The HIV/AIDS epidemic is an ongoing threat to public health. Its elimination requires greater efforts to broaden antiretroviral treatment coverage, availability and personalization. HIV drug resistance is currently a global problem due to its continuing increase in recent years, undermining efficacy of antiretroviral therapy. Pretreatment HIV drug-resistance surveillance is part of WHO’s strategy for addressing antiretroviral drug resistance. This paper describes and analyzes pretreatment HIV drug-resistance surveillance in Cuba. It presents a chronology of HIV resistance studies in untreated patients, along with their results and programmatic actions related to first- and second-line treatment regimens. Cuba’s incorporation into the Global HIV Drug Resistance Surveillance Laboratories Network and the advantages of having a WHO-designated laboratory in which to conduct periodic studies of HIV drug-resistance surveillance are described. HIV drug-resistance surveillance in Cuba is a necessary tool in HIV/AIDS monitoring and control, as it obtains population-scale data used to inform programmatic decisions related to optimizing first- and second-line treatments for children and adults, as well as helping meet goals of eliminating HIV transmission.

KEYWORDS HIV, anti-HIV agents, drug resistance, viral, antiretroviral agents, Cuba

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 x 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.

KEYWORDS HIV-1, subtype B, HAART, molecular epidemiology, molecular evolution, phylodynamics, Cuba

Introducción Los estudios serológicos y moleculares del VIH-1 en Cuba han mostrado muy baja prevalencia de seropositividad, pero una diversidad genética creciente, atribuible a la introducción de muchas variantes del virus procedentes de diferentes áreas, al intercambio de tales variantes entre personas VIH-1 positivas con varias rutas coincidentes de infección y otros factores de riesgo epidemiológicos en la población seropositiva. La alta variabilidad genética del VIH-1 observada en Cuba tiene implicaciones posibles para la transmisión y la progresión clínica.

Objetivo Estudiar la variabilidad genética para los genes estructurales env, gag y pol del VIH-1 en Cuba; determinar la prevalencia de los subtipos B y no B según las variables epidemiológicas y de comportamiento y determinar si existe una relación entre la variabilidad genética y la transmisibilidad, y entre la variabilidad genética y la progresión clínica de la enfermedad en personas que viven con VIH/SIDA.

Métodos Mediante el uso de dos ensayos moleculares (ensayo de movilidad heterodúplex y secuenciación de ácidos nucleicos), se caracterizaron los genes estructurales en 590 personas con VIH-1 (480 hombres y 110 mujeres), que representa el 3.4% de los individuos seropositivos existentes en Cuba el 31 de diciembre de 2013. Se condujo un muestreo no aleatorizado, proporcional a la prevalencia del VIH-1 en cada provincia. Las relaciones entre los resultados moleculares y los factores virales, las características de los hospederos, y las variables clínicas, epidemiológicas y de comportamiento de los pacientes se estudiaron en relación con la epidemiología molecular, la transmisión y el análisis de la progresión.

Resultados A partir del análisis molecular de los tres genes estructurales del VIH-1 se clasificaron 297 muestras como pertenecientes al subtipo B (50.3%), 269 como subtipos no B (45.6%) y 24 fueron no tipables. El subtipo B prevaleció en general, y en los hombres en aquellos que tienen sexo con hombres. Los subtipos no B prevalecieron en mujeres y en hombres heterosexuales, y mostraron múltiples variantes circulantes y formas recombinantes. La transmisión sexual fue la forma predominante de infección para todos, a lo largo de Cuba se encontraron los subtipos B y no B. No se encontró asociación entre los subtipos y la transmisión o la progresión clínica, aunque la proporción de muertes fue superior para el subtipo B. Entre los fallecidos durante el período del estudio, no existieron diferencias entre los subtipos en el tiempo promedio transcurrido entre el diagnóstico del VIH o el diagnóstico de sida y el fallecimiento.

Conclusiones Nuestros resultados sugieren que los subtipos B y no B de VIH-1 encontrados en Cuba no difieren en cuanto a transmisibilidad y progresión clínica de la enfermedad.

Palabras clave VIH-1, sida, epidemiología molecular, transmisibilidad, progresión clínica, subtipos, formas recombinantes circulantes, patogénesis, Cuba

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.

OBJECTIVE 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.

KEYWORDS HIV-1, AIDS, molecular epidemiology, transmissibility, clinical progression, subtypes, circulating recombinant forms, patho­genesis, Cuba