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New federal regulations allow HIV-positive individuals to be live kidney donors; however, potential candidacy for donation is poorly understood given the increased risk of end-stage renal disease (ESRD) associated with HIV infection. To better understand this risk, we compared the incidence of ESRD among 41 968 HIV-positive participants of North America AIDS Cohort Collaboration on Research and Design followed for a median of 5 years with the incidence of ESRD among comparable HIV-negative participants of National Health and Nutrition Examination III followed for a median of 14 years. We used risk associations from multivariable Cox proportional hazards regression to derive cumulative incidence estimates for selected HIV-positive scenarios (no history of diabetes, hypertension, AIDS, or hepatitis C virus coinfection) and compared these estimates with those from similarly selected HIV-negative scenarios. For 40-year-old HIV-positive individuals with health characteristics that were similar to those of age-matched kidney donors, viral load

Limited access to HIV drug resistance testing in low- and middle-income countries impedes clinical decision-making at the individual patient level. An efficient protocol to address this issue must be established to minimize negative therapeutic outcomes for HIV-1-infected individuals in such settings. This is an observational study to ascertain the potential of newer genomic sequencing platforms, such as the Illumina MiSeq instrument, to provide accurate HIV drug resistance genotypes for hundreds of samples simultaneously. Plasma samples were collected from Canadian patients during routine drug resistance testing (n = 759) and from a Ugandan study cohort (n = 349). Amplicons spanning HIV reverse transcriptase codons 90 to 234 were sequenced with both MiSeq sequencing and conventional Sanger sequencing methods. Sequences were evaluated for nucleotide concordance between methods, using coverage and mixture parameters for quality control. Consensus sequences were also analyzed for disparities in the identification of drug resistance mutations. Sanger and MiSeq sequencing was successful for 881 samples (80%) and 892 samples (81%), respectively, with 832 samples having results from both methods. Most failures were for samples with viral loads of

There are few published examples of absolute risk estimated from epidemiologic data subject to censoring and competing risks with adjustment for multiple confounders. We present an example estimating the effect of injection drug use on 6-year risk of acquired immunodeficiency syndrome (AIDS) after initiation of combination antiretroviral therapy between 1998 and 2012 in an 8-site US cohort study with death before AIDS as a competing risk. We estimate the risk standardized to the total study sample by combining inverse probability weights with the cumulative incidence function; estimates of precision are obtained by bootstrap. In 7,182 patients (83% male, 33% African American, median age of 38 years), we observed 6-year standardized AIDS risks of 16.75% among 1,143 injection drug users and 12.08% among 6,039 nonusers, yielding a standardized risk difference of 4.68 (95% confidence interval: 1.27, 8.08) and a standardized risk ratio of 1.39 (95% confidence interval: 1.12, 1.72). Results may be sensitive to the assumptions of exposure-version irrelevance, no measurement bias, and no unmeasured confounding. These limitations suggest that results be replicated with refined measurements of injection drug use. Nevertheless, estimating the standardized risk difference and ratio is straightforward, and injection drug use appears to increase the risk of AIDS.

BackgroundBacillary angiomatosis (BA) is a rare manifestation of infection caused by Bartonella species, which leads to vasoproliferative lesions of skin and other organs. Bacillary angiomatosis affects individuals with advanced HIV disease or other immunocompromised individuals. In sub-Saharan Africa, despite the high prevalence of HIV infection and documentation of the causative Bartonella species in humans, mammalian hosts, and arthropod vectors, BA has only rarely been described.MethodsThree adult patients from Uganda and Kenya with deep purple dome-shaped papules or nodules of the skin underwent punch biopsies for histopathologic diagnosis. The biopsies of all 3 patients were sent to a local pathologist as well as to a dermatopathologist at the University of California, San Francisco.ResultsAll 3 patients were clinically suspected to have Kaposi's sarcoma (KS), and local pathologists had interpreted the lesions as KS in 2 of the cases and nonspecific inflammation in the third. Histologic examination by dermatopathologists in the United States revealed nodular dermal proliferations of irregular capillaries lined by spindled to epithelioid endothelial cells. The surrounding stroma contained a mixed inflammatory infiltrate with lymphocytes, eosinophils, and neutrophils. Extracellular deposits of pale amphophilic granular material were noted in the surrounding stroma. A Warthin-Starry stain highlighted clumps of bacilli, confirming the diagnosis of BA.ConclusionsThese 3 cases, to our knowledge, are the first reports of BA in East Africa in the biomedical literature. Each had been originally incorrectly diagnosed as KS. We speculate BA is underdiagnosed and underreported in resource-poor regions, such as sub-Saharan Africa, that have high endemic rates of HIV infection.

