The clinical profiles and outcomes of HIV-negative cryptococcal meningitis patients in type II diabetes mellitus.

BACKGROUND: The clinical profiles and outcomes of cryptococcal meningitis have been shown to vary depending on the underlying condition. The aim of this study was to investigate clinical characteristics and outcomes in patients with and without type II diabetes mellitus. METHODS: A retrospective study was performed. Clinical data of HIV-negative cryptococcal meningitis patients with type II diabetes mellitus (n = 26) and without type II diabetes mellitus (n = 52) referring to the Jiangxi Chest Hospital between January 2012 to December 2018 were analyzed. The data were analyzed using chi square, none-parametric tests, and logistic regression. P-values < 0.05 were considered significant. RESULTS: In this study, cryptococcal meningitis patients suffering from type II diabetes mellitus had a higher mortality (23.08% vs. 7.69%; P = 0.055), and required longer hospitalization (59.58 vs. 42.88 days; P = 0.132). Moreover, cerebrospinal fluid examinations revealed that cryptococcal meningitis patients with type II diabetes mellitus had higher opening pressure (271.54 vs. 234.23 mmH2O; P = 0.125).The results of multivariate regression analysis revealed that cryptococcal meningitis patients with type II diabetes were more often presented with visual disorders (28.54% vs. 11.54%; [95% CI 0.056-0.705]; p = 0.012), and had higher cerebrospinal fluid protein levels (1027.62 ± 594.16 vs. 705.72 ± 373.88 mg/l; [95% CI 1.000-1.002]; p = 0.016). Among patients with type II diabetes mellitus, nausea and vomiting was more frequent at the initial visit in those died (100% vs. 50%; p = 0.027), and 66% of died type II diabetes mellitus patients were poorly controlled blood glucose level, compared with 30% in survival type II diabetes mellitus patients. CONCLUSION: This study suggests that cryptococcal meningitis patients with type II diabetes mellitus differ significantly from cryptococcal meningitis patients without type II diabetes mellitus with respect to clinical symptoms such as visual disorders and cerebrospinal fluid examination. The presence of nausea and vomiting among type II diabetes mellitus patients could have implication in mortality.

An Uncommon Concurrence of Cytomegalovirus Retinitis and Corneal Endotheliitis in an Immunocompromised HIV-Negative Patient.

Purpose: To describe a case of Cytomegalovirus (CMV) retinitis in both eyes complicated with unilateral corneal endotheliitis in an iatrogenic immunocompromised patient.Methods: A retrospective case report.Result: A 58-year-old male, on long-term immunosuppressive treatment for chronic glomerulonephritis and nephrotic syndrome. Ocular examination revealed bilateral vitritis and necrotizing retinitis and concurrent corneal endotheliitis with ocular hypertension in his left eye. The PCR result showed positivity for CMV infection by diagnostic aqueous aspiration. Vitritis/retinitis in both eyes resolved gradually after systemic valganciclovir use, and the endotheliitis in the left eye regressed after topical antiviral treatment. There was no recurrence of retinitis/endotheliitis with a maintenance dose of oral valganciclovir. Unfortunately, tractional macular hole developed in the left eye and complicated the visual outcome.Conclusion: CMV retinitis may occur in HIV-negative immunocompromised individuals, but CMV endotheliitis generally appears in the immunocompetent. It is a rare combination of CMV retinitis and endotheliitis in this patient.

Frequent expression of activation-induced cytidine deaminase in diffuse large B-cell lymphoma tissues from persons living with HIV.

