RESUMO
BACKGROUND: Highly active antiretroviral therapy (HAART) is provided free of charge to all human immunodeficiency virus (HIV) positive residents in Italy. As fixed dose coformulations (FDCs) are often more expensive in comparison to the same drugs administered separately in a multi-tablet regimen (MTR), we considered a cost-effective strategy involving patients in the switch from their FDCs to corresponding MTRs including generic antiretrovirals. AIM: To verify if this would affect the virological and immunological response in comparison to maintaining the FDC regimens. METHODS: From January 2012 to December 2013, we assessed the eligibility of all the HIV-1 positive adults on stable HAART being treated at our hospital-based outpatient clinic in Treviso, Italy. Participants who accepted to switch from their FDC regimen to the corresponding MTR joined the MTR group, while those who maintained a FDC regimen joined the FDC group. Clinical data, including changes in HAART regimens, respective reasons why and adverse effects, were recorded at baseline and at follow-up visits occurring at weeks 24, 48 and 96. All participants were assessed for virological and immunological responses at baseline and at weeks 24, 48 and 96. RESULTS: Two hundred and forty-three eligible HIV-1 adults on HAART were enrolled: 163 (67%) accepted to switch to a MTR, joining the MTR group, while 80 (33%) maintained their FDCs, joining the FDC group. In a parallel analysis, there were no significant differences in linear trend of distribution of HIV-RNA levels between the two groups and there were no significant odds in favour of a higher level of HIV-RNA in either group at any follow-up and on the overall three strata analysis. In a before-after analysis, both FDC and MTR groups presented no significant differences in distribution of HIV-RNA levels at either weeks 48 vs 24 and weeks 96 vs 24 cross tabulations. A steady increase of mean CD4 count was observed in the MTR group only, while in the FDC group we observed a slight decrease (-23 cells per mmc) between weeks 24 and 48. CONCLUSION: Involving patients in the switch from their FDC regimens to the corresponding MTRs for economic reasons did not affect the effectiveness of antiretroviral therapy in terms of virological response and immunological recovery.
RESUMO
The choice of an initial antiretroviral triple therapy is based mainly on two nucleoside/tide analogs (NRTIs/NtRTIs) plus either a protease inhibitor (PI) or a non nucleoside reverse transcriptase inhibitor (NNRTI). Three fixed dose coformulations are available (AZT/3TC, Combivir®; ABC/3TC, Kivexa®; TDF/FTC, Truvada®). In this review, we describe how to select one of these fixed-dose coformulations on the basis of their specific genotypic drug resistance profile. Mutations conferring resistance to NRTIs/NtRTIs are classified accord- ing to their molecular mechanism of action. A first group of mutations (K65R, L74V, Q151M, M184V) favors the incorporation of the natural dNTP into the active site of the reverse transcriptase (RT) and leads to resistance by decreasing the incorporation of the inhibitor. A second group of mutations including TAMs (thymidine analog mutations) leads to the removal of the NRTIs previously incorporated in the growing DNA chain. M184V mutation is selected by the three fixed-dose coformulations. The fixed-dose AZT/3TC selects at first M184V mutation then the TAMs that progressively confer a cross-resistance to most of NRTIs/NtRTIs. The fixed-dose coformulation ABC/3TC selects more frequently L74V mutation than K65R or Y115F mutation. The fixed-dose coformulation TDF/FTC selects the K65R mutation. Second-line therapeutic options will be chosen on the basis of these resistance profiles: ABC, ddI, or TDF as a fonction of the number and the nature of TAMs; AZT, D4T, or TDF in case of L74V mutation; AZT or D4T in case of K65R mutation.