Mehri McKellar

Diagnosing HIV Infection in Primary Care Settings: Missed Opportunities

In the United States, 20% of HIV-infected persons are unaware of their diagnosis. Improved application of HIV screening recommendations in healthcare settings may facilitate diagnosis. Clinical patient data and previous healthcare visits were reviewed from medical records of newly diagnosed HIV-infected persons in Durham County, North Carolina, who initiated HIV care at Duke University Medical Center in 2008-2011. Comparisons were made to similar data from 2002-2004 using the Pearsons chi-square test and logistic regression. 101 consecutive newly diagnosed patients were identified: 67 males; 73 black, 20 white, and 8 Hispanic/Latino. Mean age was 39 years (range, 17-69), and 73 had health insurance. Median baseline CD4 count was 313 cells/μL (range, 4-1302), and HIV-1 viral load was 45,700 copies/mL (range, 165-10,000,000). One-third had a baseline CD4 count <50 cells/μL, and 15% presented with opportunistic infections. Compared to patients newly diagnosed in 2002-2004, significantly greater proportions were black and less immunocompromised in 2008-2011. Most had been seen at least once by a healthcare provider in the year prior to HIV diagnosis: 72 had ≥1 prior visits, and 47 had ≥2 visits. Among those with prior visits, 37/72 (51%) were seen in an emergency department on the first or second visit. Men were three times more likely than women to be diagnosed at their first healthcare encounter (p=0.03, OR=3.2). Despite CDC recommendations for widespread HIV screening in healthcare settings, HIV diagnosis remains delayed, even among those with frequent healthcare encounters. Educating providers and removing barriers to HIV screening may improve this problem.

Fatal Granulomatous Acanthamoeba Encephalitis Mimicking a Stroke, Diagnosed by Correlation of Results of Sequential Magnetic Resonance Imaging, Biopsy, In Vitro Culture, Immunofluorescence Analysis, and Molecular Analysis

ABSTRACT Amebic infections involving the central nervous system are rare and difficult to diagnose. Magnetic resonance imaging (MRI) at timed intervals may be helpful, where scans reveal enhancing lesions and increased signal. We report a unique case of granulomatous amebic encephalitis that was proven pathologically with progressive radiological findings on MRI.

Dendritic Cell Immunotherapy for HIV-1 Infection Using Autologous HIV-1 RNA: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Background:The genomic heterogeneity of HIV-1 impedes the ability of consensus sequences in vaccines to elicit effective antiviral immune responses. AGS-004 amplifies translation-competent RNA molecules encoding for Gag, Rev, Vpr, and Nef from the patients autologous virus and loads them into dendritic cells. Methods:This phase IIB, multicenter, 2:1 randomized, double-blind, placebo-controlled study enrolled 54 HIV-1–infected patients on antiretroviral therapy with viral loads (VLs) <50 copies per milliliter, current CD4 T-cell counts >450 cells per cubic millimeter, and nadir counts >200 cells per cubic millimeter, to receive intradermal injections of study product into the axillary lymph node region every 4 weeks. At week 16, a 12-week analytical treatment interruption (ATI) was undertaken. Results:There was no difference in the end-of-ATI VL (average of values from weeks 11 and 12) between the 2 arms of the study [4.39 (4.17, 4.69) vs. 4.47 (3.76, 4.64) log10 HIV-1 RNA; P = 0.73]. Between arms, no change between pre–antiretroviral therapy VL and the end-of-ATI VL [−0.06 (0.24, −0.32) vs. −0.17 (0.17, −0.32) log10 HIV-1 RNA; P = 0.43] was observed. When interferon-&ggr;, interleukin-2, tumor necrosis factor &agr;, CD107a, and granzyme b expressions were measured by multicolor flow cytometry, a greater percentage of AGS-004 than of placebo recipients had multifunctional cytotoxic T-lymphocyte responses induced in the CD28+/CD45RA-CD8 effector/memory T-cell population to dendritic cells electroporated with autologous antigens. Adverse events consisted of transient, mild (grade 1) local injection site reactions. Conclusions:Despite the induction of HIV-specific effector/memory CD8 T-cell responses, no antiviral effect was seen after the administration of AGS-004 when compared with placebo.

