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HIV-associated prospective memory (ProM) impairment has emerged, in earlier studies as a significant predictor of medication management and independence in activities of daily living. The relationship between ProM and white matter integrity in HIV has not previously been investigated. Participants, including 128 HIV-infected individuals and 32 healthy controls, were assessed using a comprehensive neuropsychological evaluation and both objective and subjective measures of ProM. Diffusion tensor imaging (DTI) was utilized to investigate the relationship of white matter integrity to ProM in a randomly selected subsample of 40 HIV positive subjects, using a whole brain voxel-based approach to define fractional anisotrophy (FA) and mean diffusion (MD). Total prospective memory was significantly poorer in the HIV positive group when compared with healthy controls ( p  = 0.023). Time-based ProM was poorer in the HIV group compared to healthy controls both without prompts ( p  = 0.001) and with prompts ( p  = 0.001). Poor Total ProM score correlated with performance on neuropsychological tests of executive functioning, information processing speed, learning, and working memory ( p  < 0.05). Those HIV positive participants with poor ProM had significantly decreased FA in the regions of superior corona radiata ( p  = 0.0035), the corpus collosum ( p  = 0.006) and the cingulum ( p  = 0.0033) when compared to those who were HIV positive with good ProM. This study reinforces the importance of ProM assessment in HIV.

Heterosexual transmission of HIV-1 is characterized by a genetic bottleneck that selects a single viral variant, the transmitted/founder (TF), during most transmission events. To assess viral characteristics influencing HIV-1 transmission, we sequenced 167 near full-length viral genomes and generated 40 infectious molecular clones (IMC) including TF variants and multiple non-transmitted (NT) HIV-1 subtype C variants from six linked heterosexual transmission pairs near the time of transmission. Consensus-like genomes sensitive to donor antibodies were selected for during transmission in these six transmission pairs. However, TF variants did not demonstrate increased viral fitness in terms of particle infectivity or viral replicative capacity in activated peripheral blood mononuclear cells (PBMC) and monocyte-derived dendritic cells (MDDC). In addition, resistance of the TF variant to the antiviral effects of interferon-α (IFN-α) was not significantly different from that of non-transmitted variants from the same transmission pair. Thus neither in vitro viral replicative capacity nor IFN-α resistance discriminated the transmission potential of viruses in the quasispecies of these chronically infected individuals. However, our findings support the hypothesis that within-host evolution of HIV-1 in response to adaptive immune responses reduces viral transmission potential.

Introduction HIV infection is characterized by a persistent immune activation associated to a compromised gut barrier immunity and alterations in the profile of the fecal flora linked with the progression of inflammatory symptoms. The effects of high concentration multistrain probiotic (Vivomixx®, Viale del Policlinico 155, Rome, Italy in EU; Visbiome®, Dupont, Madison, Wisconsin in USA) on several aspects of intestinal immunity in ART‐experienced HIV‐1 patients was evaluated. Methods A sub‐study of a longitudinal pilot study was performed in HIV‐1 patients who received the probiotic supplement twice a day for 6 months (T6). T‐cell activation and CD4+ and CD8+ T‐cell subsets expressing IFNγ (Th1, Tc1) or IL‐17A (Th17, Tc17) were stained by cytoflorimetric analysis. Histological and immunohistochemical analyses were performed on intestinal biopsies while enterocytes apoptosis index was determined by TUNEL assay. Results A reduction in the frequencies of CD4+ and CD8+ T‐cell subsets, expressing CD38+, HLA‐DR+, or both, and an increase in the percentage of Th17 cell subsets, especially those with central or effector memory phenotype, was recorded in the peripheral blood and in gut‐associated lymphoid tissue (GALT) after probiotic intervention. Conversely, Tc1 and Tc17 levels remained substantially unchanged at T6, while Th1 cell subsets increase in the GALT. Probiotic supplementation was also associated to a recovery of the integrity of the gut epithelial barrier, a reduction of both intraepithelial lymphocytes density and enterocyte apoptosis and, an improvement of mitochondrial morphology sustained in part by a modulation of heat shock protein 60. Conclusions These findings highlight the potential beneficial effects of probiotic supplementation for the reconstitution of physical and immunological integrity of the mucosal intestinal barrier in ART‐treated HIV‐1‐positive patients. (i) Probiotic supplementation causes a reduction in the frequencies of CD4+ and CD8+ T‐cell subsets, expressing CD38+, HLA‐DR+, or both, in HIV‐1 patients; (ii) probiotics intervention leads to an increase of the frequency of Th17 cell subsets (central memory and effector memory) in HIV‐1 patients; (iii) probiotic supplementation was associated to a reduction of diffuse interstitial inflammatory infiltrate, and an increase in the number and area of the GALT structures associated to the mucosa in HIV‐1 patients; (iv) probiotic supplementation leads to a reduction of both IELs density and enterocytes death via apoptosis in HIV‐1 patients; (v) probiotics improves mitochondrial morphology through a localization of mitochondrial chaperonin, HPS60, from cytosol to mitochondrial compartment in HIV‐1 patients.

