Efficacy, safety, and adherence with a twice-daily combination lamivudine/zidovudine tablet formulation, plus a protease inhibitor, in HIV infection.

OBJECTIVE: A randomized, open-label, multicenter study to establish clinical equivalence (non-inferiority) of a regimen employing a lamivudine 150 mg/zidovudine 300 mg combination tablet, administered twice daily, plus a marketed protease inhibitor, compared with a conventional regimen of 150 mg lamivudine twice daily, 600 mg zidovudine daily, and a protease inhibitor, in antiretroviral-experienced patients infected with HIV-1. PATIENTS: Adults who were seropositive for HIV-1 infection with plasma HIV-1 RNA levels < 10000 copies/ml (Roche Amplicor polymerase chain reaction assay, lower limit of quantitation (LLOQ) 400 copies/ml) and CD4+ cell counts > or = 300 x 10(6)/l). All patients had been receiving the conventional lamivudine/zidovudine/protease inhibitor regimen for > or = 10 weeks immediately prior to the study. INTERVENTION: Patients were randomized to the conventional regimen (n = 113) or combination tablet regimen (n = 110) for 16 weeks. The primary study endpoint was treatment failure, defined as an increase in HIV-1 RNA > or = 0.5 log10 above baseline in patients with viral load > LLOQ at randomization and as HIV-1 RNA increasing to > or = 1250 copies/ml in patients with viral load < LLOQ at randomization. RESULTS: The combination tablet regimen was associated with a 3.5% greater success rate than the conventional regimen (96.4 versus 92.9%), with four and eight patients failing treatment due to increases in HIV-1 RNA levels, respectively. The lower limit of the associated confidence interval for the difference was -2.4%, which was well within the -10% margin predefined as clinically unimportant. This establishes the clinical equivalence (non-inferiority) of the combination tablet regimen to the conventional regimens regarding virologic response. The combination tablet and conventional regimens were similar with respect to percentage of patients maintaining HIV-1 RNA levels < LLOQ at the end of study or improving from baseline to undetectability (94 versus 91%; P= 0.063), overall incidence of drug-related adverse events (21 versus 19%) (P=0.868), and mean area under the curve for CD4+ cell counts [treatment difference, 5.9 cells (95% confidence interval, -15.8 to 27.6 x 10(6) cells/l)]. A self-reported adherence questionnaire indicated that patients in the combination tablet group were less likely to miss doses of nucleoside analogue medication at weeks 8 (P= 0.007) and 16 (P= 0.046). CONCLUSIONS: The combination lamivudine/zidovudine tablet/protease inhibitor regimen is clinically equivalent (non-inferior) to the conventional regimen with respect to virologic response and may offer adherence advantages.

Fracional-fringe holographic plasma interferometry.

Holographic interferometry can be applied to plasmas whose density results in shifts of less than one fringe by superposing the small shifts on an arbitrarily shaped and positioned background fringe pattern. The sensitivity of holographic interferometry is thereby increased to that of conventional interferometry, while the inherent advantages of holography are retained. The background fringes also simplify detection of the spurious phase changes that can arise in holography from motions of the apparatus.

Evaluation of a modified enzyme immunoassay for Neisseria gonorrhoeae in high- and low-risk females.

A recently modified commercial enzyme immunoassay (Gonozyme; Abbott Laboratories, North Chicago, IL) for Neisseria gonorrhoeae antigens was compared with bacteriological culture for diagnostic sensitivity, specificity, and predictive value. A total of 480 specimens were tested by both methods; 355 from females attending a sexually transmitted disease clinic ("high-risk") and 125 from female Family Planning clients ("low-risk"). Sensitivity and specificity of enzyme immunoassay for sexually transmitted disease clinic specimens were 79.7 and 97.9%, respectively (55 positive, 280 negative, 6 false positive, 14 false negative). In the low-risk population, sensitivity and specificity were 100 and 97.5%, respectively (3 positive, 119 negative, 3 false positive, 0 false negative). Despite modification, sensitivity of the method remains low for our sexually transmitted disease clinic population, but the test may have applicability for preliminary screening in low-prevalence settings.