Effect of HIV-1 infection on T-Cell-based and skin test detection of tuberculosis infection

RATIONALE: Two forms of the IFN-gamma release assay (IFNGRA) to detect tuberculosis infection are available, but neither has been evaluated in comparable HIV-infected and uninfected persons in a high tuberculosis incidence environment. OBJECTIVE: To compare the ability of the T-SPOT.TB (Oxford Immunotec, Abingdon, UK), QuantiFERON-TB Gold (Cellestis, Melbourne, Australia), and Mantoux tests to identify latent tuberculosis in HIV-infected and uninfected persons. METHODS: A cross-sectional study of 160 healthy adults without active tuberculosis attending a voluntary counseling and testing center for HIV infection in Khayelitsha, a deprived urban South African community with an HIV antenatal seroprevalence of 33% and a tuberculosis incidence of 1,612 per 100,000. MEASUREMENTS AND MAIN RESULTS: One hundred and sixty (74 HIV(+) and 86 HIV(-)) persons were enrolled. A lower proportion of Mantoux results was positive in HIV-infected subjects compared with HIV-uninfected subjects (p < 0.01). By contrast, the proportion of positive IFNGRAs was not significantly different in HIV-infected persons for the T-SPOT.TB test (52 vs. 59%; p = 0.41) or the QuantiFERON-TB Gold test (43 and 46%; p = 0.89). Fair agreement between the Mantoux test (5- and 10-mm cutoffs) and the IFNGRA was seen in HIV-infected people (kappa = 0.52-0.6). By contrast, poor agreement between the Mantoux and QuantiFERON-TB Gold tests was observed in the HIV-uninfected group (kappa = 0.07-0.30, depending on the Mantoux cutoff). The pattern was similar for T-SPOT.TB (kappa = 0.18-0.24). Interpretation: IFNGRA sensitivity appears relatively unimpaired by moderately advanced HIV infection. However, agreement between the tests and with the Mantoux test varied from poor to fair. This highlights the need for prospective studies to determine which test may predict the subsequent risk of tuberculosis

Effect of a Patient-Centered Phone Call by a Clinical Officer at Time of HIV Testing on Linkage to Care in Rural Kenya.

In a randomized controlled trial, we tested whether a structured, patient-centered phone call from a clinical officer after HIV testing improved linkage to/re-engagement in HIV care. Among 130 HIV-positive persons, those randomized to the phone call were significantly more likely to link to care by 7 and 30 days (P = .04)

The "ART" of Linkage: Pre-Treatment Loss to Care after HIV Diagnosis at Two PEPFAR Sites in Durban, South Africa

BACKGROUND. Although loss to follow-up after antiretroviral therapy (ART) initiation is increasingly recognized, little is known about pre-treatment losses to care (PTLC) after an initial positive HIV test. Our objective was to determine PTLC in newly identified HIV-infected individuals in South Africa. METHODOLOGY/PRINCIPAL FINDINGS. We assembled the South African Test, Identify and Link (STIAL) Cohort of persons presenting for HIV testing at two sites offering HIV and CD4 count testing and HIV care in Durban, South Africa. We defined PTLC as failure to have a CD4 count within 8 weeks of HIV diagnosis. We performed multivariate analysis to identify factors associated with PTLC. From November 2006 to May 2007, of 712 persons who underwent HIV testing and received their test result, 454 (64%) were HIV-positive. Of those, 206 (45%) had PTLC. Infected patients were significantly more likely to have PTLC if they lived =10 kilometers from the testing center (RR=1.37; 95% CI: 1.11-1.71), had a history of tuberculosis treatment (RR=1.26; 95% CI: 1.00-1.58), or were referred for testing by a health care provider rather than self-referred (RR=1.61; 95% CI: 1.22-2.13). Patients with one, two or three of these risks for PTLC were 1.88, 2.50 and 3.84 times more likely to have PTLC compared to those with no risk factors. CONCLUSIONS/SIGNIFICANCE. Nearly half of HIV-infected persons at two high prevalence sites in Durban, South Africa, failed to have CD4 counts following HIV diagnosis. These high rates of pre-treatment loss to care highlight the urgent need to improve rates of linkage to HIV care after an initial positive HIV test.US National Institute of Allergy and Infectious Diseases (R01 AI058736, K24 AI062476, K23 AI068458); the Harvard University Center for AIDS Research (P30 AI42851); National Institutes of Health (K24 AR 02123); the Doris Duke Charitable Foundation (Clinical Scientist Development Award); the Harvard University Program on AID

Cryptococcal Meningitis Diagnostics and Screening in the Era of Point-of-Care Laboratory Testing.

