In treatment-experienced patients with baseline nucleoside resistance mutations, TDF provided dose-related, durable reductions in HIV-1 RNA. Through 24 weeks, the safety profile of TDF was similar to that of placebo.

Objective Study 903 was a 144‐week, randomized, double‐blind, active‐controlled study of tenofovir disoproxil fumarate (TDF) therapy in treatment‐naive HIV‐1‐infected patients. Patients received either TDF (n=299) or stavudine (d4T) (n=301) with lamivudine (3TC) and efavirenz (EFV). Resistance analyses were performed at baseline and at virological failure to determine the effects of baseline resistance and the patterns of resistance at virological failure. Methods Plasma HIV‐1 from patients at baseline and at virological failure (>400 HIV‐1 RNA copies/mL at week 144 or early discontinuation) was analysed phenotypically and by population sequencing. Results Sixteen per cent of patients were classified as having virological failure (47 on TDF and 49 on d4T; P=0.91). Patients with non‐B HIV‐1 subtypes or baseline nucleoside reverse transcriptase inhibitor (NRTI)‐associated mutations responded similarly to the overall population. Resistance to EFV (K103N and others) or 3TC (M184V) developed most frequently (8.3% and 5.8%, respectively) and similarly in the two arms. In the d4T arm, a variety of NRTI mutations developed: K65R (n=2), L74V (n=2), V75M (n=1), and T69A+Y115H (n=1). K65R developed in eight TDF patients (2.7%); in seven of these eight patients, within 48 weeks. All eight patients began new regimens with a protease inhibitor (PI) and NRTIs, including two patients who remained on TDF; five of the eight patients achieved HIV RNA <50 copies/mL in second‐line therapy with the remaining patients having no follow‐up or being nonadherent. Conclusions Treatment of HIV‐1 with TDF, 3TC and EFV was highly effective, with <3% of patients developing resistance to TDF over 144 weeks.

Taken at face value, these findings suggest that prolonged exposure to very low radiation doses may increase leukaemia risk as much as or even more than acute exposure. However the large and statistically significant dose-response might be accounted for, at least in part, by an overestimate of risk in Ukraine. Therefore, we conclude this study provides no convincing evidence of an increased risk of childhood leukaemia as a result of exposure to Chernobyl radiation, since it is unclear whether the results are due to a true radiation-related excess, a sampling-derived bias in Ukraine, or some combination thereof. However, the lack of significant dose-responses in Belarus and Russia also cannot convincingly rule out the possibility of an increase in leukaemia risk at low dose levels.