Implementing early-warning indicators of HIV drug resistance in the Caribbean.

A key component of the World Health Organization's (WHO's) Global HIV Drug Resistance (HIVDR) prevention and assessment strategy is to monitor HIVDR early-warning indicators (EWIs), which provide strategic information for HIVDR containment. The Pan American Health Organization (PAHO)/WHO supported implementation of HIVDR EWI monitoring in 16 Caribbean countries. Results from 15 countries were analyzed by year of patient initiation of antiretroviral therapy for the period 2005-2009. This report demonstrates the need for capacity-building to standardize prescribing practices and to strengthen adherence strategies and antiretroviral drug procurement management systems.

Progress of implementation of the World Health Organization strategy for HIV drug resistance control in Latin America and the Caribbean.

By the end of 2010, Latin America and the Caribbean (LAC) achieved 63% antiretroviral treatment (ART) coverage. Measures to control HIV drug resistance (HIVDR) at the country level are recommended to maximize the efficacy and sustainability of ART programs. Since 2006, the Pan American Health Organization has supported implementation of the World Health Organization (WHO) strategy for HIVDR prevention and assessment through regional capacity-building activities and direct technical cooperation in 30 LAC countries. By 2010, 85 sites in 19 countries reported early warning indicators, providing information about the extent of potential drivers of drug resistance at the ART site. In 2009, 41.9% of sites did not achieve the WHO target of 100% appropriate first-line prescriptions; 6.3% still experienced high rates (> 20%) of loss to follow-up, and 16.2% had low retention of patients (< 70%) on first-line prescriptions in the first year of treatment. Stock-outs of antiretroviral drugs occurred at 22.7% of sites. Haiti, Guyana, and the Mesoamerican region are planning and implementing WHO HIVDR monitoring surveys or threshold surveys. New HIVDR surveillance tools for concentrated epidemics would promote further scale-up. Extending the WHO HIVDR lab network in Latin America is key to strengthening regional lab capacity to support quality assured HIVDR surveillance. The WHO HIVDR control strategy is feasible and can be rolled out in LAC. Integrating HIVDR activities in national HIV care and treatment plans is key to ensuring the sustainability of this strategy.

HIV-1 epidemic in the Caribbean is dominated by subtype B.

BACKGROUND: The molecular epidemiology of HIV-1 in the Caribbean has been described using partial genome sequencing; subtype B is the most common subtype in multiple countries. To expand our knowledge of this, nearly full genome amplification, sequencing and analysis was conducted. METHODOLOGY/PRINCIPAL FINDINGS: Virion RNA from sera collected in Haiti, Dominican Republic, Jamaica and Trinidad and Tobago were reverse transcribed, PCR amplified, sequenced and phylogenetically analyzed. Nearly full genomes were completed for 15 strains; partial pol was done for 67 strains. All but one of the 67 strains analyzed in pol were subtype B; the exception was a unique recombinant of subtypes B and C collected in the Dominican Republic. Of the nearly full genomes of 14 strains that were subtype B in pol, all were subtype B from one end of the genome to the other and not inter-subtype recombinants. Surprisingly, the Caribbean subtype B strains clustered significantly with each other and separate from subtype B from other parts of the pandemic. CONCLUSIONS: The more complete analysis of HIV-1 from 4 Caribbean countries confirms previous research using partial genome analysis that the predominant subtype in circulation was subtype B. The Caribbean strains are phylogenetically distinct from other subtype B strains although the biological meaning of this finding is unclear.

Lessons from a multisite international trial in the Caribbean and South America of an HIV-1 Canarypox vaccine (ALVAC-HIV vCP1452) with or without boosting with MN rgp120.

BACKGROUND: The first multicenter, international National Institutes of Allergy and Infectious Diseases (NIAID)-sponsored HIV vaccine trial took place in Brazil, Haiti, Peru and Trinidad. This randomized, double-blind, placebo-controlled, phase 2 trial evaluated the safety and immunogenicity of a clade B-derived, live canarypox HIV vaccine, vCP1452. vCP1452 was administered alone or with a heterologous boost of MN rgp120 glycoprotein. The trial was pivotal in deciding whether these vaccines advanced to phase 3 efficacy trials. METHODS: Forty seronegative volunteers per site were randomized to ALVAC alone, ALVAC plus MN rgp120, or placebo in a 0, 1, 3, and 6 month schedule. Immunogenicity was assayed by chromium-release cytotoxic T lymphocyte (CTL) responses; interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot assays (ELISpot); lymphocyte proliferation assays (LPA); neutralization; and enzyme-linked immunosorbent assays (ELISA). RESULTS: Enrollment and follow-up were excellent. Both vaccines were well tolerated. Neutralizing antibody to the laboratory-adapted MN strain was detected. Cellular immune responses, as measured by CTL, ELISpot, and LPA, did not differ between vaccines and placebos. CONCLUSIONS: The observation of disappointing immunogenicity in this and a parallel domestic study has informed future vaccine development. Equally important, challenges to doing an integrated trial across countries, cultures, languages, and differing at-risk populations were overcome. The identification of specific safety, ethical, logistic, and immunological issues in this trial established the foundation for current larger international studies.

