Journal of AIDS & Clinical Research

We compared the absolute CD4+ count, at different CD4+ percentages (CD4%), between Asian (n=442) and Caucasian (n=674) untreated HIV-infected individuals, using linear regression methods. At any given CD4%, Asians had lower CD4+ count than Caucasians (p=0.001). The difference varied from 38.9 cells/mm3 (95% CI: 3.3-74.5 cells/ mm3) at CD4% of 15% to 108.7 cells/mm3 (95% CI: 42.5-174.9 cells/mm3) at CD4% of 40%. The impact of these differences on prognosis is uncertain, but it may be that the prognostic thresholds for CD4+ count used in Caucasian populations are inappropriate in Asian populations.

Objectives: Natural killer (NK) cell function was investigated in Malaysian HIV patients beginning antiretroviral therapy (ART) with advanced immunodeficiency. Some patients experienced immune restoration disease (IRD) presenting as exacerbations of pre-existing infections. Whilst most IRD are attributed to interferon-gamma (IFN?) produced by T-cells, NK cells may also contribute. Methods: Blood leukocytes were collected prospectively from 100 HIV patients over 1 year on ART, plus 36 healthy controls. Eleven patients who experienced an IRD and 14 matched controls were assayed. Cells producing IFN? were quantitated by ELISpot after stimulation with an NK target (K562 cells) or antigens from pathogens associated with the IRD. NK cell subsets, CD16 and perforin expression were determined by flow cytometry Results: NK cell IFN? responses were lower in HIV patients at baseline (p<0.001), improved by Week 24 (p<0.01) but remained lower than uninfected controls (p<0.05). Proportions of CD56hi NK cells increased (p<0.01) above controls at Week 24. Perforin expression on these cells was higher than controls at baseline (p<0.01), but declined on ART. Proportions of CD56hl NK cells were similar in patients and controls throughout. IRD patients showed lower CD16 expression on CD56lo NK cells than non-IRD patients before treatment (p<0.05) Conclusions: NK cells profiles were restored on ART, but NK cell IFN? production remained impaired. Low CD16 expression on CD56lo NK cells may mark a predisposition for an IRD.

Background: There is uncertainty about the comparative safety and effi cacy of the fi xed-dose-combination tablets tenofovir 300mg+emtricitabine 200mg (TDF/FTC); and abacavir 600mg+lamivudine 300mg (ABC/3TC).

Methods: We used random effects meta-analysis to compare 96 week data for ABC/3TC and TDF/FTC randomised arms from the BICOMBO (n=333) and STEAL (n=357) treatment experienced and virologically suppressed switch studies. Endpoints included: virological failure (VF, repeat plasma HIV RNA >400 copies/mL); mean change to week 96 in CD4 and metabolic parameters; proportion with serious non-AIDS events (SNAEs, retrospectively collected in BICOMBO). We used exact statistics for relative difference in proportions (RD), and ANOVA for differences between means. Difference was for ABC/3TC minus TDF/FTC.

Results: There was no signifi cant difference between arms in VF (RD% 0.7 95%CI -3.4, 4.8). Change from baseline in CD4 was of marginal signifi cance (ITT 0.16 cells/mL 95%CI 0.0, 0.32). Mean change in HDL, LDL, total cholesterol triglycerides were signifi cantly greater in the ABC/3TC arm (p <0.01 for all), there was no difference in total cholesterol:HDL ratio (0.11 95%CI -0.16, 0.29). There was a greater proportion of SNAEs in the ABC/3TC arm (relative difference 3.8%, 95%CI 0.1, 7.6) primarily arising from the STEAL study.

Conclusions: In a switch study setting ABC/3TC based therapy was virologically non-inferior over 96 weeks to TDF/FTC based therapy. Lipid markers were generally elevated in the ABC/3TC arm.