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Introduction: Delayed‐type hypersensitivity (DTH) testing is an in vivo assessment of cell‐mediated immunity. Although highly active antiretroviral therapy (HAART) improves immunologic parameters, the relationship between DTH responsiveness and CD4 gains on HAART is not completely understood. We investigated CD4 reconstitution and the change in DTH responses from treatment baseline through 24 months of viral load (VL)‐suppressive HAART in the U.S. Military HIV Natural History Study. Methods: Treatment‐naïve subjects with VL Results: Non‐anergic responses were observed in 216 (72%) participants, while 86 (28%) individuals were anergic prior to HAART initiation. Demographically there were similar distributions of age at HIV diagnosis and HAART initiation, as well as gender and race or ethnicity. There were no significant differences between non‐anergic and anergic participants in pre‐HAART CD4 count (409 cells/μL, interquartile range (IQR) 315–517 vs. 373 cells/μL, IQR 228–487; p=0.104) and VL (4.3 log[sub.10] copies/mL, IQR 3.4–4.9 vs. 4.4 log[sub.10] copies/mL, IQR 3.6–5.0; p=0.292). Median CD4 gains 24 months after HAART initiation were similar between the non‐anergic (220 cells/μL, IQR 115–358) and anergic groups (246 cells/μL, IQR 136–358; p=0.498). For individuals anergic before HAART initiation, DTH normalization occurred at 24 months post‐HAART in the majority of participants (51 of 86, 59%). Normalization of DTH responses was not associated with CD4 count at HAART initiation (OR 0.73, 95% CI 0.47, 1.09 per 100 cells; p=0.129) nor with AIDS diagnoses prior to HAART (OR 0.34, 95% CI 0.04, 2.51; p=0.283). Conclusions: DTH responsiveness has been shown to predict HIV disease progression independent of CD4 count in untreated individuals. In the setting of HAART, pre‐HAART anergy does not appear to impact CD4 gains or the ability to normalize DTH responses after 24 months of VL‐suppressive HAART., Introduction With the increased success of newer highly active antiretroviral therapy (HAART) regimens, the morbidity and mortality of patients taking HAART in the United States continue to decline [1–4]. The [...]

Background. Treatment guidelines recommend the use of a single dose of benzathine penicillin G (BPG) for treating early syphilis in human immunodeficiency virus (HIV)-infected persons. However, data supporting this recommendation are limited. We examined the efficacy of single-dose BPG in the US Military HIV Natural History Study. Methods. Subjects were included if they met serologic criteria for syphilis (ie, a positive nontreponemal test [NTr] confirmed by treponemal testing). Response to treatment was assessed at 13 months and was defined by a ≥4-fold decline in NTr titer. Multivariate Cox proportional hazard regression models were utilized to examine factors associated with treatment response. Results. Three hundred fifty subjects (99% male) contributed 478 cases. Three hundred ninety-three cases were treated exclusively with BPG (141 with 1 dose of BPG). Treatment response was the same among those receiving 1 or >1 dose of BPG (92%). In a multivariate analysis, older age (hazard ratio [HR], 0.82 per 10-year increase; 95% confidence interval [CI], .73–.93) was associated with delayed response to treatment. Higher pretreatment titers (reference NTr titer <1:64; HR, 1.94 [95% CI, 1.58–2.39]) and CD4 counts (HR, 1.07 for every 100-cell increase [95% CI, 1.01–1.12]) were associated with a faster response to treatment. Response was not affected by the number of BPG doses received (reference, 1 dose of BPG; HR, 1.11 [95% CI, .89–1.4]). Conclusions. In this cohort, additional BPG doses did not affect treatment response. Our data support the current recommendations for the use of a single dose of BPG to treat HIV-infected persons with early syphilis. [ABSTRACT FROM AUTHOR]

Background: Understanding the impact of hepatitis B virus (HBV) coinfection on HIV outcomes in the highly active antiretroviral therapy (HAART) era continues to be a critical priority given the high prevalence of coinfection and the potential for impaired immunologic, virologic, and clinical recovery., Methods: Participants from the US Military HIV Natural History Study with an HIV diagnosis on HAART and serologically confirmed HBV infection status at HAART initiation (HI) were classified into 4 HBV infection (HB) groups. HIV virologic, immunologic, and clinical outcomes were evaluated by HB status., Results: Of 2536 HIV-positive HAART recipients, with HBV testing results available to determine HB status in the HI window, HB status at HI was classified as HB negative (n = 1505; 66%), resolved HB (n = 518; 23%), isolated hepatitis B core antigen (n = 139; 6%), or chronic HB (n = 131; 6%). HIV virologic suppression and failure at 6 months or 1 year were not significantly different by HB status. A significantly faster rate of increase in CD4 cell count during the period between 4 and 12 years was observed for chronic HB relative to HB negative. Chronic and resolved HB were associated with an increased risk of AIDS/death compared with HB-negative individuals (chronic HB-hazard ratio = 1.68, 95% confidence interval: 1.05 to 2.68; resolved HB-hazard ratio = 1.61, 95% confidence interval: 1.15 to 2.25)., Conclusions: HB status did not have a significant impact on HIV virologic outcomes, however, CD4 cell count reconstitution after HI and the risk of an AIDS event or death after HI may be associated with HB status.

Background: The Veterans Aging Cohort Study (VACS) index is a weighted combination of age and 8 clinical variables. It has been well correlated with all-cause mortality among HIV-infected patients. The US Military HIV Natural History Study (NHS) cohort provides a different validation population profile, being younger and healthier. A significant portion of the US HIV population is similarly composed; so, evaluation of the VACS index in this population is of great interest., Methods: NHS subjects have medical history and laboratory data collected at 6-month visits. We performed an external validation of the VACS index in the NHS evaluating correlation, discrimination, and calibration for all-cause mortality after highly active antiretroviral therapy initiation (HI). We then tested whether combining longitudinal VACS index values at different time points improves prediction of mortality., Results: The VACS index at 1 year after HI was well correlated with all-cause mortality (Harrell c statistic 0.78), provided good discrimination (log-rank P < 0.05), and was marginally well calibrated using Brier score. Accounting for VACS index at HI and 6 months after HI significantly improved a standard model, including only the VACS index at 1 year after HI (net reclassification improvement = 25.2%, 95% CI: 10.9% to 48.9%)., Conclusions: The VACS index was well correlated and provided good discrimination with respect to all-cause mortality among highly active antiretroviral therapy initiating subjects in the NHS. Moderate overprediction of mortality in this young, healthy population suggests minor recalibration that could improve fit among similar patients. Considering VACS index at HI and 6 months improved outcome prediction and allowed earlier risk assessment.