Lipase and factor V (but not viral load) are prognostic factors for the evolution of severe yellow fever cases

BACKGROUND Despite a highly efficacious vaccine, yellow fever (YF) is still a major threat in developing countries and a cause of outbreaks. In 2018, the Brazilian state of São Paulo witnessed a new YF outbreak in areas where the virus has not been detected before. OBJECTIVE The aim is to describe the clinical and laboratorial characteristics of severe cases of YF, evaluate viral to determine markers associated with fatal outcome. METHODS Acute severe YF cases (n = 62) were admitted to the Intensive Care Unit of a reference hospital and submitted to routine laboratorial evaluation on admission. YFV-RNA was detected in serum and urine by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and then sequenced. Patients were classified in two groups: survival or death. FINDINGS In the univariate analysis the following variables were associated with outcome: alanin aminotransferase (ALT), aspartat aminotransferase (AST), AST/ALT ratio, total bilirubin (TB), chronic kidney disease epidemiology collaboration (CKD-EPI), ammonia, lipase, factor V, international normalised ratio (INR), lactate and bicarbonate. Logistic regression model showed two independent variables associated with death: lipase [odds ratio (OR) 1.018, 95% confidence interval (CI) 1.007 to 1.030, p = 0.002], and factor V (OR -0.955, 95% CI 0.929 to 0.982, p = 0.001). The estimated lipase and factor V cut-off values that maximised sensitivity and specificity for death prediction were 147.5 U/L [area under the curve (AUC) = 0.879], and 56.5% (AUC = 0.913). MAIN CONCLUSIONS YF acute severe cases show a generalised involvement of different organs (liver, spleen, heart, kidneys, intestines and pancreas), and different parameters were related to outcome. Factor V and lipase are independent variables associated with death, reinforcing the importance of hemorrhagic events due to fulminant liver failure and pointing to pancreatitis as a relevant event in the outcome of the disease.

Risk factors for cytomegalovirus disease in systemic lupus erythematosus (SLE): a systematic review

Abstract Background: Cytomegalovirus (CMV) is an opportunistic pathogen causing reactivation and disease in Systemic Lupus Erythematosus (SLE) patients. This study aims to systematically review the literature for risk factors associated with CMV disease in SLE patients, in order to identify those more susceptible to CMV infection during their treatment. Methods: A systematic review was conducted on 4 different search engines and via hand search until May 2017. Studies were included after quality assessment via the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields (HTA KMET). Results: Two studies on CMV disease were included. Elevated CMV viral load, higher steroid doses, use of immunosuppressants and disease duration were the most commonly associated risk factors for CMV disease. Conclusion: High CMV viral loads, longer SLE disease duration and higher steroid doses were associated with CMV disease. Further studies studying the risk of treatment drugs and role of interventions in the development of CMV infection are needed.

Safety of monitoring antiretroviral therapy response in HIV-1 infection using CD4+ T cell count at long-term intervals / Segurança do monitoramento da resposta à terapia antirretroviral em pacientes com infecção pelo HIV-1 através da contagem de linfócitos T CD4+ a intervalos mais longos / Seguridad en la monitorización de la respuesta a la terapia antirretroviral ante el VIH-1, usando el recuento celular CD4+ T en intervalos a largo plazo

Abstract: The latest Brazilian guideline recommended the reduction of routine CD4+ T cell counts for the monitoring of patients with human immunodeficiency virus type 1 (HIV-1) under combination antiretroviral therapy (cART). The aim of this study was to evaluate the safety of monitoring response to cART in HIV-1 infection using routine viral load at shorter intervals and CD4+ T cell count at longer intervals. CD4+ T cell counts and HIV-1 viral load were evaluated in 1,906 HIV-1-infected patients under cART during a three-year follow-up. Patients were stratified as sustained, non-sustained and non-responders. The proportion of patients who showed a CD4+ T > 350cells/µL at study entry among those with sustained, non-sustained and non-responders to cART and who remained with values above this threshold during follow-up was 94.1%, 81.8% and 71.9%, respectively. HIV-1-infected patients who are sustained virologic responders and have initial CD4+ T cell counts > 350cells/µL showed a higher chance of maintaining the counts of these cells above this threshold during follow-up than those presenting CD4+ T ≤ 350cells/µL (OR = 39.9; 95%CI: 26.5-60.2; p < 0.001). This study showed that HIV-1-infected patients who had sustained virologic response and initial CD4+ T > 350cells/µL were more likely to maintain CD4+ T cell counts above this threshold during the next three-year follow-up. This result underscores that the evaluation of CD4+ T cell counts in longer intervals does not impair the safety of monitoring cART response when routine viral load assessment is performed in HIV-1-infected patients with sustained virologic response.

