Differences in presentation and outcome of invasive pneumococcal disease among patients with and without HIV infection in the pre-HAART era.

Invasive pneumococcal disease (PD) occurs frequently among HIV-infected patients, but it is unclear whether its manifestations and outcome are different compared to those observed among patients without HIV-1 infection. Because the immune reconstitution that accompanies antiretroviral therapy may change some of these features and because most cases of HIV- 1 infection occur in resource-poor settings of the world where access to antiretroviral agents is limited, we compared PD among patients with and without HIV-1 infection in a North American population before the introduction of highly active antiretroviral therapy (HAART). The records of all pneumococcal cultures processed at this medical center over a period of 20 months were used to identify patients with invasive PD. Hospital records were reviewed for 103 of these patients (52 with and 51 without HIV-1 infection) and demographic, clinical, laboratory, radiographic, and microbiologic information was abstracted and subsequently analyzed. Despite similarities in presenting signs and symptoms, we found a higher incidence of bacteremia but a more favorable outcome with less frequent requirements for intubation and admission to intensive care units and better survival among individuals with HIV infection. Factors such as less advanced age, the presence of fewer comorbid conditions, or a less florid inflammatory response among HIV-infected individuals may account for differences in outcome of invasive PD.

Effect of class-specific therapy interruption on persistence of HIV type 1 antiretroviral resistance.

Interruption of all antiretroviral therapy for HIV-1 infection when therapy is failing and antiretroviral resistance has emerged is frequently associated with the disappearance of detectable resistance-associated protease and reverse transcriptase substitutions. However, the effect that discontinuation of treatment with a particular antiretroviral class has on resistance to that class when other antiretroviral therapy is continued is unknown. We investigated differences in detectable genotypic resistance to protease inhibitors (PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) among two populations: patients undergoing testing at the moment class-specific treatment failed (Group 1) and patients undergoing testing for varying periods after class-specific treatment failed and was discontinued but therapy with other antiretroviral classes continued with incomplete viral suppression (Group 2). We found that the prevalence of detectable resistance to the PI and NNRTI classes was similar in both groups despite the absence of class-specific selective pressure for lengthy periods of time in Group 2. We hypothesize that this finding may be due to nonspecific selective pressure (i.e., to nucleoside reverse transcriptase inhibitors) selecting out PI- and, to a lesser extent, NNRTI-resistant viral variants.

Differences in the frequency of resistance to antiretroviral drug classes among human immunodeficiency virus type 1 clinical isolates.

Genotypic resistance to all antiretroviral classes was widespread among human immunodeficiency virus type 1 isolates failing therapy. Resistance to nonnucleoside reverse transcriptase inhibitors was found most frequently and resistance to protease inhibitors was found least frequently, most likely due to differences in the number of enzymatic amino acid substitutions leading to resistance to each particular drug class.

Randomized trial of pallidotomy versus medical therapy for Parkinson's disease.

Thirty-six patients with Parkinson's disease (PD) were randomized to either medical therapy (N = 18) or unilateral GPi pallidotomy (N = 18). The primary outcome variable was the change in total Unified Parkinson's Disease Rating Scale (UPDRS) score at 6 months. Secondary outcome variables included subscores and individual parkinsonian symptoms as determined from the UPDRS. At the six month follow-up, patients receiving pallidotomy had a statistically significant reduction (32% decrease) in the total UPDRS score compared to those randomized to medical therapy (5% increase). Following surgery, patients' showed improvement in all the cardinal motor signs of PD including tremor, rigidity, bradykinesia, gait and balance. Drug-induced dyskinesias were also markedly improved. Although the greatest improvement occurred on the side contralateral to the lesion, significant ipsilateral improvement was also observed for bradykinesia, rigidity and drug-induced dyskinesias. A total of twenty patients have been followed for 2 years to assess the effect of time on clinical outcome. These patients have shown sustained improvement in the total UPDRS (p < 0.0001), "off" motor (p < 0.0001) and complications of therapy subscores (p < 0.0001). Sustained improvement was also seen for tremor, rigidity, bradykinesia, percent on time and drug-induced dyskinesias.