The lifetime cost of current human immunodeficiency virus care in the United States

OBJECTIVE: We sought to project the lifetime cost of medical care for human immunodefiency virus (HIV)-infected adults using current antiretroviral therapy (ART) standards. METHODS: Medical visits and hospitalizations for any reason were from the HIV Research Network, a consortium of high-volume HIV primary care sites. HIV treatment drug regimen efficacies were from clinical guidelines and published sources; data on other drugs used were not available. In a computer simulation model, we projected HIV medical care costs in 2004 U.S. dollars. RESULTS: From the time of entering HIV care, per person projected life expectancy is 24.2 years, discounted lifetime cost is Dollars 385,200, and undiscounted cost is Dollars 618,900 for adults who initiate ART with CD4 cell count < 350/microL. Seventy-three percent of the cost is antiretroviral medications, 13% inpatient care, 9% outpatient care, and 5% other HIV-related medications and laboratory costs. For patients who initiate ART with CD4 cell count < 200/microL, projected life expectancy is 22.5 years, discounted lifetime cost is Dollars 354,100 and undiscounted cost is Dollars 567,000. Results are sensitive to drug manufacturers' discounts, ART efficacy, and use of enfuvirtide for salvage. If costs are discounted to the time of infection, the discounted lifetime cost is Dollars 303,100. CONCLUSIONS: Effective ART regimens have substantially improved survival and have increased the lifetime cost of HIV-related medical care in the U.S.     

Adenovirus vector-based vaccines for human immunodeficiency virus type 1

Recombinant adenovirus (rAd) vectors have received considerable attention for gene therapy because of their high transduction efficiency. However, recombinant gene expression from rAd vectors elicits rapid and potent immune responses to foreign transgene products. Such immunogenicity limits the duration of transgene expression and poses a major challenge to the use of rAd vectors for gene therapy. In contrast, the inherent immunogenicity of these vectors is a desirable feature for vaccine development. The immunogenicity and protective efficacy of rAd vector-based vaccines have now been demonstrated in a number of animal models, and rAd vaccines for a variety of pathogens are currently being explored in early-phase clinical trials. In this review, we describe progress in the development of rAd vector-based vaccines with a focus on human immunodeficiency virus type 1.     

Detection of antibodies to human immunodeficiency virus type 2 (HIV-2) in blood donor sera using United States assay methods for anti-HIV type 1

Twelve serum samples from French blood donors that were uniformly reactive in tests for antibody to human immunodeficiency virus type 2 (anti-HIV-2) also were reactive in 92 to 100 percent of tests with three anti-HIV type 1 (anti-HIV-1) enzyme-linked immunoassays currently in widespread use for donor screening in the United States. Supplemental tests for anti-HIV-1 on these anti-HIV-2-reactive samples differed in their responses. All samples reacted in a licensed anti-HIV-1 Western blot, but there was an atypical band near the p41 position, which could be a clue to the fact that this result was a cross-reaction with anti-HIV-2. A recombinant immunoblot gave an indeterminate result for anti-HIV-1 in all 12 samples. A local immunofluorescence assay for anti-HIV-1 reacted with 92 percent of the samples, but a commercial one detected only 58 percent.     

Serologic markers for staging human immunodeficiency virus infections

In the present study, 80 serum specimens were tested for human immunodeficiency virus (HIV) antibody by enzyme immunoassay (EIA) and indirect fluorescent antibody tests, HIV (p24) antigen, and Western Blot analyses. A total of 40 specimens were HIV antigen-positive, 35 were antigen-negative and five were indeterminant. Among the 40 antigen-positive sera, 38 had positive antibodies by EIA with confirmation by Western Blot. Two cases were antigen-positive and were thought to be early stages where antibodies had not yet developed. Among the 38 sera, 30 (79%) had decreased or had no reactions by indirect fluorescent antibody tests. Among the 35 antigen-negative cases, all 35 had positive antibodies by EIA and all 35 had bands at gp41 by Western Blot. Among 84 HIV-infected patients, 30 had >400 CD4+ cells per cubic millimeter, 21 patients had 200–400 CD4+ cells and 33 had <200 CD4+ cells. A total of 28 (93%) of the HIV antigen-negative cases with full banding patterns by Western Blot had >400 CD4+ cells. In contrast 18 (55%) of the patients with antigen positivity and incomplete banding on Western Blot had <200 CD4+ cells.     

Therapy of human immunodeficiency virus infections

Although therapy is currently available for many of the infections and neoplastic complications of AIDS, there is no effective therapy for the underlying immunodeficiency state. The authors review various attempts at treatment to date, and conclude that a major decrease in HIV-associated morbidity will require a combined approach, making use of our knowledge of the epidemiology, as well as the molecular and cellular biology, of the virus.     

Human immunodeficiency virus and immigration status in the United States.

The number of HIV-infected immigrants is increasing in cities across the United States. A case study explores the complexities of the immigration process as it relates to HIV infection; implications for nursing practice are discussed. By understanding the immigration process, nurses are able to identify and refer illegal residents who are HIV infected to appropriate social-service agencies, thereby providing more comprehensive care to patients and their families.     

