Utility of a Short Neuropsychological Protocol for Detecting HIV-Associated Neurocognitive Disorders in Patients with Asymptomatic HIV-1 Infection

Human Immunodeficiency Virus type 1 (HIV-1) infection is a chronic disease that affects ~40 million people worldwide. HIV-associated neurocognitive disorders (HAND) are common in individuals with HIV-1 Infection, and represent a recent public health problem. Here we evaluate the performance of a recently proposed short protocol for detecting HAND by studying 60 individuals with HIV-1-Infection and 60 seronegative controls from a Caribbean community in Barranquilla, Colombia. The short evaluation protocol used significant neuropsychological tests from a previous study of asymptomatic HIV-1 infected patients and a group of seronegative controls. Brief screening instruments, i.e., the Mini-mental State Examination (MMSE) and the International HIV Dementia Scale (IHDS), were also applied. Using machine-learning techniques, we derived predictive models of HAND status, and evaluated their performance with the ROC curves. The proposed short protocol performs exceptionally well yielding sensitivity, specificity, and overall prediction values >90%, and better predictive capacity than that of the MMSE and IHDS. Community-specific cut-off values for HAND diagnosis, based on the MMSE and IHDS, make this protocol suitable for HAND screening in individuals from this Caribbean community. This study shows the effectivity of a recently proposed short protocol to detect HAND in individuals with asymptomatic HIV-1-Infection. The application of community-specific cut-off values for HAND diagnosis in the clinical setting may improve HAND screening accuracy and facilitate patients’ treatment and follow-up. Further studies are needed to assess the performance of this protocol in other Latin American populations.

Trends in asymptomatic STI among HIV-positive MSM and lessons for systematic screening

The burden of STIs is particularly high in HIV-infected MSM patients. A recent increase in STIs prevalence has been noticed in the US and western European countries. We aim to assess trends in asymptomatic STIs following the publication of recommendations for STIs screening, i.e. Chlamydia (CT) and gonorrhea (NG). Seventeen centers located in the Paris area participated in the study. All asymptomatic HIV-infected MSM patients attending a follow up consultation were proposed to participated in the study. Asymptomatic patients were included over 2 periods: period 1 from April to December 2015 and period 2 from September to December 2017. Etiologic diagnosis of STIs including hepatitis B, C, syphilis, was performed using a serological test, including a non-treponemal titer with a confirmatory treponemal assay for syphilis. CT and NG were screened using a nucleic acid amplification test (NAATs) on 3 anatomical sites, i.e. urine, rectal and pharyngeal. Overall, 781 patients were included: 490 and 291 in periods 1 and 2 respectively. Asymptomatic CT, NG, and syphilis were diagnosed in 7.5%, 4.8% and, 4.2% respectively. The rate of patients having a multisite asymptomatic infection was 10.2% and 21.1% for CT and NG respectively. The most frequently involved anatomical sites for CT and NG asymptomatic infections were anorectal (66.1% and 55.2% respectively) and pharyngeal (47.4% and 60.5% respectively). CT and NG asymptomatic infection increased by 1.3- and 2-fold respectively between the two periods while syphilis decreased by 3 folds. Our results encourage to reconsider multisite screening for CT and NG in asymptomatic HIV positive MSM as the yield of screening urinary samples only might be low. Despite the more systematic STI screening of asymptomatic HIV positive MSM the prevalence of STI is increasing in MSM in France. Therefore, this strategy has not led to alter CT and NG transmission. The decrease of syphilis might involve self-medication by doxycycline, and the intensification of syphilis screening.

Prevalence of cervical abnormalities amongst HIV-positive women

To study the prevalence and variety of cervical squamous intra-epithelial lesions (SIL) by Pap smear screening as an indicator of suspected HPV infection among HIV-infected women in Surat, Gujarat, India.All consecutive asymptomatic HIV seropositive women 18 years and older and attending the Anti-Retroviral Therapy Centre at New Civil Hospital, Surat, India between October 2009 to September 2011 were eligible for inclusion in the study. Participants constituted 439 asymptomatic HIV seropositive women receiving care at the ART centre underwent detailed history taking, physical examination and Pap smear screening. The incidence of SIL was 8.7% (38/439) in the participants. Further, statistical significance (p value > 0.05) was observed in parity more than two, lost their husband, duration of marriage more than 10 years and CD4 count greater than 250.An association between HIV infection with pre-invasive changes in the cervical epithelium is noted. Early detection and prompt treatment of these changes after a thorough understanding of the natural history of disease in these women would go a long way in improving the survival as well as the quality of life in this increasing seropositive younger population.

The CD8+ T Cell Noncytotoxic Antiviral Responses

SUMMARY The CD8+ T cell noncytotoxic antiviral response (CNAR) was discovered during studies of asymptomatic HIV-infected subjects more than 30 years ago. In contrast to CD8+ T cell cytotoxic lymphocyte (CTL) activity, CNAR suppresses HIV replication without target cell killing. This activity has characteristics of innate immunity: it acts on all retroviruses and thus is neither epitope specific nor HLA restricted. The HIV-associated CNAR does not affect other virus families. It is mediated, at least in part, by a CD8+ T cell antiviral factor (CAF) that blocks HIV transcription. A variety of assays used to measure CNAR/CAF and the effects on other retrovirus infections are described. Notably, CD8+ T cell noncytotoxic antiviral responses have now been observed with other virus families but are mediated by different cytokines. Characterizing the protein structure of CAF has been challenging despite many biologic, immunologic, and molecular studies. It represents a low-abundance protein that may be identified by future next-generation sequencing approaches. Since CNAR/CAF is a natural noncytotoxic activity, it could provide promising strategies for HIV/AIDS therapy, cure, and prevention.

