Publications

BACKGROUND

Antiretroviral treatment (ART) regimens in HIV patients commonly cause significant lipid elevations, including increases in both triglycerides and cholesterol. Standard treatments for hypercholesterolemia include the HMG CoA reductase inhibitors, or "statins." Because many ART agents and statins share a common metabolic pathway that uses the cytochrome P450 enzyme system, coadministration of ART with statins could increase statin plasma levels significantly. The oyster mushroom, Pleurotus ostreatus, has been shown in animal models to decrease lipid levels--a finding that has been supported by preliminary data in a small human trial.

METHODS

To assess the safety and efficacy of P. ostreatus in patients with HIV and ART-induced hyperlipidemia, a single-arm, open-label, proof-of-concept study of 8 weeks' duration with a target enrollment of 20 subjects was conducted. Study patients with ART-induced elevated non-HDL cholesterol levels (> 160 mg/dL) were enrolled. Participants received packets of freeze-dried P. ostreatus (15 gm/day) to be administered orally for the 8 week trial period. Lipid levels were drawn every two weeks to assess efficacy. Safety assessments included self-reported incidence of muscle aches and measurement of liver and muscle enzymes. Mean within-person change in lipid levels were estimated using generalized estimating equations to account for repeated observations on individuals. A 30 mg/dL decrease in non-HDL cholesterol was deemed clinically significant.

RESULTS

126 patients were screened to enroll 25, of which 20 completed the 8-week study. The mean age was 46.4 years (36-60). Patients had a mean 13.7 yrs of HIV infection. Mean non-HDL cholesterol was 204.5 mg/dL at day 0 and 200.2 mg/dL at day 56 (mean within-person change = -1.70; 95% confidence interval (CI) = -17.4, 14.0). HDL cholesterol levels increased from 37.8 mg/dL at day 0 to 40.4 mg/dL on day 56 (mean within-person change = 2.6; 95% CI = -0.1, 5.2). Triglycerides dropped from 336.4 mg/dL on day 0 to 273.4 mg/dL on day 56 (mean within-person change = -63.0; 95% CI = -120.9, -5.1). Only 3 individuals achieved a sustained clinically significant (30 mg/dL) decline in non-HDL cholesterol after 8 weeks of therapy. There were no adverse experiences reported other than patients' distaste for the preparation. Liver function tests and muscle enzymes were not affected by the 8 weeks of treatment.

CONCLUSIONS

Pleurotus ostreatus as administered in this experiment did not lower non-HDL cholesterol in HIV patients with ART-induced hypercholesterolemia. Small changes in HDL and triglycerides were not of a clinical magnitude to warrant further study.

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 24 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form.

MAIN RESULTS

One randomised controlled trial and seven observational studies were included in the review. These eight studies identified 464 episodes of HIV transmission, 72 among treated couples and 392 among untreated couples. The rate ratio for the single randomised controlled trial was 0.04 [95% CI 0.00, 0.27]. All index partners in this study had CD4 cell counts at baseline of 350-550 cells/µL. Similarly, the summary rate ratio for the seven observational 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 estimated 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 among the observational studies 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 is a potent intervention for prevention of HIV in discordant couples in which the index partner has ≤550 CD4 cells/µL. A new multicentre randomised controlled trial confirms the suspected benefit seen in earlier observational studies. Questions remain about durability of protection, the balance of benefits and adverse events associated with earlier therapy, long-term adherence and transmission of ART-resistant strains to partners. Resource limitations and implementation challenges must also be addressed.Counselling, support, and follow up, as well as mutual disclosure, may have a role in supporting adherence, so programmes should be designed with these components. In addition to ART provision, the operational aspects of delivering such programmes must be considered.

Lung transplantation in mechanically ventilated (MV) patients has been associated with decreased posttransplant survival. Under the Lung Allocation Score (LAS) system, patients at greatest risk of death on the waiting list, particularly those requiring MV, are prioritized for lung allocation. We evaluated whether pretransplant MV is associated with poorer posttransplant survival in the LAS era. Using a national registry, we analyzed all adults undergoing lung transplantation in the United States from 2005 to 2010. Propensity scoring identified nonventilated matched referents for 419 subjects requiring MV at the time of transplantation. Survival was evaluated using Kaplan-Meier methods. Risk of death was estimated by hazard ratios employing time-dependent covariates. We found that pretransplant MV was associated with decreased overall survival after lung transplantation. In the first 6 months posttransplant, ventilated subjects had a twofold higher risk of death compared to nonventilated subjects. However, after 6 months posttransplant, survival did not differ by MV status. We also found that pretransplant MV was not associated with decreased survival in noncystic fibrosis obstructive lung diseases. These results suggest that under the LAS, pretransplant MV is associated with poorer short-term survival posttransplant. Notably, the increased risk of death appears to be strongest the early posttransplant period and limited to certain pretransplant diagnoses.