The athlete gut microbiota: state of the art and practical guidance.

The gut microbiota has been proposed to grant the athlete a metabolic advantage that might be key when optimising performance. While a taxonomic core set of microorganisms characterising the athlete's gut microbiota has not been delineated, some compositional features might be associated with improved metabolic efficiency, which appears to be driven by the production of bacterial metabolites, such as short-chain fatty acids. Not only long-term exercise but also dietary patterns associated with high-level sports practice contribute to this microbial environment, yet isolating the impact of individual dietary components is challenging. The present review synthetises the available evidence on the compositional aspects of the athlete's gut microbiota, discusses mechanisms involved in the bidirectional association between exercise and the gut environment, and evaluates the role of athletes' diet in this interplay. Additionally, a practical approach to indicators commonly reported in metagenomic and metabolomic analyses is provided to explore how these insights can translate to support dietary protocols.

Structure, morphology and magnetic properties of Mg((x))Zn((1 - x))Fe2O4 ferrites prepared by polyol and aqueous co-precipitation methods: a low-toxicity alternative to Ni((x))Zn((1 - x))Fe2O4 ferrites.

The synthesis and properties of Mg((x))Zn((1 - x))Fe(2)O(4) spinel ferrites as a low-toxicity alternative to the technologically significant Ni((x))Zn((1 - x))Fe(2)O(4) ferrites are reported. Ferrite nanoparticles have been formed through both the polyol and aqueous co-precipitation methods that can be readily adapted to industrial scale synthesis to satisfy the demand of a variety of commercial applications. The structure, morphology and magnetic properties of Mg((x))Zn((1 - x))Fe(2)O(4) were studied as a function of composition and particle size. Scanning electron microscopy images show particles synthesised by the aqueous co-precipitation method possess a broad size distribution (i.e. ∼ 80-120 nm) with an average diameter of the order of 100 nm ± 20 nm and could be produced in high process yields of up to 25 g l(-1). In contrast, particles synthesised by the polyol-based co-precipitation method possess a narrower size distribution with an average diameter in the 30 nm ± 5 nm range but are limited to smaller yields of ∼ 6 g l(-1). Furthermore, the polyol synthesis method was shown to control average particle size by varying the length of the glycol surfactant chain. Particles prepared by both methods are compared with respect to their phase purity, crystal structure, morphology, magnetic properties and microwave properties.

HIV-1 immunogen induction of HIV-1-specific delayed-type hypersensitivity: results of a double-blind, adjuvant-controlled, dose-ranging trial.

OBJECTIVE: To investigate the capacity of an HIV-1 immunogen to induce or augment HIV-1-specific delayed-type hypersensitivity (DTH) over a range of doses in asymptomatic HIV-1-seropositive adults. DESIGN: A single center, double-blind, adjuvant-controlled, dose-ranging trial involving 48 HIV-1-seropositive asymptomatic patients. Each dose group consisted of 12 subjects, eight receiving HIV-1 immunogen and four incomplete Freund's adjuvant (IFA). The doses studied were 50, 100, 200, or 400 micrograms (total protein). The HIV-1 immunogen was administered intramuscularly every 4 weeks for 36 weeks, with dosing contingent on the lack of an HIV-1 immunogen DTH response. A maximum of six doses was permitted. METHODS: Immunogenicity was assessed every 4 weeks by DTH skin testing to the inactivated HIV-1 antigen in saline with > 9 mm induration representing a response to immunization. Changes in p24-antibody levels were determined by endpoint titration using an enzyme-linked immunosorbent assay and Western blot. RESULTS: At doses of > or = 100 micrograms, all treated patients demonstrated significant differences in the ability to mount an HIV-1-specific cell-mediated response relative to adjuvant controls. Dose-related response patterns were observed in the period between doses and the occurrence of rises in HIV-1 DTH. Treatment appeared to increase p24-antibody titers as well as reactivities to other HIV-1 antigens as determined by Western blots. The HIV-1 immunogen was well tolerated. CONCLUSIONS: The minimum dose of the HIV-1 immunogen in IFA required to induce HIV-1 DTH relative to the IFA control group was 100 micrograms in this patient population.

Development and validation of a polymerase chain reaction method for the precise quantitation of HIV-1 DNA in blood cells from subjects undergoing a 1-year immunotherapeutic treatment.

