High Level of Pretreatment and Acquired Human Immunodeficiency Virus Drug Resistance in El Salvador: A Nationally Representative Survey, 2018-2019.

Background: Human immunodeficiency virus drug resistance (HIVDR) can negatively impact the effectiveness of antiretroviral therapy (ART). We aimed to estimate the prevalence of pretreatment HIVDR (PDR) among ART initiators and the prevalence of viral load (VL) suppression and acquired HIVDR among individuals receiving ART for 12 ± 3 months (ADR12) and ≥48 months (ADR48) in El Salvador. Methods: Nationally representative cross-sectional PDR, ADR12 and ADR48 surveys were conducted among adults with HIV from October 2018 to August 2019, following World Health Organization-recommended methods. Demographic and clinic data and blood specimens were collected. Results: Two hundred sixty participants were enrolled in the PDR survey, 230 in ADR12 and 425 in ADR48. Twenty-seven percent (95% confidence interval [CI], 17.1%-39.9%) of ART initiators had PDR to efavirenz or nevirapine. The prevalence of VL suppression was 88.8% (95% CI, 83.1%-92.8%) in ADR12 and 80.5% (95% CI, 76.6%-84.0%) in ADR48 surveys. Among people with HIV receiving a first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART regimens and with unsuppressed VL, the prevalence of ADR to efavirenz or nevirapine was 72.0% (95% CI, 32.3%-93.3%) and 95.0% (68.5%-99.4%) in the ADR12 and ADR28 surveys, respectively. ADR12 to boosted protease inhibitors (PI/r) or integrase strand transfer inhibitors (INSTIs) was not observed. ADR48 was 1.3% (95% CI, 0.2%-9.6%) and 2.1% (0.3%-13.7%), respectively. Conclusions: Programmatic improvements in ART delivery are urgently needed in El Salvador to address the high levels of resistance to efavirenz or nevirapine among ART initiators and the low VL suppression prevalence among individuals on treatment.

High level of pre-treatment and acquired HIV drug resistance in Honduras: a nationally representative survey, 2016-17.

BACKGROUND: Pre-treatment HIV drug resistance (HIVDR) to NNRTIs has consistently increased in low-/middle-income countries during the last decade. OBJECTIVES: To estimate the prevalence of pre-treatment HIVDR and acquired HIVDR among persons living with HIV (PLHIV) on ART for 12 ±âŸ3 months (ADR12) and ≥48 months (ADR48) in Honduras. PATIENTS AND METHODS: A nationwide cross-sectional survey with a two-stage cluster sampling was conducted from October 2016 to November 2017. Twenty-two of 54 total ART clinics representing >90% of the national cohort of adults on ART were included. HIVDR was assessed for protease and reverse transcriptase Sanger sequences using the Stanford HIVdb tool. RESULTS: A total of 729 PLHIV were enrolled; 26.3% (95% CI 20.1%-33.5%) ART initiators reported prior exposure to antiretrovirals. Pre-treatment HIVDR prevalence was 26.9% (95% CI 20.2%-34.9%) to any antiretroviral and 25.9% (19.2%-33.9%) to NNRTIs. NNRTI pre-treatment HIVDR was higher in ART initiators with prior exposure to antiretrovirals (P = 0.001). Viral load (VL) suppression rate was 89.7% (85.1%-93.0%) in ADR12 and 67.9% (61.7%-73.6%) in ADR48. ADR12 to any drug among PLHIV with VL ≥1000 copies/mL was 86.1% (48.9%-97.6%); 67.1% (37.4%-87.5%) had HIVDR to both NNRTIs and NRTIs, and 3.8% (0.5%-25.2%) to PIs. ADR48 was 92.0% (86.8%-95.3%) to any drug; 78.1% (66.6%-86.5%) to both NNRTIs and NRTIs, and 7.3% (1.8%-25.1%) to PIs. CONCLUSIONS: The high prevalence of NNRTI pre-treatment HIVDR observed in Honduras warrants consideration of non-NNRTI-based first-line regimens for ART initiation. Programmatic improvements in HIVDR monitoring and adherence support may also be considered.

High levels of pretreatment and acquired HIV drug resistance in Nicaragua: results from the first nationally representative survey, 2016.

