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Abstract：
BACKGROUND: In 2022, the WHO reported that 29.8 million people around the world were living with HIV (PLHIV) and receiving antiretroviral treatment (ART), including 25 375 people in Gabon (54% of all those living with HIV in the country). The literature reports a frequency of therapeutic failure with first-line antiretrovirals (ARVs) of between 20% and 82%. Unfortunately, data relating to the failure of second-line ARVs are scarce in Gabon. This study aims to determine the profiles of HIV drug resistance mutations related to protease inhibitors in Gabon.
METHODS: Plasma from 84 PLHIV receiving ARVs was collected from 2019 to 2021, followed by RNA extraction, amplification, and sequencing of the protease gene. ARV resistance profiles were generated using the Stanford interpretation algorithm version 8.9-1 ( https://hivdb.stanford.edu ) and statistical analyses were performed using EpiInfo software version 7.2.1.0 (CDC, USA).
RESULTS: Of 84 HIV plasma samples collected from 45 men and 39 women, 342 mutations were detected. Of these, 43.3% (148/342) were associated with nucleoside reverse transcriptase inhibitors (NRTIs), 30.4% (104/342) with non-nucleoside reverse transcriptase inhibitors (NNRTIs), and 26.3% (90/342) with protease inhibitors (PIs). Most NRTI mutations were associated with thymidine analogues (TAMs) (50.7%; 75/148), including T215F/V (14.9%; 22/148), D67DN/E/G/N/T (10.1%; 15/148), M41L (9.5%; 14/148), and K70E/KN/S/R (9.5%; 14/148). Resistance mutations related to non-TAM NRTIs (33.1%; 49/148) were M184V (29.1%; 43/148), and L74I/V (8.1%; 12/148). NNRTI mutations were predominantly K103N/S (32.7%; 34/104), V108I (10.6%; 11/104), A98G (10.6%; 11/104), and P225H (9.6%; 10/104). Minor mutations associated with PIs (60.0%; 54/90) were predominantly K20I (15.6%; 14/90) and L10F/I/V (14.5%; 13/90). The major mutations associated with PIs (40.0%; 36/90) were M41L (12.2%; 11/90), I84V (6.7%; 06/90), and V82A (6.7%; 06/90). The four most prescribed therapeutic regimens were TDF + 3TC + LPV/r (20.3%; 17/84), ABC + DDI + LPV/r (17.9%; 15/84), TDF + FTC + LPV/r (11.9%; 10/84), and ABC + 3TC + LPV/r (11.9%; 10/84).
CONCLUSIONS: This study revealed that HIV drug resistance mutations are common in Gabon. The major mutations associated with PIs were M41L, I84V, and V82A. There is a need for access to new NRTIs, NNRTIs, and PIs for a better therapeutic management of PLHIV in Gabon.
METHODS: Plasma from 84 PLHIV receiving ARVs was collected from 2019 to 2021, followed by RNA extraction, amplification, and sequencing of the protease gene. ARV resistance profiles were generated using the Stanford interpretation algorithm version 8.9-1 ( https://hivdb.stanford.edu ) and statistical analyses were performed using EpiInfo software version 7.2.1.0 (CDC, USA).
RESULTS: Of 84 HIV plasma samples collected from 45 men and 39 women, 342 mutations were detected. Of these, 43.3% (148/342) were associated with nucleoside reverse transcriptase inhibitors (NRTIs), 30.4% (104/342) with non-nucleoside reverse transcriptase inhibitors (NNRTIs), and 26.3% (90/342) with protease inhibitors (PIs). Most NRTI mutations were associated with thymidine analogues (TAMs) (50.7%; 75/148), including T215F/V (14.9%; 22/148), D67DN/E/G/N/T (10.1%; 15/148), M41L (9.5%; 14/148), and K70E/KN/S/R (9.5%; 14/148). Resistance mutations related to non-TAM NRTIs (33.1%; 49/148) were M184V (29.1%; 43/148), and L74I/V (8.1%; 12/148). NNRTI mutations were predominantly K103N/S (32.7%; 34/104), V108I (10.6%; 11/104), A98G (10.6%; 11/104), and P225H (9.6%; 10/104). Minor mutations associated with PIs (60.0%; 54/90) were predominantly K20I (15.6%; 14/90) and L10F/I/V (14.5%; 13/90). The major mutations associated with PIs (40.0%; 36/90) were M41L (12.2%; 11/90), I84V (6.7%; 06/90), and V82A (6.7%; 06/90). The four most prescribed therapeutic regimens were TDF + 3TC + LPV/r (20.3%; 17/84), ABC + DDI + LPV/r (17.9%; 15/84), TDF + FTC + LPV/r (11.9%; 10/84), and ABC + 3TC + LPV/r (11.9%; 10/84).
