Impact of the number of failed therapeutic regimes on the development of resistance mutations to HIV-1 in northeast Brazil

Abstract

Highly-potent antiretroviral therapy is necessary to avoid viral replication in HIV patients; however, it can favor the appearance of resistance mutations. The mutations 41L, 67N, 70R, 210W, 215Y/F, 219E/Q, 44D and 118I are defined as nucleoside analogous mutations (NAMs), because they affect the efficacy of all nucleoside reverse transcriptase inhibitors (NRTI). The mutation most frequently associated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) is 103N. 33W/F, 82A/F/L/T, 84V and 90M are called protease inhibitor resistance-associated mutations (PRAM), because they are associated with resistance to several protease inhibitors (PI). This study evaluated the development of resistance mutations and examine the susceptibility of HIV with these mutations to antiretrovirals in HIV-1 patients who have failed one or more therapy regimes. Analyses were made of 101 genotypic tests of patients with therapeutic failure to 2 or 3-drug regimens with NRTI, NNRTI or PI. We used the Stanford database to define the susceptibility profile of the viruses. The samples were divided into three treatment-failure groups: first (F), second (S) and multi-failure (MF) to antiretroviral regimens, and we correlated these groups with resistance profiles and principal mutations. There was a significant increase in resistance mutations V82A/F/L/T, I84V, L90M, M41L, K70R, L210W, T215Y/F and K219Q/E in MF. We also found significantly higher resistance to zidovudine, didanosine, stavudine and abacavir in MF. There was no increase in resistance to tenofovir (p=0.28) and lopinavir (p=0.079) in MF. A high degree of resistance to NNRTIs was observed in all groups. Increased resistance mutations will affect future therapeutic options for HIV patients in Brazil because it results in a significant increase in resistance to antiretroviral drugs.

The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil

“…The continuous replication of HIV under the selective pressure of antiretrovirals (ARVs) will eventually lead to the selection of HIV mutations associated with resistance [ 12 ]. The accumulation of mutations further compromises HIV treatment and limits future options if cross-resistance to other ARVs is developed [ 13 , 14 ]. Therefore, early detection of viral failure is extremely important.…”

Manifestações bucais da AIDS e o perfil de mutações e de resistência do HIV em pacientes experimentando falha terapêutica

“…(internacional e nacional) de que a TARV seja iniciada com regimes que incluam essa classe de ARVs (Yeni et al, 2004, Brasil, 2013 As mutações 215Y, 118I e 44D são bem conhecidas e estão entre as mutações definidas como mutações análogas dos nucleosídeos (NAMs -nucleoside analogous mutations) porque afetam a eficiência de todos os ITRNs (Whitcombe et al, 2002a;Medeiros et al, 2007). Dois diferentes padrões de NAMs foram identificados, o primeiro, composto pelas mutações 44D, 41L, 118I, 210W e 215Y, causa altos níveis de resistência a todos os ITRNs; o segundo, composto por 67N, 70R, 219QE e 215F, possui apenas um efeito leve na suscetibilidade a alguns…”