The benefit of immediate compared with deferred antiretroviral therapy on CD4+ cell count recovery in early HIV infection.

OBJECTIVE: To assess the impact of immediate vs. deferred antiretroviral therapy (ART) on CD4 recovery among individuals early in HIV infection. DESIGN: Using serologic markers of early infection together with self-reported dates of infection and HIV diagnosis, ART-naive participants who were randomized to immediate vs. deferred ART in the Strategic Timing of Antiretroviral Treatment trial were classified into subgroups of duration of HIV infection at baseline. CD4 cell count recovery over follow-up according to duration of HIV infection was investigated. METHODS: Three subgroups were defined: first, infected 6 months or less (n = 373); second, infected 6-24 months (n = 2634); and third, infected 24 months or longer (n = 1605). Follow-up CD4, CD8, and CD4 : CD8 ratio for the immediate and deferred ART groups were compared by subgroup using linear models. For the deferred ART group, decline to CD4 less than 350 cells/µl or AIDS according to infection duration was compared using time-to-event methods. RESULTS: Follow-up CD4 cell count differences (immediate minus deferred) were greater for those recently infected (+231 cells/µl) compared with the two other subgroups (202 and 171 cells/µl; P < 0.001). CD4 : CD8 ratio treatment differences varied significantly (P < 0.001) according to duration of infection. In the deferred ART group, decline to CD4 less than 350 cells/µl or AIDS was greater among those recently infected (16.1 vs. 13.2 and 10.5 per 100 person years for those infected 6-24 and ≥24 months; P = 0.002). CONCLUSION: In this randomized comparison of immediate vs. deferred ART, the CD4 cell count difference was greatest for those recently infected with HIV, emphasizing the importance of immediate ART initiation.

Comparison of Self-report to Biomarkers of Recent HIV Infection: Findings from the START Trial.

Identifying individuals with recent HIV infection is critical to research related to viral reservoirs, outbreak investigations and intervention applications. A multi-assay algorithm (MAA) for recency of infection was used in conjunction with self-reported date of infection and documented date of diagnosis to estimate the number of participants recently infected in the Strategic Timing of AntiRetroviral Treatment (START) trial. We tested samples for three groups of participants from START using a MAA: (1) 167 individuals who reported being infected ≤ 6 months before randomization; (2) 771 individuals who did not know their date of infection but were diagnosed within 6 months before randomization; and (3) as controls for the MAA, 199 individuals diagnosed with HIV ≥ 2 years before randomization. Participants with low titer and avidity and a baseline viral load > 400 copies/mL were classified as recently infected. A significantly higher percentage of participants who self-reported being infected ≤ 6 months were classified as recently infected compared to participants diagnosed ≥ 2 years (65% [109/167] vs. 2.5% [5/199], p < 0.001). Among the 771 individuals who did not know their duration of infection at randomization, 206 (26.7%) were classified as recently infected. Among those diagnosed with HIV in the 6 months prior to enrollment, the 373 participants who reported recent infection (n = 167) or who had confirmed recent infection by the MAA (n = 206) differed significantly on a number of baseline characteristics from those who had an unknown date of infection and were not confirmed by the MAA (n = 565). Participants recently infected by self-report and/or MAA were younger, more likely to be Asian, less likely to be black, less likely to be heterosexual, more likely to be enrolled at sites in the U.S., Europe or Australia, and have higher HIV RNA levels. There was good agreement between self-report of recency of infection and the MAA. We estimate that 373 participants enrolled in START were infected within 6 months of randomization. Compared to those not recently infected, these participants were younger, had higher HIV RNA levels and were more likely to come from high income countries and from populations such as MSM with more regular HIV testing.

Short Communication: Comparison of Maxim and Sedia Limiting Antigen Assay Performance for Measuring HIV Incidence.

Accurate methods for cross-sectional incidence estimation are needed for HIV prevention research. The Limiting Antigen Avidity (LAg-Avidity) assay has been marketed by two vendors, Maxim Biomedical and Sedia BioSciences Corporation. Performance differences between the two versions of the assay are unknown. We tested a total 1,410 treatment-naive samples with both versions of the assay. The samples came from 176 seroconverters from the Zimbabwe Hormonal Contraception and HIV Study. The correlation between the two versions of the assay was 0.93 for the optical density (OD) and 0.86 for the normalized OD. As the difference was more pronounced for the normalized OD, the difference in assays can be attributed to the calibrators. The mean duration of recent infection (MDRI), the average time individuals infected <2 years appear recently infected, was determined for both versions using an assay cutoff of 1.5 OD-n alone or in combination with a viral load cutoff of >1,000 copies/ml. The MDRI was 137 days for Sedia and 157 days for Maxim, with a difference of 20 days (95% CI 11-30). The MDRIs decreased to 102 and 120 days with the inclusion of a viral load cutoff of >1,000 copies/ml. These results imply that use of the Sedia LAg-Avidity will result in estimates of incidence ∼13% lower than those using the Maxim LAg-Avidity.

Comparison of cross-sectional HIV incidence assay results from dried blood spots and plasma.

BACKGROUND: Assays have been developed for cross-sectional HIV incidence estimation using plasma samples. Large scale surveillance programs are planned using dried blood spot (DBS) specimens for incidence assessment. However, limited information exists on the performance of HIV cross-sectional incidence assays using DBS. METHODS: The assays evaluated were: Maxim HIV-1 Limiting Antigen Avidity EIA (LAg-Avidity), Sedia HIV-1 BED-Capture EIA (BED-CEIA), and CDC modified BioRad HIV-1/2 Plus O Avidity-based Assay (CDC-BioRad Avidity) using pre-determined cutoff values. 100 matched HIV-1 positive plasma and DBS samples, with known duration of infection, from the Consortium for the Evaluation and Performance of HIV Incidence Assays repository were tested. All assays were run in duplicate. To examine the degree of variability within and between results for each sample type, both categorical and continuous results were analyzed. Associations were assessed with Bland Altman, R2 values and Cohen's kappa coefficient (ĸ). RESULTS: Intra-assay variability using the same sample type was similar for all assays (R2 0.96 to 1.00). The R2 values comparing DBS and plasma results for LAg-Avidity, BED-CEIA, and CDC-BioRad Avidity were 0.96, 0.94, and 0.84, respectively. The concordance and ĸ values between DBS and plasma for all three assays were >87% and >0.64, respectively. The Bland-Altman analysis showed significant differences between plasma and DBS samples. For all three assays, a higher number of samples were classified as recent infections using DBS samples. CONCLUSIONS: DBS and plasma sample results were highly correlated. However, when compared to plasma, each assay performed somewhat differently in DBS at the lower and higher ends of the dynamic range. DBS samples were more likely to be classified as recently infected by all three assays, which may lead to overestimation of incidence in surveys using performance criteria derived for plasma samples.