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
INTRODUCTION Differentiating between HIV-1 and HIV-2 infection is the first step to understanding HIV transmission, epidemiology and pathogenesis in geographical areas where both viruses circulate. In Cuba, positive results in mixed HIV-1/2 screening assays are confirmed by HIV-1 Western blot. Indeterminate results constitute the main limitation of this test and HIV-2 infection is among their possible causes; hence the importance of second-stage screening and confirmatory tests for HIV-2 infection.
OBJECTIVE Investigate the contribution of HIV-2 antibodies to negative or indeterminate HIV-1 Western blot results in serum samples from 2005 through 2008 in Cuba.
METHODS HIV-2 reactivity was studied using the ELISA DAVIH–VIH-2 diagnostic kit (Cuba) in 1723 serum samples with negative or indeterminate results for HIV-1 Western blot from January 2005 through December 2008. Duplicate sera reactive by ELISA were confirmed by HIV-2 Western blot, results interpreted according to WHO criteria. The epidemiological interview established by Cuba’s National Program for Prevention and Control Sexually-Transmitted Diseases and HIV/AIDS was applied to HIV-2 Western blot-positive patients.
RESULTS Among all sera studied, HIV-2 ELISA identified 12 reactive serum samples (0.70%) and 1711 non-reactive (99.30%). Western blot analysis of the 12 ELISA-reactive samples confirmed two positive samples (16.67%), 4 negative (33.33%) and 6 indeterminate (50%). Positive samples reacted against the p16, p26, gp36, p53, p56, p68 and gp105 proteins. All 12 ELISA-reactive samples belonged to the HIV-1 Western blot indeterminate group. The two HIV-2–positive samples showed well defined reactivity to gp160, p53, p55 and p34 of HIV-1. HIV-1 seroconversion was observed in all 10 remaining samples during serological followup.
CONCLUSIONS Two new HIV-2 seropositive cases were diagnosed using DAVIH–VIH-2 and HIV-2 Western blot in indeterminate HIV-1 Western blot samples. Results support the recommendation that HIV-2 Western blot be included in the diagnostic algorithm for HIV-1/2 to followup negative or indeterminate HIV-1 Western blot results.
KEYWORDS Diagnosis, laboratory techniques and procedures, antibodies, HIV-2, Western blot, enzyme-linked immunosorbent assay, algorithm, Cuba
Timely and accurate detection of HIV infection is critical due to the seriousness of AIDS and its impact on individuals and families, the long symptom-free incubation period, the benefits of enrolling patients as early as possible in therapy and follow-up, and as a pillar of population-based prevention strategies aimed at curbing the epidemic. Thus, an essential component of Cuba’s
National HIV/AIDS Program (full title, National Program for Prevention and Control of Sexually-Transmitted Diseases and HIV/AIDS) is laboratory diagnosis,[1,2] based on an extensive laboratory network, effective confirmatory algorithms and quality control with external evaluation.