Chronic HIV infection is associated with increased risk of cardiovascular disease (CVD), including in patients with virological suppression. Persistent innate immune activation may contribute to the development of CVD via activation of monocytes in these patients. We investigated whether changes in monocyte phenotype predict subclinical atherosclerosis in virologically suppressed HIV‐positive individuals with low cardiovascular risk. We enroled 51 virologically suppressed HIV‐positive individuals not receiving protease inhibitors or statins and 49 age‐matched uninfected controls in this study. Carotid artery intima‐media thickness (cIMT) was used as a surrogate marker for CVD, and traditional risk factors, including Framingham risk scores, were recorded. Markers of monocyte activation (CD14, CD16, CCR2, CX3CR1, CD38, HLA‐DR and CD11b) were measured in whole‐blood samples by flow cytometry. Associations were assessed using univariate and multivariate median regressions. Median cIMT was similar between HIV‐positive and HIV‐negative participants (P=0.3), although HIV‐positive patients had significantly higher Framingham risk score (P=0.009) and systemic inflammation. Expression of two monocyte markers, CD11b and CX3CR1, independently predicted carotid artery thickness in HIV‐positive individuals after controlling for Framingham risk score (P=0.025 and 0.015, respectively). These markers were not predictive of carotid artery thickening in controls. Our study indicates that monocyte surface markers may serve as novel predictors of CVD in HIV‐positive individuals and is consistent with an important role for monocyte activation in the progression of HIV‐related cardiovascular pathology.

Background Oncogenic Human papillomavirus (HPV) infections are closely associated with anal cancer which is high among human immunodeficiency virus (HIV) infected males. There are no data regarding anal HPV infection and cytological abnormalities in HIV positive males receiving free therapy in the national program. Thus, this cross-sectional study was performed to assess the prevalence and risk factors of anal HPV infection and cytological abnormalities in HIV positive males. Methods We screened 126 HIV-positive male patients attending the antiretroviral treatment center (ART) between 2014 and 2015 with anal papanicolaou smear cytology and HPV-DNA testing. HPV-DNA was detected by using polymerase chain reaction (PCR) method with two consensus primer sets E6 and MY09/11 and further analyzed for the presence of various HPV genotype by Sanger sequencing. Risk factors associated with anal cytological abnormalities and HPV infection was analyzed by using univariate and multivariate logistic regression models. Results Out of 126, 52 were on antiretroviral therapy. 91% were married to female partners but during the study 48 (38%) gave positive history of anal intercourse with other men. Anal cytology was done in 95 patients, out of which 60 (63.15%) had cytological abnormalities. LSIL (low-grade squamous intraepithelial lesions) was present in 27 (45%), ASCUS (atypical squamous cells of undetermined significance) in 31 (52%) and ASC-H (atypical squamous cells cannot exclude a high-grade squamous intraepithelial lesion) in 2 (3.33%). In multivariate analysis, the risk factors for cytological abnormality were presence of history of anal intercourse (OR, 6.1; 95% CI, 2.0–18.7) and WHO stage III & IV (OR, 2.7; 95% CI, 1.1–7.5). HPV-DNA was detected in 33/119 (27.73%) patients. The most prevalent HPV type in the study was HPV-16 (10.08%), other HPV types detected were 18,31,35,17,66,72,52,68 and 107 (17.65%). Conclusions High prevalence of anal cytological abnormalities in our study suggests that regular anal Pap smear screening should be done in HIV positive males in the ART center.