INTRODUCTION: A nationally representative HIV drug resistance (HIVDR) survey in Nicaragua was conducted to estimate the prevalence of pretreatment HIVDR (PDR) among antiretroviral therapy (ART) initiators and acquired HIVDR among people living with HIV (PLHIV) who had received ART for 12 ± 3 months (ADR12) and ≥48 months (ADR48). METHODS: A nationwide cross-sectional survey with a two-stage cluster sampling was conducted from March to November 2016. Nineteen of 45 total ART clinics representing >90% of the national cohort of adults on ART were included. ART initiators were defined as PLHIV initiating or reinitiating first-line ART. HIVDR was assessed for protease, reverse transcriptase and integrase Sanger sequences using the Stanford HIVdb algorithm. Viral load (VL) suppression was defined as <1000 copies/mL. Results were weighted according to the survey design. RESULTS AND DISCUSSION: A total of 638 participants were enrolled (PDR: 171; ADR12: 114; ADR48: 353). The proportion of ART initiators with prior exposure to antiretrovirals (ARVs) was 12.3% (95% CI: 5.8% to 24.3%). PDR prevalence to any drug was 23.4% (95% CI: 14.4% to 35.6%), and 19.3% (95% CI: 12.2% to 29.1%) to non-nucleoside reverse transcriptase inhibitors (NNRTI). NNRTI PDR was higher in ART initiators with previous ARV exposure compared with those with no exposure (76.2% vs. 11.0%, p < 0.001). Protease inhibitors (PI) and integrase strand transfer inhibitors PDR was not observed. VL suppression rate was 77.8% (95% CI: 67.1% to 85.8%) in ADR12 and 70.3% (95% CI: 66.7% to 73.8%) in ADR48. ADR12 prevalence to any drug among PLHIV without VL suppression was 85.1% (95% CI: 66.1% to 94.4%), 82.4% to NNRTI and 70.2% to nucleoside reverse transcriptase inhibitors (NRTI). ADR48 prevalence to any drug among PLHIV without VL suppression was 75.5% (95% CI: 63.5% to 84.5 %), 70.7% to NNRTI, 59.4% to NRTI and 4.6% to PI. CONCLUSIONS: Despite implementation challenges yielding low-precision HIVDR estimates, high rates of NNRTI PDR were observed in Nicaragua, suggesting consideration of non-NNRTI-based first-line regimens for ART initiators. Strengthened HIVDR monitoring, systematic VL testing, and improved ART adherence support are also warranted.

Evolutionary history and spatiotemporal dynamics of the HIV-1 subtype B epidemic in Guatemala.

Different explanations exist on how HIV-1 subtype B spread in Central America, but the role of Guatemala, the Central American country with the highest number of people living with the virus, in this scenario is unknown. We investigated the evolutionary history and spatiotemporal dynamics of HIV-1 subtype B in Guatemala. A total of 1,047 HIV-1 subtype B pol sequences, from newly diagnosed ART-naïve, HIV-infected Guatemalan subjects enrolled between 2011 and 2013 were combined with published subtype B sequences from other Central American countries (n = 2,101) and with reference sequences representative of the BPANDEMIC and BCAR lineages from the United States (n = 465), France (n = 344) and the Caribbean (n = 238). Estimates of evolutionary, demographic, and phylogeographic parameters were obtained from sequence data using maximum likelihood and Bayesian coalescent-based methods. The majority of Guatemalan sequences (98.9%) belonged to the BPANDEMIC clade, and 75.2% of these sequences branched within 10 monophyletic clades: four also included sequences from other Central American countries (BCAM-I to BCAM-IV) and six were mostly (>99%) composed by Guatemalan sequences (BGU clades). Most clades mainly comprised sequences from heterosexual individuals. Bayesian coalescent-based analyses suggested that BGU clades originated during the 1990s and 2000s, whereas BCAM clades originated between the late 1970s and mid 1980s. The major hub of dissemination of all BGU, and of BCAM-II, and BCAM-IV clades was traced to the Department of Guatemala, while the root location of BCAM-I and BCAM-III was traced to Honduras. Most Guatemalan clades experienced initial phases of exponential growth (0.23 and 3.6 year-1), followed by recent growth declines. Our observations suggest that the Guatemalan HIV-1 subtype B epidemic is driven by dissemination of multiple BPANDEMIC founder viral strains, some restricted to Guatemala and others widely disseminated in the Central American region, with Guatemala City identified as a major hub of viral dissemination. Our results also suggest the existence of different sub-epidemics within Guatemala for which different targeted prevention efforts might be needed.

