Emily Westheimer

The Multispot rapid HIV-1/HIV-2 differentiation assay is comparable with the Western blot and an immunofluorescence assay at confirming HIV infection in a prospective study in three regions of the United States ☆☆

BACKGROUND A new HIV diagnostic algorithm has been proposed which replaces the use of the HIV-1 Western blot and HIV-1 immunofluorescence assays (IFA) as the supplemental test with an HIV-1/HIV-2 antibody differentiation assay. OBJECTIVES To compare an FDA-approved HIV-1/HIV-2 antibody differentiation test (Multispot) as a confirmatory test with the HIV-1 Western blot and IFA. STUDY DESIGN Participants were screened with an HIV-1/HIV-2 combination Antigen/Antibody (Ag/Ab) screening assay. Specimens with repeatedly reactive results were tested with Multispot and either Western blot or IFA. Specimens with discordant screening and confirmatory results were resolved with HIV-1 RNA testing. RESULTS Individuals (37,876) were screened for HIV infection and 654 (1.7%) had a repeatedly reactive Ag/Ab assay result. On Multispot, 554 (84.7%) were HIV-1 reactive, 0 (0%) were HIV-2 reactive, 1 (0.2%) was reactive for both HIV-1 and HIV-2 (undifferentiated), 9 (1.4%) were HIV-1 indeterminate, and 90 (13.8%) were non-reactive. HIV-1 RNA was detected in 47/90 Multispot non-reactive (52.2%) specimens. Among specimens confirmed to have HIV infection (true positives), Multispot and Western blot detected HIV-1 antibody in a similar proportion of cases (93.7% vs. 94.4% respectively) while Multispot and IFA also detected HIV-1 antibody in a similar proportion of cases (84.5% vs. 83.4% respectively). CONCLUSIONS In this study, Multispot confirmed HIV infections at a similar proportion to Western blot and IFA. Multispot, Western blot, and IFA, however, did not confirm all of the reactive Ag/Ab assay results and underscores the importance of HIV NAT testing to resolve discordant screening and confirmatory results.

Screening Yield of HIV Antigen/Antibody Combination and Pooled HIV RNA Testing for Acute HIV Infection in a High-Prevalence Population

IMPORTANCE Although acute HIV infection contributes disproportionately to onward HIV transmission, HIV testing has not routinely included screening for acute HIV infection. OBJECTIVE To evaluate the performance of an HIV antigen/antibody (Ag/Ab) combination assay to detect acute HIV infection compared with pooled HIV RNA testing. DESIGN, SETTING, AND PARTICIPANTS Multisite, prospective, within-individual comparison study conducted between September 2011 and October 2013 in 7 sexually transmitted infection clinics and 5 community-based programs in New York, California, and North Carolina. Participants were 12 years or older and seeking HIV testing, without known HIV infection. EXPOSURES All participants with a negative rapid HIV test result were screened for acute HIV infection with an HIV Ag/Ab combination assay (index test) and pooled human immunodeficiency virus 1 (HIV-1) RNA testing. HIV RNA testing was the reference standard, with positive reference standard result defined as detectable HIV-1 RNA on an individual RNA test. MAIN OUTCOMES AND MEASURES Number and proportion with acute HIV infections detected. RESULTS Among 86,836 participants with complete test results (median age, 29 years; 75.0% men; 51.8% men who have sex with men), established HIV infection was diagnosed in 1158 participants (1.33%) and acute HIV infection was diagnosed in 168 participants (0.19%). Acute HIV infection was detected in 134 participants with HIV Ag/Ab combination testing (0.15% [95% CI, 0.13%-0.18%]; sensitivity, 79.8% [95% CI, 72.9%-85.6%]; specificity, 99.9% [95% CI, 99.9%-99.9%]; positive predictive value, 59.0% [95% CI, 52.3%-65.5%]) and in 164 participants with pooled HIV RNA testing (0.19% [95% CI, 0.16%-0.22%]; sensitivity, 97.6% [95% CI, 94.0%-99.4%]; specificity, 100% [95% CI, 100%-100%]; positive predictive value, 96.5% [95% CI, 92.5%-98.7%]; sensitivity comparison, P < .001). Overall HIV Ag/Ab combination testing detected 82% of acute HIV infections detectable by pooled HIV RNA testing. Compared with rapid HIV testing alone, HIV Ag/Ab combination testing increased the relative HIV diagnostic yield (both established and acute HIV infections) by 10.4% (95% CI, 8.8%-12.2%) and pooled HIV RNA testing increased the relative HIV diagnostic yield by 12.4% (95% CI, 10.7%-14.3%). CONCLUSIONS AND RELEVANCE In a high-prevalence population, HIV screening using an HIV Ag/Ab combination assay following a negative rapid test detected 82% of acute HIV infections detectable by pooled HIV RNA testing, with a positive predictive value of 59%. Further research is needed to evaluate this strategy in lower-prevalence populations and in persons using preexposure prophylaxis for HIV prevention.

