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Biomedical subjects

M H Losso

Publications and source records attributed to M H Losso.

5 recordsLinked to original sources
PubMed2006

Pharmacokinetic parameters of nevirapine and efavirenz in relation to antiretroviral efficacy.

Optimal adherence is essential for successful antiretroviral therapy. We analyzed the relation between minimum plasma drug concentration (Cmin) and total drug exposure over 24 hr (AUC24) with virologic failure for therapy-adherent patients in the nevirapine (NVP) and efavirenz (EFV) groups of the double nonnucleoside study (2NN), which compared the efficacy of NVP and/or EFV together with stavudine and lamivudine. The objective was to find cutoff values of the Cmin and AUC24 below which the risk of virologic failure increased. The relation between Cmin and AUC24 with virologic failure (never a plasma viral load [pVL] < 50 copies/ml or a rebound to two consecutive pVL > 50 copies/ml) was analyzed with proportional hazard analyses. Data were censored at end of study or change of allocated treatment. The risk of virologic failure with NVP (n = 511) started to increase at a Cmin < 3.1 mg/L (hazard ratio [HR], 1.33; 95% confidence interval [CI], 0.89-1.97), but there was no cutoff value below which a statistically significant increased risk occurred. Neither was such a cutoff point identified for the AUC24. The risk of virologic failure with EFV (n = 312) was significantly increased at a Cmin < 1.1 mg/L (HR, 1.95; 95% CI, 1.08-3.54) and an AUC24 < 40 mg x hr x L1 (HR, 1.95; 95% CI, 1.07-3.54). Both cutoff values represent the median values for adherent patients. These associations were driven by patients from Thailand. Adjusting for geographical region made the association between Cmin and AUC24 with virologic failure statistically nonsignificant. The sensitivity of the Cmin values was too low (29% for NVP, 64% for EFV) to be an adequate predictor for virologic failure. We conclude that identifying the Cmin value for the sole purpose of predicting virologic failure in patients who report to be adherent to NVP or EFV is questionable because of the absence of a concentration-response relation (NVP) or the low sensitivity for such a cutoff value (NVP and EFV).

Adult↗
PubMed2004

Prospective evaluation of in-house polymerase chain reaction for diagnosis of mycobacterial diseases in patients with HIV infection and lung infiltrates.

SETTING: Rapid diagnosis of tuberculosis (TB) in AIDS is critical for optimal treatment to reduce mycobacterial dissemination, HIV-1 replication and mortality. The inadequate sensitivity of Ziehl-Neelsen staining and its inability to distinguish atypical mycobacteria delays accurate diagnosis. OBJECTIVE: To evaluate the polymerase chain reaction (PCR) for diagnosis of TB in bronchoalveolar lavage (BAL), blood and extra-pulmonary samples from patients with AIDS and pulmonary infiltrates. DESIGN: Specimens from 103 HIV-1-infected patients were prospectively analysed using bacteriological methods and IS6110-PCR. Smear-positive samples were also tested using 16S ribosomal-DNA-PCR to identify Mycobacterium avium complex (MAC) infections. Gold standard diagnosis relied on positive cultures or treatment outcome. RESULTS: Thirty-four patients exhibited TB, one TB and MAC and four MAC. The sensitivity of IS6110-PCR was 100% in smear-positive samples, 81.8% in smear-negative BAL, 66.7% in extra-pulmonary samples and 42.9% in blood. Its specificity was 97.1% in BAL and 100% in extra-pulmonary and blood specimens. The 16S rDNA-PCR identified M. avium from all smear-positive samples that grew MAC. CONCLUSIONS: IS6110-PCR proved useful in evaluating episodes with probable clinical diagnosis of pulmonary or mixed TB and negative smears, whereas 16S rDNA-PCR would be helpful for prompt differential diagnosis of MAC in smear-positive specimens.

AIDS-Related Opportunistic Infections↗
PubMed2000

A randomized, controlled, phase II trial comparing escalating doses of subcutaneous interleukin-2 plus antiretrovirals versus antiretrovirals alone in human immunodeficiency virus-infected patients with CD4+ cell counts >/=350/mm3.

A total of 73 patients with baseline CD4+ cell counts >/=350 cells/mm3 who were receiving combination antiretroviral therapy (ART) were randomized to receive subcutaneous interleukin-2 (IL-2; n=36) in addition to ART or to continue ART alone (n=37). Subcutaneous IL-2 was delivered at 1 of 3 doses (1.5 million international units ¿MIU, 4.5 MIU, and 7.5 MIU per dose) by twice-daily injection for 5 consecutive days every 8 weeks. After 24 weeks, the time-weighted mean change from baseline CD4+ cell count was 210 cells/mm3 for recipients of subcutaneous IL-2, compared with 29 cells/mm3 for recipients of ART alone (P<.001). There were no significant differences between treatment groups for measures of plasma human immunodeficiency virus RNA (P=.851). Subcutaneous IL-2 delivered at doses of 4.5 MIU and 7.5 MIU resulted in significant increases in CD4+ cell count (P=.006 and P<.001, respectively), compared with that seen in control patients. These changes were not significant in the 1.5 MIU dose group compared with that in the control patients (P=.105). Side effects that occurred from subcutaneous IL-2 administration were generally low grade, of short duration, and readily managed in an outpatient environment.

Adult↗
PubMed1997

[Advances in antiretroviral treatment].

Recent findings have led to important changes in the understanding of HIV kinetics that allowed a novel therapeutic approach. This article reviews the most common methods used to gauge viral load and their use in medical decision making, the characteristics of the protease inhibitors just released in Argentina, and preliminary reports from several trials of combined treatment that have changed the standard of care. The viral load is a surrogate marker with predictive value independent of the CD4 cell count. Combined treatment is the election in case it is decided to initiate treatment.

Acquired Immunodeficiency Syndrome↗