Cell-based fluorescence assay for human immunodeficiency virus type 1 protease activity

The human immunodeficiency virus type 1 (HIV-1) protease is essential for production of infectious virus and is therefore a major target for the development of drugs against AIDS. Cellular proteins are also cleaved by the protease, which explains its cytotoxic activity and the consequent failure to establish convenient cell-based protease assays. We have exploited this toxicity to develop a new protease assay that relies on transient expression of an artificial protease precursor harboring the green fluorescent protein (GFP-PR). The precursor is activated in vivo by autocatalytic cleavage, resulting in rapid elimination of protease-expressing cells. Treatment with therapeutic doses of HIV-1 protease inhibitors results in a dose-dependent accumulation of the fluorescent precursor that can be easily detected and quantified by flow cytometric and fluorimetric assays. The precursor provides a convenient and noninfectious model for high-throughput screenings of substances that can interfere with the activity of the protease in living cells.     

Bis-anthracycline antibiotics inhibit human immunodeficiency virus type 1 transcription

The increasing numbers of human immunodeficiency virus type 1 (HIV-1) strains that exhibit resistance to antiretroviral agents used at present require the development of new effective antiretroviral compounds. Tat transactivation was recognized early on as an attractive target for drug interference. To screen for and analyze the effects of compounds that interfere with Tat transactivation, we developed several cell-based reporter systems in which enhanced green fluorescence protein is a direct and quantitative marker of HIV-1 expression or Tat-dependent long terminal repeat activity. Using these reporter cell lines, we found that the bis-anthracycline WP631, a recently developed DNA intercalator, efficiently inhibits HIV-1 expression at subcytotoxic concentrations. WP631 also abrogated acute HIV-1 replication in peripheral blood mononuclear cells infected with various primary virus isolates. We demonstrate that WP631-mediated HIV-1 inhibition is caused by the inhibition of Tat transactivation. The data presented suggest that WP631 could serve as a lead compound for a new type of HIV-1 inhibitor.     

Inactivation of human immunodeficiency virus type 1 by porphyrins

We have evaluated the anti-human immunodeficiency virus (HIV) activity of a series of natural and synthetic porphyrins to identify compounds that could potentially be used as microbicides to provide a defense against infection by sexually transmitted virus. For assays we used an epithelial HeLa-CD4 cell line with an integrated long terminal repeat-beta-galactosidase gene. For structure-activity analysis, we divided the porphyrins tested into three classes: (i) natural porphyrins, (ii) metallo-tetraphenylporphyrin tetrasulfonate (metallo-TPPS4) derivatives, and (iii) sulfonated tetra-arylporphyrin derivatives. None of the natural porphyrins studied reduced infection by more than 80% at a concentration of 5 micro g/ml in these assays. Some metal chelates of TPPS4 were more active, and a number of sulfonated tetra-aryl derivatives showed significantly higher activity. Some of the most active compounds were the sulfonated tetranaphthyl porphyrin (TNapPS), sulfonated tetra-anthracenyl porphyrin (TAnthPS), and sulfonated 2,6-difluoro-meso-tetraphenylporphine [TPP(2,6-F2)S] and its copper chelate [TPP(2,6-F2)S,Cu], which reduced infection by 99, 96, 94, and 96%, respectively. Our observations indicate that at least some of these compounds are virucidal, i.e., that they render the virus noninfectious. The active compounds were found to inhibit binding of the HIV type 1 gp120 to CD4 and also to completely inhibit the ability of Env proteins expressed from recombinant vectors to induce cell fusion with receptor-bearing target cells. These results support the conclusion that modified porphyrins exhibit substantial activity against HIV and that their target is the HIV Env protein.     

Tripeptide interference with human immunodeficiency virus type 1 morphogenesis

Capsid assembly during virus replication is a potential target for antiviral therapy. The Gag polyprotein is the main structural component of retroviral particles, and in human immunodeficiency virus type 1 (HIV-1), it contains the sequences for the matrix, capsid, nucleocapsid, and several small polypeptides. Here, we report that at a concentration of 100 micro M, 7 of 83 tripeptide amides from the carboxyl-terminal sequence of the HIV-1 capsid protein p24 suppressed HIV-1 replication (>80%). The three most potent tripeptides, glycyl-prolyl-glycine-amide (GPG-NH(2)), alanyl-leucyl-glycine-amide (ALG-NH(2)), and arginyl-glutaminyl-glycine-amide (RQG-NH(2)), were found to interact with p24. With electron microscopy, disarranged core structures of HIV-1 progeny were extensively observed when the cells were treated with GPG-NH(2) and ALG-NH(2). Furthermore, nodular structures of approximately the same size as the broad end of HIV-1 conical capsids were observed at the plasma membranes of treated cells only, possibly indicating an arrest of the budding process. Corresponding tripeptides with nonamidated carboxyl termini were not biologically active and did not interact with p24.