Performance evaluation of the FDA-approved Determine™ HIV-1/2 Ag/Ab Combo assay using plasma and whole blood specimens

BACKGROUND The Determine™ HIV-1/2 Ag/Ab Combo (DC) rapid test can identify HIV-1 infection earlier than rapid antibody-only tests in plasma specimens. OBJECTIVES We compared the performance of DC with a laboratory-based antigen/antibody (Ag/Ab) combo assay in plasma and evaluated antigen reactivity in whole blood specimens. STUDY DESIGN We tested by DC 508 plasma specimens collected in a prospective study and 107 sequential plasma and simulated whole blood specimens from 20 seroconversion panels. Previous results using the ARCHITECT (ARC) Ag/Ab combo assay were compared to DC results. In seroconversion panels, the days from the first HIV1 RNA-positive test to first DC-reactive in plasma and whole blood was compared. McNemars and Wilcoxon signed rank tests were used for statistical analysis. RESULTS Of 415 HIV-positive samples, ARC detected 396 (95.4%) and DC 337 (81.2%) (p<0.0001). DC was reactive in 50.0% of ARC-reactive/MS-negative, 78.6% of ARC-reactive/MS-indeterminate, and 99.6% of ARC-reactive/MS-HIV-1-positive or -undifferentiated specimens. DC antigen reactivity was higher among ARC-reactive/MS-negative than MS-indeterminate samples. In 20 HIV-1 seroconversion panels, there was a significant difference between DC reactivity in plasma (91.1%) and whole blood (56.4%) (p<0.0001). DC with whole blood showed a significant delay in reactivity compared to plasma (p=0.008). CONCLUSIONS In plasma, DC was significantly less sensitive than an instrumented laboratory-based Ag/Ab combo assay. DC in plasma was significantly more sensitive compared to whole blood in early HIV-1 infections. With the U.S. laboratory-based diagnostic algorithm, DC as the first step would likely miss a high proportion of HIV-1 infections in early stages of seroconversion.

Linking HIV and Viral Hepatitis Surveillance Data: Evaluating a Standard, Deterministic Matching Algorithm Using Data From 6 US Health Jurisdictions

Accurate interpretations and comparisons of record linkage results across jurisdictions require valid and reliable matching methods. We compared existing matching methods used by 6 US state and local health departments (Houston, Texas; Louisiana; Michigan; New York, New York; North Dakota; and Wisconsin) to link human immunodeficiency virus and viral hepatitis surveillance data with a 14-key automated, hierarchical deterministic matching method. Applicable years of study varied by disease and jurisdiction, ranging from 1979 to 2016. We calculated percentage agreement and Cohens κ coefficient to compare the matching methods used within each jurisdiction. We calculated sensitivity, specificity, and positive predictive value for each matching method, as compared with a new standard that included manual review of discrepant cases. Agreement between the existing matching method and the deterministic matching method was 99.6% or higher in all jurisdictions; Cohens κ values ranged from 0.87 to 0.98. The sensitivity of the deterministic matching method ranged from 97.4% to 100% in the 6 jurisdictions; specificity ranged from 99.7% to 100%; and positive predictive value ranged from 97.4% to 100%. Although no gold standard exists, prior assessments of existing methods and review of discrepant classifications suggest good accuracy and reliability of our deterministic matching method, with the advantage that our method reduces the need for manual review and allows for standard comparisons across jurisdictions when linking human immunodeficiency virus and viral hepatitis data.

