Trends and predictors of HIV-1 acquired drug resistance in Minas Gerais, Brazil: 2002–2012

Abstract

Several studies show that the prevalence of multidrug-resistant HIV-1 virus is declining over time. A retrospective cohort study was carried out to evaluate the trends of drug resistance in antiretroviral treatment-exposed individuals in a state of a middle-income country, Minas Gerais, southeast region of Brazil. We analyzed 2115 HIV-1 sequences from 2002 up to 2012, from 52 cities of Minas Gerais. The groups were analyzed according to the definitions: "IAS - 3 class mutations", if ≥1 drug resistance mutation from IAS 2015 list (DRM) was present in each class; "No fully susceptible drugs" as the absence of any fully susceptible drug in Stanford algorithm; and "GSS≥2″, when a maximum calculated GSS (genotypic susceptibility score) was ≥2 or ≥3, counting only drugs available in Brazil and USA at given calendar years. Time trends of resistance were analyzed by Cochran-Armitage test. We observed a decrease in the rate resistance mutations for PI, NRTI, "IAS - 3 class mutations", and "No fully susceptible drugs" over these 11 years, from 69.2% to 20.7%, 92.3% to 90.2%, 46.2% to 22.5%, and 12.8% to 5.7%, respectively (p<0.05). Resistance to NNRTI increased from 74.4% to 81.6%, mainly because of K103N mutation. The GSS score ≥2 increased during the years from 35.9% to 87.3% (p<0.001). We demonstrate that resistance to PI and to the three main classes simultaneously are declining, although the number of patients on of antiretroviral therapy has doubled in the last ten years in Brazil (125,000 in 2002 to 400,000 in 2014). Broader resistance testing and the availability of more therapeutic options might have influenced this decline. The increase in NNRTI resistance can limit this class as first line treatment in Brazil in the future.

Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China

“…Although M184V/I causes high-level in vitro resistance to 3TC, M184V/I is not a contraindication to continued treatment with 3TC because it increases susceptibility to AZT, and in addition, it is associated with clinically significant reductions in HIV-1 replication [14,24,25]. Similar to our study finding, a high prevalence of M184 V/I mutation has been reported in Asia, Sub-Saharan Africa and Latin America, but a lower prevalence in western Europe [26][27][28][29][30][31]. This difference can be explained by the more frequent use of 3TC in low-and middle-income countries than in West European countries.…”

“…The prevalence of NNRTIs DRMs (91.91%) was higher than NRTIs (74.00%) and PIs (7.44%) in this study. This is due to the fact that NNRTIs have a low genetic barrier to resistance and a single major mutation was often leads to multiple and high-level resistance to NNRTIs drugs [30,35,36], which is why the second-line therapy did not include NNRTIs. K103N/S (41.32%) was the most frequently observed resistance mutation in NNRTIs, followed by Y181C(27.83%) and G190A(26.21%), This is a consequence of the frequent use of NNRTI-based (EFV/ NVP) first-line therapy for more than a decade in China, and these results are similar to the data from low-and middle-income countries [27,[37][38][39].…”

A decade of viral mutations and associated drug resistance in a population of HIV-1+ Puerto Ricans: 2002–2011

“…For both women and men, a marked decrease was seen for overall drug resistance and for protease mutations in particular, with the sharpest decline occurring after 2006 (Fig 6). The reduced HIV-1 mutation and drug resistance trends that we observed are consistent with previous reports from multi-year cohort studies conducted around the world for the same time period [46–49]. Our results are also consistent with population genetic studies, which contend that the transition from early HIV drug therapies to the newer, more efficacious drug treatment regimes, including multi-drug cocktails, limited the ability of the virus to mutate and evolve drug resistance.…”

Prevalence of Antiretroviral Drug Resistance Mutations in HIV Seropositive Patients from an Outpatient Clinic of a Large University Hospital from São Paulo, Brazil

“…However, these findings are similar to those in patients from Minas Gerais state, where the resistance to NNRTI increased from 74.4% to 81.6%, mainly due to K103N mutation. 28 Also the high rates of transmitted NNRTI mutations limit the use of this class as first-line treatment in Brazil in the future, and validate the most recent Brazilian guideline to include as a first option dolutegravir.…”