Elementary students who participated in the program reported greater HIV knowledge and lower HIV stigma (p < .001) than those who had not. The majority of youth in grades 9-12 report having sexual relations (55.6%), despite low levels of HIV testing (29.9%) in this high HIV prevalence region of South Africa. The results highlight the importance of supporting community-based HIV educational initiatives that engage high-risk youth in HIV prevention and the need for youth-friendly health services.

Association between spontaneous internal carotid artery dissection and perivascular adipose tissue attenuation on computed tomography angiography.

BACKGROUND: Spontaneous cervical artery dissection (sCAD) is a leading cause of ischemic stroke in young patients. Studies using high-resolution magnetic resonance imaging and positron emission tomography have suggested vessel wall inflammation to be a pathogenic factor in sCAD. Computed tomography (CT) attenuation of perivascular adipose tissue (PVAT) is an established non-invasive imaging biomarker of inflammation in coronary arteries, with higher attenuation values reflecting a greater degree of vascular inflammation. OBJECTIVES: We evaluate the CT attenuation of PVAT surrounding the internal carotid artery (PVATcarotid) with and without spontaneous dissection. METHODS: Single-center prospective observational study of 56 consecutive patients with CT-verified spontaneous dissection of the internal carotid artery (ICA). Of these patients, six underwent follow-up computed tomography angiography (CTA). Twenty-two patients who underwent CTA for acute neurological symptoms but did not have dissection formed the control group. Using semi-automated research software, PVATcarotid was measured as the mean Hounsfield unit (HU) attenuation of adipose tissue within a defined volume of interest surrounding the ICA. RESULTS: PVATcarotid was significantly higher around dissected ICA compared with non-dissected contralateral ICA in the same patients (-58.7 ± 10.2 vs -68.9 ± 8.1 HU, p < 0.0001) and ICA of patients without dissection (-58.7 ± 10.2 vs -69.3 ± 9.3 HU, p < 0.0001). After a median follow-up of 89 days, there was a significant reduction in PVATcarotid around dissected ICA (-57.5 ± 13.4 to -74.3 ± 10.5 HU, p < 0.05), while no change was observed around non-dissected contralateral ICA (-71.0 ± 4.4 to -74.1 ± 4.1 HU, p = 0.19). ICA dissection was an independent predictor of PVATcarotid following multivariable adjustment for age and the presence of ICA occlusion. CONCLUSION: PVATcarotid is elevated in the presence of sCAD and may decrease following the acute event.

Coronary computed tomography angiography-based assessment of vascular inflammation in patients with obstructive sleep apnoea and coronary artery disease.

Background: Obstructive sleep apnoea (OSA) is associated with increased coronary artery disease (CAD) plaque burden, but the role of vascular inflammation in this relationship is unclear. Coronary computed tomography angiography (CTA) enables surrogate assessment of systemic inflammation via subcutaneous adipose tissue attenuation (SCAT-a), and of coronary inflammation via epicardial adipose tissue volume and attenuation (EAT-v and EAT-a) and pericoronary adipose tissue attenuation (PCAT-a). We investigated whether patients with severe OSA and high plaque burden have increased vascular inflammation. Methods: Patients with overnight polysomnography within ≤12 months of coronary CTA were included. Severe OSA was classified as apnoea/hypopnoea index (AHI) >30. High plaque burden was defined as a CT-adapted Leaman score (CT-LeSc) ≥8.3. Patients with both severe OSA and high plaque burden were defined as 'Group 1', all other patients were classified as 'Group 2'. ScAT, PCAT and EAT attenuation and volume were assessed on semi-automated software. Results: A total of 91 patients were studied (59.3±11.1 years). Severe OSA was associated with high plaque burden (P=0.02). AHI correlated with CT-LeSc (r=0.24, P=0.023). Group 1 had lower EAT-a and PCAT-a compared to Group 2 (EAT-a: -87.6 vs. -84.0 HU, P=0.011; PCAT-a: -90.4 vs. -83.4 HU, P<0.01). However, among patients with low plaque burden, EAT-a was higher in the presence of severe OSA versus mild-moderate OSA (-80.3 vs. -84.0 HU, P=0.020). On multivariable analysis, severe OSA and high plaque burden associated with EAT-a (P<0.02), and severe OSA and high plaque burden (P<0.01) and hypertension (P<0.01) associated with PCAT-a. Conclusions: EAT and PCAT attenuation are decreased in patients with severe OSA and high plaque burden, but EAT attenuation was increased in patients with severe OSA and low plaque burden. These divergent results suggest vascular inflammation may be increased in OSA independent of CAD, but larger studies are required to validate these findings.