OBJECTIVE: The increased risk for persons living with HIV to develop diffuse large B-cell lymphoma (DLBCL) even in the post-antiretroviral therapy eras suggests a role beyond immunosuppression in lymphoma development. However, the mechanisms leading to lymphoma in the HIV setting are not fully understood. HIV is known to induce activation-induced cytidine deaminase (AID) levels in nonneoplastic B cells in vitro and chronic AID expression may play an important role in lymphomagenesis. Although AID expression is observed in B-cell lymphoma, studies in HIV-associated DLBCL are limited. DESIGN: In this study, we conducted a retrospective review of DLBCL tissues from patients with and without HIV infection to compare expression of AID and B-cell receptors potentially involved in HIV and B-cell interaction. METHODS: We evaluated DLBCL formalin-fixed paraffin-embedded tissues from 72 HIV-seropositive and 58 HIV-seronegative patients for AID, DC-SIGN, and CD40 protein expression. BCL2 and MYC, two well established prognostically significant oncoproteins in DLBCL, were also assessed at the protein and mRNA levels. Subset analysis was performed according to DLBCL subtype and EBV status. RESULTS: Of note, AID expression was more frequent in HIV-associated DLBCL compared with non-HIV-associated DLBCL regardless of cell-of-origin subtype, and also displayed significantly less BCL2 expression. Despite no direct correlation with AID expression, the HIV-DLBCL tissues also exhibited high levels of the DC-SIGN receptor. CONCLUSION: Collectively, these findings support a potential role for AID in the pathogenesis of HIV-associated lymphomas and suggest the need of further investigations into the involvement of the DC-SIGN receptor-signaling pathway.

Sterol metabolism modulates susceptibility to HIV-1 Infection.

BACKGROUND: 25-hydroxylase (CH25H) is an interferon-stimulated gene (ISG), which catalyzes the synthesis of 25-hydroxycholesterol (25HC). 25HC intervenes in metabolic and infectious processes and controls cholesterol homeostasis and influences viral entry into host cells. We verified whether natural resistance to HIV-1 infection in HIV-1-exposed seronegative (HESN) individuals is at least partially mediated by particularities in sterol biosynthesis. METHODS: Peripheral blood mononuclear cells (PBMCs) and monocyte-derived macrophages (MDMs) isolated from 15 sexually exposed HESN and 15 healthy controls were in vitro HIV-1-infected and analyzed for: percentage of IFNα-producing plasmacytoid dendritic cells (pDCs); cholesterol signaling and inflammatory response RNA expression; resistance to HIV-1 infection. MDMs from five healthy controls were in vitro HIV-1-infected in the absence/presence of exogenously added 25HC. RESULTS: IFNα-producing pDCs were augmented in HESN compared with healthy controls both in unstimulated and in in vitro HIV-1-infected PBMCs (P < 0.001). An increased expression of CH25H and of a number of genes involved in cholesterol metabolism (ABCA1, ABCG1, CYP7B1, LXRα, OSBP, PPARγ, SCARB1) was observed as well; this, was associated with a reduced susceptibility to in-vitro HIV-1-infection of PBMCs and MDMs (P < 0.01). Notably, addition of 25HC to MDMs resulted in increased cholesterol efflux and augmented resistance to in-vitro HIV-1-infection. CONCLUSION: Results herein show that in HESN sterol metabolism might be particularly efficient. This could be related to the activation of the IFNα pathway and results into a reduced susceptibility to in-vitro HIV-1 infection. These results suggest a possible basis for therapeutic interventions to modulate HIV-1 infection.

Changes in T-lymphocyte subsets and risk factors in human immunodeficiency virus-negative patients with active tuberculosis.

PURPOSE: Immune function imbalance is closely associated with the occurrence and development of infectious diseases. We studied the characteristics of changes in T-lymphocyte subsets and their risk factors in HIV-negative patients with active tuberculosis (ATB). METHODS: T-lymphocyte subsets in 275 HIV-negative ATB patients were quantitatively analyzed and compared with an Mycobacteriumtuberculosis-free control group. Single-factor and multifactor analyses of clinical and laboratory characteristics of patients were also conducted. RESULTS: In ATB patients, CD4 and CD8 T-cell counts decreased, and the levels were positively interrelated (r = 0.655, P < 0.0001). After 4 weeks of antituberculosis treatment, CD4 and CD8 T-cell counts increased significantly but remained lower than in the control group. CD4 and CD8 cell counts were negatively associated with the extent of lesions detected in the chest by computed tomography (all P < 0.05). Although not reflected in the CD4/CD8 ratio, CD4 and CD8 cell counts differed between drug-resistant TB patients and drug-susceptible TB patients (P = 0.030). The multivariate analysis showed prealbumin, alpha-1 globulin, body mass index, and platelet count were independent risk factors for decreased CD4 cell count (all P < 0.05), while age and platelet count were independent risk factors for decreased CD8 cell count (all P < 0.05). CONCLUSION: CD4 and CD8 T-cell counts showed the evident value in predicting ATB severity. An increase in the CD4/CD8 ratio may be a critical clue of drug resistance in ATB. Although the factors influencing CD4 and CD8 are not identical, our results indicated the importance of serum protein and platelets to ATB patients' immune function.

