CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

458 PROMISING RESULTS OF DOLUTEGRAVIR + LAMIVUDINE MAINTENANCE IN ANRS 167 LAMIDOL TRIAL

Veronique Joly 1 , Charles Burdet 2 , Roland Landman 3 , François Raffi 4 , Christine Katlama 5 , André Cabié 6 , Aida Benalycherif 3 , Gilles Peytavin 1 , Diane Descamps 1 , Yazdan Yazdanpanah 2 1 Hôpital Bichat, Paris, France, 2 INSERM, Paris, France, 3 IMEA, Paris, France, 4 CHU Hotel-Dieu Nantes, Nantes, France, 5 Pierre and Marie Curie Univ, Paris, France, 6 CHU Fort de France, Fort de France, Martinique, France Background: Dolutegravir (DTG) is a potent INSTI with high genetic barrier. The once-daily (QD) DTG-3TC combination is attractive, both drugs being safe, highly efficient and convenient. Methods: ANRS 167 LAMIDOL trial is an ongoing open-label, single-arm, multicenter trial assessing the efficacy and tolerance of DTG (50mgQD) - 3TC (300mgQD) in HIV-1 virologically suppressed patients (Pts) on first line cART with 2 NRTIs and either a PI, a NNRTI, or an INSTI. Inclusion criteria were age ≥18yrs, CD4 nadir >200/mm3, normal standard biological parameters, plasma HIV-RNA (pVL)≤50 cps/mL for at least 2 yrs, and wild-type HIV genotype prior to cART initiation (including for INSTI when tested). History of cART modification for intolerance or simplification was allowed. FromWk0 to Wk8 (Phase 1), third agent was switched to DTG, the 2 NRTIs being unchanged. FromWk8 to Wk56 (Phase 2), Pts received QD combination of DTG 50mg-3TC 300mg except if intolerance or pVL>50cps/mL during Phase 1. Virologic failure was defined as pVL>50cps/mL on 2 consecutive samples during Phase 2. Results: 110 Pts were enrolled in Phase 1 in 19 HIV clinics in France from 10/1/2015 to 02/29/2016. Six Pts were not included in Phase 2 (intolerance to DTG in 3 Pts, pVL>50cps/ mL in 3 Pts). 104 Pts initiated DTG-3TC combination with following characteristics at inclusion: 86%male, 72%MSM, median age 45yrs (min-max 24-70), 87% stage A, median CD4 nadir 339/mm3 (min-max 203-1155), median time since HIV diagnosis 6.3 yrs (min-max 2.3-24.5), median time on actual cART 4.0 yrs (min-max 0.5-11.3), median CD4 743/ mm3 (min-max 373-1115). The baseline regimen contained PI, NNRTI and INSTI in 22%, 58% and 20% Pts, respectively. On 9/26/2016, 103 Pts reached Wk32 corresponding to 24 Wks DTG-3TC combination. No Pt withdrew from study treatment. One protocol-defined virologic failure occurred (pVL=77cps/mL at Wk16) despite adequate plasma C12h of 3TC (299ng/mL) and DTG (2,401ng/mL). Three SAEs occurred in 3 Pts: 2 biological including one 10-fold ALT elevation related to an acute hepatitis C infection and one > 10-fold elevation in creatinine kinase concomitantly with fitness activity, and one depression leading to hospitalization in a Pt with previous psychiatric disorders. DTG-3TC combination was maintained in these 3 Pts with improvement of abnormalities. Conclusion: When used as 2-drug maintenance therapy, DTG-3TC combination was efficient and well tolerated after 24 Wks of follow-up in highly selected, virologically suppressed Pts. 459 ADVERSE DRUG REACTIONS AMONG PATIENTS RECEIVING SECOND-LINE ART IN SOUTH AFRICA Dorina Onoya 1 , Kamban Hirasen 1 , Lawrence Long 1 , Matthew Fox 2 1 Univ of the Witwatersrand, Johannesburg, South Africa, 2 Boston Univ, Boston, MA, USA Background: As first-line antiretroviral therapy (ART) programmes mature, an increasing number of patients are being switched to second-line regimens. Adverse drug reactions (ADRs) which result primarily frommedicines toxicity and drug interactions may compromise the effectiveness of treatment programs through its potential impact on treatment adherence and retention. Understanding the timing and rate of ADRs among patients on second-line ART is important in preventing switches to more expensive third-line regimens, particularly in resource limited settings. Methods: Retrospective cohort study of HIV positive adult patients (≥18 years) who initiated standard second-line ART at a large urban clinic in Johannesburg, South Africa, from 01 April 2004 – 31 March 2015. Our primary outcome was the development of an ADR defined as one of the following diagnosed conditions within 12 months of initiating second- line ART: dyslipidaemia, diarrhoea, pain, skin conditions, neuropathy, gynecomastia/breast conditions, hepatitis and lactic acidosis. Kaplan Meier survival analysis was used to determine ADR incidence in the first 12 months on second-line ART. Models were controlled for age and sex. Person-time accrued from second-line treatment initiation to earliest of ADR, 12 months post second-line initiation or last clinic visit date. Results: A total of 2907 patients initiated standard second-line ART. Of these patients, 12.7% (369/2907) had developed an ADR during the 12 months of follow-up. The highest ADR incidence was observed among patients receiving AZT+ddl+LPVr (23.0/100 PY, 95% CI: 19.3-27.5) and AZT+3TC+LPVr/ATVr (9.4/100 PY; 95% CI: 7.6-11.7) while the lowest rate was observed among patients receiving TDF+FTC/3TC+LPVr (7.1/100 PY, 95% CI: 5.5-9.1). These ADRs occurred in a median time of 4.2 months (IQR: 2.9-7.2), 5.5 months (IQR: 2.0-8.1) and 2.8 months (IQR: 0.9-7.1) respectively. Conclusion: Patients on recently recommended regimens such as TDF+FTC/3TC+LPVr show lower rates of ADRs which is encouraging. The declining ADR incidence over time indicates that single/multi-drug substitutions may have taken place. The occurrence of ADRs early on in treatment (within 6 months) may indicate poor tolerability and require early drug substitution. This earlier substitution may facilitate greater adherence and retention in treatment.

Poster and Themed Discussion Abstracts

CROI 2017 192