Over the past ten years, standard diagnostics for cryptococcal meningitis in HIV-infected persons have evolved from culture to India ink to detection of cryptococcal antigen (CrAg), with the recent development and distribution of a point-of-care lateral flow assay. This assay is highly sensitive and specific in cerebrospinal fluid (CSF), but is also sensitive in the blood to detect CrAg prior to meningitis symptoms. CrAg screening of HIV-infected persons in the blood prior to development of fulminant meningitis and preemptive treatment for CrAg-positive persons are recommended by the World Health Organization and many national HIV guidelines. Thus, CrAg testing is occurring more widely, especially in resource-limited laboratory settings. CrAg titer predicts meningitis and death and could be used in the future to customize therapy according to burden of infection

Measuring Population Transmission Potential for HIV: An Alternative Metric of Transmission Risk in Men who have Sex with Men (MSM) in the US

Background Various metrics for HIV burden and treatment success [e.g. HIV prevalence, community viral load (CVL), population viral load (PVL), percent of HIV-positive persons with undetectable viral load] have important public health limitations for understanding disparities. Methods and Findings Using data from an ongoing HIV incidence cohort of black and white men who have sex with men (MSM), we propose a new metric to measure the prevalence of those at risk of transmitting HIV and illustrate its value. …See full text for complete abstract

Parietal resting-state EEG alpha source connectivity is associated with subcortical white matter lesions in HIV-positive people

Objective Parietal resting-state electroencephalographic (rsEEG) alpha (8–10 Hz) source connectivity is abnormal in HIV-positive persons. Here we tested whether this abnormality may be associated with subcortical white matter vascular lesions in the cerebral hemispheres. Methods Clinical, rsEEG, and magnetic resonance imaging (MRI) datasets in 38 HIV-positive persons and clinical and rsEEG datasets in 13 healthy controls were analyzed. Radiologists visually evaluated the subcortical white matter hyperintensities from T2-weighted FLAIR MRIs (i.e., Fazekas scale). In parallel, neurophysiologists estimated the eLORETA rsEEG source lagged linear connectivity from parietal cortical regions of interest. Results Compared to the HIV participants with no/negligible subcortical white matter hyperintensities, the HIV participants with mild/moderate subcortical white matter hyperintensities showed lower parietal interhemispheric rsEEG alpha lagged linear connectivity. This effect was also observed in HIV-positive persons with unimpaired cognition. This rsEEG marker allowed good discrimination (area under the receiver operating characteristic curve &gt; 0.80) between the HIV-positive individuals with different amounts of subcortical white matter hyperintensities. Conclusions The parietal rsEEG alpha source connectivity is associated with subcortical white matter vascular lesions in HIV-positive persons, even without neurocognitive disorders. Significance Those MRI-rsEEG markers may be used to screen HIV-positive persons at risk of neurocognitive disorders

Soluble levels of receptor for advanced glycation endproducts and dysfunctional high-density lipoprotein in persons infected with human immunodeficiency virus: ACTG NWCS332.

