The Ebola virus is a pathogen that causes high morbidity and mortality in epidemic events during which health personnel are frequently infected. Such an epidemic occurred in West Africa, prompting WHO to issue a call in 2014 for health personnel to be dispatched to affected countries. Cuba responded and signed an assistance agreement under which 265 Cuban health professionals, members of the Henry Reeve Emergency Medical Contingent, volunteered their services in the Republic of Guinea, Sierra Leone and Liberia. This article presents Cuba’s strategy of medical aid and organization of the three medical teams formed; refers to the teams’ contribution to epidemic control in treatment centers where they worked alongside other personnel; and describes measures taken in Cuba to prevent the virus from entering the country through returning volunteers or other means. In the centers where Cuban medical teams worked with other health professionals in West Africa, case fatality decreased from 80%–90% to 24%, contributing to control of the epidemic; no Ebola outbreaks occurred in Cuba. During the epidemic, two Cuban health professionals died of malaria and one physician fell ill with Ebola. This paper includes an overview of the treatment and evolution of the latter case, a doctor who contracted the disease in Sierra Leone and was treated in Geneva and Havana.

KEYWORDS Ebola virus, treatment, strategy, followup, medical collaboration, Republic of Guinea, Sierra Leone, Liberia, Cuba

INTRODUCTION Approximately 73% of persons with HIV who receive antiretroviral therapy in Cuba are in viral suppression. The non-response of the remaining 27% could be due to several factors including adverse drug reactions and HIV resistance to antiretroviral drugs, as well as social factors and idiosyncratic characteristics of each patient. Genetic information explains from 20% to 95% of a drug’s effects and variations in response. Considering optimization of therapeutic efficacy in our country, genetic factors of the host should be identified.

OBJECTIVE Identify polymorphisms affecting genetic variability of responses to antiretroviral drugs.

EVIDENCE ACQUISITION A literature review was conducted (of original articles, published theses, clinical reports and bibliographic review studies, from 2000 to 2018, in Spanish and English listed in MEDLINE/PubMed, SciELO, LILACS, PharmGKB and Google Scholar) with the following key words: pharmacogenetics, human immunodeficiency virus, anti-retroviral agents, genetic polymorphism, genetic techniques, pharmacogenomic variants.

DEVELOPMENT The review identified 77 relevant publications meeting specific quality criteria. A summary table was built with data collected on antiretroviral drugs, genes and proteins involved in polymorphic variations, their associated effects and relevant scientific references. Information was included on polymorphisms related to 12 antiretroviral drugs used in HIV therapy. Polymorphisms determine variations in proteins involved in drug transport and metabolism and in elements of immunity. Relevant pharmacogenetic biomarkers recognized by drug regulatory agencies were identified.

CONCLUSIONS The study identified genetic variations (single-nucleotide polymorphisms) associated with 12 antiretroviral drugs. In most cases, no statistically significant causal association was found. Identifying polymorphic variations is a medium- and long-term objective that requires statistical support and adoption of strategies to optimize antiretroviral therapy. An approach combining plasma-level monitoring and pharmacogenetic analysis is recommended to optimize therapy for HIV patients.

KEYWORDS Pharmacogenetics, HIV, anti-retroviral agents, antiretroviral therapy, genetic polymorphism, genetic techniques, pharmacogenomic variants.

INTRODUCTION By the end of 2017, there were more than 28,000 individuals living with HIV in Cuba, over 80% receiving antiretroviral therapy, which dramatically reduces viral replication, improves immune status and decreases risk of transmission. These results could be jeopardized by emergence of HIV-1 drug resistance. In 2009, a test for HIV-1 genotypic resistance was introduced in routine clinical practice in Cuba.

OBJECTIVE Investigate antiretroviral resistance and its relation to subtype distribution in HIV-1 treatment-naïve and previously treated patients in Cuba.

METHODS Resistance and HIV-1 subtype distribution were determined in 342 antiretroviral treatment-naïve patients and 584 previously treated for HIV-1 whose blood specimens were sent to the Pedro Kourí Tropical Medicine Institute during 2009–2014. Transmitted drug resistance was determined using the Calibrated Population Resistance Tool v.6. Drug resistance analysis was conducted using the algorithm Rega v9.1.0.

