Elizabeth L. Cooney

Nevirapine induced opiate withdrawal among injection drug users with Hiv infection receiving methadone

BACKGROUND Pharmacokinetic interactions complicate and potentially compromise the use of antiretroviral and other HIV therapeutic agents in patients with HIV disease. This may be particularly so among those receiving treatment for substance abuse. OBJECTIVE We describe seven cases of opiate withdrawal among patients receiving chronic methadone maintenance therapy following initiation of therapy with the non-nucleoside reverse transcriptase inhibitor, nevirapine. DESIGN Retrospective chart review. RESULTS In all seven patients, due to the lack of prior information regarding a significant pharmacokinetic interaction between these agents, the possibility of opiate withdrawal was not anticipated. Three patients, for whom methadone levels were available at the time of development of opiate withdrawal symptoms, had subtherapeutic methadone levels. In each case, a marked escalation in methadone dose was required to counteract the development of withdrawal symptoms and allow continuation of antiretroviral therapy. Three patients continued nevirapine with methadone administered at an increased dose; however, four chose to discontinue nevirapine. CONCLUSION To maximize HIV therapeutic benefit among opiate users, information is needed about pharmacokinetic interactions between antiretrovirals and therapies for substance abuse.

Review of pneumococcal endocarditis in adults in the penicillin era.

Streptococcus pneumoniae is an infrequent cause of infectious endocarditis in adults. In the past 2 years, however, we have encountered several cases at our institution, and additional cases have been reported in the literature. This infection typically follows pneumonia in the setting of chronic alcoholism and may additionally be complicated by meningitis. Less commonly, pneumococcal endocarditis occurs in other hosts or follows primary infection at other extrapulmonary sites. In such cases, the diagnosis may be initially missed, with a resultant delay in institution of appropriate therapy. Moreover, there are controversies regarding the optimal therapy for infections of this nature in the era of penicillin resistance. Since a comprehensive review of this topic has not been published since 1990, we reviewed cases of pneumococcal endocarditis in the penicillin era, with particular attention to disease recognition, the role of echocardiography, and the dilemmas surrounding medical and surgical therapeutic interventions.

Cellular restoration in HIV infected persons treated with abacavir and a protease inhibitor: Age inversely predicts naive CD4 cell count increase

ObjectiveTo characterize early and later indices of cellular restoration among HIV-1 infected persons treated with abacavir and one protease inhibitor and to identify predictors of CD4 cell increases. MethodsFlow-cytometric analyses of lymphocyte phenotypes among 71 antiretroviral treatment naive adults in a 48 week treatment trial. ResultsDuring the first 4 weeks of therapy, increases in naive and memory CD4 cells and in B cells were seen; naive CD8 cells increased while CD8 cells remained stable as memory CD8 cells decreased. During the second phase total CD4 and naive CD4 and CD8 cells increased while total CD8 and memory CD8 cells decreased. The numbers of CD4 cells that expressed CD28 increased from a median of 308 × 106/l at baseline to 477 × 106/l at week 48. Higher baseline plasma HIV-1 RNA levels predicted the magnitude of early CD4 (r = 0.35;P = 0.01), memory CD4 (r = 0.38;P = 0.001) and CD28 CD4 cell (r = 0.29;P = 0.01) restoration but was not related to second phase changes. Younger age predicted a greater second phase (but not first phase) increase in naive CD4 cells (r = −0.31;P = 0.03). ConclusionsHigher baseline levels of HIV-1 replication determine the magnitude of first phase CD4 cell increases after suppression of HIV-1 replication. Second phase (primarily naive) CD4 cell increases are not related to HIV-1 replication but are inversely relate to age suggesting that thymic potential is a major determinant of long term cellular restoration in HIV-1 infected persons receiving antiretroviral therapy.

Clinical Indicators of Immune Restoration following Highly Active Antiretroviral Therapy

The course of human immunodeficiency virus (HIV) disease is characterized by a progressive decline in immune function. The advent of highly active antiretroviral therapy (HAART) has allowed patients to experience a significant degree of immune restoration when compared with the era before the availability of HAART. Multiple studies, which have employed sophisticated in vitro measures of immune function, have demonstrated improvement in CD4(+) lymphocyte (T4) responses to various opportunistic pathogens. In addition, for patients treated during acute HIV infection, HIV-specific T4 responses have been restored. By contrast, there are a limited number of in vivo measures of T4 function available to assess immune recovery following initiation of HAART. The primary measurement is an increase in CD4 lymphocyte count, the significance of which may be underappreciated. Delayed-type hypersensitivity testing to recall antigens and serological response to prophylactic vaccines may also have a role. This review discusses available markers of immune function and offers suggestions regarding their use in HAART recipients.

