The proportion of HIVDR to at least one NRTI of the preferred second\line regimen, among PLHIV on first\line ART with unsuppressed VL, was 64.9% in DMX-5804 ADR12 and 54.5% in ADR48. 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%, em p /em ? ?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 concern of non\NNRTI\based first\line regimens for ART initiators. Strengthened HIVDR monitoring, systematic VL testing, and improved ART adherence support are also warranted. strong class=”kwd-title” Keywords: HIV, drug resistance, Nicaragua, World Health Business, antiretroviral therapy, treatment failure, surveillance 1.?Introduction A recent meta\analysis showed increasing pattern in HIV drug resistance (DR) to non\nucleoside reverse transcriptase inhibitors (NNRTI) in people living with HIV (PLHIV) starting first\line antiretroviral therapy (ART) in Latin America since 2007 1. This emergence of NNRTI pretreatment drug resistance (PDR) threatens the effectiveness of first\line NNRTI\based ART, currently the favored option in most countries of the region 2. In Nicaragua, ART scale\up has been ongoing since 2003 3. In 2018, among 9400 estimated PLHIV, 5000 DMX-5804 (53%) were on ART and 3,700 (40%) had achieved viral load (VL) suppression 4. ART abandonment rates as high as 30% have been previously reported 5. Low VL suppression rate represents an important risk for acquired drug resistance (ADR) and further PDR transmission 6. According to the national ART guidelines, the preferred first\line regimen for adults in Nicaragua is usually NNRTI\based (efavirenz (EFV)) and a protease inhibitor (PI)\based second\line regimen is used after confirmed viral failure (two consecutive unsuppressed VL measurements within a 2\month interval with adherence support, after at least six months Rabbit polyclonal to ANXA13 on ART) 3. VL and CD4 count are performed semi\annually for ART monitoring, but HIVDR testing is not routinely available 3. A 2011 to 2015 sentinel survey among ART\naive PLHIV enrolled at Nicaragua’s largest HIV clinic, Roberto Calderon Hospital, found increasing rates of NNRTI PDR, with overall prevalence of 11.3% (95% confidence interval (CI): 7.9% to 15.6%) 7. In response to rising levels of NNRTI PDR in low\ and middle\income countries (LMIC), the World Health Business (WHO) developed a Global Action Plan with a 5\12 months framework 8 that strongly recommends the implementation of nationally representative HIVDR surveys based on a standardized methodology 9. Implementation of HIVDR surveillance strategies at the country level is critical to not only inform policy and advocate for updated ART guidelines, but also to better understand HIVDR locally 6, 10. Given the worrying scenario of HIVDR in Nicaragua and following WHO recommendations, we performed a nationally representative survey to estimate PDR and ADR among PLHIV on ART for 12??3?months (ADR12) and 48?months (ADR48). 2.?Methods 2.1. Study design We carried out a cross\sectional survey with a two\stage cluster sampling, following WHO\recommended methods 11, 12. Nineteen out of a total of 45 ART clinics were selected, excluding smaller clinics (n?=?26) that combined comprised 10% of the national cohort of adults on.Resistance was defined as a penalty score 15 using the Stanford HIVdb tool (v8.2). 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%, em p /em ? ?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 concern of non\NNRTI\based first\line regimens for ART initiators. Strengthened HIVDR monitoring, systematic VL testing, and improved ART adherence support are also warranted. strong class=”kwd-title” Keywords: HIV, drug resistance, Nicaragua, World Health Business, antiretroviral therapy, treatment failure, surveillance 1.?Introduction A recent meta\analysis showed increasing pattern in HIV drug resistance (DR) to non\nucleoside reverse transcriptase inhibitors (NNRTI) in people living with HIV (PLHIV) starting first\line antiretroviral therapy (ART) in Latin America since 2007 1. This emergence of NNRTI pretreatment drug resistance (PDR) threatens the effectiveness of first\line NNRTI\based ART, the desired option generally in most countries of the spot 2. In Nicaragua, Artwork scale\up continues to be ongoing since 2003 3. In 2018, among 9400 approximated PLHIV, 5000 (53%) had been on Artwork and 3,700 (40%) got achieved viral fill (VL) suppression 4. Artwork abandonment rates up to 30% have already been previously reported 5. Low VL suppression price represents a significant risk for obtained drug level of resistance (ADR) and additional PDR transmitting 6. Based on the nationwide ART guidelines, the most well-liked first\line routine for adults in Nicaragua can be NNRTI\centered (efavirenz (EFV)) and a protease inhibitor (PI)\centered second\line regimen can be used after verified viral failing (two consecutive unsuppressed VL measurements within a 2\month period with adherence support, after at least half a year on Artwork) 3. VL and Compact disc4 count number are performed semi\yearly for Artwork monitoring, but HIVDR tests is not regularly obtainable 3. A 2011 to 2015 sentinel study among Artwork\naive PLHIV enrolled at Nicaragua’s largest HIV center, Roberto Calderon Medical center, found increasing prices of NNRTI PDR, with general prevalence of 11.3% (95% confidence period (CI): 7.9% to 15.6%) 7. In response to increasing degrees of NNRTI PDR in low\ and middle\income countries (LMIC), the Globe Health Corporation (WHO) developed a worldwide Action Plan having a 5\yr platform 8 that highly recommends the execution of nationally representative HIVDR studies predicated on a standardized strategy 9. Execution of HIVDR monitoring strategies at the united states level is crucial to not just inform plan and advocate for up to date ART recommendations, but also to raised understand HIVDR locally 6, 10. Provided the worrying situation of HIVDR in Nicaragua and pursuing WHO suggestions, we performed a nationally consultant survey to estimation PDR and ADR among PLHIV on Artwork for 12??3?weeks (ADR12) and 48?weeks (ADR48). 2.?Strategies 2.1. Research design We completed a mix\sectional survey having a two\stage cluster sampling, pursuing WHO\recommended strategies 11, 12. Nineteen out of a complete of 45 Artwork clinics were chosen, excluding smaller treatment centers (n?=?26) that combined comprised 10% from the country wide cohort of adults on Artwork. The test size was determined predicated on the possibility proportional to proxy size sampling method of obtain outcome estimations having a CI DMX-5804 of 5%. The next model assumptions had been designed for PDR survey test size computation: 10% prevalence of PDR, 20% genotyping failing, 25% of Artwork initiators with prior.