RESULTS Prevalence of transmitted drug resistance was 11.4%, and 41% of mutated viruses exhibited dual-class resistance to nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor. Overall, 84.9% of patients had ≥1 resistance mutation, 80% had ≥1 nucleoside reverse transcriptase inhibitor mutation, 71.4% had ≥1 non-nucleoside reverse transcriptase inhibitor mutation and 31.7% had ≥1 protease inhibitor mutation. K65R and K101E mutations were significantly more frequent in subtype C, L210W in CRF19_cpx, and M47V/I in CRF BGs (20, 23, 24). Full class resistance to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and multidrug resistance were detected in 21.2%, 32.4%, 8% and 4.1% of patients, respectively. Average percentage resistance to nucleoside reverse transcriptase inhibitor, protease inhibitor, full class resistance to nucleoside reverse transcriptase inhibitor, protease inhibitor and multidrug resistance increased in patients failing two or more regimens. Nevertheless, after 2011, a declining trend was observed in the frequency of multidrug resistance and full class resistance to nucleoside reverse transcriptase inhibitors and protease inhibitors.

CONCLUSIONS Detected levels of transmitted drug resistance highlight the need for a national surveillance study in treatment-naïve patients. Resistance prevalence is high in previously treated patients but appears to be decreasing over time. The frequency of resistance mutations in recombinant forms of HIV in Cuba needs further study.

KEYWORDS Antiretroviral therapy, highly active antiretroviral therapy, HIV, anti-HIV agents, drug resistance, multiple drug resistance, Cuba

After December 17, 2014, when the US and Cuban governments announced their intent to restore relations, the two countries participated in various exchange activities in an effort to encourage cooperation in public health, health research and biomedical sciences. The conference entitled Exploring Opportunities for Arbovirus Research Collaboration, hosted at Havana’s Hotel Nacional, was part of these efforts and was the first major US–Cuban scientific conference in over 50 years. Its purpose was to share information about current arbovirus research and recent findings, and to explore opportunities for future joint research. The nearly 100 participants included leading arbovirus and vector transmission experts from ten US academic institutions, NIH, CDC, FDA and the US Department of Defense. Cuban participants included researchers, clinicians and students from Cuba’s Ministry of Public Health, Pedro Kourí Tropical Medicine Institute, Center for Genetic Engineering and Biotechnology, Center for State Control of Medicines and Medical Devices and other health research and regulatory organizations. Topics highlighted at the three-day meeting included surveillance, research and epidemiology; pathogenesis, immunology and virology; treatment and diagnosis; vector biology and control; vaccine development and clinical trials; and regulatory matters. Concurrent breakout discussions focused on novel vector control, nonvector transmission, community engagement, Zika in pregnancy, and workforce development. Following the conference, the Pedro Kourí Tropical Medicine Institute and the US National Institute of Allergic and Infectious Diseases have continued to explore ways to encourage and support scientists in Cuba and the USA who wish to pursue arbovirus research cooperation to advance scientific discovery to improve disease prevention and control.

KEYWORDS Arboviruses, flavivirus, Zika virus, chikungunya virus, dengue virus, research, disease vectors, Cuba, USA

Introducción En años recientes, varias iniciativas globales para combatir la epidemia de sida han producido avances prometedores mediante el acceso a programas efectivos de tratamiento. Sin embargo, la falta de adhesión a la terapia antirretroviral es un problema en los pacientes pediátricos.

Objetivo Explorar la adhesión a la terapia antirretroviral de niños y adolescentes con VIH/SIDA en Cuba y examinar su relación con factores psicosociales, individuales y asociados al tratamiento.

Métodos Se efectuó un estudio cualitativo con 21 cuidadores de niños y adolescentes con VIH/SIDA. Mediante la revisión de documentos, se obtuvo información demográfica y del régimen de tratamiento. Se realizaron entrevistas minuciosas para evaluar la adhesión y examinar su relación con factores psicosociales, individuales y asociados al tratamiento. Las entrevistas se transcribieron y la información se agrupó según la categoría de los factores. La adhesión se analizó en relación con estos tres grupos de factores.

Resultados Los cuidadores entrevistados reportaron adhesión adecuada en 17 de los 21 niños. La falta de adhesión estuvo relacionada principalmente con factores psicosociales tales como responsabilidad adicional asumida por el cuidador mientras enfrentaba su propia enfermedad, la presencia de síntomas psicológicos no tratados en el cuidador, dificultades percibidas en el apoyo familiar, la edad del niño y la asignación de las responsabilidades en el tratamiento del niño sin tomar en cuenta su madurez psicológica.

