Viral load criteria and threshold optimization to improve HIV incidence assay characteristics.

OBJECTIVE: Assays for classifying HIV infections as 'recent' or 'nonrecent' for incidence surveillance fail to simultaneously achieve large mean durations of 'recent' infection (MDRIs) and low 'false-recent' rates (FRRs), particularly in virally suppressed persons. The potential for optimizing recent infection testing algorithms (RITAs), by introducing viral load criteria and tuning thresholds used to dichotomize quantitative measures, is explored. DESIGN: The Consortium for the Evaluation and Performance of HIV Incidence Assays characterized over 2000 possible RITAs constructed from seven assays (Limiting Antigen, BED, Less-sensitive Vitros, Vitros Avidity, BioRad Avidity, Architect Avidity, and Geenius) applied to 2500 diverse specimens. METHODS: MDRIs were estimated using regression, and FRRs as observed 'recent' proportions, in various specimen sets. Context-specific FRRs were estimated for hypothetical scenarios. FRRs were made directly comparable by constructing RITAs with the same MDRI through the tuning of thresholds. RITA utility was summarized by the precision of incidence estimation. RESULTS: All assays produce high FRRs among treated patients and elite controllers (10-80%). Viral load testing reduces FRRs, but diminishes MDRIs. Context-specific FRRs vary substantially by scenario - BioRad Avidity and Limiting Antigen provided the lowest FRRs and highest incidence precision in scenarios considered. CONCLUSION: The introduction of a low viral load threshold provides crucial improvements in RITAs. However, it does not eliminate nonzero FRRs, and MDRIs must be consistently estimated. The tuning of thresholds is essential for comparing and optimizing the use of assays. The translation of directly measured FRRs into context-specific FRRs critically affects their magnitudes and our understanding of the utility of assays.

Independent assessment of candidate HIV incidence assays on specimens in the CEPHIA repository.

OBJECTIVE: Cross-sectional HIV incidence surveillance, using assays that distinguish 'recent' from 'nonrecent' infections, has been hampered by inadequate performance and characterization of incidence assays. In this study, the Consortium for the Evaluation and Performance of HIV Incidence Assays presents results of the first independent evaluation of five incidence assays (BED, Limiting Antigen Avidity, Less-sensitive Vitros, Vitros Avidity and BioRad Avidity). DESIGN: A large repository of diverse specimens from HIV-positive patients was established, multiple assays were run on 2500 selected specimens, and data were analyzed to estimate assay characteristics relevant for incidence surveillance. METHODS: The mean duration of recent infection (MDRI, average time 'recent' while infected for less than some time cut-off T) was estimated from longitudinal data on seroconverters by regression. The false-recent rate (FRR, probability of testing 'recent' when infected for longer than T) was explored by measuring the proportions of 'recent' results in various subsets of patients. RESULTS: Assays continue to fail to attain the simultaneously large MDRI and small FRR demanded by existing performance guidelines. All assays produce high FRRs amongst virally suppressed patients (>40%), including elite controllers and treated patients. CONCLUSIONS: Results from this first independent evaluation provide valuable information about the current performance of assays, and suggest the need for further optimization. Variation of 'recent'/'nonrecent' thresholds and the use of multiple antibody-maturation assays, as well as other biomarkers, can now be explored, using the rich data generated by the Consortium for the Evaluation and Performance of HIV Incidence Assays. Consistently high FRRs amongst those virally suppressed suggest that viral load will be a particularly valuable supplementary marker.

High percentage of recent HIV infection leading to onward transmission in Odessa, Ukraine associated with young adults.

The proportion of new HIV diagnoses between May and December 2009 across Odessa recently-infected was estimated using the BED-CEIA assay. Logistic regression models were used to explore factors associated with testing as recent. Of 1,313 newly-diagnosed individuals, 321 (24 %) were classified as recent. Recent infection was less likely among older adults [odds ratio (OR) = 0.70 per 10-year increase, 95 % CI 0.60-0.82]. Compared to men residing in Odessa city, women in rural Odessa and non-resident men were more likely to be recently-infected (OR 1.85, 1.26-2.71 and 2.83, 1.15-6.97, respectively). Reason for test was not associated with recent infection. In sensitivity analysis, after excluding individuals tested due to clinical indications, the proportion recently-infected and the association with age remained virtually unchanged. Our findings suggest a high risk of onward transmission, particularly in younger age groups. These findings highlight the need for tailored prevention strategies and ongoing RITA testing to monitor and evaluate effectiveness of prevention programmes.

High percentage of recent HIV infection among HIV-positive individuals newly diagnosed at voluntary counseling and testing sites in Poland.

To gain insight into HIV transmission we estimated the proportion of those recently infected. We examined data from HIV-positive patients and a random 10% sample of HIV-negative patients tested at Voluntary Counseling and Testing sites in Poland in 2006. Archived samples from positive patients were tested by three assays to differentiate recent from long-standing infection. Using logistic regression, we examined the association of recent infection (at least one assay) with age, sex, HIV exposure category, and the interval between self-reported HIV exposure and previous HIV test. Of 13,511 tests, 154 (1.1%) were HIV positive, representing 19.7% (n=783) of new diagnoses in Poland in 2006. Demographic and behavioral data were linked for 95, of whom 45 (47%) were recently infected and 1,001 were HIV negative. New diagnoses were more likely to be injectors (17% vs. 2%), men who have sex with men (MSM) (37% vs. 12%), and less frequent condom users (7.8% vs. 14% always) compared to HIV negatives. The median number of partners during the past 12 months was one and two among positives and negatives, but was higher among MSM-four and three, respectively. Ever injectors were less likely to be recently infected (adjusted OR=0.15, 95%CI=0.03-0.73). Having two or more sexual partners in the past 12 months was an independent predictor of recent infection (4.01, 1.4-11.49). We found no evidence that age or sex predicted recent infection. These data reinforce health education campaigns for safe sex messages, especially among MSM. They also suggest, albeit based on a subset of new diagnoses, that interventions should not be limited to selected age/sex groups.