Unexpected increase of myocardial extracellular volume fraction in low cardiovascular risk HIV patients

Background People living with HIV (PLWH) are prone to develop sub-clinical Cardiovascular (CV) disease, despite the effectiveness of combined Antiretroviral Therapy (cART). Algorithms developed to predict CV risk in the general population could be inaccurate when applied to PLWH. Myocardial Extra-Cellular Matrix (ECM) expansion, measured by computed tomography, has been associated with an increased CV vulnerability in HIV-negative population. Measurement of Myocardial Extra-Cellular Volume (ECV) by computed tomography or magnetic resonance, is considered a useful surrogate for clinical evaluation of ECM expansion. In the present study, we aimed to determine the extent of cardiovascular involvement in asymptomatic HIV-infected patients with the use of a comprehensive cardiac computed tomography (CCT) approach. Materials and methods In the present study, ECV in low atherosclerotic CV risk PLWH was compared with ECV of age and gender matched HIV- individuals. 53 asymptomatic HIV + individuals (45 males, age 48 (42.5–48) years) on effective cART (CD4 + cell count: 450 cells/µL (IQR: 328–750); plasma HIV RNA: <37 copies/ml in all subjects) and 18 age and gender matched controls (14 males, age 55 (44.5–56) years) were retrospectively enrolled. All participants underwent CCT protocol to obtain native and postcontrast Hounsfield unit values of blood and myocardium, ECM was calculated accordingly. Results The ECV was significantly higher in HIV + patients than in the control group (ECV: 31% (IQR: 28%-31%) vs. 27.4% (IQR: 25%-28%), p < 0.001). The duration of cART (standardized β = 0.56 (0.33–0.95), p = 0.014) and the years of exposure to HIV infection (standardized β = 0.53 (0.4–0.92), p < 0.001), were positively and strongly associated with ECV values. Differences in ECV (p < 0.001) were also observed regarding the duration of cART exposure (< 5 years, 5–10 years and > 10 years). Moreover, ECV was independently associated with age of participants (standardized β = 0.42 (0.33–0.89), p = 0.084). Conclusions HIV infection and exposure to antiretrovirals play a detrimental role on ECV expansion. An increase in ECV indicates ECM expansion, which has been associated to a higher CV risk in the general population. The non-invasive evaluation of ECM trough ECV could represent an important tool to further understand the relationship between HIV infection, cardiac pathophysiology and the increased CV risk observed in PLWH.

Unexpected increase of myocardial extracellular volume fraction in low cardiovascular risk HIV patients

Background: People living with HIV (PLWH) are prone to develop sub-clinical Cardiovascular (CV) disease, despite the effectiveness of combined Antiretroviral Therapy (cART). Algorithms developed to predict CV risk in the general population could be inaccurate when applied to PLWH. Myocardial Extra-Cellular Matrix (ECM) expansion, measured by computed tomography, has been associated with an increased CV vulnerability in HIV-negative population. Measurement of Myocardial Extra-Cellular Volume (ECV) by computed tomography or magnetic resonance, is considered a useful surrogate for clinical evaluation of ECM expansion. In the present study, we aimed to determine the extent of cardiovascular involvement in asymptomatic HIV-infected patients with the use of a comprehensive cardiac computed tomography (CCT) approach.Materials and methods: In the present study, ECV in low atherosclerotic CV risk PLWH was compared with ECV of age and gender matched HIV- individuals. 53 asymptomatic HIV+ individuals (45 males, age 48 (42.5-48) years) on effective cART (CD4+ cell count: 450 cells/μL (IQR: 328-750); plasma HIV RNA: <37 copies/ml in all subjects) and 18 age and gender matched controls (14 males, age 55 (44.5-56) years) were retrospectively enrolled. All participants underwent CCT protocol to obtain native and postcontrast Hounsfield unit values of blood and myocardium, ECM was calculated accordingly.Results: The ECV was significantly higher in HIV+ patients than in the control group (ECV: 31% (IQR: 28%-31%) vs 27.4% (IQR: 25%-28%), p<0.001). The duration of cART (standardized β=0.56 (0.33-0.95), p=0.014) and the years of exposure to HIV infection (standardized β=0.53 (0.4-0.92), p<0.001), were positively and strongly associated with ECV values. Differences in ECV (p<0.001) were also observed regarding the duration of cART exposure (<5 years, 5-10 years and >10 years). Moreover, ECV was independently associated with age of participants (standardized β = 0.42 (0.33-0.89), p=0.084).Conclusions: HIV infection and exposure to antiretrovirals play a detrimental role on ECV expansion. An increase in ECV indicates ECM expansion, which has been associated to a higher CV risk in the general population. The non-invasive evaluation of ECM trough ECV could represent an important tool to further understand the relationship between HIV infection, cardiac pathophysiology and the increased CV risk observed in PLWH.