ABSTRACT Introduction. The World Health Organization (WHO) recommends conducting nationally representative studies to estimate the prevalence of HIV pretreatment resistance to antiretrovirals (PDRs) to assess the effectiveness of first-line therapies. The objective of the present study was to determine the prevalence of PDR in Cuban adults infected with HIV-1. Methods. HIV resistance to antiretrovirals was determined in 610 Cuban patients in two time periods (469 patients between 2009-2016 and 141 patients during the national survey of HIV-1 PDR conducted during 2017, according to the recommendations issued by the WHO). Results and Discussion. In the period 2009-2016, 19% of the patients presented viruses with some mutation associated with the PDR of HIV-1 to antiretrovirals (10,4 % to some nucleoside reverse transcriptase inhibitor (NRTI), 12,8 % to some non nucleoside reverse transcriptase inhibitor (NNRTI), 2,8 % to some protease inhibitor (PI). In 2017, the prevalence of PDR was 29,8 % (95 %, CI 22,3-38.1). The prevalence was 10,6 % (95 %, IC 6,07-16,9) for some NRTI, 23,4 % (95 %, CI 16,7-31,3) for some NNRTI, and 1,4 % (95 %, CI 0,17-5,03) for some PI. It was concluded that the NNRTI prevalence above 10 % in our study indicates that the first-line antiretroviral therapy in Cuba may be less effective and supports the need to look for new treatment options.

RESUMEN Introducción. La Organización Mundial de la Salud (OMS) recomienda la realización de estudios representativos a nivel nacional para estimar la prevalencia de la resistencia pretratamiento del VIH a los antirretrovirales (PDR) para evaluar la efectividad de las terapias de primera línea. El objetivo del presente estudio fue determinar la prevalencia de PDR en adultos cubanos infectados por el VIH-1. Métodos. Se determinó la resistencia del VIH a los antirretrovirales a 610 pacientes cubanos en dos períodos de tiempo (469 pacientes entre 2009-2016 y 141 pacientes durante la encuesta nacional de PDR del VIH-1 efectuada durante el año 2017, según las recomendaciones emitidas por la OMS). Resultados y Discusión. En el período 2009-2016, el 19 % de los pacientes presentaron virus con alguna mutación asociada a la PDR del VIH-1 a los antirretrovirales (10,4 % a algún inhibidor de la transcriptasa inversa análogo de nucleósidos (ITIAN), 12,8 % a algún inhibidor de la transcriptasa inversa no análogo de nucleósidos (ITINAN), 2,8 % a algún inhibidor de proteasa (IP). En el año 2017, la prevalencia de PDR fue de 29,8 % (95 %, IC 22,3-38,1). La prevalencia fue de 10,6 % (95 %, IC 6,07-16,9) para algún ITIAN, 23,4 % (95 %, IC 16,7-31,3) para algún ITINAN y 1,4 % (95 %, IC 0,17-5,03) para algún IP. Se concluyó que los valores por encima del 10 % en la prevalencia de la PDR a los ITINAN evidencia el comprometimiento de la primera línea de terapia antirretroviral empleada en Cuba y la necesidad de buscar nuevas opciones de tratamiento.

ABSTRACT INTRODUCTION Cuba’s HIV epidemic is characterized by high genetic diversity, with circulation of several subtypes and recombinant forms. Earlier studies described a predominance of subtype B in the HIV-positive population, but these studies did not take into account patients’ epidemiologic history. OBJECTIVE Clarify the origin and phylodynamics of HIV-1 subtype B in the Cuban epidemic. METHODS We analysed phylogenetic relationships among 120 sequences (from different geographic origins) of the pol gene in HIV-1 subtype B isolates from Cuban patients diagnosed from 1987 through 2012. Time of HIV-1 subtype B introduction and viral evolutionary rate were determined using a Bayesian coalescent method. RESULTS Based on phylogenetic relationships, subtype B was introduced into Cuba multiple times. Subtype B spread in Cuba through dissemination of strains that probably came from the USA, Canada and Europe. The time of the most recent common ancestor of Cuban subtype B was close to 1977 (95% CI 1974–1982), and the evolutionary rate was 2.7 × 10-3 nucleotide substitutions per site per year. CONCLUSIONS Our results suggest multiple introductions of HIV-1B into Cuba in the late 1970s, predominantly strains from North America and Europe. The results reflect the importance of maintaining, reviewing and updating molecular epidemiology of HIV-1 in Cuba, due to its rapid evolution and possible implications for the National STI/HIV/AIDS Program of Cuba’s Ministry of Public Health.

INTRODUCTION Serological and molecular HIV-1 studies in Cuba have shown very low prevalence of seropositivity, but an increasing genetic diversity attributable to introduction of many HIV-1 variants from different areas, exchange of such variants among HIV-positive people with several coinciding routes of infection and other epidemiologic risk factors in the seropositive population. The high HIV-1 genetic variability observed in Cuba has possible implications for transmission and clinical progression. OBJECTIVES Study genetic variability for the HIV-1 env, gag and pol structural genes in Cuba; determine the prevalence of B and non-B subtypes according to epidemiologic and behavioral variables and determine whether a relationship exists between genetic variability and transmissibility, and between genetic variability and clinical disease progression in people living with HIV/AIDS. METHODS Using two molecular assays (heteroduplex mobility assay and nucleic acid sequencing), structural genes were characterized in 590 people with HIV-1 (480 men and 110 women), accounting for 3.4% of seropositive individuals in Cuba as of December 31, 2013. Nonrandom sampling, proportional to HIV prevalence by province, was conducted. Relationships between molecular results and viral factors, host characteristics, and patients’ clinical, epidemiologic and behavioral variables were studied for molecular epidemiology, transmission, and progression analyses. RESULTS Molecular analysis of the three HIV-1 structural genes classified 297 samples as subtype B (50.3%), 269 as non-B subtypes (45.6%) and 24 were not typeable. Subtype B prevailed overall and in men, mainly in those who have sex with men. Non-B subtypes were prevalent in women and heterosexual men, showing multiple circulating variants and recombinant forms. Sexual transmission was the predominant form of infection for all. B and non-B subtypes were encountered throughout Cuba. No association was found between subtypes and transmission or clinical progression, although the proportion of deaths was higher for subtype B. Among those who died during the study period, there were no differences between subtypes in the mean time from HIV or AIDS diagnosis to death. CONCLUSIONS Our results suggest that B and non-B HIV-1 subtypes found in Cuba do not differ in transmissibility and in clinical disease progression.