History of AIDS in HIV-Infected Patients Is Associated With Higher In-Hospital Mortality Following Admission for Acute Myocardial Infarction and Stroke

BACKGROUND Although human immunodeficiency virus (HIV)-infected persons are at increased risk for major cardiovascular events, short-term prognosis after these events is unclear. METHODS To determine the association between HIV infection and acute myocardial infarction (AMI) and stroke outcomes, we analyzed hospital discharge data from the Nationwide Inpatient Sample (NIS) between 2002 and 2012. Multivariable logistic regression was used to evaluate the association between HIV infection and in-hospital death after AMI or stroke. RESULTS Overall, 18 369 785 AMI/stroke hospitalizations were included in the analysis. Patients with a history of AIDS were significantly more likely than uninfected patients to die during hospitalization after admission for AMI or stroke (odds ratio, 3.03 [95% confidence interval {CI}, 1.71-5.38] for AMI and 2.59 [95% CI, 1.97-3.41] for stroke). Additionally, patients with AIDS were more likely than HIV-uninfected patients to be discharged to nonhospital inpatient facilities after admission for AMI (OR, 3.14 [95% CI, 1.72-5.74]) or stroke (OR, 1.45; 95% CI, 1.12-1.87). There was a minimal difference in either outcome between HIV-infected patients without a history of AIDS and uninfected patients. CONCLUSIONS Patients with a history of AIDS were significantly more likely than uninfected patients to die during hospitalization after admission for AMI or stroke. This disparity was not observed when infected patients without a history of AIDS were compared to uninfected patients, implying that preserving immune function may improve cardiovascular outcomes in HIV-infected persons.

Pediatric HIV infection: the state of antiretroviral therapy.

Pediatric HIV/AIDS has become less of a problem in resource-rich countries as the number of perinatal infections has reduced dramatically since the advent of antiretrovirals, resulting in the effective prevention of mother-to-child transmission. In resource-limited settings, however, pediatric HIV infection remains a colossal problem; a separate review in this same issue of Expert Review of Anti-Infective Therapy examines the international aspects of pediatric HIV/AIDS. Treatment of HIV infection in children differs from that in adults in the use of immunologic markers and owing to drug pharmacokinetics and age-related adherence issues. This review, geared for the general pediatrician or family practitioner who may see the HIV-positive child in the clinic or the hospital, summarizes the most recent pediatric data and guidelines for the testing and treatment of HIV, including the US NIH guidelines released in February 2008. Treatment-experienced patients, who should be cared for by pediatric HIV specialists, are not addressed here specifically. Adolescents, infected either perinatally or sexually, with their own unique issues, deserve a separate review.

Acute Dengue fever causes false-positive reactivity in OraQuick rapid HIV-1/2 antibody test.