Optimización de recursos para determinar la carga viral de HIV-1 en un país con pocos recursos / Optimizing resources to reduce costs to determine HIV viral load in limited resources settings

Resumen Introducción. Las metas globales para controlar la epidemia de HIV contemplan que la carga viral sea indetectable en 90 % de las personas en tratamiento. El costo de la medición de la carga viral en lotes de muestras puede reducirse y, así, aumentar la cobertura cuando los recursos son limitados; sin embargo, su eficacia disminuye al aumentar la prevalencia del fracaso del tratamiento antirretroviral. Objetivo. Evaluar estrategias para disminuir la proporción de pacientes con fracaso del tratamiento antirretroviral en los lotes de muestras y, de esta manera, aumentar el ahorro en las pruebas de carga viral. Materiales y métodos. Las estrategias evaluadas fueron: a) la organización de los lotes de muestras según el esquema de tratamiento antirretroviral, y b) la exclusión de aquellos pacientes con antecedente reciente de fracaso del tratamiento antirretroviral, aquellos con menos de 12 meses de tratamiento antirretroviral y aquellos sin tratamiento antirretroviral previo. Los resultados de los lotes se compararon con los resultados individuales. Resultados. El valor diagnóstico negativo fue similar para los pacientes con esquema de primera línea (100,0 %; IC95% 99,5-100,0) o de segunda línea de tratamiento (99,4 %; IC95% 96,9-99,9). La incidencia del fracaso del tratamiento antirretroviral fue menor en los pacientes con tratamiento de primera línea (p<0,01), lo cual permitió un mayor ahorro en las pruebas de laboratorio en este grupo (74,0 %; IC95% 71,0-76,7) que en los pacientes con tratamiento de segunda línea (50,9 %; IC95% 44,4-57,3) (p<0,01). Conclusión. La selección de las muestras que se incluyeron en los lotes para determinar la carga viral del HIV según el tipo de esquema de tratamiento, permitió maximizar el porcentaje de ahorro en pruebas de laboratorio.

Abstract Introduction: HIV viral load testing is a key factor to evaluate the accomplishment of the UNAIDS target of 90% of viral suppression among people receiving antiretroviral therapy. Pooled samples are a potentially accurate and economic approach in resource-constrained settings, but efficiency can be negatively affected by high prevalence rates of virological failure. Objective: Strategies were assessed to increase the relative efficiency of pooled HIV viral load testing in resource-constrained settings. Materials and methods: We evaluated two strategies: a) plasma samples were not included in pools if patients had <12 months on antiretroviral therapy, patients had previous viral load >1,000 copies/ml, or were antiretroviral therapy naïve patients, and b) plasma pools were organized separately for first and second-line antiretroviral therapy regimens. Individual viral load tests were used to compare pooled results. Results: Negative predictive values were similar for patients on first (100.0%; 95% CI 99.5 to 100.0) and second-line antiretroviral therapy regimens (99.4%; 95% CI 96.9 to 99.9). However, the incidence of virological failure among individuals on first-line antiretroviral therapy was lower than second-line antiretroviral therapypatients (p <0.01), resulting in greater savings in laboratory tests in patients on first-line antiretroviral therapy (74.0%; 95% CI 71.0 to 76.7) compared with the group of patients on second-line antiretroviral therapy (50.9%; 95% CI 44.4 to 57.3) (p<0.01). Conclusion: Selecting the samples to be included in the pools and selecting the pools according to ART regimens are criteria that could lead to decreased spending on laboratory tests for HIV viral load determination in resource-constrained settings.

[Optimizing resources to reduce costs to determine HIV viral load in limited resources settings].

INTRODUCTION: HIV viral load testing is a key factor to evaluate the accomplishment of the UNAIDS target of 90% of viral suppression among people receiving antiretroviral therapy. Pooled samples are a potentially accurate and economic approach in resource-constrained settings, but efficiency can be negatively affected by high prevalence rates of virological failure. OBJECTIVE: Strategies were assessed to increase the relative efficiency of pooled HIV viral load testing in resource-constrained settings. MATERIALS AND METHODS: We evaluated two strategies: a) plasma samples were not included in pools if patients had <12 months on antiretroviral therapy, patients had previous viral load >1,000 copies/ml, or were antiretroviral therapy naïve patients, and b) plasma pools were organized separately for first and second-line antiretroviral therapy regimens. Individual viral load tests were used to compare pooled results. RESULTS: Negative predictive values were similar for patients on first (100.0%; 95% CI 99.5 to 100.0) and second-line antiretroviral therapy regimens (99.4%; 95% CI 96.9 to 99.9). However, the incidence of virological failure among individuals on first-line antiretroviral therapy was lower than second-line antiretroviral therapy patients (p <0.01), resulting in greater savings in laboratory tests in patients on first-line antiretroviral therapy (74.0%; 95% CI 71.0 to 76.7) compared with the group of patients on second-line antiretroviral therapy (50.9%; 95% CI 44.4 to 57.3) (p<0.01). CONCLUSION: Selecting the samples to be included in the pools and selecting the pools according to ART regimens are criteria that could lead to decreased spending on laboratory tests for HIV viral load determination in resource-constrained settings.