Papular-Purpuric Gloves and Socks Syndrome Associated with Acute Parvovirus B19 Infection: Case Report and Review

The papular-purpuric gloves and socks syndrome (PPGSS) was first described in 1990. This syndrome is characterized by fever, acral pruritus, edema, petechiae, and oral erosions. Subsequently, parvovirus B19 has been implicated, in most cases, as the causative agent of this syndrome. To date, with two exceptions, all published cases of PPGSS have been from Europe and the Middle East and have been mainly reported in the dermatology literature. Herein, we report what we believe to be only the second case of documented parvovirus B19-associated PPGSS occurring in the United States. The patient presented with the typical clinical syndrome, and the diagnosis of acute parvovirus B19 infection was documented by serial serologies that demonstrated development of IgM antibody to virus during the acute phase of infection and seroconversion to IgG antibody in the convalescent period. We then review the existing literature on this unusual syndrome and its association with parvovirus B19.

Cerebellar Brain Abscess Associated with Tongue Piercing

We describe a previously healthy adult who had a solitary cerebellar brain abscess diagnosed. This infection occurred 4 weeks after the patient underwent a tongue piercing procedure that was complicated by an apparent local infection. The clinical history, abscess culture results, and lack of an alternative explanation suggest that infection of the tongue piercing site was the source of the cerebellar abscess.

Two Double-Blinded, Randomized, Comparative Trials of 4 Human Immunodeficiency Virus Type 1 (HIV-1) Envelope Vaccines in HIV-1—Infected Individuals across a Spectrum of Disease Severity: AIDS Clinical Trials Groups 209 and 214

The potential role of human immunodeficiency virus type 1 (HIV-1)-specific immune responses in controlling viral replication in vivo has stimulated interest in enhancing virus-specific immunity by vaccinating infected individuals with HIV-1 or its components. These studies were undertaken to define patient populations most likely to respond to vaccination, with the induction of novel HIV-1-specific cellular immune responses, and to compare the safety and immunogenicity of several candidate recombinant HIV-1 envelope vaccines and adjuvants. New lymphoproliferative responses (LPRs) developed in <30% of vaccine recipients. LPRs were elicited primarily in study participants with a CD4 cell count >350 cells/mm(3) and were usually strain restricted. Responders tended to be more likely than nonresponders to have an undetectable level of HIV-1 RNA at baseline (P=.067). Induction of new cellular immune responses by HIV-1 envelope vaccines is a function of the immunologic stage of disease and baseline plasma HIV-1 RNA level and exhibits considerable vaccine strain specificity.

Varicella zoster virus retrobulbar optic neuritis preceding retinitis in patients with acquired immune deficiency syndrome

OBJECTIVE This study aimed to describe a recently recognized and rare presentation of varicella zoster virus (VZV) retrobulbar optic neuritis preceding retinitis in patients with acquired immune deficiency syndrome and to identify factors that may relate to improved visual outcome. METHODS Diagnosis, treatment, and clinical course are described for three eyes of two patients with this viral infection. RESULTS Patients had decreased vision, headache, and recent zoster dermatitis. Varicella zoster virus retrobulbar optic neuritis was diagnosed on the bases of clinical, laboratory, and electrophysiologic examination results. Profound vision loss and peripheral retinitis ensued despite intravenous antiviral treatment. Combination intravenous and intravitreous antiviral injections were administered with dramatic visual recovery. CONCLUSIONS Varicella zoster virus retrobulbar optic neuritis should be considered in immunocompromised patients with visual loss. Early diagnosis and aggressive combination therapy via systemic and intravitreous routes may enable return of useful vision.

Interleukin-12 Enhancement of Antigen-Specific Lymphocyte Proliferation Correlates with Stage of Human Immunodeficiency Virus Infection

The effect of interleukin (IL)-12 on T lymphocyte function was assessed in 47 human immunodeficiency virus (HIV)-infected persons of different disease stages and 16 seronegative controls. Lymphoproliferative responses (LPR) were measured to various HIV and non-HIV antigens and mitogens using peripheral blood mononuclear cells cultured with or without IL-12. Without exogenous IL-12, 96% of HIV-seropositive persons responded to mitogens, 77% to >=1 non-HIV antigen, and 11% to >=1 HIV antigen. Supplementation with IL-12 augmented LPR of HIV-seropositive persons to non-HIV antigens; however, the effect was greatest for those with higher CD4 cells (40% vs. 9% for those with >200 vs. <=200 CD4 cells/mm3). Addition of IL-12 also enhanced LPR to HIV antigens in 30% of subjects. This effect was most pronounced for those with>500 CD4 cells/mm3 (56% [P<. 05]). These findings suggest that impaired T lymphocyte recognition of foreign antigen, including HIV, can be reconstituted in part for selected HIV-seropositive persons.

Progressive outer retinal necrosis and acute retinal necrosis in fellow eyes of a patient with acquired immunodeficiency syndrome

PURPOSE To describe an unusual concurrence of acute retinal necrosis and progressive outer retinal necrosis in fellow eyes of a patient with acquired immunodeficiency syndrome (AIDS). METHODS Interventional case report. In a 37-year-old man with AIDS and herpes zoster keratitis in the right eye, progressive outer retinal necrosis developed in the right eye and acute retinal necrosis developed in the left eye. RESULTS Disparate presentations of retinitis persisted in each eye, and retinal detachment and vision loss ensued in both eyes despite antiviral therapy. CONCLUSION Distinct features of acute retinal necrosis and progressive outer retinal necrosis do not necessarily reflect systemic factors, and they may be variant manifestations of the same underlying infection.