OBJECTIVE: To validate a quantitative polymerase chain reaction method developed to measure HIV-1 DNA in peripheral blood mononuclear cells. DESIGN: The assay was used to measure HIV-1 DNA in 15 consecutive blood samples taken from subjects enrolled in a multicenter, randomly allocated, double-blind, placebo-controlled trial using an HIV-1 immunogen. The assay was validated following the United States Pharmacopeia guidelines. The analytical parameters assessed were sensitivity, specificity, linearity and precision. METHODS: The quantitative analysis was obtained by (1) co-amplifying HIV-1 DNA targets with an endogenous control (globin); (2) extrapolating the target values using HIV-1 and globin standard curves; and (3) normalizing the HIV-1 copy numbers to the globin copy numbers (genomic DNA load). RESULTS: With United States Pharmacopeia assay validation methodology, the HIV-1 DNA polymerase chain reaction assay proved to be sensitive, specific, linear and precise and the evaluation of the relative difference between two consecutive blood samples was reproducible. The intra-assay variability, which examines the reproducibility of replicates, was determined using a conservative assessment (tolerance intervals). We established that an increase of 60% or more in the number of DNA copies or a decrease of 38% or more was significantly greater than the variation due to random or experimental error and therefore attributed this variability to a significant change in the HIV-1 DNA copy number. CONCLUSION: We developed and validated a polymerase chain reaction method for the precise quantitation of HIV-1 DNA in peripheral blood mononuclear cells. This assay was able to detect changes in viral loads in HIV-1-infected asymptomatic subjects enrolled in a double-blind placebo-controlled trial using an HIV-1 immunogen.

Inactivated HIV-1 Immunogen: impact on markers of disease progression.

The pursuit of valid markers of disease progression in human immunodeficiency virus type 1 (HIV-1) infection is especially relevant considering the potential treatment alternatives that presently are under evaluation. Because HIV-1 infection results in a virally induced immune suppression characterized by the loss of cell-mediated immunity (CMI), depletion of CD4+ cells, loss of core antibody, and an increase in viral burden, these markers seemed to be appropriate to monitor in a controlled study. We monitored a number of virologic, immunologic, and cytologic markers of disease progression in 103 subjects who were enrolled in a 12-month, double-blind, randomized, adjuvant-controlled study of the HIV-1 inactivated Immunogen. The markers included HIV-1 DNA, HIV-1 RNA, CD4 percent, p24 antibody, and lymphocyte proliferation. Analysis of HIV-1 DNA with a quantitatively polymerase chain reaction (PCR) assay indicated a treatment effect on viral burden in the HIV-1 Immunogen-treated group. Analysis of HIV-1 RNA revealed a similar trend favoring the Immunogen-treated group. In addition, a significant effect was shown on CD4 percent and CMI in the Immunogen-treated group. An analysis of CMI that used stimulation indices underrepresented the immunogenicity of the Immunogen. Further examination revealed that the lymphocytes of the HIV-1 Immunogen-treated patients were proliferating in vitro without exogenous antigen. Although the clinical significance of this phenomenon currently is unknown, it may be a relevant prognostic marker for assessment of HIV-1 therapy. The data presented here support the concept that immunotherapy with the HIV-1 Immunogen may slow disease progression.(ABSTRACT TRUNCATED AT 250 WORDS)

A case-control study of the etiology of Ewing's sarcoma.

An interview case-control study was undertaken to search for risk factors for Ewing's sarcoma. The 208 cases, aged 5 months to 22 years at diagnosis and all white but one, were identified from hospitals participating in the Intergroup Ewing's Sarcoma Study therapeutic trials. Two controls were sought for each case: a sibling control and an age-matched regional population control identified through random-digit dialing telephone procedures. A questionnaire was administered to the parents of cases and controls. Parents were more likely to have smoked during the pregnancy with the case than during the pregnancy with the unaffected sibling. Risks rose with the number of cigarettes the mother smoked per day during the pregnancy. Concepti exposed to less than 1 pack/day were at 3.2 times the risk, and those exposed to 1 pack or more were at 6.7 times the risk of the nonexposed. However, risks associated with smoking were lower and not statistically significant in analyses using the region-matched controls. Hernias, mostly umbilical and inguinal, were diagnosed six times more frequently among the cases compared to region-matched controls. However, hernias occurred in just 10% of cases, and the matched siblings had hernias diagnosed with the same frequency as the cases. An apparent excess of heart disorders among cases versus siblings seems likely to be an artifact of increased medical surveillance of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

A primer on HIV type 1-specific immune function and REMUNE.

