CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

being from an LMIC, 3TC use, non-B subtype, no. of NRTI-TRAMs, no. of NNRTI-TRAMs, 65R, 184V, and 70EQNT were associated with an increased VL. In a multivariate analysis, being from an LMIC (p<1e-6) and no. of NNRTI-TRAMs (p<1e-6) remained associated with an increased VL. Conclusion: TDF-containing 1st-line regimens select for many RT mutations of which 39 are associated with NNRTIs and 31 with NRTIs. The spectrum of NRTI-TRAMs extends beyond 65R to also include 62V, 65N, 68GDN, 69del, 70EQTN, 74I, and 115F. VL was associated with being from an LMIC and the no. of NNRTI-TRAMs. 486 VIRAL SUPPRESSION AND ACQUIRED HIV DRUG RESISTANCE IN CAMEROON: A NATIONWIDE STUDY Gaëlle F. Tchouwa 1 , Jenny Domyeum 1 , Sabrina Eymard-Duvernay 2 , Amandine Cournil 2 , Eric Delaporte 2 , Martine Peeters 2 , Eitel Mpoudi-Ngole 1 , Elliot Raizes 3 , Avelin F. Aghokeng 4 1 CREMER, Yaoundé, Cameroon, 2 Univ de Montpellier, Montpellier, France, 3 CDC, Atlanta, GA, USA, 4 IRD, Yaoundé, Cameroon Background: Acquired HIV drug resistance (ADR) can significantly compromise antiretroviral treatment (ART) efficacy. In resource-limited countries where decision to treat or to switch treatment is mostly based on clinical assessment and access to virological monitoring is still limited, population-based studies on viral load suppression and HIV drug resistance (HIVDR) rates could inform programs. We present here the first nationally-representative ADR study in Cameroon. Methods: We adapted the protocol from the recently published WHO generic ADR protocol. Eligible participants were patients on ART for 12 to 24 months (ADR1) or 48 to 60 months (ADR2). ADR1 participants were recruited in 25 clinics that were randomly selected in urban and rural regions. ADR2 participants were from 7 urban clinics. Recruitment was from February to August 2015 and collected dried blood spots (DBS) and plasma specimens were sent to a WHO accredited laboratory in Yaoundé, Cameroon for viral load (VL) testing and genotyping. Specimens with VL≥1000 copies/ml were considered for HIVDR genotyping and drug resistance mutations were identified using the Stanford algorithm. Results: Overall, 1052 ADR1 and 387 ADR2 participants were recruited. Women predominated, representing 76% and 74% of patients in each group, respectively. Median ages were 39 (32-47) years and 42 (35-51) years in the ADR1 and ADR2 groups, respectively. Almost all participants were on first-line ART, predominantly TDF+3TC+EFV/NVP, and only 2% of ADR1 and 6% of ADR2 were receiving PI-based drugs. Viral suppression in the ADR1 group was 72.0% (95% CI: 70.3-73.7) overall, 74.9% (73.2-76.6) in urban sites and 67.7% (63.3-71.7) in rural sites. In the ADR2 group, viral suppression was 67.5% (62.9-71.7). HIVDR was identified in 66.6% (60.6-72.1) of ADR1 patients with VL≥1000 copies/ml, 63.1% (56.3-69.4) and 72.5% (58.1-83.4) in urban and rural sites, respectively. In the ADR2 group, HIVDR frequency was 83.6% (67.3-92.6) in participants with VL≥1000 copies/ml. Conclusion: This study represents the first nationwide assessment of virological failure and HIVDR frequency in West Africa. Results indicates that important efforts will be required to achieve the 2020 UNAIDS target of 90% viral suppression. Better ART management is urgently needed, and should focus on preventing drug stock-outs, reduction in lost to follow-up, improved access to VL testing and clinical use of the VL results. 487 HIGH HIV DRUG RESISTANCE OF FIRST-LINE ART TREATMENT IN BENIN PEDIATRIC POPULATION Djeneba Bocar Fofana 1 , Marcelline d’Almeida 2 , Pierre-Marie Girard 1 , Bernabé Lafia 3 , Sidonie Lambert 1 , Lutecia Zohoun-Guidigbi 2 , Rene Keke 4 , Cathia Soulie 5 , Anne-Geneviève Marcelin 5 , Laurence Morand-Joubert 1 1 Saint-Antoine Hosp, Paris, France, 2 Univ d’Abomey–Calavi, Benin, 3 CNHU–HKM, Cotonou, Benin, 4 Reference Lab of the Natl Cntr for the Treatment of HIV, Cotonou, Benin, 5 Pitie-Salpetriere Hosp, Paris, France Background: In recent years, the pediatric Highly Active Antiretroviral Therapy (HAART) has shown enormous progress in Africa. However, a high percentage of children continue to experience treatment failure. In Benin (West Africa), there are currently no data on human immunodeficiency virus drug resistance (HIVDR) in pediatric populations. This study aimed to assess the prevalence of HIVDR among children with continued virological ART failures in this country. Methods: Dried blood spots from sixty two HIV-infected children were collected at clinical pediatric of national hospital center in Cotonou between April and September of 2015. These were children with at least two detectable viral loads during treatment. Reverse