To assess residual cervical intraepithelial neoplasia (CIN) 2/3 disease and clearance of high-risk (hr) human papillomavirus (HPV) infections at 6 months after cryotherapy among HIV-positive women. Follow-up study. 79 HIV-positive women received cryotherapy for CIN2/3 in Nairobi, Kenya, and underwent conventional cytology 6 months later. Biopsies were performed on high grade cytological lesions and hrHPV was assessed before (cervical cells and biopsy) and after cryotherapy (cells). At 6 months after cryotherapy CIN2/3 had been eliminated in 61 women (77.2%; 95% Confidence Interval, (CI): 66.4-85.9). 18 women (22.8%) had residual CIN2/3, and all these women had hrHPV at baseline. CD4 count and duration of combination antiretroviral therapy (cART) were not associated with residual CIN2/3. CIN3 instead of CIN2 was the only significant risk factor for residual disease (odds ratio, OR vs CIN2 = 4.3; 95% CI: 1.2-15.0) among hrHPV-positive women after adjustment for age and HPV16 infection. Persistence of hrHPV types previously detected in biopsies was found in 77.5% of women and was associated with residual CIN2/3 (OR = 8.1, 95% CI: 0.9-70). The sensitivity, specificity, and negative predictive value of hrHPV test in detecting residual CIN2/3 were 0.94, 0.36, and 0.96 respectively. Nearly one quarter of HIV-positive women had residual CIN2/3 disease at 6 months after cryotherapy, and the majority had persistent hrHPV. CD4 count and cART use were not associated with residual disease or hrHPV persistence. The value of hrHPV testing in the detection of residual CIN2/3 was hampered by a low specificity.

Background Since the advent of effective antiretroviral therapy, the number of people with AIDS has increased and a certain percentage of these patients will require emergent orthopaedic surgery. Little is known regarding orthopaedic infections and the association of CD4 counts with postoperative infection in patients with HIV infection who experience orthopaedic trauma. Questions/purposes We questioned whether the postoperative infection rate is higher after orthopaedic trauma surgery for patients who are HIV positive than for patients who are HIV negative undergoing similar surgery and aimed to identify preoperative variables that may be important in predicting postoperative infection in patients who are HIV positive. Methods We determined the postoperative infection rate in 64 patients who were HIV positive and who underwent orthopaedic surgery requiring instrumentation or an implant from January 2001 to May 2007. We compared this rate with historical control data from 2003 to 2007 for all orthopaedic procedures at Grady Memorial Hospital. We examined numerous preoperative variables for association with postoperative infection, including CD4 count, length of inpatient stay, polytrauma, and malnutrition. Results Of the 64 patients, 15 had postoperative infections develop with an infection rate of 23%, compared with the 3.9% rate for the historical control subjects. Analysis of the 64 patients who were HIV positive revealed CD4 counts less than 300 were associated with development of postoperative infection. Hospital stay, polytrauma, and low serum albumin also were found to be associated with postoperative infection. Conclusions It is evident that patients who are HIV positive with low CD4 counts undergoing emergent orthopaedic intervention are a patient population at risk for infection. Further study is necessary to evaluate preoperative and perioperative interventions that may decrease infections in this population. Level of Evidence Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Introduction: Patients receiving treatment for head-and-neck squamous cell carcinoma (HNSCC) also may have coexisting viral infections caused by HIV, HBV, and HCV (seropositive). There is scarce literature regarding the clinical presentation and treatment outcomes for these patients with coexisting viral infections (seropositive HNSCC). We conducted this study to assess the clinical presentation and treatment outcomes (overall survival [OS] and disease-specific survival [DSS]) of seropositive HNSCC patients. Methodology: This was a retrospective cohort study on seropositive HNSCC patients registered at our center from 2012 to 2014. The viral infections were identified by the presence of the antibodies to these viruses in the patient's blood samples. Results: Out of the 19,137 HNSCC patients registered, 156 patients had HBV, HCV, and/or HIV infection. Among these, HBV infection was the most common (n = 86/156, 55.1%) followed by HIV infection (n = 36/156, 23.1%) and HCV infection (n = 29/156, 18.6%). The oral cavity was the most common subsite involved. Majority of these patients presented at an advanced stage (advanced T stage - 71.8% and node positive - 62.2%). The majority of the patients received curative-intent treatment (65.4%). The OS at 3 years for these HNSCC patients with coexisting HIV, HBV, and HCV infection was 60%, 62.6%, and 57.5%, respectively, and their DSS at 3 years was 58.8%, 78.6%, and 53.8%, respectively. Conclusions: Seropositive patients with HNSCC often present in the advanced stage but have a good survival if treated appropriately.

