Publications

BACKGROUND

Antiretroviral drugs have been shown to reduce risk of mother-to-child transmission of human immunodeficiency virus (HIV) and are also widely used for post-exposure prophylaxis for parenteral and sexual exposures. Observational data, ecological studies and models suggest that sexual transmission may be lower in couples in which one partner is infected with HIV and the other is not and the infected partner is on antiretroviral therapy (ART).

OBJECTIVES

To determine if ART use in an HIV-infected member of an HIV-discordant couple is associated with lower risk of HIV transmission to the uninfected partner compared to untreated discordant couples.

SEARCH STRATEGY

We used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language.

SELECTION CRITERIA

Randomised controlled trials, cohort studies and case-control studies of HIV-discordant couples in which the HIV-infected member of the couple was being treated or not treated with ART DATA COLLECTION AND ANALYSIS: Abstracts of all trials identified by electronic or bibliographic scanning were examined independently by two authors. We initially identified 1814 references and examined 23 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form.

MAIN RESULTS

Seven observational studies and no randomised controlled trials were included in the review. These seven studies identified 436 episodes of HIV transmisison, 71 among treated couples and 365 among untreated couples. The summary rate ratio for all seven studies was 0.34 [95% CI 0.13, 0.92], with substantial heterogeneity (I(2)=73%). After excluding two studies with inadequate person-time data, we found a summary rate ratio of 0.16 [95% CI 0.07, 0.35] with no noted heterogeneity (I(2)=0%). We also performed subgroup analyses to see if the effect of ART on prevention of HIV differed by the index partner's CD4 cell count. Among couples in which the infected partner had >350 CD4 cells/µL, we estimated a rate ratio of 0.02 [95% CI 0.00, 2.87]. In this subgroup, there were 61 transmissions in untreated couples and none in treated couples.

AUTHORS' CONCLUSIONS

ART appears to be a potent intervention for prevention of HIV in discordant couples. However, the most important question from a clinical standpoint is whether being in a serodiscordant sexual relationship and having >350 CD4 cells/µL should be an indication for ART. In our analysis, there were broad confidence intervals in this subgroup, overlapping the null hypothesis of no effect. There is currently one large randomised controlled trial in the field, whose results are scheduled to be ready in 2015. Significant questions remain about durability of protection, when to start treating an infected partner (for instance, at diagnosis or at a specific CD4 level) and transmission of ART-resistant strains to partners.

CONTEXT

The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) study, which provided optimal medical therapy (OMT) to all patients and demonstrated no incremental advantage of percutaneous coronary intervention (PCI) on outcomes other than angina-related quality of life in stable coronary artery disease (CAD), suggests that a trial of OMT is warranted before PCI. It is unknown to what degree OMT is applied before PCI in routine practice or whether its use increased after the COURAGE trial.

OBJECTIVE

To examine the use of OMT in patients with stable angina undergoing PCI before and after the publication of the COURAGE trial.

DESIGN, SETTING, AND PARTICIPANTS

An observational study of patients with stable CAD undergoing PCI in the National Cardiovascular Data Registry between September 1, 2005, and June 30, 2009. Analysis compared use of OMT, both before PCI and at the time of discharge, before and after the publication of the COURAGE trial. Optimal medical therapy was defined as either being prescribed or having a documented contraindication to all medicines (antiplatelet agent, β-blocker, and statin).

MAIN OUTCOME MEASURES

Rates of OMT before PCI and at discharge (following PCI) between the 2 study periods.

RESULTS

Among all 467,211 patients (173,416 before [37.1%] and 293,795 after [62.9%] the COURAGE trial) meeting study criteria, OMT was used in 206,569 patients (44.2%; 95% confidence interval [CI], 44.1%-44.4%) before PCI and in 303,864 patients (65.0%; 95% CI, 64.9%-65.2%) at discharge following PCI (P < .001). Before PCI, OMT was applied in 75,381 patients (43.5%; 95% CI, 43.2%-43.7%) before the COURAGE trial and in 131,188 patients (44.7%; 95% CI, 44.5%-44.8%) after the COURAGE trial (P < .001). The use of OMT at discharge following PCI before and after the COURAGE trial was 63.5% (95% CI, 63.3%-63.7%) and 66.0% (95% CI, 65.8%-66.1%), respectively (P < .001).

CONCLUSION

Among patients with stable CAD undergoing PCI, less than half were receiving OMT before PCI and approximately two-thirds were receiving OMT at discharge following PCI, with relatively little change in these practice patterns after publication of the COURAGE trial.

Despite muscle pain being a well-described symptom in patients with diverse forms of peripheral neuropathy, the role of neuropathic mechanisms in muscle pain have received remarkably little attention. We have recently demonstrated in a well-established model of chemotherapy-induced painful neuropathy (CIPN) that the anti-tumor drug paclitaxel (Taxol) produces mechanical hyperalgesia in skeletal muscle, of similar time course to and with shared mechanism with cutaneous symptoms. In the present study, we evaluated muscle afferent neuron function in this rat model of CIPN. The mechanical threshold of muscle afferents in rats exposed to paclitaxel was not significantly different from the mechanical threshold of muscle afferents in control animals (P = 0.07). However, paclitaxel did produce a marked increase in the number of action potentials elicited by prolonged suprathreshold fixed intensity mechanical stimulation and a marked increase in the conduction velocity. In addition, the interspike interval (ISI) analysis (to evaluate the temporal characteristics of the response of afferents to sustained mechanical stimulation) showed a significant difference in rats treated with paclitaxel; there was a significantly greater ISI percentage of paclitaxel-treated muscle afferents with 0.01- and 0.02-s ISI. In contrast, an analysis of variability of neuronal firing over time (CV2 analysis) showed no effect of paclitaxel administration. These effects of paclitaxel on muscle afferent function contrast with the previously reported effects of paclitaxel on the function of cutaneous nociceptors.