HIV-1 persistent viremia is frequently followed by episodes of low-level viremia.

After the start of antiretroviral therapy (ART), plasma HIV-RNA levels should fall below the limit of detection (LOD) within 24 weeks. Hence, the prolonged decline of HIV-RNA after ART initiation is defined as persistent viremia (PV). In this retrospective study, we analyzed factors associated with PV. Next-generation sequencing of viral RNA/DNA was performed to study viral evolution and the emergence of drug-resistance mutations in HIV-infected patients with PV (n = 20). In addition, HIV-DNA species, immunological parameters, and clinical data of the patients were analyzed. We found that the possible causes for PV were divers, and both virologic and host parameters of this particular cohort were heterogeneous. We identified viruses with therapy-associated DRMs in six patients (30%); two of these were detected as minority variants. Five patients had sub-optimal drug levels (25%) and the baseline plasma viral loads were relatively high. Strikingly, we observed that >40% of the PV patients finally reaching HIV levels below the LOD later on showed up with episodes of low-level viremia (LLV). However, the amount of PBMC derived HIV-DNA species was not correlated with the likelihood of LLV after PV. According to our data, we conclude that drug-resistant viruses, sub-optimal drug level, and high baseline viral loads might be probable reasons for the prolonged RNA decline only in a sub-set of patients. In the absence of emerging DRMs and/or compliance issues, the clinical implications of PV remain unclear; however, PV appears to be a risk factor for episodes of LLV.

Detection of abacavir hypersensitivity by ELISpot method.

The antiretroviral agent abacavir can cause hypersensitivity reaction (HSR) and the presence of HLA-B*57:01 is predictive of abacavir-HSR in Caucasian HIV-infected patients. However, abacavir-HSR also occurs in HLA-B*57:01 negative patients. In these patients, a safe diagnostic tool to dissect clinically suspected HSR against abacavir from adverse reactions against co-administered drugs is mandatory, and abacavir-ELISpot was evaluated. Peripheral blood mononuclear cells from 87 HIV patients were stimulated by abacavir and the production of interferon-γ to the ELISpot was determined. Abacavir treated patients with HSR [confirmed (n=5) or suspected (n=12)] vs without HSR (n=42) displayed significantly higher numbers of abacavir-specific cells (82.3±23.0 or 10.5±4.5 vs -0.5±1.0 spot forming cells per million PBMC, p < .005 each). In conclusion, we established the first abacavir-specific ELISpot. According to our preliminary data, a negative abacavir-ELISpot nearly excludes HSR against abacavir. Thereby the ELISpot may facilitate the decision to continue or withdraw abacavir treatment.

Diagnostic accuracy of contrast-enhanced FDG-PET/CT in primary staging of cutaneous malignant melanoma.

PURPOSE: To evaluate the diagnostic accuracy of contrast-enhanced FDG-PET/CT (ce-PET/CT), PET-only, and CT-only in patients with newly diagnosed and resected cutaneous malignant melanoma. METHODS: A final group of 56 patients (mean age 62 years, range 23-86 years; 29 women, 27 men) were staged with ce-PET/CT after resection of the primary tumour. Histopathology as well as clinical follow-up (mean 780 days, range 102-1,390 days) served as the standards of reference. Differences between the staging modalities were tested for statistical significance with McNemar's test. RESULTS: All imaging procedures provided low sensitivities in the detection of lymph nodes (sensitivity N-stage: PET/CT and PET-only 38.5%; CT-only 23.1%) and distant metastases (sensitivity M-stage: PET/CT 41.7%, PET-only 33.3%, CT-only 25.0%) in initial staging after resection of the primary tumour. No statistically significant differences were detected between the imaging procedures (p > 0.05). PET/CT resulted in an alteration in further treatment in two patients compared to PET-only and in four patients compared to CT-only. CONCLUSION: All imaging modalities had a low sensitivity on initial staging of patients with malignant melanoma. Thus, close patient follow-up must be considered mandatory.