Targeting Apollo-NADP+ to Image NADPH Generation in Pancreatic Beta-Cell Organelles.

NADPH/NADP+ redox state supports numerous reactions related to cell growth and survival; yet the full impact is difficult to appreciate due to organelle compartmentalization of NADPH and NADP+. To study glucose-stimulated NADPH production in pancreatic beta-cell organelles, we targeted the Apollo-NADP+ sensor by first selecting the most pH-stable version of the single-color sensor. We subsequently targeted mTurquoise2-Apollo-NADP+ to various organelles and confirmed activity in the cytoplasm, mitochondrial matrix, nucleus, and peroxisome. Finally, we measured the glucose- and glutamine-stimulated NADPH responses by single- and dual-color imaging of the targeted sensors. Overall, we developed multiple organelle-targeted Apollo-NADP+ sensors to reveal the prominent role of beta-cell mitochondria in determining NADPH production in the cytoplasm, nucleus, and peroxisome.

Breast arterial calcification and epicardial adipose tissue volume, but not density are independently associated with cardiovascular risk.

BACKGROUND: Mammographically detected breast arterial calcification (BAC) has been proposed as surrogate marker for coronary artery disease (CAD) in women. Epicardial adipose tissue (EAT) and peri-coronary adipose tissue (PCAT) are inflammatory fat depots linked to atherogenesis. BAC has demonstrated association with inflammation, therefore we aimed to determine the association between BAC, EAT and PCAT. METHODS: Single-centre, retrospective, cross-sectional study of women with digital mammography and coronary computed tomography angiography (CCTA). EAT and PCAT were quantitively assessed using semi-automated software. Patient demographics and cardiovascular risk factors were obtained from medical records and mammograms reviewed for BAC. Pre-test cardiovascular risk was determined with CAD Consortium Score. Chi-square, t-test and Mann-Whitney U tests were used to assess between group differences. Multivariable linear and logistic regression modelling was conducted to adjust for confounders. RESULTS: Among 153 patients (age 61, SD 11) included in this study, BAC was present in 37 (24%) patients. BAC-positive patients had higher EAT volume (EATv) (110.2 mL, SD 41 mL vs 94.4 mL, SD 41 mL, p = 0.02) but this association was not significant after adjusting for cardiovascular risk factors (p = 0.26). BAC did not associate with EAT density or PCAT. BAC and EATv were strongly associated with cardiovascular risk and CAD independent of each other: CV risk (BAC OR 7.55 (3.26-18.49), p < 0.001, EATv OR 1.02 (1.01-1.03), p < 0.001), CAD presence (BAC OR 4.26 (1.39-13), p = 0.01; EATv OR 1.01 (1.0-1.03), p = 0.04). CONCLUSION: BAC and EATv are independent predictors of CV risk and CAD, but don't independently associate with each other, the relationship confounded by shared cardiovascular risk factors. BAC doesn't appear to associate with adipose tissue density and its presence may be cumulative result of long-term exposure to CV risk factors.

Leveraging multimodal microscopy to optimize deep learning models for cell segmentation.

Deep learning provides an opportunity to automatically segment and extract cellular features from high-throughput microscopy images. Many labeling strategies have been developed for this purpose, ranging from the use of fluorescent markers to label-free approaches. However, differences in the channels available to each respective training dataset make it difficult to directly compare the effectiveness of these strategies across studies. Here, we explore training models using subimage stacks composed of channels sampled from larger, "hyper-labeled," image stacks. This allows us to directly compare a variety of labeling strategies and training approaches on identical cells. This approach revealed that fluorescence-based strategies generally provide higher segmentation accuracies but were less accurate than label-free models when labeling was inconsistent. The relative strengths of label and label-free techniques could be combined through the use of merging fluorescence channels and using out-of-focus brightfield images. Beyond comparing labeling strategies, using subimage stacks for training was also found to provide a method of simulating a wide range of labeling conditions, increasing the ability of the final model to accommodate a greater range of candidate cell labeling strategies.

Increasing use of an endotracheal intubation safety checklist in the emergency department.