To the Editors: The OraQuick ADVANCE Rapid HIV-1/2 Antibody Test, from OraSure Technologies Inc., detects antibodies to HIV-1 and HIV-2 in 20 minutes. This immunoassay can be performed on oral fluid, fingerstick whole blood, venipuncture whole blood, and plasma specimens. The manufacturer reports a sensitivity of 99.3% (95% confidence interval: = 98.4% to 99.7%) and specificity of 99.8% (95% confidence interval: = 99.6% to 99.9%) for use of the test with oral fluid specimens. However, false-positive results have been detected, including in test kits close to the expiration date. One study found a false-positive rate of 1.17% in test kits used with #1 month remaining until expiration. It is noted that these results came from an older version of the OraQuick ADVANCE test kit. Accuracy of both oral and blood HIV screening tests may also be affected by concomitant tropical infections. In sub-Saharan Africa, false-positive HIV enzyme-linked immunosorbent assay (ELISA) results were associated with a diagnosis of human African trypanosomiasis, urinary schistosomiasis, uncomplicated malaria, and visceral leishmaniasis. These false-positive results in HIV antibody detection testing have been attributed to polyclonal B-cell activation and/or high concentration of rheumatoid factor-like anti-immunoglobulin antibodies seen in these infections. In Colombia, 1 study postulated that parasitic proteins similar to the reverse transcriptase could be a possible cause of false positive HIV ELISA tests in patients infected by Trypanosoma cruzi. Since December 2008, we have been using the OraQuick test kit on oral fluid as part of a study in the Duke University Hospital Emergency Department to determine whether rapid HIV testing can be effectively offered and accepted as a routine screening test. Recently, a false-positive result occurred in a patient presenting with acute Dengue fever. The patient had just returned to the United States after traveling abroad to the island of Guadeloupe, FrenchWest Indies, for 3 weeks where she recalled receiving multiple mosquito bites. She was admitted to Duke University Hospital after presenting to the Emergency Department with acute HIV-like symptoms of recurrent fevers, night sweats, nausea, vomiting, headache, joint aches, and rash. Her initial temperature was 37.3(C, but she reported fevers up to 39.4(C at home. The patient had an erythematous, raised, nonpruritic maculopapular rash on her lower extremities. Upon presentation, her white blood cells was low at 1600 cells 3 10/L with an absolute lymphocyte count of 500. Her platelets were low at 88 3 10/L and ultimately dropped to 47 during her hospitalization. Her aspartate aminotransferase was slightly elevated at 77 U/L. In Guadeloupe, she had serologies drawn, which were positive for Dengue. Acute and convalescent serologies drawn at Duke were sent to the North Carolina State Laboratory and also confirmed to be positive. As there are no reports of malaria in Guadeloupe, a blood smear was not performed. Her initial and repeat OraQuick oral swabs were positive. The patient denied any recent high-risk behaviors that would place her at risk for acute HIV infection and had tested negative for HIV 2 years ago. As part of our protocol for confirmation of a preliminary reactive test, a Western Blot was performed which was indeterminate with a faint band at p24. Furtherworkup demonstrated a negative serum HIV ELISA and an undetectable HIV viral load. Although both OraQuick tests used had expiration dates #1 month from time of use, it is not clear if this was a contributing factor as we were using the newer version of the kit. More likely, the diagnosis of acute Dengue contributed to the false-positive result. There is only one other report documenting HIV-1 false-positive rapid ELISA tests in patients with Dengue fever. In this study, false-positive HIV screening tests on sera occurred in 4 of the 9 patients with Dengue, though there was no information on the mechanism by which Dengue infection triggered the false-positive reactivity. Our findings indicate that false positives may occur with rapid HIV assays, particularly in the case of concomitant infections. This may be a greater concern in resource-poor regions where diseases such as Dengue are most prevalent and as rapid HIV tests become more widely used.

False-positivity of Hiv-2 Immunoblots in a Cohort of Elite Suppressors Infected With Hiv-1

To the Editor: Infection with HIV-2, the second causative etiology for AIDS, is mainly present in West Africa, with a slow spread to other continents. Compared with HIV-1 infection, the course of HIV2 infection is associated with slower progression to AIDS, most likely attributable to lower plasma viral loads observed in these patients. In dual-infected patients, control of HIV-1 may be associated with the ability to respond to HIV-2 gag epitopes and to maintain HIV-specific CD4 T-cell responses. We recently tested a small group of long-term nonprogressors with HIV-1 infection (elite suppressors) to rule out coinfection with HIV-2. Three of 13 patients underwent testing with an HIV-2 enzyme immunoassay (EIA), and all 13 had HIV-2 Immunoblots performed at VircoMed Laboratories/Laboratory Corporation of America (Minnetonka, MN). One of the 13 patients had a significant HIV-2 risk factor with a previous sexual partner from West Africa of unknown HIV status. Using the commercially available assays, specimens were considered positive for the HIV-2 Immunoblot test if the gp36 band (env) was present. All patients tested positive with the HIV-2 EIA and the HIV-2 Immunoblot (of whom 2 were weakly positive). When HIV-2 qualitative polymerase chain reaction (PCR) tests were performed, all patients were negative, thus ruling out coinfection with HIV-2. Although previous studies have reported high sensitivity (91% to 100%) and specificity (81% to 100%) for HIV-2 antibody testing, this may become more challenging in coinfected patients because of cross-reactivity. The 2 viruses have similar morphology and cell tropism, with homology exhibited in the conserved genes, such as the core proteins (gag) and reverse transcriptase (pol), and in other less conserved envelope (env) genes. Although qualitative PCR testing is available at reference laboratories, quantitative viral loads are not available except in research facilities. Given the high false-positivity rate of the commercially available assays because of cross-reactivity with HIV-1, serologic testing for HIV-2 infection should be used only in patients with negative HIV-1 Western blot test results in areas in which HIV-2 is not endemic. In cases when dual infection is suspected, our recommendation would be to proceed directly to HIV-2 PCR testing.

