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Background: Human immunodeficiency virus (HIV)-infected patients have decreased immune response to vaccines. Few data are available about pandemic flu vaccination in this population., Methods: We conducted a multicenter, patient-blinded, randomized trial in a cohort of HIV-infected adults. Patients received 2 injections 21 days apart of a AS03(A)-adjuvanted H1N1v vaccine containing 3.75 μg hemagglutinin (HA) or a nonadjuvanted H1N1v vaccine containing 15 μg HA to assess hemagglutination inhibition (HI) response and safety., Results: A total of 309 patients were randomized, and 306 were vaccinated. After the first vaccine dose, HI titers ≥1:40 were observed in 93.4% of the patients in the adjuvanted group (A group) (n = 155) and in 75.5% in the nonadjuvanted group (B group) (n = 151) (P < .001); seroconversion rates were 88.8% and 71.2%, and factor increases in geometric mean titers (GMT) of 21.9 and 15.1, respectively. After 2 injections, 98.6% of patients of the A group and 92.1% of the B group demonstrated HI titers ≥1:40 (P = .018); seroconversion rates were 96.5% and 87.1%, respectively, and factor increases in GMT were 45.5 and 21.2, respectively. The majority of adverse events were mild to moderate in severity; no impact on CD4+ cell count or viral load has been detected., Conclusions: In HIV-1-infected adults, the AS03(A)-adjuvanted H1N1v vaccine yielded a higher immune response than did the nonadjuvanted one, with no impact on HIV infection.

The present study investigated the effect of enfuvirtide cross-reactive glycoprotein 41 (gp41) antibody on the efficacy or safety of enfuvirtide in patients participating in 1 of 2 24-week phase 3 clinical trials (T-20 vs. optimized regimen only [TORO] 1 and TORO 2). Serum samples from human immunodeficiency virus-infected patients receiving enfuvirtide plus optimized background (OB) and from patients receiving OB only were evaluated for enfuvirtide cross-reactive gp41 antibodies. Most patients had detectable levels of antibody at baseline; 78% of patients treated with enfuvirtide plus OB had a > or =30% decrease in level of antibody, compared with 43% of patients treated with OB only. Baseline antibody status did not influence virological responses to enfuvirtide-containing treatment. Favorable virological responses were more common among patients who experienced a > or =30% decrease from baseline than among those who experienced either an increase or a lesser decrease. A decrease in virus load correlated with a decrease in level of antibody. Safety was unaffected by the presence of positive antibody at any time point or change in level of antibody. There was no evidence that enfuvirtide cross-reactive gp41 antibody affects the efficacy or safety of enfuvirtide.

The intensity of expression of the chemokine receptor CCR5 is involved in in vitro cell infectability by human immunodeficiency virus (HIV)-1 R5 isolates. Because CCR5 expression varies among individuals, the hypothesis that this expression could determine virus load in HIV-1-infected persons was tested. The mean number of CCR5 molecules per cell was measured on peripheral blood CD4+ T lymphocytes (CCR5 density) from HIV-1-infected, asymptomatic, nontreated adults. There was a strong correlation between HIV RNA plasma level and CCR5 density (P=.009) that was independent of cell activation and was not due to an HIV-induced CCR5 up-regulation. These data are compatible with the hypothesis that CCR5 density is a key factor governing cell infectability and in vivo virus production and explain the protective effect of the Delta32CCR5 deletion, which results in low CCR5 expression. CCR5 density might be of critical predictive value in HIV infection.

In human immunodeficiency virus type 1 (HIV-1)-infected adults, the proportion of gp120-free CD4 molecules on the surface of T lymphocytes was measured by double-epitope EIA and expressed as a CD epitope concentration ratio. In 51% of these patients (n=81), CD4 T cells showed a significant decrease (up to 100%) in the accessibility of the CD4 epitope in the D1 domain remained accessible. Of interest, a significant increase in the CD4 gp120 binding site concentration, without a change in T cell counts, was observed within 10 days after initiation of zidovudine treatment. Furthermore, CD4 masking by gp120 was associated with a poor clinical patient status. The assessment of the CD4 epitope concentration ratio is proposed as a surrogate marker of disease progression in HIV-1-infected patients.

Isoenzymatic characterization was done on 100 isolates obtained from visceral leishmaniasis (VL) patients coinfected with human immunodeficiency virus (HIV); isolates had been received between 1986 and 1993 at the International Leishmania Cryobank and Identification Centre in Montpellier, France. Electrophoresis was done with 15 isoenzymes using the starch gel technique combined, where appropriate, with isoelectrofocusing. Nine Leishmania infantum zymodemes were identified; L. infantum zymodeme MON-1, the most common parasite of human VL in the Mediterranean basin, was the most frequent in coinfections. It could also occasionally be responsible for localized cutaneous leishmaniasis lesions. Several dermotropic zymodemes, which were responsible for localized cutaneous leishmaniasis in immunocompetent patients, caused VL in HIV-positive patients. In addition, in 10 patients, a second isolate obtained during relapses occurring between 1.5 and 9.0 months after treatment was identical to the original isolate.

As part of a continuous search for surrogate markers of therapeutic efficacy in AIDS, spontaneous in vitro production by peripheral blood mononuclear cells of antibody to human immunodeficiency virus type 1 (HIV-1) was investigated in 50 HIV-1-infected adults. It was independent of CD4+ cell counts, p24 antigenemia, serum beta 2-microglobulin concentration, and clinical status of the patients. The effect of zidovudine on this antibody secretion and the appearance of signs or symptoms of HIV-1 disease progression were evaluated in 20 patients over 24 weeks. Anti-HIV-1 antibody secretion decreased significantly (P = .002) as of the first month of zidovudine treatment only in the 13 HIV-1-infected patients without disease progression. This is earlier than the occurrence of variations in CD4+ cell count and serum beta 2-microglobulin concentration. These results suggest that in vitro antibody production could be a surrogate marker for evaluation of the in vivo antiretroviral efficacy of zidovudine, even in p24 antigen-negative patients.

The in vitro secretion of cytomegalovirus (CMV)-specific antibodies by peripheral blood mononuclear cells (PBMC) was analyzed in patients with acute CMV infection and CMV-seropositive patients infected with human immunodeficiency virus. This active and spontaneous in vitro secretion was not affected by the depletion of T cells or adherent cells. The number of anti-CMV antibody-secreting cells was estimated to be 28-176/10(6) PBMC; 30%-65% of the total in vitro antibody production was CMV-specific. This secretion seemed to be independent of in vitro polyclonal B cell activation, in vitro antigen-specific lymphocyte stimulation, or in vivo Epstein-Barr virus-induced B cell transformation. In vitro anti-CMV antibody production may therefore result from an in vivo stimulation of the immune system by CMV antigens and might indicate CMV replication in the host.