Endotracheal intubation (ETI) is a high-risk procedure often performed in the emergency department (ED) in critically unwell patients. The fourth National Audit Project by The Royal College of Anaesthetists found the risk of adverse events is much higher when performing the intervention in this setting compared with a theatre suite, and therefore use of a safety checklist is recommended. This quality improvement project was set in a large teaching hospital in the North West of the UK, where anaesthesia and intensive care clinicians are responsible for performing this procedure. A retrospective baseline audit indicated checklist use was 16.7% of applicable cases. The project aim was to increase the incidence of checklist use in the ED to 90% within a 6-month period. The model for improvement was used as a methodological approach to the problem along with other quality improvement tools, including a driver diagram to generate change ideas. The interventions were targeted at three broad areas: awareness of the checklist and expectation of use, building a favourable view of the benefits of the checklist and increasing the likelihood it would be remembered to use the checklist in the correct moment. After implementation checklist use increased to 84%. In addition, run chart analysis indicated a pattern of nonrandom variation in the form of a shift. This coincided with the period shortly after the beginning of the interventions. The changes were viewed favourably by junior and senior anaesthetists, as well as operating department practitioners and ED staff. Limitations of the project were that some suitable cases were likely missed due to the method of capture and lack of anonymous qualitative feedback on the changes made. Overall, however, it was shown the combination of low-cost interventions made was effective in increasing checklist use when performing emergency ETI in the ED.

Development of a Cadaveric Multiport Model of Posterior Circulation Aneurysm Clipping for Neurosurgery and Otolaryngology Residents.

Posterior circulation aneurysms are difficult to treat with the current methods of coiling and clipping. To address limitations in training, we developed a cadaveric model to train learners on endoscopic clipping of posterior circulation aneurysms. An endoscopic transclival approach (ETA) and a transorbital precaruncular approach (TOPA) to successfully access and clip aneurysms of the posterior circulation are described. The model has flexibility in that a colored silicone compound can be injected into the cadaveric vessels for the purpose of training learners on vascular anatomy. The other option is that the model could be connected to a vascular perfusion pump allowing real-time appreciation of a pulsatile or ruptured aneurysm. This cadaveric model is the first of its kind for training of endoscopic clipping of posterior circulation aneurysms. Learners will develop proficiency in endoscopic skills, appropriate dissection, and appreciation for relative anatomy while developing an algorithm that can be employed in a real operative arena. Going forward, various clinical scenarios can be developed to enhance the realism, allow learners from different specialties to work together, and emphasize the importance of teamwork and effective communication.

Establishing a Multidisciplinary Cavernous Carotid Injury Simulation to Train Neurosurgical, Otolaryngology, and Anesthesia Residents.

Carotid artery injuries are serious complications of endoscopic endonasal surgery. As these occur rarely, simulation training offers an avenue for technique and algorithm development in resident learners. This study develops a realistic cadaveric model for the training of crisis resource management in the setting of cavernous carotid artery injury. An expanded endonasal approach and right cavernous carotid injury is performed on a cadaveric head. The cadaver's right common carotid artery is cannulated and connected to a perfusion pump delivering pressurized simulated blood. A simulation mannequin is incorporated into the model to allow for vital sign feedback. Surgical and anesthesia resident learners are tasked with obtaining vascular control with a muscle patch technique and medical management over the course of 3 clinical scenarios with increasing complexity. Crisis management instructions for an endoscopic endonasal approach to the cavernous carotid artery and blood pressure control were provided to the learners prior to beginning the simulation. An independent reviewer evaluated the learners on communication skills, crisis management algorithms, and implementation of appropriate skill sets. After each scenario, residents were debriefed on how to improve technique based on evaluation scores in areas of situational awareness, decision-making, communications and teamwork, and leadership. After the simulation, learners provided feedback on the simulation and this data was used to improve future simulations. The benefit of this cadaveric model is ease of set-up, cost-effectiveness, and reproducibility.

Role of RIPK1 in SMAC mimetics-induced apoptosis in primary human HIV-infected macrophages.

Macrophages serve as viral reservoirs due to their resistance to apoptosis and HIV-cytopathic effects. We have previously shown that inhibitor of apoptosis proteins (IAPs) confer resistance to HIV-Vpr-induced apoptosis in normal macrophages. Herein, we show that second mitochondrial activator of caspases (SMAC) mimetics (SM) induce apoptosis of monocyte-derived macrophages (MDMs) infected in vitro with a R5-tropic laboratory strain expressing heat stable antigen, chronically infected U1 cells, and ex-vivo derived MDMs from HIV-infected individuals. To understand the mechanism governing SM-induced cell death, we show that SM-induced cell death of primary HIV-infected macrophages was independent of the acquisition of M1 phenotype following HIV infection of macrophages. Instead, SM-induced cell death was found to be mediated by IAPs as downregulation of IAPs by siRNAs induced cell death of HIV-infected macrophages. Moreover, HIV infection caused receptor interacting protein kinase-1 (RIPK1) degradation which in concert with IAP1/2 downregulation following SM treatment may result in apoptosis of macrophages. Altogether, our results show that SM selectively induce apoptosis in primary human macrophages infected in vitro with HIV possibly through RIPK1. Moreover, modulation of the IAP pathways may be a potential strategy for selective killing of HIV-infected macrophages in vivo.