OBJECTIVES: There are currently few data on the long-term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association. METHODS: The EuroSIDA cohort was divided into three groups: those starting RAL-based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007. Baseline characteristics were compared using logistic regression. The incidences of newly diagnosed malignancies and death were compared using Poisson regression. RESULTS: The RAL cohort included 1470 individuals [with 4058 person-years of follow-up (PYFU)] compared with 3787 (4472 PYFU) and 4467 (10 691 PYFU) in the HIST and CONC cohorts, respectively. The prevalence of non-AIDS-related malignancies prior to baseline tended to be higher in the RAL cohort vs. the HIST cohort [adjusted odds ratio (aOR) 1.31; 95% confidence interval (CI) 0.95-1.80] and vs. the CONC cohort (aOR 1.89; 95% CI 1.37-2.61). In intention-to-treat (ITT) analysis (events: RAL, 50; HIST, 45; CONC, 127), the incidence of all new malignancies was 1.11 (95% CI 0.84-1.46) per 100 PYFU in the RAL cohort vs. 1.20 (95% CI 0.90-1.61) and 0.83 (95% CI 0.70-0.99) in the HIST and CONC cohorts, respectively. After adjustment, there was no evidence for a difference in the risk of malignancies [adjusted rate ratio (RR) 0.73; 95% CI 0.47-1.14 for RALvs. HIST; RR 0.95; 95% CI 0.65-1.39 for RALvs. CONC] or mortality (adjusted RR 0.87; 95% CI 0.53-1.43 for RALvs. HIST; RR 1.14; 95% CI 0.76-1.72 for RALvs. CONC). CONCLUSIONS: We found no evidence for an oncogenic risk or poorer survival associated with using RAL compared with control groups.

• MeSH
• analýza přežití MeSH
• antiretrovirové látky aplikace a dávkování   MeSH
• dospělí MeSH
• HIV infekce komplikace   farmakoterapie   MeSH
• hodnocení rizik MeSH
• incidence MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory epidemiologie   mortalita   MeSH
• prospektivní studie MeSH
• raltegravirum kalicum aplikace a dávkování   MeSH
• vysoce aktivní antiretrovirová terapie metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

To understand the persistence of latently HIV-1 infected cells in virally suppressed infected patients, a number of in vitro models of HIV latency have been developed. In an attempt to mimic the in vivo situation as closely as possible, several models use primary cells and replication-competent viruses in combination with antiretroviral compounds to prevent ongoing replication. Latency is subsequently measured by HIV RNA and/or protein production after cellular activation. To discriminate between pre- and post-integration latency, integrase inhibitors are routinely used, preventing novel integrations upon cellular activation. Here, we show that this choice of antiretrovirals may still cause a bias of pre-integration latency in these models, as unintegrated HIV DNA can form and directly contribute to the levels of HIV RNA and protein production. We further show that the addition of reverse transcriptase inhibitors effectively suppresses the levels of episomal HIV DNA (as measured by 2-LTR circles) and decreases the levels of HIV transcription. Consequently, we show that latency levels described in models that only use integrase inhibitors may be overestimated. The inclusion of additional control conditions, such as 2-LTR quantification and the addition of reverse transcriptase inhibitors, is crucial to fully elucidate the actual levels of post-integration latency.

• MeSH
• aktivace lymfocytů MeSH
• benzoxaziny farmakologie   MeSH
• biologické modely MeSH
• CD4-pozitivní T-lymfocyty imunologie   virologie   MeSH
• DNA virů antagonisté a inhibitory   biosyntéza   genetika   MeSH
• HIV infekce farmakoterapie   imunologie   virologie   MeSH
• HIV-1 účinky léků   fyziologie   MeSH
• inhibitory HIV-integrasy farmakologie   MeSH
• inhibitory HIV-proteasy farmakologie   MeSH
• inhibitory reverzní transkriptasy farmakologie   MeSH
• integrace viru účinky léků   MeSH
• latence viru účinky léků   MeSH
• lidé MeSH
• nevirapin farmakologie   MeSH
• primární buněčná kultura MeSH
• raltegravirum kalicum farmakologie   MeSH
• replikace viru účinky léků   MeSH
• reportérové geny MeSH
• ritonavir farmakologie   MeSH
• virové proteiny antagonisté a inhibitory   biosyntéza   genetika   MeSH
• zelené fluorescenční proteiny genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• AIDS * farmakoterapie   patofyziologie   MeSH
• centrální nervový systém patofyziologie   MeSH
• HIV infekce * farmakoterapie   patofyziologie   MeSH
• HIV * fyziologie   imunologie   růst a vývoj   MeSH
• inhibitory HIV-integrasy terapeutické užití   MeSH
• látky proti HIV terapeutické užití   MeSH
• lidé MeSH
• raltegravirum kalicum terapeutické užití   MeSH
• výzkum MeSH
• Check Tag
• lidé MeSH