The ability to recognize HIV antigens is lost early in HIV-1 infection. Individuals with nonprogressive HIV disease have been observed to mount strong immune responses against the virus and have become a paradigm to emulate with immune-based therapies. Highly active antiviral drug therapy (HAART) has now become the standard of care for HIV-1-infected individuals. Because HIV-specific anergy occurs early in HIV infection, HAART initiated after primary infection may not reconstitute HIV-specific immune function. We have been investigating the effects of an immune-based therapy, called REMUNE, in HIV-1-seropositive individuals. REMUNE has been observed to stimulate HIV-1-specific immune function measured by delayed-type hypersensitivity, lymphocyte proliferation, Th1 cytokine, and beta-chemokine production. Multiple Phase II studies and a Phase III clinical end-point study are ongoing in thousands of seropositive individuals in order to test the clinical utility of REMUNE. The clinical testing of REMUNE and other promising immune-based therapies may provide additional treatment modalities useful in the chronic management of HIV-1.

HIV-1-Specific Functional Immune Measurements as Markers of Disease Progression.

The impairment of lymphocytes to proliferate to HIV antigen is a relatively early functional defect of cell-mediated immunity found in HIV-infected individuals. The finding of strong proliferative responses in nonprogressive HIV disease as well as its inverse association with viral load and clinical manifestation of AIDS supports the further use of this marker as a surrogate of disease progression. The observation that HIV-specific lymphocyte proliferation is associated with the production of CD8-derived HIV suppressive factors such as the beta-chemokines further supports this conclusion. These functional immune measurements provide an additional marker to monitor disease progression in HIV-infected individuals, along with the current standards of CD4 counts and viral load. Copyright 1997 S. Karger AG, Basel

Safety and tolerability of single intravenous doses of T cell modulatory peptide (TCMP-80) in healthy volunteers.

T Cell Modulatory Peptide (TCMP-80), L-lysine-L-serine, is a synthetic dipeptide structurally related to a selected amino acid sequence in human immunoglobulin G. Based on in vitro and preclinical in vivo testing, TCMP-80 has immunomodulatory properties. This report describes the first administration of TCMP-80 to man in a randomized, double-blind, placebo-controlled, single rising-dose tolerability trial. Healthy male volunteers received TCMP-80 or placebo as a 10-minute intravenous infusion. At weekly intervals, two of four subjects were given TCMP-80; the remaining two received placebo. Each subject could receive only one dose during the study. Dosing started at 0.01 mg/kg and was increased to 0.03, 0.1, 0.3, 1, 3, 6.5, and 10 mg/kg. CBCs, blood chemistries, urinalyses, and lymphocyte subset populations were monitored predose and postdose on Days 1, 5, and 14. Three placebo and three TCMP-80 subjects reported adverse events. Adverse events reported after TCMP-80 administration were mild in nature (headache, dizziness, hematoma at injection site), appeared to be independent of dose, and resolved without medical intervention. No clinically significant alterations in vital signs, physical examination parameters, or clinical laboratory values were observed. Based on the results of this study, TCMP-80 is safe and well-tolerated within the dose range studied when administered as single intravenous infusions. Additionally, this study design represents an approach to assess the safety of an investigational immunomodulatory drug.

Combination therapies against HIV-1 infection: exploring the concept of combining antiretroviral drug treatments with HIV-1 immune-based therapies in asymptomatic individuals.

The deleterious effect of HIV on the immune system begins at the time of infection. At seroconversion the virologic and immunologic factors that ultimately will dictate the rate of disease progression are believed to be already in place. The concept developed in this paper implies that, to impact significantly on the progression of disease, anti-HIV therapies should be initiated as early as possible in asymptomatic individuals. Published results have shown that combination drug therapies are potent in reducing HIV-1 RNA load in plasma in asymptomatic individuals, and that some HIV-1 immune-based therapies have a positive impact on immunological markers of disease progression, including HIV-1 cell-mediated immunity (CMI) and CD4 percent. The strategy discussed is to test a combination of antiretroviral therapy with HIV-1 immune-based therapy, such as the inactivated HIV-1 immunogen preparation, in asymptomatic individuals. The goal of this combination approach is to overcome the limitations of each therapy alone. Preliminary data suggest that antiretroviral therapy and the HIV-1 Immunogen can be combined with no noticeable interference and/or added toxicity in a broad range of HIV-1-infected individuals. Combining both therapies may enhance and expand the impact on key surrogate markers of disease progression, although they likely achieve this impact through different mechanisms. Thus, the primary question remains: Can these effects be synergistic?