© 2014, Public Library of Science. All rights reserved.Background: Alcohol consumption among HIV-infected patients may accelerate HIV disease progression or reduce antiretroviral therapy adherence. Self-reported alcohol use is frequently under-reported due

© 2014 Seu et al.; licensee BioMed Central Ltd.The level (or frequency) of circulating monocyte subpopulations such as classical (CD14hiCD16-) and non-classical (CD14dimCD16+) monocytes varies during the course of HIV disease progression and antiretroviral

BackgroundPruritic papular eruption (PPE) of HIV is common in HIV-infected populations living in the tropics. Its aetiology has been attributed to insect bite reactions and it is reported to improve with antiretroviral therapy (ART). Its presence after at least 6 months of ART has been proposed as one of several markers of treatment failure.ObjectivesTo determine factors associated with PPE in HIV-infected persons receiving ART.MethodsA case-control study nested within a 500-person cohort from a teaching hospital in Mbarara, Uganda. Forty-five cases and 90 controls were enrolled. Cases had received ART for ≥ 15 months and had an itchy papular rash for at least 1 month with microscopic correlation by skin biopsy. Each case was individually matched with two controls for age, sex and ART duration.ResultsTwenty-five of 45 cases (56%) had microscopic findings consistent with PPE. At skin examination and biopsy (study enrolment), a similar proportion of PPE cases and matched controls had plasma HIV RNA

Background: Human Endogenous Retroviruses (HERVs) comprise about 8% of the human genome and have lost their ability to replicate or to produce infectious particles after having accumulated mutations over time. We assessed the kinetics of expression of HERV

The ability to reconstitute a normal immune system with antiretroviral therapy in the setting of HIV infection remains uncertain. This study aimed to characterize quantitative and qualitative aspects of various T cell subpopulations that do not improve des

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.Objective: Cross-sectional HIV incidence surveillance, using assays that distinguish 'recent' from 'nonrecent' infections, has been hampered by inadequate performance and characterization of inci

HIV-mediated immune dysfunction may influence CD4+ T cell recovery during suppressive antiretroviral therapy (ART). We analyzed cellular biomarkers of immunological inflammation, maturation, and senescence in HIV-infected subjects on early suppressive ART.

Background: A subset of CD3negCD56negCD16+ Natural Killer (NK) cells is highly expanded during chronic HIV-1 infection. The role of this subset in HIV-1 pathogenesis remains unclear. The lack of NK cell lineage-specific markers has complicated the study of minor NK cell subpopulations.Results: Using CD7 as an additional NK cell marker, we found that CD3negCD56negCD16+ cells are a heterogeneous population comprised of CD7+ NK cells and CD7neg non-classical myeloid cells. CD7+CD56negCD16+ NK cells are significantly expanded in HIV-1 infection. CD7+CD56negCD16+ NK cells are mature and express KIRs, the C-type lectin-like receptors NKG2A and NKG2C, and natural cytotoxicity receptors similar to CD7+CD56+CD16+ NK cells. CD7+CD56neg NK cells in healthy donors produced minimal IFNγ following K562 target cell or IL-12 plus IL-18 stimulation; however, they degranulated in response to K562 stimulation similar to CD7+CD56+ NK cells. HIV-1 infection resulted in reduced IFNγ secretion following K562 or cytokine stimulation by both NK cell subsets compared to healthy donors. Decreased granzyme B and perforin expression and increased expression of CD107a in the absence of stimulation, particularly in HIV-1-infected subjects, suggest that CD7+CD56negCD16+ NK cells may have recently engaged target cells. Furthermore, CD7+CD56negCD16+ NK cells have significantly increased expression of CD95, a marker of NK cell activation.Conclusions: Taken together, CD7+CD56negCD16+ NK cells are activated, mature NK cells that may have recently engaged target cells. © 2013 Milush et al.; licensee BioMed Central Ltd.

Resting CD4+T cells infected with HIV persist in the presence of suppressive anti-viral therapy (ART) and are barriers to a cure. One potential curative approach, therapeutic vaccination, is fueled by recognition of the ability of a subset of elite control

Background: In resource-rich areas, risky sexual behavior (RSB) largely diminishes after initiation of anti-retroviral therapy, with notable exceptions among some populations who perceive a protected benefit from anti-retroviral therapy (ART). Yet, there i

Objective:Many people living with HIV in sub-Saharan Africa desire biological children. Implementation of HIV prevention strategies that support the reproductive goals of people living with HIV while minimizing HIV transmission risk to sexual partners and

