High rate of virologic suppression with raltegravir plus etravirine and darunavir/ritonavir among treatment-experienced patients infected with multidrug-resistant HIV: results of the ANRS 139 TRIO trial.

BACKGROUND: The introduction of 2 or 3 fully active drugs in human immunodeficiency virus (HIV)-infected patients receiving failing antiretroviral therapy is a key determinant of subsequent treatment efficacy. The aim of this study was to assess the safety and efficacy of a regimen containing raltegravir, etravirine, and darunavir/ritonavir for treatment-experienced patients infected with multidrug-resistant HIV. METHODS: Patients enrolled in this phase II, noncomparative, multicenter trial were naive to the investigational drugs and had plasma HIV RNA levels >1000 copies/mL, a history of virologic failure while receiving nonnucleoside reverse-transcriptase inhibitors (NNRTI), > or =3 primary protease inhibitor and nucleoside reverse transcriptase inhibitor (NRTI) mutations, and < or =3 darunavir and NNRTI mutations. The primary end point was the proportion of patients with plasma HIV RNA levels <50 copies/mL at 24 weeks. RESULTS: A total of 103 patients enrolled in the study. At baseline, genotypic resistance profiles showed a median of 4 primary protease inhibitor mutations, 1 NNRTI mutation, and 6 NRTI mutations. In addition to the investigational drugs, 90 patients (87%) received optimized background therapy that included NRTIs (86 patients) or enfuvirtide (12 patients). At week 24, 90% of patients (95% confidence interval, 85%-96%) had an HIV RNA level <50 copies/mL. At week 48, 86% (95% confidence interval, 80%-93%) had an HIV RNA level <50 copies/mL. The median CD4 cell count increase was 108 cells/mm(3). Grade 3 or 4 clinical adverse events were reported in 15 patients (14.6%). Only 1 patient discontinued the investigational antiretroviral regimen, because of an adverse event. CONCLUSION: In patients infected with multidrug-resistant virus who have few remaining treatment options, the combination of raltegravir, etravirine, and darunavir/ritonavir is well tolerated and is associated with a rate of virologic suppression similar to that expected in treatment-naive patients.

Failures of 1 week on, 1 week off antiretroviral therapies in a randomized trial.

BACKGROUND: Scheduled treatment interruptions are being evaluated in an effort to decrease costs and side effects of highly active antiretroviral therapy (HAART). A schedule of 1 week on and 1 week off therapy offers the promise of 50% less drug exposure with continuously undetectable HIV RNA concentration. METHODS: In the Staccato study 600 patients on successful HAART were to be randomized to either continued therapy, CD4-guided therapy, or one week on, one week off therapy. A scheduled preliminary analysis evaluated effectiveness in the 1-week-on-1-week-off arm. RESULTS: Of 36 evaluable patients, 19 (53%) had two successive HIV RNA concentrations > 500 copies/ml at the end of the week off therapy, and were classified as virological failure. Most of those who failed took didanosine, stavudine, saquinavir, and ritonavir (11 patients). In these patients, there was no evidence of mutations suggestive of drug resistance, and plasma saquinavir levels were within the expected range. Two of three patients failing on triple nucleotides had drug resistance mutations, but nonetheless responded to reintroduction of triple nucleotide therapy. One of two patients taking nevirapine, and one of eight taking efavirenz, also failed. Both had resistance mutations at the time of failure, but not at baseline. CONCLUSIONS: The 1-week-on-1-week-off schedule, as tested in the Staccato study, showed an unacceptably high failure rate and was therefore terminated.

Long-term hydroxyurea in combination with didanosine and stavudine for the treatment of HIV-1 infection. Swiss HIV Cohort Study.

OBJECTIVE AND METHODS: In 1998 we reported on a randomized comparison between stavudine plus didanosine plus placebo versus stavudine plus didanosine plus hydroxyurea (HU), in patients with a CD4 count of 200-500 x 10(6) cells/l. After 3 months, the HU group had a higher proportion of patients with viral load < 200 x 10 cells/l. At the end of the 3 months blinded period, patients in the placebo group had the option to add HU if their viral load remained > 200 x 10(6) cells/l. We report results after 24 months. RESULTS: Seventy-two patients were randomized to the HU arm, and a further 30 elected to add HU after 12 weeks. Twenty-four months after the start of the trial, only 25% of the 72 patients originally randomized to HU, and 20% of the 30 who added HU after week 12, were still taking it. The reasons for stopping HU were: lack of efficacy (45%), adverse events (37%) and patient or physician preference (18%). Side effects were more frequent in the didanosine/stavudine/HU group than in the didanosine/stavudine group: neuropathy (35 versus 15%, P< 0.02), fatigue (22 versus 7%, P< 0.01), and nausea or vomiting (26 versus 9%, P< 0.01). Of those who had discontinued HU, 73% were taking three drugs including a protease inhibitor. Patients who had started HU were compared with similar patients who had started protease inhibitors in the Swiss cohort. The probability of stopping HU was higher than the probability of stopping nelfinavir or indinavir, and similar to the probability of stopping ritonavir. CONCLUSION: HU increased the antiviral effect of stavudine plus didanosine. However, side effects were more frequent, and after 24 months the majority of patients had switched to protease inhibitor regimens.

[Post-exposure HIV prevention: eligibility of patients recently infected by sexual exposure]. / Prophylaxie post exposition au VIH: éligibilité des patients récemment infectés par voie sexuelle.

QUESTION: Post-exposure prophylaxis (PEP) is effective in preventing HIV infection after professional exposure. PEP is also recommended after inadvertent sexual exposure if two conditions are met: the source person is known to be HIV infected, and exposure to this person occurred only once or is accidental. The objective of this study is to describe the circumstances of sexual exposure and determine how frequently these conditions were present among patients diagnosed during primary HIV infection. METHODS: Physicians of 35 patients diagnosed with primary HIV infection provided detailed information on the circumstances of infection as well as on the patients and source persons. RESULTS: Most patients were homosexual (71%), and 91% were male. Only one patient (3%) had a single exposure with a known HIV-infected person and was therefore eligible for PEP. Eight patients (23%) who did not know the HIV status of their partner would have been eligible considering single exposure as a sufficient criterion for PEP. Oro-genital contact appears to account for transmission in four instances. Eleven persons (31%) were infected after sexual contact with their stable partner, of whom 7 did not known his/her HIV status. Twelve patients (34%) were infected after multiple unprotected sexual contact with unknown partners. CONCLUSION: The direct impact of PEP in terms of HIV infections prevented is likely to be small. PEP will not make up for the failure of other prevention methods. It may, however, contribute to the disclosure and the discussion of risk situations and help physicians provide individual counselling taking into account the precise context of risk behavior.

[Extra-pulmonary tuberculosis and dissemination in patients infected by the human immunodeficiency virus in Bujumbura (Burundi)]. / La tuberculose extra-pulmonaire et disséminée chez les patients infectés par le virus de l'immunodéficience humaine à Bujumbura (Burundi).

Scattered and extra pulmonary tuberculosis patients coinfected with HIV represent in Bujumbura (Burundi) more than 56% of tuberculosis cases. The high prevalence of these forms could be explained partly by the hospital recruitment, therefore by patients already strongly immunocompromised. Performing further examinations as abdominal echography, ganglionic biopsy (or firstly a puncture sucking procedure) permit to reveal multifocal affections. These examinations provide valuable diagnostic arguments specially among the negative bacteriological forms.