The role of high-density lipoprotein (HDL) function and advanced glycation end products (AGEs) in HIV-related atherosclerotic cardiovascular disease (CVD) is unclear. Both glycation and oxidation (HDLox) are major modifications of HDL that can alter its composition and function. Therefore, we explored the longitudinal association of HDLox with progression of glycation, as evaluated by measurement of circulating forms of receptor for AGE that predict morbidity (soluble Receptors for Advanced Glycation Endproducts [sRAGE], endogenous secretory Receptors for Advanced Glycation Endproducts [esRAGE]), in people with HIV-1 (PWH; HIV-1) and uninfected (HIV-1) individuals.We retrospectively assessed if levels of plasma sRAGE and esRAGE and HDL function (reduced antioxidant function is associated with increased HDL lipid hydroperoxide content; HDLox) in a subset of participants (n = 80) from a prospective 3-year study (AIDS Clinical Trials Group A5078). Primary outcomes were baseline and yearly rates of change over 96 of 144 weeks (Δ) in HDLox in HIV-1 versus uninfected HIV-1 controls (noted as HIV-1).Higher baseline levels of sRAGE in PWH on effective anti-retroviral therapy and with low CVD risk, but not in HIV-1 persons, were independently associated with higher HDLox. EsRAGE, but not sRAGE, had consistent inverse relationships with ΔHDLox in both HIV-1 and HIV-1 persons at baseline. In HIV-1 but not in HIV-1 persons, ΔHDLox had positive and inverse relationships with ΔRAGE and ΔesRAGE, respectively.Glycation and oxidation of HDL may contribute to impaired HDL function present in PWH

MMWR Morb Mortal Wkly Rep

During 2016, 6% of persons in the United States who received a diagnosis of human immunodeficiency virus (HIV) infection had their HIV infection attributed to injection drug use (1). Injection practices and sexual behaviors among HIV-positive persons who inject drugs, such as injection equipment sharing and condomless sex, can increase HIV transmission risk; nationally representative estimates of the prevalences of these behaviors are lacking. The Medical Monitoring Project (MMP) is an annual, cross-sectional survey that reports nationally representative estimates of clinical and behavioral characteristics among U.S. adults with diagnosed HIV (2). CDC used MMP data to assess high-risk injection practices and sexual behaviors among HIV-positive persons who injected drugs during the preceding 12 months and compared their HIV transmission risk behaviors with those of HIV-positive persons who did not inject drugs. During 2015-2017, approximately 10% (weighted percentage estimate) of HIV-positive persons who injected drugs engaged in distributive injection equipment sharing (giving used equipment to another person for use); nonsterile syringe acquisition and unsafe disposal methods were common. Overall, among HIV-positive persons who injected drugs, 80% received no treatment, and 57% self-reported needing drug or alcohol treatment. Compared with HIV-positive persons who did not inject drugs, those who injected drugs were more likely to have a detectable viral load (48% versus 35%; p = 0.008) and engage in high-risk sexual behaviors (p<0.001). Focusing on interventions that reduce high-risk injection practices and sexual behaviors and increase rates of viral suppression might decrease HIV transmission risk among HIV-positive persons who inject drugs. Successful substance use treatment could also lower risk for transmission and overdose through reduced injection.201931369525PMC6677170726

Trends in HIV testing and recording of HIV status in the UK primary care setting: a retrospective cohort study 1995-2005

Objectives: To provide nationally representative data on trends in HIV testing in primary care and to estimate the proportion of diagnosed HIV positive individuals known to general practitioners (GPs). Methods: We undertook a retrospective cohort study between 1995 and 2005 of all general practices contributing data to the UK General Practice Research Database (GPRD), and data on persons accessing HIV care (Survey of Prevalent HIV Infections Diagnosed). We identified all practice-registered patients where an HIV test or HIV positive status is recorded in their general practice records. HIV testing in primary care and prevalence of recorded HIV positive status in primary care were estimated. Results: Despite 11-fold increases in male testing and 19-fold increases in non-pregnant female testing between 1995 and 2005, HIV testing rates remained low in 2005 at 71.3 and 61.2 tests per 100 000 person years for males and females, respectively, peaking at 162.5 and 173.8 per 100 000 person years at 25–34 years of age. Inclusion of antenatal tests yielded a 129-fold increase in women over the 10-year period. In 2005, 50.7% of HIV positive individuals had their diagnosis recorded with a lower proportion in London (41.8%) than outside the capital (60.1%). Conclusion: HIV testing rates in primary care remain low. Normalisation of HIV testing and recording in primary care in antenatal testing has not been accompanied by a step change in wider HIV testing practice. Recording of HIV positive status by GPs remains low and GPs may be unaware of HIV-related morbidity or potential drug interactions