A subset of CD3(neg)CD56(neg)CD16 + Natural Killer (NK) cells is highly expanded during chronic HIV-1 infection. The role of this subset in HIV-1 pathogenesis remains unclear. The lack of NK cell lineage-specific markers has complicated the study of minor NK cell subpopulations. Using CD7 as an additional NK cell marker, we found that CD3(neg)CD56(neg)CD16 + cells are a heterogeneous population comprised of CD7 + NK cells and CD7(neg) non-classical myeloid cells. CD7 + CD56(neg)CD16 + NK cells are significantly expanded in HIV-1 infection. CD7 + CD56(neg)CD16 + NK cells are mature and express KIRs, the C-type lectin-like receptors NKG2A and NKG2C, and natural cytotoxicity receptors similar to CD7 + CD56 + CD16 + NK cells. CD7 + CD56(neg) NK cells in healthy donors produced minimal IFNγ following K562 target cell or IL-12 plus IL-18 stimulation; however, they degranulated in response to K562 stimulation similar to CD7 + CD56 + NK cells. HIV-1 infection resulted in reduced IFNγ secretion following K562 or cytokine stimulation by both NK cell subsets compared to healthy donors. Decreased granzyme B and perforin expression and increased expression of CD107a in the absence of stimulation, particularly in HIV-1-infected subjects, suggest that CD7 + CD56(neg)CD16 + NK cells may have recently engaged target cells. Furthermore, CD7 + CD56(neg)CD16 + NK cells have significantly increased expression of CD95, a marker of NK cell activation. Taken together, CD7 + CD56(neg)CD16 + NK cells are activated, mature NK cells that may have recently engaged target cells.

Background: Depression is associated with increased HIV transmission risk, increased morbidity, and higher risk of HIV-related death among HIV-infected women. Low sexual relationship power also contributes to HIV risk, but there is limited understanding of

During HIV-1 infection, immune dysregulation and aberrant lymphocyte functions are well-established characteristics. Cell surface molecules are important for immunological functions and changes in expression can affect lymphocyte effector functions, thereb

Many human immunodeficiency virus (HIV) infected individuals suffer from persistent immune activation. Chronic inflammation and immune dysregulation have been associated with an increased risk of age-related diseases even among patients on highly active an

Background. Preventing unintended pregnancies among women living with HIV is an important component of prevention of mother-to-child HIV transmission (PMTCT), yet few data exist on contraceptive use among women entering HIV care. Methods. This was a retros

Background: Mobile health (mHealth) technologies hold incredible promise to improve healthcare delivery in resource-limited settings. Network reliability across large catchment areas can be a major challenge. We performed an analysis of network failure fre

The evolution of drug resistance mutations in plasma samples is relatively well-characterized. However, the viral population and diversity in other body compartments such as peripheral blood mononuclear cells (PBMC) remains poorly understood. Previous stud

Human endogenous retroviruses (HERV) are remnants of ancestral retroviral infections integrated into the germ line, and constitute approximately 8% of the genome. Several autoimmune disorders, malignancies, and infectious diseases such as HIV-1 are associa

Background: Many guidelines recommend adherence counseling prior to initiating antiretrovirals (ARVs), however the additional benefit of pre-therapy counseling visits on early adherence is not known. We sought to assess for a benefit of adherence counselin

The human gut mucosa is a major site of human immunodeficiency virus (HIV) infection and infection-associated pathogenesis. Increasing evidence shows that natural killer (NK) cells have an important role in control of HIV infection, but the mechanism(s) by which they mediate antiviral activity in the gut is unclear. Here, we show that two distinct subsets of NK cells exist in the gut, one localized to intraepithelial spaces (intraepithelial lymphocytes, IELs) and the other to the lamina propria (LP). The frequency of both subsets of NK cells was reduced in chronic infection, whereas IEL NK cells remained stable in spontaneous controllers with protective killer immunoglobulin-like receptor/human leukocyte antigen genotypes. Both IEL and LP NK cells were significantly expanded in immunological non-responsive patients, who incompletely recovered CD4+ T cells on highly active antiretroviral therapy (HAART). These data suggest that both IEL and LP NK cells may expand in the gut in an effort to compensate for compromised CD4+ T-cell recovery, but that only IEL NK cells may be involved in providing durable control of HIV in the gut.