Auditory, video head impulse test and vestibular evoked myogenic potentials findings in adults with human immunodeficiency virus.

OBJECTIVES: Even though there is an association between hearing loss and human immunodeficiency virus (HIV), particularly in low- and middle-income countries, further research is needed to investigate the nature of such hearing loss. Likewise, despite documented vestibular alterations in people with HIV, the true occurrence, presentation, and nature of these manifestations are yet to be established. Advances in technology for vestibular testing has allowed for objective site-of-lesion tests such as the video head impulse test (vHIT), cervical vestibular evoked myogenic potentials (cVEMPs) and ocular vestibular evoked myogenic potential (oVEMPs). The current study aimed to compare and describe auditory, vHIT, cVEMPs and oVEMPs findings in adults with and without HIV. METHODS: The current study included an HIV positive group (n = 30) and an HIV negative group (n = 30) who underwent an auditory assessment (tympanometry and pure tone audiometry) and objective vestibular assessments. RESULTS: The occurrence of hearing loss was 53.3% in the HIV positive group compared to 33.3% in the HIV negative group. A higher occurrence of vestibular involvement was documented in the HIV positive group (73.3%) compared to 13.3% in the HIV negative group. CONCLUSION: Auditory assessment and objective measures of vestibular end-organ function (vHIT and VEMPs) can be useful to detect sub-clinical alterations. The equipment is mobile and can be performed in any health care setting such as infectious disease clinics for surveillance and monitoring purposes.

Placental Structure in Preterm Birth Among HIV-Positive Versus HIV-Negative Women in Kenya.

BACKGROUND: Preterm birth (PTB) is a major cause of infant morbidity and mortality in developing countries. Recent data suggest that in addition to Human Immunodeficiency Virus (HIV) infection, use of antiretroviral therapy (ART) increases the risk of PTB. As the mechanisms remain unexplored, we conducted this study to determine whether HIV and ART were associated with placental changes that could contribute to PTB. SETTING: We collected and evaluated placentas from 38 HIV-positive women on ART and 43 HIV-negative women who had preterm deliveries in Nairobi, Kenya. METHODS: Anatomical features of the placentas were examined at gross and microscopic levels. Cases were matched for gestational age and compared by the investigators who were blinded to maternal HIV serostatus. RESULTS: Among preterm placentas, HIV infection was significantly associated with thrombosis (P = 0.001), infarction (P = 0.032), anomalies in cord insertion (P = 0.02), gross evidence of membrane infection (P = 0.043), and reduced placental thickness (P = 0.010). Overall, preterm placentas in both groups were associated with immature villi, syncytial knotting, villitis, and deciduitis. Features of HIV-positive versus HIV-negative placentas included significant fibrinoid deposition with villus degeneration, syncytiotrophoblast delamination, red blood cell adhesion, hypervascularity, and reduction in both surface area and perimeter of the terminal villi. CONCLUSIONS: These results imply that HIV infection and/or ART are associated with morphological changes in preterm placentas that contribute to delivery before 37 weeks. Hypervascularity suggests that the observed pathologies may be attributable, in part, to hypoxia. Further research to explore potential mechanisms will help elucidate the pathways that are involved perhaps pointing to interventions for decreasing the risk of prematurity among HIV-positive women.