Resumo: O último consenso brasileiro recomenda reduzir a rotina de contagem de linfócitos T CD4+ para monitorar os pacientes com HIV-1 sob terapia antirretroviral combinada (TARV). O estudo teve como objetivo avaliar a segurança do monitoramento à TARV na infecção pelo HIV-1, realizando a carga viral a intervalos mais curtos e a contagem de linfócitos T CD4+ a intervalos mais longos. Foram avaliadas a contagem de linfócitos T CD4+ e a carga viral do HIV-1 em 1.906 pacientes com HIV-1 em uso de TARV durante um seguimento de três anos. Os pacientes foram estratificados em: resposta sustentada, não sustentada e não respondedores. As proporções de pacientes com linfócitos T CD4+ > 350células/µL na linha de base do estudo entre de resposta sustentada, não sustentada e não respondedores à TARV e que permaneceram com valores acima desse limiar ao longo do seguimento foram 94,1%, 81,8% e 71,9%, respectivamente. Os pacientes com resposta virológica sustentada e que tinham contagem de T CD4+ > 350células/µL mostraram maior probabilidade de manter a contagem acima desse limiar durante o seguimento, quando comparados àqueles com T CD4+ ≤ 350células/µL (OR = 39,9; 95%CI: 26,5-60,2; p < 0,001). O estudo mostrou que pacientes HIV-1+ com resposta virológica sustentada e contagem de linfócitos T CD4+ > 350células/µL tinham maior probabilidade de manter a contagem de células T CD4+ acima desse limiar durante o seguimento de três anos subsequentes. O resultado corrobora que a contagem de linfócitos T CD4+ com intervalos mais longos não compromete a segurança do monitoramento da resposta à TARV quando a avaliação da carga viral é feita de rotina em pacientes HIV-1+ com resposta virológica sustentada.

Resumen: Las últimas directrices brasileñas recomendaron la reducción de la rutina en el recuento celular CD4+ T para pacientes con el virus de inmunodeficiencia humano tipo 1 (VIH-1), con terapia de combinación antirretroviral (cART por sus siglas en inglês). El objetivo de este estudio fue evaluar la seguridad de la monitorización de la respuesta a la cART en una infección por VIH-1, usando rutinas de carga viral en intervalos más cortos y recuento celular CD4+ T en intervalos más largos. Se evaluaron el recuento celular CD4+ T y la carga viral VIH-1 en 1.906 pacientes infectados con VIH-1 y con cART durante un seguimiento que duró tres años. Los pacientes fueron estratificados como constantes, inconstantes y sin respuesta. La proporción de pacientes que mostraron CD4+ T > 350células/µL en el estudio entran dentro del grupo de los constantes, inconstantes y sin respuesta al cART, y quienes permanecieron con valores por encima de este umbral durante los seguimientos fueron 94,1%, 81,8% y 71,9%, respectivamente. Los pacientes infectados por VIH-1 que cuentan con la respuesta virológica constante y tienen un recuento inicial CD4+ T > 350células/µL mostraron una oportunidad más alta de mantener el recuento de estas células por encima del umbral durante los seguimientos, respecto a quienes presentaban CD4+ T células ≤ 350células/µL (OR = 39,9; IC95%: 26,5-60,2; p < 0,001). Este estudio expuso que los pacientes infectados por VIH-1, que habían tenido una respuesta virológica constante e inicial CD4+ T > 350células/µL, eran más propensos a mantener el recuento de células CD4+ T por encima de este umbral durante los tres años posteriores de seguimiento. Este resultado destaca que la evaluación del cómputo de células CD4+ T en intervalos más largos no obstaculiza la seguridad al realizar una monitorización en la respuesta a cART, cuando la evaluación de la carga viral rutinaria se realiza en pacientes infectados por VIH-1 con una respuesta virológica constante.