Production of probiotic cheese (cheddar-like cheese) using enriched cream fermented by Bifidobacterium infantis.

Probiotic cheeses (Cheddar-like cheese) were produced with microfiltered milk standardized with cream enriched with native phosphocaseinate retentate and fermented by Bifidobacterium infantis. During the manufacture and storage of cheeses, viability of the bifidobacteria was determined. Biochemical changes such as proteolysis, sugar metabolism, and organic acids production were estimated. No bifidobacteria growth was observed during cheese-making steps. Bifidobacteria survived very well in cheeses packed in vacuum sealed bags kept at 4 degrees C for 84 d and remained above 3 x 10(6) cfu/g of cheese. No significant difference was observed between cheeses produced with or without bifidobacteria for fat, protein, moisture, salt, ash, or pH. After 12 wk of storage, more than 56% of the as1-CN was hydrolyzed in cheeses that were produced with bifidobacteria and inoculated at 10(8) cfu/g in the cream, and > 45% of hydrolysis was observed in the control cheese. However, no significant differences in the electrophoretic sodium dodecyl sulfate-PAGE patterns were observed in cheeses at any period of storage. At the first day after manufacture, lactose was completely hydrolyzed in cheeses made with bifidobacteria, which suggested high beta-galactosidase activity by B. infantis. Small quantities of acetic acid were detected in bifidus cheeses. The results indicated that B. infantis introduced into hard pressed cheese exhibited excellent viability during storage for 12 wk and could be metabolically active.

The effect of cholinergic stimulation on rat pup ultrasonic vocalizations.

As cholinergic stimulation increases vocalizations in adult rats, the present study investigated the effects of systemic oxotremorine, a cholinergic agonist, on the production of separation calls in rat pups of different ages and whether these effects are in response to central versus peripheral stimulation. The first experiment examined the dose-response effects of oxotremorine on the number of vocalizations and acoustic parameters of 10-, 15-, and 17-day-old rat pups. In contrast to other studies on adult rats, pup vocalizations were decreased while marginally changing acoustic parameters. The second experiment, using muscarinic antagonists, showed that pretreatment with atropine sulfate, which can cross the blood-brain barrier (BBB), reversed the call-reducing effect of oxotremorine whereas pretreatment with atropine methyl nitrate, which does not cross BBB, did not. Suppression of vocalizations by oxotremorine may be explained by central activation and not the peripheral effects of the drug. Dissimilar effects of cholinergic stimulation of infant and adult rat brains may be attributed to a differential role of the cholinergic system during development and maturity.

Myelosuppression associated with co-trimoxazole as a prophylactic antibiotic in the maintenance phase of childhood acute lymphocytic leukemia.

Thirty-seven children with acute lymphocytic leukemia in clinical remission for at least 6 months completed a 1-year trial in which they were randomly assigned in a double-blind fashion to receive co-trimoxazole twice daily for 6 months followed by placebo for 6 months (18 patients) or placebo followed by co-trimoxazole (19 patients). Total amounts of maintenance chemotherapy administered during both periods were similar. During administration of co-trimoxazole significant reductions were documented in the patients' average total white blood count (P less than 0.001), absolute neutrophil count (P less than 0.001), absolute lymphocyte count (P = 0.009), and platelet count (P = 0.002) compared with values obtained during the placebo period. Patients had on the average 1.6 infections during the co-trimoxazole period compared with 2.5 infections during placebo administration (P = 0.008). It is concluded that, although co-trimoxazole is an effective prophylactic antibiotic in children with acute lymphocytic leukemia, the resultant myelosuppression could potentially hamper the administration of maintenance cancer chemotherapy.

Viral load in peripheral blood mononuclear cells as surrogate for clinical progression.

