Palmoplantar Pustulosis (PPP) is a rare form of psoriasis presenting with painful pustular eruptions localized to palms and soles. While PPP is potentially disabling, the factors that underlie disease severity remain poorly understood. To address this issue, we undertook a cross-sectional analysis of a deeply phenotyped British cohort (N=181; 41 males, 140 females; mean age of onset: 45.7 years). Given that PPP shows a strong sex bias, we first examined disease severity in males vs females. While the age of onset was comparable in the two groups, the Palmo-plantar Pustular Psoriasis Area Severity Index (PPPASI) was significantly lower in males than females (4.3 vs 11.1; p=0.006), with a similar trend observed for the Dermatology Life Quality Index (3.5 vs 9.5; p=0.002). Next, we sought to assess whether smoking, a key risk factor for PPP, was also associated with severity. We found that the mean PPASI was high in current smokers, moderate in ex-smokers and low in non-smokers (13.1 vs. 11.1 vs 8.4, p=0.039). To further explore this data, we conducted a hierarchical cluster analysis of 138 cases for whom data was available for a broad set of demographics (sex, ethnicity, smoking status, family history of psoriasis) and clinical variables (age of onset, PPPASI, concomitant psoriasis vulgaris, nail involvement). Using Gower's distance, we identified 4 distinct patient clusters. In line with the above findings, one cluster was composed entirely of males suffering from mild disease (median PPPASI: 3.6). Of note, none of these individuals was a current smoker. While our results will require independent validation, they suggest that sex and smoking drive clinical differences in the presentation of PPP.

BACKGROUND:We obtained estimates of the incidence of tuberculosis (TB) among patients receiving HAART and identified determinants of the incidence. METHODS:We analyzed the incidence of TB during the first 3 years after initiation of HAART among 17,142 treatment-naive, AIDS-free persons starting HAART who were enrolled in 12 cohorts from Europe and North America. We used univariable and multivariable Poisson regression models to identify factors associated with the incidence. RESULTS:During the first 3 years (36,906 person-years), 173 patients developed TB (incidence, 4.69 cases per 1000 person-years). In multivariable analysis, the incidence rate was lower for men who have sex with men, compared with injection drug users (relative rate, 2.46; 95% confidence interval [CI], 1.51-4.01), heterosexuals (relative rate, 2.42; 95% CI, 1.64-3.59), those with other suspected modes of transmission (relative rate, 1.66; 95% CI, 0.91-3.06), and those with a higher CD4+ count at the time of HAART initiation (relative rate per log2 cells/microL, 0.87; 95% CI, 0.84-0.91). During 28,846 person-years of follow-up after the first 6 months of HAART, 88 patients developed TB (incidence, 3.1 cases per 1000 person-years of follow-up). In multivariable analyses, a low baseline CD4+ count (relative rate per log2 cells/microL, 0.89; 95% CI, 0.83-0.96), 6-month CD4+ count (relative rate per log2 cells/microL, 0.90; 95% CI, 0.81-0.99), and a 6-month HIV RNA level >400 copies/mL (relative rate, 2.21; 95% CI, 1.33-3.67) were significantly associated with the risk of acquiring TB after 6 months of HAART. CONCLUSION:The level of immunodeficiency at which HAART is initiated and the response to HAART are important determinants of the risk of TB. However, this risk remains appreciable even among those with a good response to HAART, suggesting that other interventions may be needed to control the TB epidemic in the HIV-infected population.

Background: Little is known about the long term risk of development of HIV-1 drug resistance for patients starting antiretroviral therapy (ART) with three or four drug regimens in routine clinical practice. Methods: We analysed a large cohort study of patients seen in one of six large HIV clinics in and around London, UK. The focus of this analysis was on patients who started ART with two nucleosides plus either a single protease inhibitor (PI), a PI with ritonavir, abacavir or a non-nucleoside reverse transcriptase inhibitor (NNRTI). Results: 4306 patients were followed; 1436 (33%) started with a single PI, 279 (6%) with a PI plus ritonavir, 156 (4%) with triple nucleosides and 2435 (57%) with an NNRTI. The overall cumulative risk of viral load failure was 38% by 6 years. Risk of ≥1 major IAS-USA mutation was 27% by 6 years; risk of mutations from at least two of the three main drug classes was 20% over the same period. These are lower limit estimates as test results were not available for many with viral load failure. Risk of PI mutations being detected in people who started ART with regimens containing a PI with ritonavir was significantly lower than the risk of NNRTI mutations being detected in those starting with NNRTI-containing regimens (relative hazard 0.3195% CI 0.15-0.61; p = 0.0008). Conclusion: In routine practice, rates of viral load failure and of resistance detection in patients who started ART with three or four drugs are appreciable.

To audit the use of antiretroviral (ARV) treatment in a large treatment clinic in the UK against the British HIV Association (BHIVA) ARV treatment guidelines.

ObjectiveTo describe the reasons for, and factors associated with, modification and discontinuation of highly active antiretroviral therapy (HAART) regimens at a single clinic. SubjectsA total of 556 patients who started HAART at the Royal Free Hospital were included in analyses. Modification was defined as stopping or switching any antiretrovirals in the regimen, whereas discontinuation was defined as the simultaneous stopping of all antiretrovirals included in the initial regimen. Reasons were classified as immunological/virological failure (IVF) and toxicities and patient choice/poor compliance (TPC). ResultsThe median CD4 count at starting HAART was 171 × 106 cells/l and viral load 5.07 log copies/ml. During a median follow-up of 14.2 months, 247 patients (44.4%) modified their HAART regimen, 72 due to IVF (29.1%) and 159 due to TPC (64.4%) and a total of 148 patients (26.6%) discontinued HAART. Older patients were less likely to modify HAART [relative hazard (RH), 0.73 per 10 years;P = 0.0008], as were previously treatment-naive patients (RH, 0.65;P = 0.0050), those in a clinical trial (RH, 0.64;P = 0.027) and those who started nelfinavir (RH, 0.57;P = 0.035). Patients who started with four or more drugs (RH, 2.21, P < 0.0001), who included ritonavir in the initial regimen (RH, 1.41;P = 0.035) or who had higher viral loads during follow-up (RH per log increase, 1.51;P < 0.0001) were more likely to modify HAART. ConclusionsThere was a high rate of modification and discontinuation of HAART regimens in the first 12 months, particularly due to toxicities, patient choice or poor compliance.