The HIV care cascade in Buenos Aires, Argentina: results in a tertiary referral hospital / La cascada en la atención de la infección por el VIH en Buenos Aires, Argentina: resultados en un hospital de referencia de atención terciaria

ABSTRACT Objective To determine rates of retention, antiretroviral therapy (ART) use, and viral suppression in an adult cohort from a public tertiary referral hospital in the city of Buenos Aires, Argentina. Methods HIV-positive ART-naïve patients ≥ 18 years old starting care 2011-2013 contributed data until the end of 2014. Three outcomes were assessed in 2014: retention in care, ART use, and viral suppression. Patient characteristics associated with each outcome were assessed through logistic regression. Results A total of 1 031 patients were included. By the end of 2014, 1.5% had died and 14.8% were transferred to a different center. Of the remaining 859 patients, 563 (65.5%) were retained in 2014. Among those retained, 459 (81.5%) were on ART in 2014. Of those 459 on ART, 270 (58.8%) were virologically suppressed. Younger age was associated with lower retention (OR (odds ratio): 0.67; 95% CI (confidence interval): 0.44-0.92 for ≥ 35 vs. < 35 years), but unrelated with ART use or viral suppression. Low CD4 count at first visit was associated with ART use (OR: 35.72 for CD4 < 200, 7.13 for CD4 200-499 vs. ≥ 500, P < 0.001) and with virologic suppression (OR: 2.17 for CD4 < 200, 2.46 for CD4 200-499 vs. ≥ 500, P: 0.023). Conclusions Our hospital in Buenos Aires is still below the recommended 90-90-90 targets of the Joint United Nations Programme on HIV/AIDS (UNAIDS) for ART use and viral suppression. We found a major gap in retention in care. Identifying younger age as being associated with worse retention will help in the design of targeted interventions.

RESUMEN Objetivo Determinar las tasas de retención, uso de tratamiento antirretroviral (TAR) y supresión viral en una cohorte adulta de un hospital público de referencia de atención terciaria en la ciudad de Buenos Aires (Argentina). Métodos Pacientes de 18 años de edad o mayores seropositivos al VIH que no habían recibido tratamiento con antirretrovirales y que comenzaron a ser atendidos entre el 2011 y el 2013 aportaron datos hasta finales del 2014. En el 2014 se evaluaron tres resultados: la retención de los pacientes en los servicios de atención, el uso de TAR y la supresión viral. Se usó la regresión logística para evaluar las características de los pacientes asociadas con cada resultado. Resultados Se estudió a 1 031 pacientes. A finales del 2014, 1,5% habían fallecido y 14,8% fueron transferidos a otro centro. De los 859 pacientes restantes, en el 2014 se retuvieron en los servicios a 563 (65,5%). Entre los que siguieron asistiendo a los servicios, 459 (81,5%) recibieron tratamiento antirretroviral ese año. De esos 459 que recibieron tratamiento antirretroviral, se alcanzó la supresión viral en 270 (58,8%). Se determinó que una menor edad estaba asociada a una menor tasa de retención (razón de posibilidades (OR): 0,67; intervalo de confianza de 95% (IC): 0,44-0,92 para ≥ 35 frente a < 35 años), pero no con el uso de tratamiento antirretroviral o la supresión viral. También se determinó que un bajo nivel de CD4 en la primera consulta estaba asociado al uso de tratamiento antirretroviral (OR: 35,72 para CD4 < 200, 7,13 para CD4 200-499 frente a ≥ 500, P < 0,001) y a la supresión viral (OR: 2,17 para CD4 < 200, 2,46 para CD4 200-499 frente a ≥ 500, P: 0,023). Conclusiones Nuestro hospital en Buenos Aires todavía está por debajo de las metas 90‑90‑90 recomendadas por el Programa Conjunto de las Naciones Unidas sobre el VIH/SIDA (ONUSIDA) para el uso de terapia antirretroviral y la supresión viral. Encontramos una brecha importante en la retención de los pacientes en los servicios de atención. La asociación de una menor edad con peores tasas de retención será útil en el diseño de intervenciones destinadas a poblaciones específicas.