Pneumocystis jirovecii pneumonia (PCP) PCR-negative conversion predicts prognosis of HIV-negative patients with PCP and acute respiratory failure.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is often fatal in human immunodeficiency (HIV)-negative patients and typically presents with respiratory insufficiency. Predicting treatment failure is challenging. This study aimed to identify prognostic factors and examine PCP polymerase chain reaction (PCR)-negative conversion in non-HIV PCP patients with respiratory failure. METHOD: We retrospectively enrolled 81 non-HIV patients diagnosed with and treated for PCP with respiratory failure in the intensive care unit at a tertiary hospital over a 3-year period. PCP was diagnosed via nested PCR-mediated detection of Pneumocystis jirovecii in induced sputum samples, endotracheal aspirates, and bronchoalveolar lavage fluids. PCP PCR was performed weekly to check for negative conversion. RESULTS: The overall survival rate was 35.8%. Seventy-four patients (91.3%) required mechanical ventilation, and 6 (7.4%) required high-flow nasal oxygen treatment. The PCP PCR-negative conversion rate was 70.5% (survivors, 97%; non-survivors, 63.5%); the median time to conversion was 10 (7.0-14.0) days. On univariate analysis, the APACHE II score (p < 0.001), renal failure requiring renal replacement therapy (p = 0.04), PCP PCR-negative conversion (p = 0.003), and the PaO2/FiO2 ratio (first 24 hours) (p < 0.001) significantly correlated with mortality. On multivariate analysis, PCP PCR-negative conversion (hazard ratio, 0.433; 95% confidence interval, 0.203-0.928; p = 0.031) and the PaO2/FiO2 ratio (first 24 hours) (hazard ratio, 0.988; 95% confidence interval, 0.983-0.993; p < 0.001) independently predicted prognosis. CONCLUSIONS: Determination of PCP PCR-negative conversion and PaO2/FiO2 ratios may help physicians predict treatment failure and mortality in non-HIV PCP patients with respiratory failure.

HIV infection does not prevent the metabolic benefits of diet-induced weight loss in women with obesity.

OBJECTIVE: To test the hypothesis that HIV infection impairs the beneficial effects of weight loss on insulin sensitivity, adipose tissue inflammation, and endoplasmic reticulum (ER) stress. METHODS: A prospective clinical trial evaluated the effects of moderate diet-induced weight loss on body composition, metabolic function, and adipose tissue biology in women with obesity who were HIV-seronegative (HIV-) or HIV-positive (HIV+). Body composition, multiorgan insulin sensitivity (assessed by using a two-stage hyperinsulinemic-euglycemic clamp procedure with stable isotopically labeled tracer infusions), and adipose tissue expression of markers of inflammation, autophagy, and ER stress were evaluated in 8 HIV- and 20 HIV+ women with obesity before and after diet-induced weight loss of 6% to 8%. RESULTS: Although weight loss was not different between groups (∼7.5%), the decrease in fat-free mass was greater in HIV+ than HIV- subjects (-4.4 ± 0.7% vs. -1.7 ± 1.0%, P < 0.05). Weight loss improved insulin sensitivity in adipose tissue (suppression of palmitate rate of appearance [Ra]), liver (suppression of glucose Ra), and muscle (glucose disposal) similarly in both groups. Weight loss did not affect adipose tissue expression of markers of inflammation or ER stress in either group. CONCLUSIONS: Moderate diet-induced weight loss improves multiorgan insulin sensitivity in HIV+ women to the same extent as women who are HIV-. However, weight loss causes a greater decline in fat-free mass in HIV+ than HIV- women.

Role of intestinal dysfunction in the nutritional compromise seen in human immunodeficiency virus-infected adults in rural India.

Human immunodeficiency virus (HIV) disease progression is often marked by significant weight loss with or without chronic diarrhoea. We studied the extent of intestinal dysfunction using a D-xylose absorption test and association with nutritional compromise as measured by body mass index (BMI) and serum antioxidants levels in HIV-infected individuals through a cross-sectional survey of 45 ART naïve, HIV-positive and 45, age-socioeconomic status matched negative controls in a rural population in India. More than 40% of HIV-positive and HIV-negative participants had intestinal dysfunction (42.2% vs. 44.4%). However an increasing gradient of low D-xylose absorption was noted with decreasing CD4 counts (32%, 50% and 58.3% among those with >350, 200-350 and <200 cells/mm3, respectively). Multivariate analysis revealed a significant association between intestinal dysfunction and low BMI (P = 0.03) independent of HIV infection and calorie intake per day (P = 0.02). Weight loss in HIV-infected individuals should be investigated for intestinal dysfunction especially in low resource settings.

The prevalence of renal impairment in individuals seeking HIV testing in Urban Malawi.

