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Background HIV-1-infected patients can be superinfected with additional HIV-1 variants. Therapy failure can be the consequence of an infection with a resistant strain. Methods A patient was diagnosed with a recent HIV-1 infection in April 2005 and subsequently clinically monitored. HIV-1 evolution was studied by population sequencing of the first 984 bases of the pol gene as well as 454 ultra-deep pyrosequencing (UDPS) of parts of the pol and env genes. Results The patient was diagnosed with a wild-type HIV-1 strain, but experienced rapid virological failure after initiating a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based treatment regimen 3 years later. Population sequencing and UDPS revealed the presence of a second HIV-1 strain with a Y188L NNRTI resistance mutation in a sample obtained shortly prior to initiation of therapy. Phylogenetic analyses showed that the two HIV-1 strains were genetically distinct, providing evidence for superinfection. Conclusions The virological treatment failure in this patient was probably due to the superinfection with an NNRTI-resistant HIV-1 variant. Superinfection with drug-resistant strains can undermine HIV-1 treatment regimens selected on the basis of resistance testing at diagnosis. Patients, especially in high-risk groups, as well as their clinicians, should be aware of the risks and dangers of superinfections.

IntroductionThere is an increased interest in developing once-daily regimens for the treatment of HIV-infected patients. A Phase II study was conducted to investigate the pharmacokinetics, and short-term safety and efficacy of an indinavir/ritonavir combination as part of a once-daily regimen.MethodsHIV-infected patients with either proven poor compliance to HAART regimens in the past or an anticipated poor compliance to such a regimen in the future were eligible for this study. They received a once-daily regimen consisting of indinavir 1200 mg, ritonavir 400 mg, and one or two nucleoside reverse transcriptase inhibitors (NRTIs), also administered once daily with food. A 24 h pharmacokinetic profile was constructed in a subset of patients. Short-term safety and efficacy were evaluated at 4, 12 and 24 weeks after initiation of treatment.ResultsA total of 64 patients were included in this study, of whom 27 (42.2%) were treatment-naive. The geometric mean (+95% CI) of indinavir AUC0–24h, Cmaxand Cminas determined in an unselected group of 16 patients were 84.9 (69.7–103.5) mg/l.h, 12.0 (10.2–14.1) mg/l and 0.15 (0.09–0.26) mg/l, respectively. A large interpatient variability was observed, with five out of the 16 subjects having a Cminvalue below the minimum effective concentration of 0.10 mg/l. During the 24 weeks of follow-up nine patients (14.1%) discontinued study medication, two due to medication-related toxicity. Gastrointestinal adverse events were reported most frequently (50.0%), followed by skin effects (45.3%), joint pain (9.4%) and urological complaints (7.8%). No patient developed nephrolithiasis. The median (+interquartile range) serum creatinine level in the 64 patients increased slightly from 74 (63–88) μmol/l to 79 (66–92) μmol/l during the 24 weeks of follow-up. One new patient reached a grade 1 elevation in serum creatinine, which normalized during the follow-up; five other patients with elevated serum creatinine at baseline remained stable. During the 24 weeks of follow-up, the proportion of patients with a viral load 3in these two sub-groups, respectively.ConclusionThe 24-week follow-up data of this study indicate favourable pharmacokinetics of an indinavir/ritonavir 1200/400 mg combination as part of a once-daily regimen consisting also of one or two NRTIs. Short-term safety and efficacy were also satisfactory. Long-term follow up is planned to evaluate the durability of these results.