Suchergebnisse

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

Purpose of the studyTo assess the impact of lamivudine (3TC) monotherapy in failing patients with multidrug‐resistant HIV and limited therapeutic options.MethodsProspective, open‐label, multicenter, randomised (1:1), pilot study. HIV‐1 failing pts with M184V mutation, HBsAg negative were assigned to 3TC 300mg QD for 24 weeks followed by a new regimen for 24 weeks (Arm A) or to a new regimen for 48 weeks (Arm B). The new HAART regimen was decided before randomisation in both groups, based on clinical history, genotype and viral tropism. Primary endpoint was the proportion of pts with HIV‐RNA<50 copies/mL (VS) at week 48 (W48). ITT and OT analysis performed. Results described by median (IQR).Summary of results109 screened, 34 screening failures, 75 randomised, 72 initiated the assigned treatment [38 and 34 pts in Arm A and B, respectively]: 69% males; age: 47.4 (43.2–51.9) years; years of HIV infection: 17 (14–23); nadir CD4+: 150 (47–231) cells/μL. Similar baseline demographic and clinical characteristics were found in Arm A vs Arm B [CD4+: 413 (294–550) vs 377 227–520) cells/µL; HIV‐RNA: 3.94 (2.89–4.43) vs 3.66 (2.78–4.20) log10copies/mL; number of mutations: 9 (5–13) vs 9 (3–19); R5‐virus: 67% vs 50%; new regimen GSS: 2 (2–3) vs 2 (2–2); 60% vs 56% pts included in the new regimen at least two of the following drugs: DRV/r, MVC, RAL, ETR, T‐20]. At W48, pts with VS were 15/38 (39%) vs 17/34 (50%) in Arm A and B, respectively (ITT: P=0.477). In Arm A, 25/38 (66%) completed the 24‐weeks of monotherapy and 21 reached week 48 vs 27 pts in Arm B (P=0.045). Pts with VS were 15/21 (71%) vs 17/27 (63%) in Arm A and B, respectively (OT: P=0.758). VS according to nadir CD4+, screening HIVRNA and GSS of the new regimen shown in 1. SAEs occurred in 4 (11%) and 2 (6%) in Arm A and B, respectively; all but 1 in Arm A unrelated to the regimen; 4 CDC events: 3 oral candidiasis and 1 recurrence of CMV infection in Arm A; 1 oral candidiasis in Arm B. W48 CD4 change from baseline was: ITT:−4 (−108/+56) and 53 (−37/+110) cells/L (P=0.735); OT: 8 (−62/+58) and 68 (−24/+148) cells/L in arm A and B, respectively (P=0.500). Mutations associated with resistance at W48 were 4 (0–7) and 7 (2–13) in Arm A and B, respectively (P=0.031). R5 virus at W48: Arm A=55% vs Arm B=29% (P=0.124).ConclusionsUse of 3TC monotherapy was associated with greater discontinuation. It may be considered in patients without effective therapeutic options to favour virological efficacy of the subsequent regimen.

Virological success according to Nadir CD4+, screening HIVRNA and GSS of the new regimen.










ITT ANALYSIS


Characteristic
Strata
Percent of patients with HIV‐RNA < 50 copies/mL at week 48 in Arm A
Percent of patients with HIV‐RNA < 50 copies/mL at week 48 in Arm B
P‐value
Breslow‐Day Test P‐value




Nadir Cd4+(cells/μL)
<200
10/24 42%
10/24 42%
0.999
0.173



≥200
5/14 (36%)
7/10 (70%)
0.214



Screening HIV‐RNA
51–10000
15/26 (58%)
15/26 (58%)
0.999
0.092


   (copies/mL)
>10000
0/12
2/8 (25%)
0.147



New Regimen GSS
<2
3/7 (43%)
3/8 (38%)
0.999
0.479



≥2
12/31 (39%)
14/26 (54%)
0.294



OT Analysis



Characteristic
Strata
Percent of patients with HIV‐RNA < 50 copies/mL at week 48 in Arm A
Percent of patients with HIV‐RNA < 50 copies/mL at week 48 in Arm B
P‐value
Breslow‐Day Test P‐value


Nadir Cd4+(cells/μL)
<200
10/12 (83%)
10/19 (53%)
0.128
0.027



≥200
5/9 (56%)
7/8 (88%)
0.294



Screening HIV‐RNA
51–10000
15/17 (88%)
15/22 (68%)
0.251
0.052


   (copies/mL)
>10000
0/4 (0%)
2/5 (40%)
0.444



New Regimen GSS
<2
3/4 (75%)
3/5 (60%)
0.999
0.816



≥2
12/17 (71%)
14/22 (64%)
0.740

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

There is debate about whether lopinavir/r mono‐therapy (LPV/r‐MT) is a valid treatment option for HIV‐infected patients who have shown perfect adherence to therapy. The objective was to evaluate the durability of LPV/r‐MT in terms of time to virological rebound (VR), time to discontinuation/intensification or a composite endpoint considering both (=treatment failure). We also identified factors associated with faster progression to treatment failure and estimated the median CD4 count over time while people were still on LPV/r‐MT. Patients enrolled in 10 clinical sites in Italy who ever started LPV/r‐MT with a viral load ≤50 copies/mL (baseline) are included. Patients' follow‐up accrued from baseline to the date of the event of interest (VR, defined using the thresholds of 50 and 200 copies/mL, or discontinuation/intensification) or at the date of last available visit/VL measurement. Standard survival analysis employing Kaplan‐Meier curves was used. We studied 139 patients starting LPV/r‐MT on average in 2010 (IQR: 2009–2011) with a VL≤50 copies/mL already for a median of 1 month (range: 1–17). Median age 45 years (IQR: 39–50), 35% females, 32% IDU. Median time from first initiation of ART was 33 months (16–58) with no history of virological failure. Median (IQR) marker values at baseline were 611 (432–741) CD4 count cells/mm3, 937 (655–1254) CD8 count and 28 (19–47) IU/L of ALT. Median CD4 count were 519 cells/mm3 at 3 months, 660 at 6 months, 603 at 9 months and 467 at 12 months. The table shows the Kaplan‐Meier estimates by 1 year and 2 years for a number of endpoints examined. There was a wide range of estimates depending on the endpoint used. Of those stopping/intensifying, 6 people (4%) added Truvada (n=4), Kivexa (n=1) and darunavir (n=1), the remaining 8 restarted cART.













1 year
2 years


End point
No. events
Point estimate
95% CI
Point estimate
95% CI




Stop/ intensification
14
4.6%
0.7–8.5
14.0%
6.2–21.8


Single VL>50
32
19.3%
11.1–26.8
29.7%
19.2–38.8


Confirmed VL>50
8
5.7%
1.8–9.6
7.4%
1.5–13.3


Single VL>200
10
7.5%
1.6–13.4
11.1%
3.2–18.8


Single VL>200 or stop / intensification
18
10.5%
4.6–16.4
19.1%
9.2–28.8




In our 'real‐life' setting, by 2 years of starting LPV/r‐MT, 70% of patients remained persistently suppressed ≤50 copies/mL. This percentage was >80% when considering only confirmed virological failures while people still remaining on the drug. Our results, though lacking precision because of the small number of events, are consistent with those of recent clinical trials.