BACKGROUND: Chronic kidney disease (CKD) poses a major health threat to people living in low- and middle-income countries, especially when it is combined with HIV, antiretroviral treatment (ART) or communicable and non-communicable diseases. Data about the prevalence of CKD and its association with other diseases is scarce, particularly in HIV-negative individuals. This study estimated the prevalence of CKD in individuals who were either HIV-positive (and ART-naïve) or HIV-negative in an urban Malawian population. METHODS: This cross-sectional study was conducted at a HIV Testing and Counselling Centre in Lilongwe, Malawi. Consecutive clients who were ≥18 years and consented to participate were enrolled over a 3-month period. Clients were screened for potential renal disease and other conditions. Their blood pressure was measured, urine examined via dipstick and albumin/creatinine ratio and blood drawn for creatinine, cystatin C and sero-markers for schistosomiasis. Estimated glomerular filtration (eGFR) rate was calculated using a cystatin C-based formula and classified according to the matching CKD stages by K/DOQI (The National Kidney Foundation Kidney Disease Outcome Quality Initiative). We performed a descriptive analysis and compared differences between HIV-positive (and ART naïve) and -negative participants. RESULTS: Out of 381 consecutive clients who were approached between January and March 2012, 366 consented and 363 (48% female; 32% HIV-positive) were included in the analysis. Reasons for exclusion were missing samples or previous use of ART. HIV-positive and negative clients did not differ significantly with regard to age, sex or medical history, but they did differ for BMI-21.3 (±3.4) vs. 24 (±5.1), respectively (p < 0.001). Participants also differed with regard to serum cystatin C levels, but not creatinine. Reduced kidney function (according to CKD stages 2-5) was significantly more frequent 15.5 vs. 3.6%, respectively (p < 0.001) among HIV-positive clients compared to the HIV-negative group. Differences in renal function were most pronounced in the eGFR range 60-89 ml/min/1.73 m2 accompanied by proteinuria with results as 11.2% vs. 1.2%, respectively for clients who were HIV-positive vs. HIV-negative (p = 0.001). CONCLUSIONS: Reduced glomerular filtration and/or proteinuria occurred in 15.5% of HIV-positive, and 3.6% of HIV-negative patients in this urban Malawian cohort. Since generalized renal monitoring is not feasible in Malawi or other resource-limited countries, strategies to identify patients at risk for higher stages of CKD and appropriate preventive measures are needed for both HIV-positive and HIV-negative patients.

Association between HIV infection and bone mineral density in climacteric women.

UNLABELLED: A cross-sectional study was conducted with the purpose of evaluating bone mineral density in HIV seropositive and seronegative climacteric women. HIV infection was negatively associated with bone mineral density in the lumbar spine PURPOSE: To assess bone mineral density (BMD) and its associated factors in HIV seropositive and seronegative climacteric women METHODS: A cross-sectional study with 537 women (273 HIV seropositive and 264 HIV seronegative) aged between 40 and 60 years old receiving follow-up care at two hospitals in Brazil. A questionnaire on clinical and sociodemographic characteristics was completed. Laboratory tests were performed, and BMD was measured at the lumbar spine and hip. Statistical analysis was carried out by Yates and Pearson chi-squared tests, Mann-Whitney test, and multiple linear regression. RESULTS: The mean age was 47.7 years in HIV-seropositive women, and 75 % had nadir CD4 above 200, and 77.8 % had viral load below the detection limit. The mean age in the HIV-seronegative women was 49.8 years. The prevalence of low spinal BMD was 14.6 % in the HIV-seropositive and 4.6 % in the HIV-seronegative women (p < 0.01). The prevalence of low BMD at the femoral neck was 5.6 % in HIV-seropositive and 3.3 % in the HIV-seronegative women (p = 0.38). Multiple analyses showed that the factors associated with lower BMD at the spine were being postmenopausal and being HIV-seropositive. Being overweight was associated with a higher BMD. At the femoral neck, factors associated with lower BMD were being postmenopausal and being white. Being overweight and having a greater number of pregnancies were associated with higher BMD CONCLUSIONS: HIV-seropositive women on long-term antiretroviral treatment and in good immunological conditions exhibited low BMD in the spine (L1-L4). However, BMD in the femoral neck was similar to non-infected women.

A Scoring Tool to Identify East African HIV-1 Serodiscordant Partnerships with a High Likelihood of Pregnancy.