Objective: A systematic review of the literature was conducted to answer the following question: are there enhancements to standard peripartum hysterectomy technique that minimize unintentional urinary tract (UT) injury in pregnancies complicated by invasive placental attachment (INPLAT)? Methods: A PubMed search of English language articles on INPLAT published by June 2010 was conducted. Data regarding the following parameters was required for inclusion in the quantitative analysis of the review's objective: (1) type of INPLAT, (2) details pertaining to medical and surgical management of INPLAT, and (3) complications, if any, associated with management. An attempt was made to identify approaches that may lower the risk of unintentional UT injury. Results: Most cases (285 of 292) were managed by hysterectomy. There were 83 (29%) cases of unintentional UT injury. Antenatal diagnosis of INPLAT lowered the rate of UT injury (39% vs. 63%; P = 0.04). Information regarding surgical technique or medical management was available for 90 cases; 14 of these underwent a standard hysterectomy technique. Methotrexate treatment and 11 modifications of the surgical technique were associated with 16% unintentional UT injury rate as opposed to 57% for standard hysterectomy (P = 0.002). The use of ureteral stents reduced risk of urologic injury (P = 0.01). Multiple logistic regression analysis identified antenatal diagnosis as the significant predictor of an intact UT. Conclusions: Antenatal diagnosis of INPLAT is paramount to minimize UT injury. Utilization of management modifications identified in this review may reduce urologic injury due to INPLAT. [ABSTRACT FROM AUTHOR]

Casp8p41 is a protein fragment generated by cleavage of procaspase 8 by human immunodeficiency virus (HIV) protease. We measured Casp8p41 content in memory CD4 T cells and analyzed the association of Casp8p41 content with CD4 T cell count, cross-sectionally and longitudinally. Casp8p41 content was inversely correlated with CD4 T cell count, and change in Casp8p41 content was associated with absolute CD4 T cell count with change over time. Casp8p41 change was a better predictor of CD4 T cell count change than activated CD8 T cell percentage or viral load and was comparable to bacterial 16s DNA levels. This suggests that Casp8p41 is a relevant mediator of CD4 T cell death during HIV infection. [ABSTRACT FROM AUTHOR]

Background: Although untreated human immunodeficiency virus (HIV)-infected patients maintaining undetectable plasma HIV RNA levels (elite controllers) have high HIV-specific immune responses, it is unclear whether they experience abnormal levels of T cell activation, potentially contributing to immunodeficiency.Methods: We compared percentages of activated (CD38(+)HLA-DR(+)) T cells between 30 elite controllers, 47 HIV-uninfected individuals, 187 HIV-infected individuals with undetectable viremia receiving antiretroviral therapy (antiretroviral therapy suppressed), and 66 untreated HIV-infected individuals with detectable viremia. Because mucosal translocation of bacterial products may contribute to T cell activation in HIV infection, we also measured plasma lipopolysaccharide (LPS) levels.Results: Although the median CD4(+) cell count in controllers was 727 cells/mm(3), 3 (10%) had CD4(+) cell counts <350 cells/mm(3) and 2 (7%) had acquired immunodeficiency syndrome. Controllers had higher CD4(+) and CD8(+) cell activation levels (P < .001 for both) than HIV-negative subjects and higher CD8(+) cell activation levels than the antiretroviral therapy suppressed (P = .048). In controllers, higher CD4(+) and CD8(+) T cell activation was associated with lower CD4(+) cell counts (P = .009 and P = .047). Controllers had higher LPS levels than HIV-negative subjects (P < .001), and in controllers higher LPS level was associated with higher CD8(+) T cell activation (P = .039).Conclusion: HIV controllers have abnormally high T cell activation levels, which may contribute to progressive CD4(+) T cell loss even without measurable viremia. [ABSTRACT FROM AUTHOR]

Rationale: Although interferon (IFN)-gamma release assays are approved for the diagnosis of latent tuberculosis infection (LTBI), limited data exist regarding their performance in HIV infection.Objectives: To compare tuberculin skin test (TST) results to the commercial IFN-gamma release assay QuantiFERON-TB Gold In-Tube (QFT) for the diagnosis of LTBI in HIV-infected adults.Methods: A total of 294 HIV-infected subjects sampled from two San Francisco cohorts underwent TST, using 5 TU of purified protein derivative, and QFT, measuring IFN-gamma response to Mycobacterium tuberculosis-specific RD-1 antigens.Main Results: Of 294 participants, 205 (70%) returned for an evaluable TST. Concordance between QFT and TST was 89.3% (kappa=0.37, p=0.007). However, in subjects with positive test results by either TST or QFT, only 28% (8/29) had positive test results by both modalities. TST-positive/QFT-negative discordant results were found in 5.1% of subjects and TST-negative/QFT-positive discordance in 5.6%. Indeterminate QFT results occurred in 5.1%, all due to a failure to respond to the phytohemagglutinin-positive control. Subjects with a CD4(+) count of less than 100 cells/mm(3) had a relative risk of an indeterminate result of 4.24 (95% confidence interval, 1.55-11.61; p=0.003) compared with those with a CD4(+) count of 100 or more.Conclusions: Overall concordance between QFT and TST in HIV infection was high, but agreement among subjects with positive tests by either modality was low. [ABSTRACT FROM AUTHOR]