Diagnóstico, seguimiento y tratamiento de las infecciones por hepatitis B y C en personas privadas de su libertad en Argentina / Diagnosis, monitoring and treatment of hepatitis B and C in Argentinian prisoners

Hasta un tercio de las personas privadas de su libertad presentan serología positiva para virus de la hepatitis C y hasta un 5% refiere ser HIV positivo. No hay a la fecha estudios específicos de esta población en nuestro país. Objetivo: implementar en el Servicio Penitenciario un protocolo de diagnóstico, seguimiento y tratamiento de internos infectados con virus de hepatitis B y C. Material y métodos: Estudio prospectivo de diagnóstico, seguimiento y tratamiento realizado entre marzo 2010 y noviembre 2012 en una prisión federal de máxima seguridad. Se ofreció realizar biopsia hepática previo al tratamiento de hepatitis C. Resultados: Fueron evaluados en total de 55 internos con serologías positivas, para Anti HBc (n=15) o Elisa HCV (n=51). El 62% de los mismos (n=34) se encontraban co-infectados con HIV. El genotipo HCV más frecuente fue el número 1. La biopsia hepática se realizó en 16 pacientes. El 44% de ellos (n=7) fueron informados como METAVIR FO-F1. El tratamiento con interferón pegilado-ribavirina fue indicado a 10 internos. Conclusiones: En un lapso de 2 años se implementó con éxito un servicio de atención médica para el diagnóstico, seguimiento y tratamiento de las hepatitis crónicas por HBV-HCV en personas privadas de libertad. Se trata de un modelo único en Latinoamérica. Una correcta selección inicial de los pacientes permitió en el corto plazo tener una respuesta al tratamiento en HCV similar a reportes internacionales...

Up to one third of prisoners have tested positive for hepatitis C and up to 5% report being HIV positive. Until now, there are no reports of treatment in this population in our country. Objective: to implement in federal prisons a protocol for diagnosis, monitoring and treatment of inmates infected with hepatitis B and C. Methods: prospective study of monitoring and treatment between March 2010 and November 2012 in a maximum security federal prison. Liver biopsy was offered prior to treatmente of hepatitis C. Results: We evaluated a total of 55 inmates, with Anti HBc positive serology (n=15) or HCV positive (n=51). 62% of them (n=34) were co-infected with HIV. The most frequent hepatitis C genotype was number 1. Liver biopsy was performed in 16 patients. 44% of them (n=7) were informed as METAVIR FO-F1. Treatmente with pegylated interferon-ribavirin was given to 10 inmates. Conclusions: with in a 2 year period we successfully implemented a health care service for the monitoring and treatment of chronic hepatitis B and C. This is a unique model in Latin America. Proper initial selection of patients allowed us in the short term to have treatment responses in hepatitis C similar to international reports...

Interacción entre el virus de la inmunodeficiencia humana y el virus GB tipo-C durante el estado de co-infección / Interaction between HIV-1 and GB virus type-C during coinfection status

The human immunodeficiency virus (HIV) infection is one of the most important problems in public health. It is estimated that 3 3 million people are infected around the world. HIV and GBV-C share the same transmission route, being frequent the co-infection. Since both viruses replicate in CD4+ lymphocytes, recent studies have described an interaction. Decreasing of HIV viral load and higher CD4 counts have been observed in co-infected patients, leading a better clinical outcome. Nevertheless, some epidemiological studies have shown contradictory results. Additionally, in vitro models report inhibition of HIV by E1, E2, NS3 and NS5A GBV-C proteins, resulting in a decreasing of p24 antigen. This review summarizes the principal findings about co-infection and mechanisms that have been proposed for HIV-1 inhibition.

La infección por el virus de la inmunodeficiencia humana (VIH) continúa siendo uno de los principales problemas en salud pública; se estima que existen actualmente más de 33 millones de personas infectadas en el mundo. El VIH y el virus GB tipo C (GBV-C) comparten la misma vía de transmisión, por lo que es frecuente encontrar individuos co-infectados. Estudios recientes han descrito un efecto inhibitorio asociado a disminución en la carga viral de VIH, altos recuentos de CD4 y mayor tiempo de sobrevida en pacientes co-infectados, resultando en un mejor pronóstico y menor progreso a SIDA; adicionalmente, estudios in vitro indican que las proteínas virales E1, E2, NS3 y NS5A del GBV-C estarían implicadas en la inhibición del VIH-1. En el presente artículo se revisan los principales aspectos de la co-infección, y se describen los mecanismos propuestos para la inhibición de la replicación del VIH-1 mediada por las proteínas virales del GBV-C.