During the symposium on surrogate markers of HIV, the Scientific Advisory Committee posed the following question: "Which surrogate markers currently deserve the greatest commitment of investigative resources to validate them in a clinical setting?" The Committee concluded that for antiretroviral drugs measurements of HIV RNA in plasma deserve the greatest priority, and for immune-based therapies assessing viral load still had the highest priority. But it was recognized that assessing viral load should not be restricted to plasma RNA because the primary mechanisms of action are different from antiretroviral drugs. Thus, the Committee voted that based on current knowledge, investigating the clinical relevance of changes in HIV-1 DNA and RNA copy number in peripheral blood mononuclear cells (PBMCs) with validated assays should be given equal focus for immune-based therapies. This article reviews the rationale for using HIV-1 DNA and RNA load in PBMCs for the monitoring of clinical trials and presents recent data that indicate that the postseroconversion level and the dissemination of proviral DNA in the blood cells have prognostic value, i.e., high levels correlate with disease progression. In addition, longitudinal studies show that an increase in proviral DNA and/or HIV mRNA load correlates with disease progression. We present evidence that these markers are relevant activity markers for anti-HIV therapies. Changes in both DNA and RNA load can be achieved using either antiretroviral drugs or immune-based therapies. These results suggest that these markers should be evaluated in clinical studies to firmly establish their value as surrogates of clinical progression.

Safety and immunogenicity of a gp120-depleted, inactivated HIV-1 immunogen: results of a double-blind, adjuvant controlled trial.

We report the safety and immunogenicity results of a double-blind adjuvant controlled trial of the human immunodeficiency virus type 1 (HIV-1) immunogen. Healthy, asymptomatic HIV-1-seropositive individuals received either three 100 microgram doses of the inactivated HIV-1 antigen in incomplete Freund's adjuvant (IFA) or three doses of IFA alone. The results of this study show that this HIV-1 immunogen is safe, with mild and transient adverse events. No difference in the number or type of adverse events was noted between the treatment groups. Rises in HIV-1-specific humoral and cell-mediated immune (CMI) responses were also noted, favoring the HIV-1 immunogen-treated group. The results of this study confirm and extend the safety and immunogenicity profile of this HIV-1 immunotherapeutic agent. The observation that this treatment can augment HIV-1-specific CMI is encouraging because this immunological marker may represent a key surrogate end point in HIV-1 infection and disease.

Pentigetide nasal solution: a multicenter study evaluating efficacy and safety in patients with seasonal allergic rhinitis.

The safety and efficacy of pentigetide (Pentyde) nasal solution, administered as 1 mg into each nostril four times daily, was compared with placebo for controlling symptoms associated with seasonal allergic rhinitis. This was a randomized, multicenter, double-blind, parallel-group trial involving 431 patients divided equally between pentigetide and placebo treatment. The study was conducted during the 1986 spring allergy season and consisted of 1 week of baseline followed by 2 weeks of treatment. Physicians evaluated the frequency and severity of nasal symptoms at study entry (day 1) and the final visit (day 22). Physicians and patients assessed the global condition of the patient at the end of the study and patients also recorded the severity of symptoms in a daily diary. Pentigetide-treated patients showed a statistically significant greater reduction in the frequency (P = .004) and severity (P = .05) of total nasal symptom score (sneezing, nasal congestion, and rhinorrhea) and in the individual nasal symptom scores compared with placebo-treated patients. Diary results showed consistently lower total nasal symptom scores on each treatment day for pentigetide-treated patients (P = .02). Both the physicians and patients globally rated more pentigetide-treated patients improved than placebo-treated patients. The incidence and types of adverse experiences were similar between treatment groups and there were no reports of sedation or fatigue in the pentigetide group. No clinically significant changes occurred for laboratory tests, physical examination parameters or vital sign measurements. Pentigetide nasal solution was safe and effective for the treatment of seasonal allergic rhinitis.

Maternal drug use and risk of childhood nonlymphoblastic leukemia among offspring. An epidemiologic investigation implicating marijuana (a report from the Childrens Cancer Study Group).

The Childrens Cancer Study Group conducted a case-control study designed to assess in utero and postnatal exposures in children with acute nonlymphoblastic leukemia (ANLL). Analyses were performed for reported maternal use of medications and drugs in the year preceding and during the index pregnancy of the 204 case-control pairs. An 11-fold risk (P = 0.003) was found for maternal use of mind-altering drugs just prior to or during the index pregnancy. Compared with ANLL cases not exposed to marijuana, exposed cases were significantly younger at diagnosis of ANLL (P less than 0.01) and were more often of the myelomonocytic and monocytic subtypes (P less than 0.01). Use of antinausea medication for more than 11 weeks was also associated with a significantly elevated relative risk of 2.81 and a dose-response relationship was noted (P = 0.05 for trend). These results suggest that maternal drug use of marijuana may have an etiologic role in childhood ANLL and may be specific for morphologically defined subgroups.