Antiretroviral therapy (ART) and condom use have been proven to reduce the risk of sexual transmission of human immunodeficiency virus (HIV) among HIV sero-different couples, but its full implementation remains a challenge. This study aims to assess HIV seroconversion rate of HIV-negative spouse and its associated risk factors among HIV sero-different couples in rural China. An open cohort of HIV sero-different couples enrolled in 30 counties in China between October 1, 2010, and September 30, 2012, and followed-up to December 31, 2012, was constructed retrospectively. A nested case-control study of risk factors of HIV seroconversion among sero-different couples was conducted in April and May of 2013, based on the open cohort. Sero-different couples with the HIV-negative spouse seroconverting at least 3 months after the previous negative diagnosis during cohort observation period were labeled as \"case couples\". The \"control couples\" were selected randomly from the same cohort that did not have the HIV-negative spouse seroconversion during the same period. The \"case couples\" and \"control couples\" were matched on gender, age, and region of residence. Sexual behaviors among HIV sero-different couples before and after the index spouses notifying their HIV infection status to their HIV-negative spouses were collected via face-to-face interview. Univariate and multivariate logistic regression models were used to assess factors associated with HIV seroconversion among HIV sero-different couples. Of 4481 HIV sero-different couples, a total of 53 seroconversions were observed within 5218 person-years of follow-up. The incidence rate was 1.02 (95%CI: 0.76-1.33) per 100 person-years. Forty \"case couples\" confirmed HIV-negative spouse seroconversions infected via marital sexual transmission, were matched to 80 \"control couples\". Of the 120 couples, 81(67.5%) were receiving ART, and 70 (58.3%) reported consistently used condoms during intercourse after the index spouse was diagnosed HIV infection. Multivariate conditional logistic regression analysis showed that the desire to conceive a child (OR = 5.18, 95% CI: 1.19-22.58) significantly increased the odds of HIV seroconversion. Protective factors of spousal HIV seroconversion were currently receiving ART (OR = 0.09, 95% CI: 0.01-0.67) and consistent condom use (OR = 0.05, 95% CI: 0.01-0.28). Intention to conceive a child is the most important risk factor for HIV seroconversion among sero-different couples. Specific efforts on scientific use of ART to assist sero-different couples to achieve their wish to conceive a healthy child are needed to minimize the risk of HIV transmission.

The risk/benefit of initiating ART in primary HIV infection (PHI) is unclear. The benefits are more likely to outweigh the risks in patients with severe PHI. An accepted definition of severe PHI is, however, lacking. CASCADE patients with HIV test interval <6 months were classified as severe and non-severe PHI based on whether the following traits were recorded in the first 6 months following seroconversion: severe specific pre-defined symptoms, central nervous system-implicated illness, and ≥1, ≥2 CD4<350 (and <500) cells/mm(3). For each definition, we used Kaplan-Meier curves and Cox survival models to compare time to AIDS/death, censoring at the earlier of last clinic visit or 1/1/1997, when combination antiretroviral therapy (cART) became available. Among 1108 included patients mostly males (85%) infected through sex between men (71%), 366 were diagnosed with AIDS/died. The risk of AIDS/death was significantly higher for individuals with severe symptoms, those with ≥1 CD4<350 cells/mm(3) or ≥2 CD4 <500 cells/mm(3) in the first 6 months [aHR (95% confidence interval) 2.1 (1.4,3.2), 2.0 (1.5,2.7), and 2.3, (1.5-3.5) respectively]. Median [interquantile range] survival for patients with ≥2, ≥1 and no CD4<350 cells/mm(3) within 6 months of seroconversion was 3.9 [2.7,6.5], 5.4 [4.5,8.4] and 8.1 [4.3,10.3] years, respectively. The diagnosis of CNS-implicated symptoms was rare and did not appear to be prognostic. One CD4 count <350 or two <500 cells/mm(3) within 6 months of seroconversion and/or severe illness in PHI may be useful early indicators of individuals at high risk of disease progression.