INTRODUCTION: HIV-1 prevention programs targeting HIV-1 serodiscordant couples need to identify couples that are likely to become pregnant to facilitate discussions about methods to minimize HIV-1 risk during pregnancy attempts (i.e. safer conception) or effective contraception when pregnancy is unintended. A clinical prediction tool could be used to identify HIV-1 serodiscordant couples with a high likelihood of pregnancy within one year. METHODS: Using standardized clinical prediction methods, we developed and validated a tool to identify heterosexual East African HIV-1 serodiscordant couples with an increased likelihood of becoming pregnant in the next year. Datasets were from three prospectively followed cohorts, including nearly 7,000 couples from Kenya and Uganda participating in HIV-1 prevention trials and delivery projects. RESULTS: The final score encompassed the age of the woman, woman's number of children living, partnership duration, having had condomless sex in the past month, and non-use of an effective contraceptive. The area under the curve (AUC) for the probability of the score to correctly predict pregnancy was 0.74 (95% CI 0.72-0.76). Scores ≥ 7 predicted a pregnancy incidence of >17% per year and captured 78% of the pregnancies. Internal and external validation confirmed the predictive ability of the score. DISCUSSION: A pregnancy likelihood score encompassing basic demographic, clinical and behavioral factors defined African HIV-1 serodiscordant couples with high one-year pregnancy incidence rates. This tool could be used to engage African HIV-1 serodiscordant couples in counseling discussions about fertility intentions in order to offer services for safer conception or contraception that align with their reproductive goals.

Neurodevelopmental benefits of antiretroviral therapy in Ugandan children aged 0-6 years with HIV.

BACKGROUND: Insufficient data on neurodevelopmental benefits of antiretroviral therapy (ART) in children. METHODS: Prospective study of 329 mothers and children aged 0-6 years to assess neurodevelopment. Results stratified by the maternal (M) and child (C) HIV status (MHIV⁻/CHIV⁻, MHIV⁺/CHIV⁻, and MHIV⁺/CHIV⁺). Gross Motor, Visual Reception, Fine Motor, Receptive, and Expressive Language scores were assessed by Mullen Scales of Early Learning. Global cognitive function was derived from an Early Learning Composite (ELC) score. Standardized weight and height for age z scores were constructed, and the lowest 15% cutoff defined disability. Generalized linear models were used to estimate prevalence rate ratios (PRR) adjusted for the child's age, weight, and height. In HIV-positive children, generalized linear models assessed the impact of ART initiation and duration on neurodevelopment. RESULTS: Compared with MHIV⁻/CHIV⁻ children, HIV-positive children were more likely to have global deficits in all measures of neurodevelopment except gross motor skills, whereas in MHIV⁺/CHIV⁻ children, there was impairment in receptive language [adjusted PRR = 2.67; confidence interval (CI): 1·08 to 6.60] and the ELC (adjusted PRR = 2.94; CI: 1.11 to 7.82). Of the children born to HIV-positive mothers, HIV-positive children did worse than MHIV⁺/CHIV⁻ only in visual reception skills (adjusted PRR = 2.86; CI: 1.23 to 6.65). Of the 116 HIV-positive children, 44% had initiated ART. Compared with ART duration of <12 months, ART durations of 24-60 months were associated with decreased impairments in Fine Motor, Receptive Language, Expressive Language, and ELC scores. CONCLUSIONS: Longer duration on ART is associated with reduction of some neurologic impairment and early diagnosis and treatment of HIV-positive children is a priority.

Clinical and laboratory factors in the differential diagnosis of tuberculous and cryptococcal meningitis in adult HIV-negative patients.

Objective It is difficult to make the differential diagnosis between tuberculous meningitis (TBM) and cryptococcal meningitis (CM) when the smear is negative. The objective of this study was to create a diagnostic rule for differentiating TBM from CM in adult HIV-negative patients based on clinical and laboratory features. Methods The clinical and laboratory data of 219 adult HIV-negative patients satisfying the diagnostic criteria for tuberculous (n=100) and cryptococcal (n=119) meningitis hospitalized at the Third Affiliated Hospital of Sun Yat-Sen University during the period 2000-2009 were retrospectively analyzed. Features found to be independently predictive of tuberculous meningitis were modeled using a multivariate logistic regression to create a diagnostic rule. The performance of the diagnostic rule was assessed using a prospective test data method. Results Six factors were found to be predictive of a diagnosis of tuberculous meningitis: gender, mental disorders, vision and/or hearing damage, proteins in the cerebrospinal fluid, the total cerebrospinal fluid white cell count and the coexistence of tuberculosis in peripheral organs. The diagnostic rule developed using these features exhibited 78.0% sensitivity, 95.2% specificity, 92.9% positive predictive value and 84.4% negative predictive value. The corresponding values for the diagnostic rule were 70.0% and 88.0% using prospective test data. Conclusion Clinical and laboratory features can be helpful in the differential diagnosis of tuberculous meningitis and cryptococcal meningitis in adult HIV-negative patients.

