RESUMO
BACKGROUND: HIV pretreatment drug resistance (PDR) to NNRTIs in persons initiating ART is increasing in Mexico. OBJECTIVES: To compare HIV PDR in eight sub-regions of Mexico. PATIENTS AND METHODS: A large PDR survey was implemented in Mexico (September 2017-March 2018) across eight sub-regions. All larger clinics (which provide ART to 90% of all initiators) were included, allocating sample size using the probability-proportional-to-size method. Both antiretroviral-naive and prior antiretroviral-exposed persons were included. HIV PDR levels were estimated from pol Sanger sequences obtained at a WHO-designated laboratory. RESULTS: A total of 2006 participants were enrolled from 74 clinics. PDR to NNRTIs was higher than to other drug classes (P < 0.0001), crossing the 10% threshold in the North-East, East, South-West and South-East. NNRTI PDR was higher in the South-West (P = 0.02), coinciding with the highest proportion of restarters in this sub-region (14%). We observed higher PDR prevalence to any drug in women compared with men (16.5% versus 12.2%, P = 0.04). After multivariable adjustment, higher NNRTI PDR remained significantly associated with previous antiretroviral exposure in the Centre-North, North-West, South-West and South-East [adjusted OR (aOR): 21, 5, 8 and 25, respectively; P < 0.05]. Genetic network analyses showed high assortativity by sub-region (P < 0.0001), with evidence of drug resistance mutation transmission within local clusters. CONCLUSIONS: Diversification of the public health response to HIV drug resistance based on sub-regional characteristics could be considered in Mexico. Higher NNRTI PDR levels were associated with poorer regions, suggesting opportunities to strengthen local HIV programmes. Price and licensing negotiations of drug regimens containing integrase inhibitors are warranted.
Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Feminino , Frequência do Gene , Genótipo , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Masculino , México/epidemiologia , Mutação , Prevalência , Análise de Sequência de DNA , Fatores Socioeconômicos , Carga Viral , Adulto JovemRESUMO
BACKGROUND: WHO has developed a global HIV-drug resistance surveillance strategy, including assessment of pretreatment HIV-drug resistance. We aimed to do a nationally representative survey of pretreatment HIV-drug resistance in Mexico using WHO-recommended methods. METHODS: Among 161 Ministry of Health antiretroviral therapy (ART) clinics in Mexico, the largest, including 90% of ART initiators within the Ministry of Health (66 in total), were eligible for the survey. We used a probability-proportional-to-size design method to sample 25 clinics throughout the country. Consecutive ART-naive patients with HIV about to initiate treatment were invited to participate in the survey; individuals with previous exposure to ART were excluded. We assessed pretreatment HIV-drug resistance by Sanger sequencing and next-generation sequencing of viruses from plasma specimens from eligible participants with Stanford University HIV Drug Resistance Database methods. We obtained follow-up data for a median of 9·4 months (range 6-12) after enrolment. We investigated possible relations between demographic variables and pretreatment drug resistance with univariate and multivariate logistic regression. FINDINGS: Between Feb 3 and July 30, 2015, we screened 288 patients in 25 clinics, from whom 264 provided successfully sequenced viruses with no evidence of current exposure to antiretroviral drugs. With the Sanger method, of these 264 participants, 41 (15·5%, 95% CI 11·4-20·5) had pretreatment resistance to any antiretroviral drug and 28 (10·6%, 7·2-15·0) had pretreatment resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs). At least low-level pretreatment resistance (Stanford penalty score ≥15) was noted in 13 (4â·â9%) of participants to efavirenz and in 23 (8·7%) to the combination tenofovir plus emtricitabine plus efavirenz. With next-generation sequencing, of 264 participants, 38 (14·4%, 95% CI 10·4-19·2) had pretreatment resistance to any antiretroviral drug and 26 (9·8%, 6·5-14·1) had pretreatment resistance to NNRTIs. After median follow-up of 8 months (IQR 6·5-9·4, range 5-11) after ART initiation, 97 (72%) of 135 NNRTI initiators achieved viral suppression (<50 copies per mL) compared with ten (40%) of 25 individuals who started with protease inhibitor-based regimens (p=0·0045). After multivariate regression considering pretreatment resistance and initial ART regimen as composite variables, people starting NNRTIs with pretreatment drug resistance achieved significantly lower viral suppression (odds ratio 0·24, 95% CI 0·07-0·74; p=0·014) than patients without NNRTI resistance. INTERPRETATION: High levels of pretreatment drug resistance were noted in Mexico, and NNRTI pretreatment drug resistance significantly reduced the effectiveness of first-line ART regimens based on these drugs. Baseline HIV-drug resistance testing for initial ART follow-up and decision making should be considered. FUNDING: The Mexican Government and Consejo Nacional de Ciencia y Tecnología.