Progress of implementation of the World Health Organization strategy for HIV drug resistance control in Latin America and the Caribbean / Progreso en la aplicación de la estrategia de la Organización Mundialde la Salud para el control de la farmacorresistencia del VIH en América Latina y el Caribe

By the end of 2010, Latin America and the Caribbean (LAC) achieved 63% antiretroviral treatment (ART) coverage. Measures to control HIV drug resistance (HIVDR) at the countrylevel are recommended to maximize the efficacy and sustainability of ART programs. Since 2006, the Pan American Health Organization has supported implementation of the WorldHealth Organization (WHO) strategy for HIVDR prevention and assessment through regional capacity-building activities and direct technical cooperation in 30 LAC countries. By 2010, 85 sites in 19 countries reported early warning indicators, providing information about the extent of potential drivers of drug resistance at the ART site. In 2009, 41.9% of sites did notachieve the WHO target of 100% appropriate first-line prescriptions; 6.3% still experienced high rates (> 20%) of loss to follow-up, and 16.2% had low retention of patients (< 70%) on first-line prescriptions in the first year of treatment. Stock-outs of antiretroviral drugs occurred at 22.7% of sites. Haiti, Guyana, and the Mesoamerican region are planning and implementing WHO HIVDR monitoring surveys or threshold surveys. New HIVDR surveillance tools for concentrated epidemics would promote further scale-up. Extending the WHO HIVDR lab network in Latin America is key to strengthening regional lab capacity to support quality assuredHIVDR surveillance. The WHO HIVDR control strategy is feasible and can be rolled out in LAC. Integrating HIVDR activities in national HIV care and treatment plans is key to ensuring the sustainability of this strategy.

Hacia fines del 2010, América Latina y el Caribe lograron una cobertura de tratamiento antirretroviral de 63%. Se recomienda la ejecución de medidas para controlar la farmacorresistencia del VIH a nivel de país para potenciar al máximo la eficacia y la sostenibilidad de los programas de tratamiento antirretroviral. Desde el 2006, la Organización Panamericana de la Salud ha apoyado la aplicación de la estrategia de la Organización Mundial de la Salud (OMS) para la prevención y la evaluación de la farmacorresistenciadel VIH mediante actividades regionales de formación de capacidad y de cooperación técnica directa en 30 países de América Latina y el Caribe. En 2010, 85 centros en 19 países notificaron indicadores de alerta temprana y suministraron información acerca del alcance de los posibles impulsores de la farmacorresistencia enlos centros de tratamiento antirretroviral. En el 2009, 41,9% de los centros no lograron la meta de la OMS de 100% de prescripción de medicamentos de primera línea apropiados; 6,3% todavía tenían tasas elevadas (> 20%) de pérdida de seguimiento y 16,2% tenían una baja retención de pacientes (< 70%) en tratamiento con antirretrovirales deprimera línea en el primer año de tratamiento. Se registraron desabastecimientos de medicamentos antirretrovirales en 22,7% de los centros. Haiti, Guyana y la zona mesoamericana están planificando y ejecutando estudios de vigilancia de la farmacorresistencia del VIH o estudios del umbral de la OMS. Las nuevas herramientas para la vigilancia de la farmacorresistencia del VIH en las epidemias concentradas permitiránuna mejor vigilancia. La ampliación de la red de laboratorios de farmacorresistenciadel VIH acreditados por la OMS en América Latina es fundamental para el fortalecimientode la capacidad de los laboratorios regionales, a fin de de efectuar una vigilancia de la farmacorresistencia del VIH de calidad garantizada...

Improved classification of recent HIV-1 infection by employing a two-stage sensitive/less-sensitive test strategy.

Current serologic techniques for the classification of recent HIV-1 infection produce some misclassifications, and, together with the loss to follow-up of individuals, results in decreased enrollment of HIV-infected persons into appropriate intervention programs. We report on the development of a sensitive/less sensitive (S/LS) test strategy that includes a rapid assay to quickly identify persons most likely to have recent infection, followed by an enzyme immunoassay (EIA) with exquisite specificity. The Uni-Gold Recombigen HIV rapid assay (UG; Trinity Biotech, Dublin, Ireland) was procedurally-modified and calibrated as an LS test to differentiate recent (<133 days) from established HIV infections using 178 samples from persons with known dates of infection. This method correctly classified 83.0% of recent infections, but with a high misclassification rate of persons with established infection. By performing the rapid test followed by a modified S/LS EIA, the positive predictive value of the combined results for recent infections was increased to 100%. This two-stage testing algorithm can result in an increased efficiency for the enrollment of recent infection cases over a standard EIA S/LS method alone due to provisional enrollment during an initial testing visit, and because of an increased accuracy for identifying truly recent infections. We conclude that the rapid S/LS assay provides a tool for capturing recent infection cases quickly and is particularly valuable in resource-limited settings, and that the two-stage strategy provides a more accurate identification of persons with recent HIV infection.

Rapid clearance of virus after acute HIV-1 infection: correlates of risk of AIDS.

OBJECTIVE: Our objective was to define early virologic and immunologic determinants of human immunodeficiency virus (HIV) type 1 disease progression among 22 case subjects with acute infection from the Trinidad Seroconvertor Cohort. METHODS: A linear segmented regression model was fitted to sequential quantitative virus load measurements. Parameters of virus kinetics during different phases of primary infection were correlated with clinical and immunologic end points, by use of Kaplan-Meier estimates and Cox regression. RESULTS: Ten individuals developed acquired immunodeficiency syndrome (AIDS)-defining events. In univariate analysis, progression to AIDS was associated with rate of initial HIV clearance (P=.002), virus load during set point (P=.008), and CD4(+) cell count during steady state (P=.04). In the multivariate analysis, a rapid rate of initial clearance was the sole independent predictor of subsequent progression to AIDS and was associated with a 92% reduction in the risk of AIDS. The rate of initial clearance is inversely correlated with the number of early symptoms (r=-0.66; P=.0008). However, symptoms did not predict subsequent risk of AIDS. CONCLUSION: Among a subset of patients, rapid clearance of plasma HIV-1 after peak viremia is associated with lower viral set point, prolonged virus suppression before loss of virologic control, and decreased risk of AIDS. These findings are consistent with the hypothesis that effective immune responses during the earliest phase of infection are important determinants of the subsequent natural history.