[Sexuality and risk for sexual transmission of HIV among serodiscordant couples in Ouagadougou, Burkina Faso]. / Sexualité et risque de transmission du VIH chez les couples sérodiscordants suivis à l'hôpital de jour du CHU de Ouagadougou (Burkina Faso).

This article is a contribution to improve the management of serodiscordant couples in Ouagadougou. The aim of the study was to explore sexuality and the risk for sexual transmission of HIV among serodiscordant couples followed-up in CHU-YO. The study consisted of a descriptive cross-sectional study conducted over 6 months, from 1 January 2010 to 30 June 2010. A total of 80 heterosexual serodiscordant couples participated. Women were infected with HIV in most cases (75%). The mean age was 37.5 years for HIV partners and 40 years for seronegatives. Men were significantly older than women (p = 0.01). The couples weremarried (83.7%) or cohabiting (16.3%). The average of serodiscordance duration was 4 years. Seventy-four couples (92.5%) engaged in sexual intercourses, mostly vaginal intercourses. Both partners were satisfied only in 9 couples (12.2%). Although most couples (97.5%) knew the use of condoms for HIV prevention, 59.5% did not use it consistently, particularly when women were the seropositive partners (p = 0.01). The lack of privacy (37.5%) and desire of childbearing (26.25%) were the main reasons for not consistently using condoms among couples. Sexual dysfunction was a concern with 97.5% of the couples. The decrease in libido was most common (37.2%). Sexual intercourses with an outside partner were reported in 20 couples (25%), mostly regarding men (p = 0.03). Specific management could improve the quality of sexual life for couples in the light of the difficulties they face and reduce the risk for HIV transmission to negative partners.

Myasthenia gravis developing in an HIV-negative patient with Kaposi's sarcoma.

Myasthenia gravis is a disorder of neuromuscular transmission caused by autoimmune mechanisms. We reported a possible association between seropositive myasthenia gravis and Kaposi's sarcoma in a HIV-negative subject and the observed interactions between the treatment regimen for these two conditions. A 62-year-old man came to our attention for ocular myasthenia gravis. He suffered from a classic form of Kaposi's sarcoma since about 1 year. When myasthenic symptoms worsened, the patient was started on prednisone and azathioprine. The patient had a significant worsening of Kaposi's sarcoma, so prednisone and azathioprine were reduced and he was treated with vinblastine, with improvement both in dermatologic than in neurological symptomatology. We propose some considerations: the potential correlation between Kaposi's sarcoma and myasthenia gravis through immunological mechanism; myasthenia gravis as a paraneoplastic manifestation of Kaposi's sarcoma, and the role of an antitumoral agent as a treatment for both the conditions.

Expression analysis of LEDGF/p75, APOBEC3G, TRIM5alpha, and tetherin in a Senegalese cohort of HIV-1-exposed seronegative individuals.

BACKGROUND: HIV-1 replication depends on a delicate balance between cellular co-factors and antiviral restriction factors. Lens epithelium-derived growth factor (LEDGF/p75) benefits HIV, whereas apolipoprotein B mRNA-editing catalytic polypeptide-like 3G (APOBEC3G), tripartite motif 5alpha (TRIM5α), and tetherin exert anti-HIV activity. Expression levels of these proteins possibly contribute to HIV-1 resistance in HIV-1-exposed populations. METHODOLOGY/PRINCIPAL FINDINGS: We used real-time PCR and flow cytometry to study mRNA and protein levels respectively in PBMC and PBMC subsets. We observed significantly reduced LEDGF/p75 protein levels in CD4+ lymphocytes of HIV-1-exposed seronegative subjects relative to healthy controls, whereas we found no differences in APOBEC3G, TRIM5α, or tetherin expression. Untreated HIV-1-infected patients generally expressed higher mRNA and protein levels than healthy controls. Increased tetherin levels, in particular, correlated with markers of disease progression: directly with the viral load and T cell activation and inversely with the CD4 count. CONCLUSIONS/SIGNIFICANCE: Our data suggest that reduced LEDGF/p75 levels may play a role in resistance to HIV-1 infection, while increased tetherin levels could be a marker of advanced HIV disease. Host factors that influence HIV-1 infection and disease could be important targets for new antiviral therapies.

