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

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Abstract

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.

Translated abstract

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 farmacorresistencia del 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 en los 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 de primera 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 farmacorre-sistencia del VIH o estudios del umbral de la OMS. Las nuevas herramientas para la vigilancia de la farmacorresistencia del VIH en las epidemias concentradas permitirán una mejor vigilancia. La ampliación de la red de laboratorios de farmacorresistencia del VIH acreditados por la OMS en América Latina es fundamental para el fortalecimiento de la capacidad de los laboratorios regionales, a fin de de efectuar una vigilancia de la farmacorresistencia del VIH de calidad garantizada. La estrategia para el control de la farmacorresistencia del VIH de la OMS es factible y puede implantarse en América Latina y el Caribe. La integración de las actividades de vigilancia de la farmacorresistencia del VIH con los planes nacionales de atención y tratamiento del VIH es fundamental para garantizar la sostenibilidad de esta estrategia.

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Brazilian Network for HIV Drug Resistance Surveillance: a survey of individuals recently diagnosed with HIV

Lilian Inocencio, Anderson Pereira, Maria Sucupira … (2009)

Use of antiretrovirals is widespread in Brazil, where more than 200,000 individuals are under treatment. Although general prevalence of primary antiretroviral resistance in Brazil is low, systematic sampling in large metropolitan areas has not being performed. The HIV Threshold Survey methodology (HIV-THS, WHO) was utilized, targeting Brazil's four major regions and selecting the six most populated state capitals: Sao Paulo, Rio de Janeiro, Salvador, Porto Alegre, Brasilia and Belem. We were able to sequence samples from 210 individuals with recent HIV diagnosis, 17 of them (8.1%) carrying HIV isolates with primary antiretroviral resistance mutations. Five, nine and four isolates showed mutations related to resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), respectively. Using HIV-THS, we could find an intermediate level of transmitted resistance (5% to 15%) in Belem/Brasilia, Sao Paulo and Rio de Janeiro. Lower level of transmitted resistance (<5%) were observed in the other areas. Despite the extensive antiretroviral exposure and high rates of virologic antiretroviral failure in Brazil, the general prevalence of primary resistance is still low. However, an intermediate level of primary resistance was found in the four major Brazilian cities, confirming the critical need to start larger sampling surveys to better define the risk factors associated with transmission of resistant HIV.

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Brazilian Network for HIV Drug Resistance Surveillance (HIV-BResNet): a survey of chronically infected individuals.

Kátia Sabino, Rodrigo Brindeiro, R. Graciani Diaz … (2003)

To study the prevalence of HIV drug resistance mutations and subtype distribution in a Brazilian drug-naive population. Asymptomatic, drug-naive HIV-1-infected individuals were targeted in 13 voluntary counseling and testing centers spread around the country. Plasma viral RNA was extracted from 535 HIV-1-positive subjects. Protease (PR) and reverse transcriptase (RT) genomic regions were sequenced for subtype determination and analysis of drug resistance mutations. Eight samples (2.24 %) showed primary mutations related to protease inhibitor (PI) resistance, eight (2.36%) to nucleoside reverse transcriptase inhibitors (NRTI) and seven (2.06%) to non-nucleoside reverse transcriptase inhibitors (NNRTI). Accessory mutations were found in the PR gene at the following positions: L63P/V/T/A/I [153/345 (44.3%)], M36I/L [149/345 (43.2%)], L10I/F/V [82/345 (23.8%)], V77I [60/345 (17.4%)], A71V/T [11/345 (3.2%)], K20M/R [10/345 (2.9%)], and V82I [4/345 (1.2%)]. Mutations known to be associated with reduced sensitivity to NRTI or NNRTI (V118I, E44D, K219R, T69A, and V75L) were found in a low prevalence (0.6-2.4%). A high proportion of the isolates from subtype C was found in the southern states. Subtype F-related viruses were the main non-B variant in the rest of the country. Brazil has a low prevalence of drug-resistant strains circulating among recently diagnosed individuals. However, there was an increase in these rates compared with similar studies performed with samples collected in Brazil from 1996 to 1998. Continued surveys are required to detect trends in these rates, but routine genotypic testing in the drug-naive population prior to antiretroviral initiation is not required in Brazil.

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Primary antiretroviral drug resistance among HIV type 1-infected individuals in Brazil.

João P. M. S. Lima, Roberto Zajdenverg, Carlos Machado … (2009)

Infection with drug-resistant human immunodeficiency virus type 1 (HIV-1) has been documented in all countries that have surveyed for it and may result in an unfavorable response to therapy. The prevalence and characteristics of individuals with transmitted resistance to antiretroviral drugs have been scarcely described in Brazil. We performed antiretroviral resistance testing prior to initiation of therapy in 400 subjects enrolled from 20 centers in 13 Brazilian cities between March and September 2007. Genotyping was conducted using PCR-amplified HIV pol products by automated sequencing, and genotype interpretation was done according to the IAS-USA consensus. Of 400 eligible participants, 387 (95.8%) were successfully tested. Seven percent of antiretroviral-naive patients carried viruses with one or more major mutation associated with drug resistance. The prevalence of these mutations was 1.0% for protease inhibitors, 4.4% for nonnucleoside reverse transcriptase inhibitors, and 1.3% for nucleoside reverse transcriptase inhibitors. The frequency of multidrug resistance among the resistant strains was 13.6%. Among subjects infected with drug-resistant virus, the majority were infected with subtype B viruses (91%). Subjects from the city of São Paulo had higher transmitted resistance mutations compared to the rest of the country. Reporting a partner taking antiretroviral medications was associated with a higher chance of harboring HIV variants with major drug resistance mutations [odds ratio = 2.57 (95% confidence interval, 1.07-6.16); p = 0.014]. Resistance testing in drug-naive individuals identified 7% of subjects with mutations associated with reduced susceptibility to antiretroviral drugs. Continued surveillance of drug-resistant HIV-1 in Brazil is warranted when guidelines for HIV prophylaxis and treatment are updated. Resistance testing among drug-naive patients prior to treatment initiation should be considered, mainly directed at subjects whose partners are already on antiretroviral therapy.