Impact of lamivudine monotherapy in failing patients with multidrug‐resistant HIV: final 48 weeks results (MONO‐AIFA FARM7PAZS3)
Authors: Castagna A , Galli L , Bigoloni A , Carini E , Segala D , Antinori A , Molteni C , Cossarini F , Nozza S , Spagnuolo V , Gianotti N , Lazzarin A 
Published: November 2012

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