CONCLUSIONS: This study revealed that HIV drug resistance mutations are common in Gabon. The major mutations associated with PIs were M41L, I84V, and V82A. There is a need for access to new NRTIs, NNRTIs, and PIs for a better therapeutic management of PLHIV in Gabon.
摘要：
背景：2022年，世界卫生组织报告说，全世界有2980万人感染艾滋病毒（PLHIV）并接受抗逆转录病毒治疗（ART），包括加蓬的25-375人（占该国所有艾滋病毒感染者的54％）。文献报道一线抗逆转录病毒药物（ARV）的治疗失败频率为20％至82％。不幸的是,加蓬缺乏与二线抗逆转录病毒药物失败有关的数据。这项研究旨在确定加蓬与蛋白酶抑制剂相关的HIV耐药突变的概况。
方法：从2019年至2021年收集84例接受抗逆转录病毒药物的PLHIV的血浆，然后进行RNA提取，扩增,和蛋白酶基因的测序。使用斯坦福解释算法版本8.9-1（https://hivdb。斯坦福.edu)和统计分析使用EpiInfo软件7.2.1.0版(CDC，美国）。
结果：在从45名男性和39名女性收集的84份HIV血浆样本中，检测到342个突变。其中,43.3%(148/342)与核苷逆转录酶抑制剂(NRTIs)相关,30.4％（104/342）与非核苷逆转录酶抑制剂（NNRTIs），和26.3%(90/342)与蛋白酶抑制剂(PIs)。大多数NRTI突变与胸苷类似物(TAMs)相关(50.7%;75/148),包括T215F/V（14.9%；22/148），D67DN/E/G/N/T(10.1%;15/148),M41L（9.5%；14/148），和K70E/KN/S/R（9.5%；14/148）。与非TAMNRTIs相关的抗性突变(33.1%;49/148)为M184V(29.1%;43/148),和L74I/V（8.1%；12/148）。NNRTI突变主要为K103N/S(32.7%;34/104),V108I（10.6%；11/104），A98G（10.6%；11/104），和P225H（9.6%；10/104）。与PIs相关的次要突变(60.0%;54/90)主要是K20I(15.6%;14/90)和L10F/I/V(14.5%;13/90)。与PIs相关的主要突变(40.0%;36/90)为M41L(12.2%;11/90),I84V（6.7%；06/90），和V82A（6.7%；06/90）。四种最常用的治疗方案是TDF+3TC+LPV/r(20.3%;17/84)，ABC+DDI+LPV/r（17.9%；15/84），TDF+FTC+LPV/r（11.9%；10/84），和ABC+3TC+LPV/r（11.9%；10/84）。
结论：这项研究表明，艾滋病毒耐药突变在加蓬很常见。与PI相关的主要突变是M41L，I84V,和V82A。需要访问新的NRTI，NNRTIs,和PI更好的治疗管理PLHIV在加蓬。
方法：从2019年至2021年收集84例接受抗逆转录病毒药物的PLHIV的血浆，然后进行RNA提取，扩增,和蛋白酶基因的测序。使用斯坦福解释算法版本8.9-1（https://hivdb。斯坦福.edu)和统计分析使用EpiInfo软件7.2.1.0版(CDC，美国）。
结果：在从45名男性和39名女性收集的84份HIV血浆样本中，检测到342个突变。其中,43.3%(148/342)与核苷逆转录酶抑制剂(NRTIs)相关,30.4％（104/342）与非核苷逆转录酶抑制剂（NNRTIs），和26.3%(90/342)与蛋白酶抑制剂(PIs)。大多数NRTI突变与胸苷类似物(TAMs)相关(50.7%;75/148),包括T215F/V（14.9%；22/148），D67DN/E/G/N/T(10.1%;15/148),M41L（9.5%；14/148），和K70E/KN/S/R（9.5%；14/148）。与非TAMNRTIs相关的抗性突变(33.1%;49/148)为M184V(29.1%;43/148),和L74I/V（8.1%；12/148）。NNRTI突变主要为K103N/S(32.7%;34/104),V108I（10.6%；11/104），A98G（10.6%；11/104），和P225H（9.6%；10/104）。与PIs相关的次要突变(60.0%;54/90)主要是K20I(15.6%;14/90)和L10F/I/V(14.5%;13/90)。与PIs相关的主要突变(40.0%;36/90)为M41L(12.2%;11/90),I84V（6.7%；06/90），和V82A（6.7%；06/90）。四种最常用的治疗方案是TDF+3TC+LPV/r(20.3%;17/84)，ABC+DDI+LPV/r（17.9%；15/84），TDF+FTC+LPV/r（11.9%；10/84），和ABC+3TC+LPV/r（11.9%；10/84）。
结论：这项研究表明，艾滋病毒耐药突变在加蓬很常见。与PI相关的主要突变是M41L，I84V,和V82A。需要访问新的NRTI，NNRTIs,和PI更好的治疗管理PLHIV在加蓬。