Effect of immunization with inactivated gp120-depleted human immunodeficiency virus type 1 (HIV-1) immunogen on HIV-1 immunity, viral DNA, and percentage of CD4 cells.

A 1-year study measured the effect of administration of an inactivated human immunodeficiency virus type 1 (HIV-1) immunogen in incomplete Freund's adjuvant (IFA) on HIV-1-specific immunity and viral burden in asymptomatic HIV-1-infected patients. A total of 103 patients were enrolled in this double-blind, randomized study comparing immunogen in adjuvant with adjuvant alone. This study was conducted at nine medical centers throughout the United States. Significant differences in cell-mediated immune responses to HIV-1 and p24 core antigen were observed between the treated and control groups (P < .01). Compared with controls, treated patients as a group had a significantly lower rate of increase in viral DNA as determined by quantitative HIV-1 DNA-polymerase chain reaction (P = .016). Significant differences in the rate of percent CD4 cell decline were also observed between the 2 groups (P = .024). These data suggest that augmentation of HIV-1-specific immunity via immunotherapy may alter the rate of increase of HIV-1 DNA in peripheral blood mononuclear cells and stabilize the percent of CD4 cell decline in relatively healthy HIV-1-infected persons.

Tumor necrosis factor alpha and human immunodeficiency virus-specific functional immune responses after immunization with Gp120-depleted, inactivated HIV-1 in incomplete Freund's adjuvant (REMUNE) in HIV-1-seropositive subjects.

OBJECTIVE: We examined the relation between tumor necrosis factor-alpha (TNF-alpha) levels and human immunodeficiency virus type 1 (HIV-1)-specific functional immune responses, as measured by HIV-1 antigen-stimulated lymphocyte proliferation and beta-chemokine production after immunization with gp120-depleted, inactivated HIV-1 in incomplete Freund's adjuvant (i.e., HIV-1 Immunogen; REMUNE, The Immune Response Corporation, Carlsbad, CA, U.S.A.). STUDY DESIGN/METHODS: HIV-1-seropositive subjects who enrolled in an open-label study were immunized with REMUNE every 12 weeks and monitored for 60 weeks. HIV-1 antigen-stimulated lymphocyte proliferation and RANTES production were measured in peripheral blood mononuclear cells (PBMCs). TNF-alpha levels were measured in serum. RESULTS: TNF-alpha (P = 0.0003) significantly decreased and HIV-1 antigen-stimulated RANTES production (P = 0.002) and lymphocyte proliferation (P = 0.07) increased after immunization with REMUNE. TNF-alpha levels negatively correlated with HIV-1 antigen-stimulated RANTES production (r = -0.71; P = 0.0002) and lymphocyte proliferation (r = -0.37; P = 0.09). CONCLUSIONS: This study demonstrated decreased TNF-alpha levels with a concomitant augmentation of HIV-specific functional immunity in subjects immunized with REMUNE. Because TNF-alpha has been implicated in the induction of anergy in HIV-1 infection, the ability to decrease TNF-alpha may allow the immune system to respond to HIV and non-HIV antigens. Larger studies are being conducted to confirm the clinical utility of REMUNE in combination with potent antiviral drugs.

Viral load, CD4 percentage, and delayed-type hypersensitivity in subjects receiving the HIV-1 immunogen and antiviral drug therapy.

Two trials of subjects inoculated with the inactivated, gp120-depleted HIV-1 Immunogen are reported. In one study, in which 19 subjects received ZDV and 8 subjects received ddI, treatment with the HIV-1 Immunogen did not affect the pharmacokinetic parameters of the antiviral drugs. In another study, 65 subjects who were previously immunized with the HIV-1 Immunogen over a mean period of 4.0 years (range, 1.2-5.4 years) received inoculations at 0 and 6 months. At some point during this 48-week study, 72% of the subjects (47/65) were receiving antiviral drug therapy. The HIV-1 DNA load in CD4 cells and CD4 percentage were found to be stable over the 48-week period. Delayed-type hypersensitivity to HIV-1 antigens increased after two inoculations with the HIV-1 Immunogen. In these two trials, no serious treatment-related adverse events were documented in the subjects. The two studies presented herein are the first to suggest that an immune-based therapy such as the HIV-1 Immunogen can be combined safely with antiviral drugs, supporting further study to evaluate the clinical utility of this approach.