Prevalence of discordant immunologic and virologic responses in patients with AIDS under antiretroviral therapy in a specialized care center in Brazil / Prevalência da resposta imunológica e virológica discordante em pacientes com AIDS sob terapêutica antirretroviral em ambulatório de centro de cuidados especializados no Brasil

Some patients under antiretroviral therapy (ART) do not reach immune recovery when the viral load becomes undetectable. This is called discordant immunologic and virologic responses. Its prevalence varies between 8 percent and 24 percent. This study describes its prevalence and the characteristics of the affected subjects in the outpatient clinic of a Brazilian specialized-care center. Of 934 patients on ART, 536 had undetectable viral loads. Prevalence was 51/536 or 9 percent (95 percent confidence interval: 6.6 percent to 11.4 percent). Median age at the beginning of ART was 37 years (interquartile range - IQR: 31 to 45). Male gender and mixed race predominated (76.5 percent and 47.1 percent respectively). AIDS-defining illnesses were absent at the beginning of ART in 60.8 percent. Fifty-one percent were taking protease inhibitors, 43.2 percent Efavirenz and 5.8 percent both. Median time on ART was 36 months (IQR: 17-81 months). Irregular treatment was recorded for 21.6 percent. ART had been modified for 63 percent prior to the study, and 15.7 percent had used monotherapy or double therapy. Median CD4 count was 255 cells/mm³ (IQR: 200-284). Median viral load before ART was 4.7 log10 copies/mL (IQR: 4.5-5.2). Discordant responders were not different from AIDS patients in general, but there was a high frequency of multiple schedules of treatment.

Alguns pacientes sob terapêutica antirretroviral (TARV) não obtêm recuperação imune quando a carga viral se torna indetectável. Isto é chamado resposta imunológica e virológica discordante. A prevalência varia entre 8 por cento e 24 por cento. Este estudo descreve sua prevalência e características dos afetados em ambulatório de um centro de cuidados especializados brasileiro. De 934 pacientes sob TARV, 536 tinham carga viral indetectável. A prevalência foi 51/536, ou 9 por cento (Intervalo de Confiança de 95 por cento de 6,6 por cento a 11,4 por cento). Idade mediana no início da TARV foi 37 anos (distância interquartílica - DQ: 31 a 45). Gênero masculino e cor parda predominaram (76,5 por cento e 47,1 por cento, respectivamente). Doenças definidoras de Aids estavam ausentes no início da TARV em 60,8 por cento. Cinquenta e um por cento recebiam inibidores da Protease, 43,2 por cento Efavirenz e 5,8 por cento ambos. Tempo mediano de TARV foi 36 meses (DQ: 17-81). Tratamento irregular foi registrado em 21,6 por cento. TARV havia sido anteriormente modificado em 63 por cento e 15,7 por cento haviam usado mono ou dupla terapêutica. A contagem mediana de CD4 foi 255 células/mm³ (DQ: 200-284). O logaritmo mediano da carga viral antes do TARV foi 4,7 (DQ: 4,5-5,2). Aqueles com resposta discordante não eram diferentes dos pacientes com AIDS em geral, mas houve alta frequência de múltiplos esquemas terapêuticos.

Prevalencia de trombocitopenia en niños con HIV/sida / Prevalence of thrombocytopenia in HIV infected children

La trombocitopenia es una de las múltiples alteraciones hematológicas presentes en pacientes infectados con el virus de la inmunodeficiencia humana (HIV). Puede ser de curso crónico, en la cual la destrucción inmune, el secuestro esplénico o el daño en la producción son los mecanismos primariamente involucrados, o aguda, acompañando a otra intercurrencia. En este trabajo se evaluó la prevalencia de trombocitopenia en un lapso de 14 años, en una población pediátrica con HIV/sida, analizando las características clínicas y la relación con el estado inmuno-virológico. La prevalencia de trombocitopenia fue de 8.5%, (29 de los 339 niños en seguimiento). En 22 fue de curso crónico y en 7 aguda. Los pacientes evaluados presentaron niveles porcentuales de TCD4+ variables y la presencia de trombocitopenia no estuvo en relación con el compromiso inmunitario. Los pacientes trombocitopénicos tuvieron niveles de carga viral significativamente mayores que los que no la presentaron. En 10 de los 29 niños con recuentos plaquetarios disminuidos, la trombocitopenia fue la manifestación inicial de la infección por HIV. Las manifestaciones hemorrágicas de las trombocitopenias crónicas fueron leves, presentes en el 23% de los niños y no se asociaron al deterioro inmunológico, mientras que en las agudas fueron más graves y condicionadas a la evolución de la enfermedad coexistente. El desarrollo de trombocitopenias se ve favorecido por la continua actividad viral y la falla en la implementación del tratamiento antirretroviral adecuado.