HIV-1 drug resistance surveillance in antiretroviral treatment-naive individuals from a reference hospital in Guatemala, 2010-2013.

The recent expansion of antiretroviral treatment (ART) coverage in middle/low-income countries has been associated with increasing prevalence of HIV pre-ART drug resistance (PDR). We assessed PDR prevalence, patterns, and trends in Guatemala. Blood samples from 1,084 ART-naive individuals, enrolled from October 2010 to December 2013 at the Roosevelt Hospital in Guatemala City, were obtained. PDR was evaluated using the WHO mutation list for transmitted drug resistance (TDR) surveillance. An overall PDR prevalence of 7.3% (95% CI 5.8-9.0%) was observed for the whole study period. TDR to nonnucleoside reverse transcriptase inhibitors (NNRTI) was the highest (4.9%, p<0.001), followed by nucleoside RT inhibitors (1.8%) and protease inhibitors (1.0%). No significant trends in PDR prevalence were observed during the study period. However, higher NNRTI PDR levels were found in individuals with >500 and 350-500 CD4(+) T cells/µl (7.4% and 8.7%, respectively) compared to individuals with <350 CD4(+) T cells/µl (3.7%; p=0.039 and p=0.007, respectively), as well as a tendency of higher levels of NNRTI transmitted drug resistance (DR) in individuals with recent infection determined by HIV incidence tests (9.7%), suggesting increasing trends in time. Clusters of viruses with NNRTI PDR suggesting complex transmission networks were observed. No associations between PDR and demographic variables were found. PDR in Guatemala remains at an intermediate level. Nevertheless, we have shown evidence suggesting increasing trends in NNRTI PDR, which need to be taken into account in national HIV management policies.

Scale-up, retention and HIV/STI prevalence trends among female sex workers attending VICITS clinics in Guatemala.

BACKGROUND: Since 2007, Guatemala integrated STI clinical service with an HIV prevention model into four existing public health clinics to prevent HIV infection, known as the VICITS strategy. We present the first assessment of VICITS scale-up, retention, HIV and STI prevalence trends, and risk factors associated with HIV infection among Female Sex Workers (FSW) attending VICITS clinics in Guatemala. METHODS: Demographic, behavioral and clinical data were collected using a standardized form. Data was analyzed by year and health center. HIV and STI prevalence were estimated from routine visits. Retention was estimated as the percent of new users attending VICITS clinics who returned for at least one follow-up visit to any VICITS clinic within 12 months. Separate multivariate logistic regression models were conducted to investigate factors associated with HIV infection and program retention. RESULTS: During 2007-2011 5,682 FSW visited a VICITS clinic for the first-time. HIV prevalence varied from 0.4% to 5.8%, and chlamydia prevalence from 0% to 14.3%, across sites. Attending the Puerto Barrios clinic, having a current syphilis infection, working primarily on the street, and using the telephone or internet to contact clients were associated with HIV infection. The number of FSW accessing VICITS annually increased from 556 to 2,557 (361%) during the period. In 2011 retention varied across locations from 7.7% to 42.7%. Factors negatively impacting retention included current HIV diagnosis, having practiced sex work in another country, being born in Honduras, and attending Marco Antonio Foundation or Quetzaltenango clinic sites. Systematic time trends did not emerge, however 2008 and 2010 were characterized by reduced retention. CONCLUSIONS: Our data show local differences in HIV prevalence and clinic attendance that can be used to prioritize prevention activities targeting FSW in Guatemala. VICITS achieved rapid scale-up; however, a better understanding of the causes of low return rates is urgently needed.

