Stephen M. Smith

Infectious complications in asplenic hosts.

Hyposplenism, secondary to splenectomy or disease state, predisposes the host to overwhelming infection with certain bacteria, such as S. pneumoniae. Recognition of the hyposplenic state and preventive measures, including patient education and vaccination, appear to reduce the rate of this highly fatal infection. In addition to considering chemoprophylaxis, a clinician should promptly evaluate or empirically treat all febrile episodes in hyposplenic patients.

HIV vaccine development in the nonhuman primate model of AIDS

Development of a prophylactic human immunodeficiency virus type 1 (HIV-1) vaccine is a leading priority in biomedical research. Much of this work has been done with the nonhuman primate model of AIDS. In a historical context, vaccine studies, which use this model, are summarized and discussed.

Pre-exposure chemoprophylaxis for HIV: It is time

The HIV-1 plague continues unabatedly across sub-Saharan Africa. In Botswana and Swaziland, nearly 40% of the entire adult population is already infected. No current program is capable of slowing the advancing tide. An effective vaccine and widespread treatment are years, if not, decades away. In this most urgent situation, I propose that pre-exposure chemoprophylaxis be studied as a means to reduce the spread of HIV-1 among at-risk individuals.

A peptide-loaded dendritic cell based cytotoxic T-lymphocyte (CTL) vaccination strategy using peptides that span SIV Tat, Rev, and Env overlapping reading frames.

CTL based vaccine strategies in the macaque model of AIDS have shown promise in slowing the progression to disease. However, rapid CTL escape viruses can emerge rendering such vaccination useless. We hypothesized that such escape is made more difficult if the immunizing CTL epitope falls within a region of the virus that has a high density of overlapping reading frames which encode several viral proteins. To test this hypothesis, we immunized macaques using a peptide-loaded dendritic cell approach employing epitopes in the second coding exon of SIV Tat which spans reading frames for both Env and Rev. We report here that autologous dendritic cells, loaded with SIV peptides from Tat, Rev, and Env, induced a distinct cellular immune response measurable ex vivo. However, conclusive in vivo control of a challenge inoculation of SIVmac239 was not observed suggesting that CTL epitopes within densely overlapping reading frames are also subject to escape mutations.

The pathogenesis of HIV infection: stupid may not be so dumb after all

In the mid-1990s, researchers hypothesized, based on new viral load data, that HIV-1 causes CD4+ T-cell depletion by direct cytopathic effect. New data from non-human primate studies has raised doubts about this model of HIV-1 pathogenesis. Despite having high levels of viremia, most SIV infections are well tolerated by their natural hosts. Two recent studies of these models provide information, which may be useful in determining how HIV-1 causes CD4+ T-cell loss. A full understanding of pathogenesis may lead to novel therapies, which preserve the immune system without blocking virus replication.

Prevalence of GB virus type C in urban Americans infected with human immunodeficiency virus type 1

GBV-C virus infection has been linked to improved clinical outcome in HIV-1 co-infected individuals. The epidemiology of GBV-C has, thus far, been limited to the gay male, HIV+ population. Here we describe the prevalence of antibodies against GBV-C envelope glycoprotein E2 and GBV-C viremia in an HIV+ inner city population. This study group is predominantly African-American; 41% of the participants are women. The major risk factor for HIV infection is intravenous drug use. Overall, 56% of the study population had evidence of current or past infection with GBV-C. GBV-C exposure was not associated with hepatitis C virus infection. The group of participants, who had GBV-C viremia and anti-E2 antibodies, had high percentage of patients with an undetectable HIV-1 viral load. These data provide increased insight into the prevalence of GBV-C co-infection in the HIV epidemic in this understudied population.

Current clinical treatments of AIDS.

Publisher Summary The treatment of human immunodeficiency virus (HIV) infection has always posed a unique challenge. The number of medications, their various formulations and combinations, their potential toxicities, and drug–drug interactions make HIV one of the most difficult diseases to manage. This chapter focuses on each food and drug administration (FDA)—approved anti‐HIV compound. The chapter discusses issues of HIV treatment, including initiating therapy, choosing a first regimen, monitoring patients with HIV, avoiding complications of therapy, and when to change. HIV therapy has made tremendous advances in the past decade. The newer medicines are more effective, easier to take, and have fewer side effects than in the late 1990s. Although HIV is a rapidly adaptive virus, the new drugs are powerful weapons. In the United States where most patients have access to antiretroviral therapies, the only remaining stumbling block for patients is nonadherence. In essence, every HIV‐infected individual in the United States should have an undetectable viral load. Unfortunately, many patients are still not fully adherent and therefore, progress toward immunodeficiency.

New York City HIV superbug: fear or fear not?

On February 11, 2005, the New York City Department of Health and Mental Hygiene announced that a city resident had recently been infected with a multi-drug resistant form of HIV and rapidly progressed to AIDS. The Health Commissioner, Thomas R. Frieden, called for increased vigilance against this new strain. Is this situation an emerging crisis or simply an unusual case report of rapid HIV progression?