Thrombocytopenia is a common hematologic finding in patients infected with the human immunodeficiency virus. Multiple mechanisms may contribute to the development of chronic thrombocytopenia as immune-mediated platelet destruction, enhanced platelet splenic sequestration and impaired platelet production. Acute thrombocytopenia is frequently associated with coexisting disorders. In this study, the prevalence of thrombocytopenia was evaluated in a cohort of HIV infected children analyzing the clinical features and the association with the immunological and virological status of the disease in a 14 year-follow-up period. Thrombocytopenia prevalence was of 8.5% (29 out 339 children evaluated). Chronic and acute thrombocytopenia was observed in 22 and 7 children respectively. The percentages of CD4+ T cells were variable and not related with the presence of thrombocytopenia. Thrombocytopenic patients showed viral load levels significantly increased; being the thrombocytopenia the initial clinical manifestation of HIV infection in 10 out 29 children. Mild chronic thrombocytopenia bleeding found in 23% of children evaluated was not correlated with the immunologic status of the disease. In contrast, the severity of acute thrombocytopenia depended on the evolution of associated clinical conditions. Constant viral activity and failure in the use of antiretroviral agents might induce the development of thrombocytopenia in HIV-infected children.

Resistência do HIV-1 aos antirretrovirais e novas perspectivas de tratamento / Resistance of the HIV-1 to the antiretroviral and new treatment perspectives

O acesso à terapia antirretroviral (TARV) tem garantido uma melhoria significativa na qualidade de vida dos indivíduos HIV--positivos, sobretudo em países onde a distribuição destes medicamentos é gratuita, como no Brasil. Entretanto, um dos principais fatores associados à falha terapêutica é o surgimento de resistência às drogas e a transmissão de vírus resistentes. O presente artigo apresenta os mecanismos de atuação das drogas antirretrovirais (ARVs) em uso, a epidemiologia da resistência do HIV-I, suas consequências, bem como novas perspectivas de tratamento.

Access to antiretroviral therapy has granted a significant improvement in quality of life for HIV-I positive individuals, especially in countries where treatment is free-of-charge, such as Brazil. However, one of the leading factors associated with treatment failure is the development and transmission of resistant viruses. This present article presents the mechanisms of action of antiretroviral drugs (ARVs) in use, the epidemiology and consequences of HIV-I resistance, and new treatment perspectlves.

Is an HIV vaccine possible?

The road to the discovery of a vaccine for HIV has been arduous and will continue to be difficult over the ensuing twenty years. Most vaccines are developed by inducing neutralizing antibodies against the target pathogen or by using attenuated strains of the particular pathogen to engender a variety of protective immune responses. Unfortunately, simple methods of generating anti-HIV antibodies have already failed in a phase III clinical trial. While attenuated SIV variants work well against homologous challenges in non-human primates, the potential for reversion to a more pathogenic virus and recombination with challenge viruses will preclude the use of attenuated HIV in the field. It has been exceedingly frustrating to vaccinate for HIV-specific neutralizing antibodies given the enormous diversity of the Envelope (Env) glycoprotein and its well-developed glycan shield. However, there are several antibodies that will neutralize many different strains of HIV and inducing these types of antibodies in vaccinees remains the goal of a vigorous effort to develop a vaccine for HIV based on neutralizing antibodies. Given the difficulty in generating broadly reactive neutralizing antibodies, the HIV vaccine field has turned its attention to inducing T cell responses against the virus using a variety of vectors. Unfortunately, the results from Merck's phase IIb STEP trial proved to be disappointing. Vaccinees received Adenovirus type 5 (Ad5) expressing Gag, Pol, and Nef of HIV. This vaccine regimen failed to either prevent infection or reduce the level of HIV replication after challenge. These results mirrored those in non-human primate testing of Ad5 using rigorous SIV challenge models. This review will focus on recent developments in HIV vaccine development. We will deal largely with attempts to develop a T cell-based vaccine using the non-human primate SIV challenge model.