[Structured therapeutic interruption in patients infected with HIV-1 experiencing a block in their antiretroviral treatment: preliminary results]. / Interruption thérapeutique programmée chez des patients infectés par le VIH-1 en échec d'un traitement antirétroviral: résultats préliminaires.

Structured therapeutic interruption (STI) has been offered to HIV-1 infected patients with virological failure (viral load > 1500 copies/mL) of potent antiretroviral therapy (ART) (three or four drugs for at least one year). CD4 lymphocyte count, HIV-1 viral load, clinical status, were assessed every month during STI and after ART reintroduction. Genotype analysis by plasma virus sequencing was done before and after treatment interruption. The results of 14 patients who resumed ART for at least two months are presented. Median duration of STI was 7.5 months (range: 2-13 months). Median CD4 count was low (45/mm3) when treatment was stopped, and decreased during STI (-37/mm3 after six months). Several patients exhibited important CD4 diminutions. Viral load slightly increased (+0.83 log at M6). Few clinical events occurred: one: severe HIV-related prurigo and one CMV viremia. Reversion of resistance mutations was only seen in 2/13 (15: 4%) patients (who had previously a major CD4 deficiency, and a long treatment history), a partial reversion occurred in 5/13 (38.5%) subjects, and the mutations didn't change in the other cases (genotyping non interpretable in the last patient). ART reintroduction induced a good immune response: CD4/mm3 after six months, with significant increases in 10/14 subjects. There was an initial viral response (median viral load: -2.34 log at M1), but a quick rebound most often occurred. However, viral load remained < 50 copies/mL in four patients. In conclusion, a rapid and important decline in CD4 cell count can occur when treatment is discontinued, in patients with virological failure of ART, but the clinical risk appears to be limited. Treatment re-initiation induces a good response, but virologically transient in most cases. Patients with a shift to wild-type virus seem to have a better response.

Efavirenz as a substitute for protease inhibitors in HIV-1-infected patients with undetectable plasma viral load on HAART: a median follow-up of 64 weeks.

We investigated, in a prospective cohort follow-up study, whether substituting efavirenz (EFV) for protease inhibitors (PIs) could be safe in HIV-infected patients with optimal viral suppression achieved on PI-containing regimens. In patients with undetectable plasma viral load (pVL) <50 copies/ml who were naive to therapy with nonnucleoside reverse transcriptase inhibitors (NNRTIs), PIs were replaced by EFV whereas associated nucleoside analogs (NAs) were retained. 62 patients were enrolled. Median follow-up on EFV was 64 weeks (2-88 weeks). Side effects due to EFV occurred in 48 patients. Two patients experienced a high level viral rebound due to diminished compliance; 55 (88.7%) maintained a pVL <50 copies/ml; 3 showed one episode of viremia (52-89 copies/ml); 2 stopped EFV before any VL control. Mean CD4 cell count did not change significantly. One AIDS patient experienced a single cutaneous recurrence of Kaposi's sarcoma after 40 weeks on EFV. Replacing PI with EFV in patients with optimal pVL suppression appears to be safe both virologically and immunologically.

[Emergence of resistant hepatitis B virus strains during long-term lamivudine therapy in human immunodeficiency virus co-infected patients]. / Emergence de souches résistantes de virus de l'hépatite B, sous traitement prolongé par lamivudine, chez des malades co-infectés par le virus de l'immunodéficience humaine.

Seven patients co-infected with hepatitis B virus (HBsAg and HBeAg carriers, quantifiable HBV DNA with the bDNA technic) and human immunodeficiency virus received a triple antiretroviral combination therapy, including lamivudine (150 mg twice a day). Hepatitis B viral load rapidly became undetectable in 6/7 patients. It remained below the level of detection in 2 subjects, after 20 and 22 months of treatment, with one of them achieving HBeAg/anti-HBe seroconversion. However, in the other 4 individuals, hepatitis B viremia increased again after 8 to 16 months of lamivudine-containing regimen. The last patient was a non-responder. The 4 relapsers developed a double mutation Leu(528) for Met(528) and Met(552) for Val(552), on hepatitis B virus polymerase, either concomitant (M8 and M16) with a hepatitis B virus DNA increase, or 2 months earlier (M10 and M12). The high frequency of hepatitis B virus resistance to lamivudine emphasizes the necessity of identifying more effective strategies, such as double combination therapies.

Increasing the number of hepatitis B vaccine injections augments anti-HBs response rate in HIV-infected patients. Effects on HIV-1 viral load.

Preventing hepatitis B by vaccination is essential in HIV-infected patients (higher progression rate of HBV infection to chronicity, lower rate of serum HBe Ag loss). However, it has been shown a decreased anti-HBs response in these individuals after a standard vaccination (3 doses of 20 micrograms). Thus, we tested the hypothesis that doubling the number of hepatitis B vaccine injections might increase anti-HBs response rate. HIV-infected patients with CD4 > 200/microliter, who were on stable antiretroviral treatment, as well as seronegative for HBV markers, and who have never been vaccinated against HBV, were given 3 intramuscular injections of Genhevac B 20 micrograms at 1 month intervals. Initial non responders were given 3 additional monthly injections. Anti-HBs titer was followed. We also evaluated the effects on HIV-1 viral load. Twenty patients with a median CD4 cell count of 470/microliter were enrolled. The response rate after three 20 micrograms injections was 55% (11/20), lower in individuals with CD4 between 200 and 500/microliter (4/12 = 33.3%), compared to patients with CD4 above 500/microliter (7/8 = 87.5%, P = 0.02). Among 9 initial non-responders, only 2 did not respond to 3 additional doses; thus, the overall response rate was 90% (18/20). Geometric mean titers of anti-HBs were 133 IU/l and 77.5 IU/l, after 3 and 6 Genhevac doses, respectively (P = 0.38). One year later, only 10/17 (58.8%) patients had protective anti-HBs. Five patients experienced a significant viral load increase, transient in 3 cases. These preliminary results suggest that doubling the number of hepatitis B vaccinations in HIV-infected patients might significantly improve anti-HBs response rate; however, close monitoring of anti-HBs is necessary because of its short-lived persistence. The effects on HIV-1 viral load are limited.

[What is the fructosamine test and what is its clinical significance?]. / Was ist der Fructosamin-Test, worin besteht seine klinische Bedeutung?

The clinical usefulness of the fructosamine assay is reviewed. Problems of external standardization are discussed and possibilities to circumvent these problems are considered.