Bone mineral density in HIV-negative men participating in a tenofovir pre-exposure prophylaxis randomized clinical trial in San Francisco.

BACKGROUND: Pre-exposure prophylaxis (PrEP) trials are evaluating regimens containing tenofovir-disoproxil fumarate (TDF) for HIV prevention. We determined the baseline prevalence of low bone mineral density (BMD) and the effect of TDF on BMD in men who have sex with men (MSM) in a PrEP trial in San Francisco. METHODS/FINDINGS: We evaluated 1) the prevalence of low BMD using Dual Energy X-ray Absorptiometry (DEXA) in a baseline cohort of 210 HIV-uninfected MSM who screened for a randomized clinical trial of daily TDF vs. placebo, and 2) the effects of TDF on BMD in a longitudinal cohort of 184 enrolled men. Half began study drug after a 9-month delay to evaluate changes in risk behavior associated with pill-use. At baseline, 20 participants (10%) had low BMD (Z score≤-2.0 at the L2-L4 spine, total hip, or femoral neck). Low BMD was associated with amphetamine (OR = 5.86, 95% CI 1.70-20.20) and inhalant (OR = 4.57, 95% CI 1.32-15.81) use; men taking multivitamins, calcium, or vitamin D were less likely to have low BMD at baseline (OR = 0.26, 95% CI 0.10-0.71). In the longitudinal analysis, there was a 1.1% net decrease in mean BMD in the TDF vs. the pre-treatment/placebo group at the femoral neck (95% CI 0.4-1.9%), 0.8% net decline at the total hip (95% CI 0.3-1.3%), and 0.7% at the L2-L4 spine (95% CI -0.1-1.5%). At 24 months, 13% vs. 6% of participants experienced >5% BMD loss at the femoral neck in the TDF vs. placebo groups (p = 0.13). CONCLUSIONS: Ten percent of HIV-negative MSM had low BMD at baseline. TDF use resulted in a small but statistically significant decline in BMD at the total hip and femoral neck. Larger studies with longer follow-up are needed to determine the trajectory of BMD changes and any association with clinical fractures. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00131677.

Test-retest stability of calibrated BOLD-fMRI in HIV- and HIV+ subjects.

Subject performance, scanner hardware, or biological factors can affect single session neuroimaging measures. Stability studies using calibrated blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) have been performed in health but not disease. We utilized calibrated BOLD-fMRI to determine the effects of HIV on neurovascular coupling. Six clinically stable HIV-infected patients (HIV+) and 10 seronegative controls (HIV-) were scanned at two separate sessions approximately 3 months apart. Both mild hypercapnia (5% CO(2)) exposure and a visual functional activation task were performed. Intraclass correlation coefficients (ICC) and inter-subject variance were determined for calibrated BOLD-fMRI measures (baseline cerebral blood flow (CBF), functional CBF, BOLD, and cerebral metabolic rate of oxygen consumption (CMRO(2)) changes) for HIV+ and HIV- subjects. The two groups did not differ in age, sex, or education. HIV+ subjects had lower mean baseline CBF (p<0.04, Cohen's d=-1.07) and functional BOLD responses (p<0.001, Cohen's d=-2.47) and a trend towards a decrease in mean functional CBF responses (p=0.07, Cohen's d=-0.92) despite similar mean functional CMRO(2) changes (p=0.71, Cohen's d=0.19). The stability of each calibrated BOLD-fMRI measure, as assessed by ICC, was significantly lower for HIV+ subjects. In addition, HIV+ participants had greater inter-subject variability for baseline CBF (p<0.02), functional BOLD (p<0.001), CBF (p<0.001), and CMRO(2) (p<0.002) responses. Our results demonstrate that calibrated BOLD-fMRI measures have excellent stability within healthy controls. In contrast, these values have greater variability in clinically stable HIV+ subjects and may reflect alterations in coupling between CBF and CMRO(2) with disease.