Blake Max

Early development of non-hodgkin lymphoma following initiation of newer class antiretroviral therapy among HIV-infected patients - implications for immune reconstitution

BackgroundIn the HAART era, the incidence of HIV-associated non-Hodgkin lymphoma (NHL) is decreasing. We describe cases of NHL among patients with multi-class antiretroviral resistance diagnosed rapidly after initiating newer-class antiretrovirals, and examine the immunologic and virologic factors associated with potential IRIS-mediated NHL.MethodsDuring December 2006 to January 2008, eligible HIV-infected patients from two affiliated clinics accessed Expanded Access Program antiretrovirals of raltegravir, etravirine, and/or maraviroc with optimized background. A NHL case was defined as a pathologically-confirmed tissue diagnosis in a patient without prior NHL developing symptoms after starting newer-class antiretrovirals. Mean change in CD4 and log10 VL in NHL cases compared to controls was analyzed at week 12, a time point at which values were collected among all cases.ResultsFive cases occurred among 78 patients (mean incidence = 64.1/1000 patient-years). All cases received raltegravir and one received etravirine. Median symptom onset from newer-class antiretroviral initiation was 5 weeks. At baseline, the median CD4 and VL for NHL cases (n = 5) versus controls (n = 73) were 44 vs.117 cells/mm3 (p = 0.09) and 5.2 vs. 4.2 log10 (p = 0.06), respectively. The mean increase in CD4 at week 12 in NHL cases compared to controls was 13 (n = 5) vs. 74 (n = 50)(p = 0.284). Mean VL log10 reduction in NHL cases versus controls at week 12 was 2.79 (n = 5) vs. 1.94 (n = 50)(p = 0.045).ConclusionsAn unexpectedly high rate of NHL was detected among treatment-experienced patients achieving a high level of virologic response with newer-class antiretrovirals. We observed trends toward lower baseline CD4 and higher baseline VL in NHL cases, with a significantly greater decline in VL among cases by 12 weeks. HIV-related NHL can occur in the setting of immune reconstitution. Potential immunologic, virologic, and newer-class antiretroviral-specific factors associated with rapid development of NHL warrants further investigation.

A HAART‐Breaking Review of Alternative Antiretroviral Administration: Practical Considerations with Crushing and Enteral Tube Scenarios

Selection of an appropriate antiretroviral regimen for the patient infected with human immunodeficiency virus can be challenging, as various considerations must be taken into account including viral resistance mutations, patient comorbidities, drug interactions, and the potential for drug‐related adverse effects and toxicities. Treatment is further complicated when a clinical scenario arises requiring an alteration in the dosage form. Factors ranging from dysphagia to administration through an enteral feeding tube can affect decisions regarding antiretroviral dosage forms. Limited pharmacokinetic data exist regarding the alteration of antiretroviral medications from their original form. Bioavailability may vary substantially between dosage forms, which can lead to unpredictable drug concentrations. Supratherapeutic or subtherapeutic antiretroviral drug concentrations can result in increased toxicity, virologic failure, or the emergence of drug resistance. We performed a systematic literature search to review the available antiretroviral literature on the modification of solid dosage forms as well as alternative routes of administration of oral antiretroviral agents and their application to clinical practice.

Renal Function Recovery and HIV Viral Suppression Following Tenofovir Discontinuation for Renal Impairment

BACKGROUND Tenofovir associated nephrotoxicity (TDFN) is well recognized. This study describes the trend of renal function recovery and virologic consequences after cessation of tenofovir (TDF) for suspected TDFN. METHODS This was a retrospective chart review of 241 patients who underwent HLA-B*5701 allele testing between January 2007-December 2010. Demographics and clinical characteristics were compared at baseline, 3, 6, and 12 month between patients that continued and discontinued TDF. Factors associated with renal function recovery were assessed by multivariable logistic regression. RESULTS Eighty patients were identified with TDFN; 84% male, 74% African American (AA) with a median age of 55 years, and median length of TDF use for 122 weeks. Renal recovery at 12 months differed in those who stopped versus (vs.) continued TDF (83% vs. 57% p=0.03). In a crude analysis, baseline chronic kidney disease was negatively associated with renal recovery (p=0.01). An adjusted analysis showed that those who stopped TDF had 3.76 higher odds of renal recovery compared to those who did not stop TDF (95% CI: 1.26-11.27, p=0.02). There were no significant differences in virologic response after switching TDF to an alternative agent. CONCLUSION In this mostly AA male population with suspected TDFN, discontinuation of TDF was strongly associated with renal function recovery without affecting viral suppression.

Severe dyslipidaemia after the addition of raltegravir to a lopinavir/ritonavir-containing regimen

We describe a 55-year-old HIV-1-infected male who developed severe dyslipidaemia (total cholesterol 600 mg/dl, triglycerides >5,000 mg/dl, high density lipoprotein <5 mg/dl) after raltegravir was added to his lopinavir/ritonavir-containing regimen. To our knowledge, this is the first reported case of severe dyslipidaemia associated with the addition of raltegravir to a lopinavir/ritonavir-based regimen, suggestive of a possible drug interaction. The lipid profile quickly normalized following discontinuation of lopinavir/ritonavir and continuation of raltegravir, suggesting that lopinavir/ritonavir was the primary driver for the adverse event. With increasing interest in nucleoside-sparing regimens, knowledge of clinically significant adverse events such as this is important for HIV clinicians when selecting regimens for patients with highly resistant virus or drug tolerability issues.

Thalidomide-associated thrombosis in the treatment of HIV-associated severe aphthous disease: a case report and review of the literature.

Venous thrombosis is a well-described complication of thalidomide therapy in patients with multiple myeloma (MM). However, an association between thalidomide use and thrombosis in HIV-positive patients has not been previously described. We present the case of a 48-year-old HIV-positive man who developed a deep venous thrombosis while on thalidomide for the treatment of severe aphthous ulcers. We review the management of severe aphthous disease and the potential adverse effects of thalidomide therapy. We examine the association between thalidomide and thrombosis in patients with MM and discuss how the same relationship may or may not exist in HIV-positive patients. Although the strength of the association between thalidomide use and thrombosis in HIV-positive patients being treated for aphthous disease remains unclear, HIV providers should be aware of the potential risk of thrombosis in all patients receiving thalidomide.