An educational initiative in response to identified PrEP prescribing needs among PCPs in the Southern U.S.

ABSTRACT Pre-exposure prophylaxis (PrEP) is an effective HIV prevention method, but many primary care physicians (PCPs) have not incorporated PrEP into practice. While PrEP may be a key strategy to reducing high HIV transmission rates in the southern US, knowledge about PrEP prescribing patterns among PCPs in this region is lacking. An online survey was sent to a large network of PCPs at an academic medical center in North Carolina in October 2015. The survey was repeated in September 2016, after an educational intervention that included on-site trainings at 14 PCP offices. Chi-square tests were used to compare PrEP prescribing patterns among providers. The initial survey was sent to 389 PCPs, with 115 (30%) responding. Of these, 78% reported seeing men who have sex with men (MSM). Only 17% had prescribed PrEP. The most frequently identified barrier was lack of knowledge (60%). When the survey was repeated after the educational initiative, 79 PCPs (20%) responded. Of these, 90% reported seeing MSM, and 35% had prescribed PrEP. PCPs who had attended a training were more likely to have prescribed PrEP (OR 4.84, CI 1.77–13.21). In conclusion, PrEP prescribing among PCPs in the southern US is low. A survey among PCPs identified lack of knowledge as a barrier to prescribing, motivating an institutional-wide educational campaign in response. Further efforts are needed to continue to raise awareness and educate PCPs in the South about PrEP.

HIV care and treatment for children in resource-limited settings

Although efforts to combat the HIV epidemic have focused on the perinatal reduction of HIV transmission, many children are still being infected with HIV in resource-limited settings. Access to HIV care, cotrimoxazole and antiretroviral therapy (ART) for HIV-infected children has greatly improved in recent years, and has proven to be very effective in reducing mortality in all age categories. Many challenges remain to be resolved, such as the retention in care of children born to HIV-infected mothers, the lack of pharmacokinetic data on ART in malnourished children, optimum timing of ART, treatment and diagnosis of concomitant tuberculosis, and the effects of ART and HIV on the child’s development. In the long term, treatment success might be negated due to lower rates of viral suppression in children and the accumulation of resistance mutations. Evidenced-based comprehensive care models should allow for decentralizing care up to the level of the community, allowing larger numbers of children to receive HIV care.

Sexual Orientation Differences in HIV Testing Motivation among College Men.

ABSTRACT Objective: To investigate sexual orientation differences in college mens motivations for HIV testing. Participants: 665 male college students in the Southeastern United States from 2006 to 2014. Methods: Students completed a survey on HIV risk factors and testing motivations. Logistic regressions were conducted to determine the differences between heterosexual men (HM) and sexual minority men (SMM). Results: SMM were more motivated to get tested by concern over past condomless sex, while HM were more often cited supporting the testing program “on principle” and wanting a free t-shirt. SMM and HM differed in behaviors that impact HIV risk and other demographics. However, differences in testing motivation by concern over past condomless sex or wanting a free t-shirt persisted when controlling for these demographic and behavioral differences. Conclusions: Appropriately designed HIV prevention interventions on college campuses should target SMMs distinct concern over past condomless sex as a testing motivation.