Persons living with diagnosed HIV in New York City: over 50% over 50 years old

ABSTRACT Using NYC HIV surveillance data, we estimated the annual median age of persons living with diagnosed HIV (PLWDH) and the proportion of PLWDH over 50 years old in NYC between 2008 and 2015, and described the characteristics, retention in care and viral suppression status among PLWDH in NYC in 2015, by age (<50 vs. ≥50 years old). The median age of PLWDH in NYC increased from 46.4 years (interquartile range [IQR]: 39.4, 53.2) in 2008 to 50.2 years (IQR: 39.8, 57.5) in 2015, and the proportion of PLWDH over 50 years old increased from 35.9% in 2008 to 50.6% in 2015. In 2015, by race/ethnicity, whites had the highest proportion over 50 years old (57.0%) and Asian/Pacific Islanders had the lowest (36.2%); by transmission risk, men who have sex with men were the lowest (40.0%) and injection drug users were the highest (76.1%). A large and increasing proportion of PLWDH over 50 years old presents challenges for HIV-infected individuals and healthcare system. Better social support services for HIV-infected individuals and additional training for medical and public health staff are needed.

Cancer Mortality among Persons with Human Immunodeficiency Virus Infection in New York City, 2001-2015

Abstract Background With the prolonged life-span of persons with HIV (PWH) due to anti-retroviral therapy, their cancer burden has increased. Cancer continues to be a leading cause of death among PWH. Studying cancer mortality can inform and guide the development of cancer screening and prevention strategies for PWH. Methods We analyzed data for all persons > = 13 years who were diagnosed with HIV from 2001 to 2015 and reported to the New York City (NYC) HIV surveillance registry (HSR). Using the HSR and the underlying cause of death obtained from the NYC vital statistics registry and the National Death Index, we examined age-specific and age-standardized mortality rates from cancer and compared time trends of deaths due to HIV-related8 cancer to deaths from non-HIV-related cancers. Results There were 34,190 deaths reported among 154,688 PWH of whom nearly half (n = 16,804; 49.1%) died due to HIV (excluding HIV-related cancers). Among all deaths, HIV was the leading cause, followed by cancer (both HIV and non-HIV-related) (n = 5,271; 15.4%) and cardiovascular disease (n = 3,724, 10.9%). The top three causes of non-HIV-related cancer deaths were lung cancer (n = 1,040; 19.7%), liver cancer (n = 552; 10.5%), and colorectal cancer (n = 315; 5.6%). Although the mortality rate among PWH decreased over time (24.4 to 13.9 per 1,000 person-years from 2001 to 2015), the proportion of deaths attributable to all cancers increased (10.6% in 2001 to 19.9% in 2015, p < .0001). This increase was driven by non-HIV-related cancers (6.1% of all deaths in 2001 to 15.8% in 2015, p < .0001). The mean age increased from 2001 to 2015 among the dead (46 to 56 years) and among the censored (35 to 49 years). After controlling for demographic factors, transmission risk, and last CD4 count, the hazard ratio for cancer deaths was higher among people who inject drugs (HR = 1.5; 95% CI = 1.4–1.7) and those with last CD4 count < 200 (HR = 9.3; 95% CI = 8.3–10.5). Conclusion Although mortality rates are decreasing in PWH, deaths due to non-HIV-related cancers are increasing. The upward trend in the mean age suggests that aging may be contributing to this increase. Routine screening for liver and colon cancers along with smoking cessation may reduce lung, liver and colon cancer deaths. Disclosures All authors: No reported disclosures.

Diagnosing acute HIV infection: The performance of quantitative HIV-1 RNA testing (viral load) in the 2014 laboratory testing algorithm

New recommendations for laboratory diagnosis of HIV infection in the United States were published in 2014. The updated testing algorithm includes a qualitative HIV-1 RNA assay to resolve discordant immunoassay results and to identify acute HIV-1 infection (AHI). The qualitative HIV-1 RNA assay is not widely available; therefore, we evaluated the performance of a more widely available quantitative HIV-1 RNA assay, viral load, for diagnosing AHI. We determined that quantitative viral loads consistently distinguished AHI from a false-positive immunoassay result. Among 100 study participants with AHI and a viral load result, the estimated geometric mean viral load was 1,377,793copies/mL.