Conclusiones El estudio reveló un alto nivel de adhesión a la terapia antirretroviral. Confirmó la importancia fundamental del cuidador y del apoyo familiar para el éxito terapéutico en niños y adolescentes que padecen VIH/SIDA. Estos resultados, así como los factores identificados en casos de no adhesión, ofrecen un marco para la evaluación y para intervenciones especializadas para optimizar la adhesión pediátrica a la terapia antirretroviral.

Palabras clave VIH, sida, terapia antirretroviral, adhesión del paciente, conformidad del paciente, adhesión a tratamiento, conformidad con tratamiento, no adhesión a tratamiento, Cuba

AIDS is a major cause of death in the Caribbean, a region with a high prevalence of HIV. However, prevalence in Cuba’s population aged 15 to 49 years, despite a slight increase in recent years, is considered extremely low (0.1%). At the close of 2010, 5692 Cuban patients were receiving antiretroviral therapy. SIDATRAT, an informatics system, was developed at the Pedro Kourí Tropical Medicine Institute in Havana to ensure proper monitoring and followup of drug administration. Functioning on a web platform utilizing an Apache server, PHP and MySQL, it records patients’ general information, CD4 counts, viral load and data from other laboratory tests, as well as endoscopic and imaging studies. It also compiles information on their AIDS classification, opportunistic infections, HIV subtype and resistance studies, followup consultations, drug regimen, adverse reactions to medications, changes in drug combinations, and survival; and tracks total number of individuals under treatment. SIDATRAT follows the client-server philosophy and enables access by authorized users throughout Cuba via the health informatics network. SIDATRAT has been found effective in supporting quality care for persons living with HIV/AIDS and universal access to antiretroviral therapy, compiling most of the information needed for decisionmaking on patient health and therapies. SIDATRAT has been offered to the UNDP office in Havana for sharing with other developing countries that may wish to adapt or implement it.

INTRODUCTION The use of highly active antiretroviral therapy has reduced progression to AIDS and increased survival among seropositive persons; yet, appearance of resistant viruses may jeopardize these benefits. In Cuba, HIV mainly affects adults; at the end of 2009 of the 41 children infected, 25 were still alive; of these, 22 were under antiretroviral treatment. Until now, nothing was known about HIV-1 antiviral resistance and viral subtypes in the pediatric population in Cuba.

OBJECTIVE This study aims to identify presence of antiretroviral-resistant HIV-1 strains in Cuban children and their mothers, and to provide a phylogenetic characterization and comparison of pol gene sequences in the same.

METHODS Plasma samples were collected from 22 children and their mothers, all HIV-1–infected, from 2004 through 2009. Reverse transcription polymerase chain reaction was used to amplify the pol gene fragment coding for HIV protease and reverse transcriptase enzymes; this was then sequenced and subjected to phylogenetic analysis of HIV subtypes and recombinant forms to compare sequences between mothers and children. HIV mutations conferring antiretroviral resistance were determined.

RESULTS Viral amplification was achieved in samples from 11 children and 8 mothers. Subtypes detected were: CRF19_cpx in five children, subtype B in three, CRF18_cpx in two, and subtype C in one child. In all mother–child pairs, samples were grouped within the same viral subtype in the phylogenetic tree. One mother was under treatment and five children had been treated before the sample was collected. In viruses amplified from samples of children under treatment, resistance was most frequently found to lamivudine (3 cases) and nevirapine (4 cases). Two untreated children carried resistant viruses possibly acquired from their mothers.

CONCLUSIONS This is the first study to describe HIV-1 antiviral resistance in the pediatric population in Cuba; it also identified viral subtypes infecting the mother−child pairs studied. We recommend antiretroviral resistance assays before initiating treatment in pregnant seropositive women and their newborns.

KEYWORDS HIV, AIDS, antiretroviral therapy, antiviral drug resistance, phylogeny, infectious disease transmission, vertical, Cuba

The following errata have been corrected in all versions of this article

Page 24: Byline, ”Joan Alemán” should read “Yoan Alemán.”

Page 31, The Authors: ”Joan Alemán” should read “Yoan Alemán Campos.”