The level of CD38 expression on different T-cell subsets is differentially upregulated in drug-naive HIV-infected patients. After successful HAART, immune activation decreases in all T-cell subsets, although it still remains elevated in most cases after 12 months of HAART. The extent of immune deactivation under successful HAART correlates with the ability to reconstitute CD4 counts.

The IL-7-CD127 system is impaired in HIV-infected patients. CD127 down-regulation is associated with T cell activation and with CD4(+) cell restoration after HAART.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Complications in pediatric regional anesthesia are rare, so a large sample size is necessary to quantify risk. The Pediatric Regional Anesthesia Network contains data on more than 100,000 blocks administered at more than 20 children’s hospitals. This study analyzed the risk of major complications associated with regional anesthesia in children. Methods This is a prospective, observational study of routine clinical practice. Data were collected on every regional block placed by an anesthesiologist at participating institutions and were uploaded to a secure database. The data were audited at multiple points for accuracy. Results There were no permanent neurologic deficits reported (95% CI, 0 to 0.4:10,000). The risk of transient neurologic deficit was 2.4:10,000 (95% CI, 1.6 to 3.6:10,000) and was not different between peripheral and neuraxial blocks. The risk of severe local anesthetic systemic toxicity was 0.76:10,000 (95% CI, 0.3 to 1.6:10,000); the majority of cases occurred in infants. There was one epidural abscess reported (0.76:10,000, 95% CI, 0 to 4.8:10,000). The incidence of cutaneous infections was 0.5% (53:10,000, 95% CI, 43 to 64:10,000). There were no hematomas associated with neuraxial catheters (95% CI, 0 to 3.5:10,000), but one epidural hematoma occurred with a paravertebral catheter. No additional risk was observed with placing blocks under general anesthesia. The most common adverse events were benign catheter-related failures (4%). Conclusions The data from this study demonstrate a level of safety in pediatric regional anesthesia that is comparable to adult practice and confirms the safety of placing blocks under general anesthesia in children.

HIV-specific T cells response and T cell activation are frequently seen in exposed seronegative individuals (ESN). In this study, we report HIV-specific response and level of T cell activation in ESN partners of HIV-infected patients presenting low or undetectable levels of HIV-RNA. We evaluated 24 HIV-serodiscordant couples. ESN were classified into three categories of exposure to HIV (very low, low, and moderate-high), considering levels of HIV-RNA in their infected partner and frequency of sexual high-risk practices within the last 12 mo. HIV-specific T cell responses and activation levels in T cell subsets were evaluated by flow cytometry. We reported that 54% of ESN had detectable HIV-specific T cells response, being the highest prevalence seen in the low exposure group (64%). Several T cell subsets were significantly increased in ESN when compared with controls: CD4+CD38+ (p = 0.006), CD4+HLA-DR−CD38+ (p = 0.02), CD4+CD45RA+CD27+HLA-DR−CD38+ (p = 0.002), CD8+CD45RA+CD27+CD38−HLA-DR+ (p = 0.02), and CD8+CD45RA+CD27−CD38+HLA-DR+ (p = 0.03). Activation of CD8+ T cells was increased in ESN with detectable HIV T cell responses compared with ESN lacking these responses (p = 0.04). Taken together, these results suggest that persistent but low sexual HIV exposure is able to induce virus-specific T cells response and immune activation in a high proportion of ESN, suggesting that virus exposure may occur even in conditions of maximal viral suppression in the HIV-infected partner.

Viral tropism plays an important role in HIV pathogenesis. However, its correlation with the clinical outcome and following exposure to antiretroviral drugs are still unclear. HIV-1 co-receptor usage was examined in 206 infected individuals: 67 seroconverters, 52 chronically drug-naïve, and 87 antiretroviral-experienced patients. The V3 loop was sequenced from plasma HIV-RNA and co-receptor usage was inferred using a phenotype predictor software (http://genomiac2.ucsd.edu:8080/wetcat/v3.html), which classifies V3 sequences as R5 or X4. The overall prevalence of X4 viruses was 26.2%, with significant differences among groups: 13.4% in seroconverters, 25% in drug-naïve, and 36.8% in antiretroviral- experienced patients (P = 0.001). The presence of X4 variants in the latter group was associated with higher viral load (P = 0.002) but not with lower CD4 counts. There was no association between HIV tropism and gender, transmission route or age. Neither with the CCR5 Delta32 genotype. Moreover, no association was found between HIV-1 tropism and drug resistance mutations nor with failure to regimens based on either protease inhibitors or non-nucleoside reverse transcriptase inhibitors. Finally, no significant association was found between IL-7 plasma levels with HIV-1 tropism. In summary, X4 viruses are particularly frequent among antiretroviral-experienced patients with high viral loads, irrespective of the CD4 count. Thus, CCR5 antagonists should be used with special caution in this subset of patients.