transcriptase, protease and integrase genes were amplified, sequenced, analyzed for the presence of HIV drug resistance and interpreted according to the latest version of the National Agency for HIV and Hepatitis Research algorithm. Demographic data and treatment received were collected. Results: The characteristics of the population show a median age of 10 years (IQR 6 - 13), a median duration on ART of 5 years (IQR 3-7), and a median HIV-1 RNA level of 54000 copies/mL (IQR 5543 - 170000 copies/mL). We observed a very few diversity of HIV in this population of CRF02_AG at 82%. At treatment failure, 92% of patients were on first-line with an ART combination of two, NRTIs (zidovudine or abacavir and lamivudine) and one non-NRTI (nevirapine or efavirenz) or PI-based regimen (lopinavir/ritonavir). Only 8% of the patients were on second line. Of thefifty one sequences amplified. NRTIs, non-NRTI, and dual-class resistance was present in 71%, 84% and 65%, respectively. The proportion of patients with intermediate resistance to TDF (tenofovir) and ETR (etravirine) and RPV (rilpivirine) was, 24%, 42% and 36%, respectively. None major mutations of resistance to PI observed, except two children who presented resistance to all drugs with a low sensibility to darunavir. None of the children had major mutation of resistance to Integrase Inhibitors Conclusion: Our results had shown that the development of drug resistance could be one of the main consequences of high and continuous viral replication in children in Benin. Thus, the inadequate attention in monitoring lifelong ART in children can prevent to achieve the goal of viral suppression by 90% of UNAIDS. 488 DRUG-RESISTANT HIV-1 DURING LONG-TERM SECOND-LINE ANTIRETROVIRAL TREATMENT IN KENYA Seth Inzaule 1 , Raph L. Hamers 1 , Irene Mukui 2 , Kennedy Were 3 , Preston Owiti 3 , Daniel Kwaro 3 , Tobias R. de Wit 1 , Clement Zeh 4 1 Academic Med Cntr of the Univ of Amsterdam, Amsterdam, Netherlands, 2 Natl AIDS and STI Control Prog, Nairobi, Kenya, 3 Kenya Med Rsr Inst, Kisumu, Kenya, 4 US CDC, Kisumu, Kenya Background: We performed a nationwide assessment of HIV drug resistance (HIVDR) among patients with virological failure (VF) on 2nd-line boosted-protease-inhibitor (PI)- based antiretroviral therapy (ART) in Kenya, and predicted susceptibility to WHO-recommended 3rd-line regimens. Methods: We included all patients who were referred for HIVDR testing from facilities in western Kenya (2010-2012) and nationally (2013-2015). VF was defined as either two sequential viral loads (VL)>1000 cps/ml or immunological failure plus confirmatory VL>1000 cps/ml. We performed Sanger pol sequencing, scored drug resistance mutations (DRMs) with the IAS-USA list, and assigned genotypic susceptibility scores (GSS) based on the Stanford algorithm. GSS of WHO-recommended 1st, 2nd and 3rd-line regimens were calculated as the arithmetic sum of the individual-drug GSS, with GSS<2 considered complete loss of activity to the available drug options. Factors associated with PI-resistance were assessed using multivariable logistic regression. Results: Of 126 patients, 123 viral isolates were successfully genotyped. Median age and CD4 counts were 24 (IQR 10-36) years and 114.5 (IQR 24-251) cells/µL respectively. Mean VL was 4.8 (SD0.1) log10 cps/mL. Prior median ART duration was 6.4 (IQR 4.3-8.1) years, of which 3.1 (1.9-4.6) on 2nd-line. 119 (97%) patients were on lopinavir/ritonavir-based 2nd-line. 111 (82%) of patients had ≥1 DRM, of whom 77 (63%) to nucleoside reverse-transcriptase inhibitors (NRTIs) (63 M184V, 51%; 46 ≥1 thymidine analogue mutations (TAMs), 37%; 8 K65R, 7%; 7 L74I, 6%; 6 Y115F, 5%; 2 each for F116Y, Q151M and T69i, 2%) and 39 (31%) to PIs (29 M46I/L, 24%; 27 I54V, 22%; 24 V82A/T/F/S, 20%; 11 L76V, 9%; 7 each for Q58E and L74S, 6%; 4 I84V, 3%; 3 I50V, 2.4%, 2 each for N83D and V32I, 2%; 1 D30N, 1%). 28 (23%) patients had GSS<2 for all 1st and 2nd-line drugs. Factors associated with PI-resistance were high VL at failure, presence of >4NRTI mutations and >1 TAMS. For 3rd-line regimens, probability of GSS≥2 was highest if boosted-darunavir plus integrase inhibitor was combined with etravirine (0.70), followed by AZT+3TC (0.61, p=0.219), TDF+3TC (0.55, p=0.102), 3TC/FTC (0.48, p=0.04), ABC (0.48, p=0.04), TDF (0.42, p=0.013), AZT (0.39, p=0.04) (Figure) Conclusion: 1 in 4 Kenyans failing 2nd-line ART may have completely exhausted the available 1st and 2nd-line regimens, highlighting the need for increased access to 3rd-line regimens. 489 ELIMINATING DRUG RESISTANCE IN SOUTH AFRICA BY USING DOLUTEGRAVIR Katie Sharp 1 , Thibault Mesplede 2 , Mark A. Wainberg 2 , Sally Blower 1

Poster and Themed Discussion Abstracts

CROI 2017 204