Perfil de resistencia del VIH-1 a anti-retrovirales en pacientes con fallo virològico: Hospital Roosevelt-Guatemala 2008-2012 / Patterns of HIV-1 resistance to antiretroviral drugs in patients with virologic failure: Roosevelt Hospital, Guatemala 2008-2012

Objective: To assess the secondary resistance patterns of HIV-1to Anti-Retroviral Agents drugs (ART) in patients with virological failure in the main HIV care center in Guatemala. Methods: Using the Stanford HIV Database,HIV pol sequences were analyzed to obtain resistance patterns in patients with first-failure to ART or multiple-failures (2 or more regimens failed), from 2008 to 2012. Proportions and odds ratio (OR) with 95% confidence intervals (95%CI) were calculated. Results: 83% (43) in the first-failure and 75% (30) in multiple-failures had resistance. The highest frequency (70%)of resistance was found in the non-nucleoside-inhibitors ART family. 44% (42) showed resistance to two ART families and 4% (4) to the three families. First-failure patients had higher risk of nucleoside-inhibitor resistance (OR:3.0, 95%CI 1.29-6.98) and multidrug resistance (OR:4.94, 95%CI 1.98-12.32). Most frequent mutations were: M184V, K103N and K65R (71, 50 and 22%, respectively). 70% of patients with first-failure were resistant to at least one of the drugs used as second ART in Guatemala (ABC, ddI or AZT). Conclusions: The high level of HIV-1 resistance to ART observed, suggest the need to amend the current second line regimen treatments in Guatemala and the importance of viral genotyping in all patients with first-failure to ART.

Objetivo: Evaluar el perfil de resistencia secundaria del VIH-1 a anti-retrovirales (ARV) en pacientes con fallo virológico en la clínica de atención integral más grande de Guatemala. Métodos: Uso de Stanford HIV Database para análisis de secuencias pol para perfiles de resistencia de VIH en pacientes con fallo virológico al primer esquema ARV o fallo múltiple (dos o más esquemas ARV fallidos), entre los años 2008 y 2012. Determinación de proporciones y análisis de riesgo. Resultados: Evidencia de resistencia de 83% (n: 43) en primer fallo y 75% (n: 30) en fallo múltiple. La mayor frecuencia de resistencia se presentó en los inhibidores-no-nucleosídicos (70%). Cuarenta y cuatro por ciento (n: 42) evidenció resistencia a dos familias de ARV y 4% (n: 4) a las tres familias. Pacientes con primer fallo tuvieron más riesgo de resistencia a inhibidores-nucleosídicos (OR: 3,0; IC 95% 1,29-6,98) y más riesgo de multi-resistencia (OR: 4,94; IC 95% 1,98-12,32). Mutaciones más frecuentes fueron: M184V, K103N y K65R (71, 50 y 22%, respectivamente). Setenta por ciento de los pacientes con primer fallo presentaron resistencia a al menos uno de los medicamentos utilizado como segunda línea en Guatemala (ABC/ddI/AZT). Conclusiones: El alto nivel de resistencia del VIH-1 a los ARV observada, sugiere la necesidad de modificar el actual esquema terapéutico de rescate en Guatemala y la importancia de realizar genotipificación viral en todos los pacientes con fallo al primer esquema.

[Patterns of HIV-1 resistance to antiretroviral drugs in patients with virologic failure: Roosevelt Hospital, Guatemala 2008-2012]. / Perfil de resistencia del VIH-1 a anti-retrovirales en pacientes con fallo virològico: Hospital Roosevelt-Guatemala 2008-2012.

OBJECTIVE: To assess the secondary resistance patterns of HIV-1to Anti-Retroviral Agents drugs (ART) in patients with virological failure in the main HIV care center in Guatemala. METHODS: Using the Stanford HIV Database,HIV pol sequences were analyzed to obtain resistance patterns in patients with first-failure to ART or multiple-failures (2 or more regimens failed), from 2008 to 2012. Proportions and odds ratio (OR) with 95% confidence intervals (95%CI) were calculated. RESULTS: 83% (43) in the first-failure and 75% (30) in multiple-failures had resistance. The highest frequency (70%)of resistance was found in the non-nucleoside-inhibitors ART family. 44% (42) showed resistance to two ART families and 4% (4) to the three families. First-failure patients had higher risk of nucleoside-inhibitor resistance (OR:3.0, 95%CI 1.29-6.98) and multidrug resistance (OR:4.94, 95%CI 1.98-12.32). Most frequent mutations were: M184V, K103N and K65R (71, 50 and 22%, respectively). 70% of patients with first-failure were resistant to at least one of the drugs used as second ART in Guatemala (ABC, ddI or AZT). CONCLUSIONS: The high level of HIV-1 resistance to ART observed, suggest the need to amend the current second line regimen treatments in Guatemala and the importance of viral genotyping in all patients with first-failure to ART.