Background:  African and Asian cohort studies have demonstrated the feasibility and efficacy of first line of HAART in resource-poor settings. However, the number of patients on second-line regimen is increasing and no data about these treatments are yet available in such contexts. We analyzed the main outcomes of pooled HIV⁺ patients on second-line therapy from several HAART cohorts in Cambodia.

Methods:  All patients followed on second-line therapy for at least 6 months were included for immuno-virological evaluation. Plasmatic viral load was determined by real-time polymerase chain reaction (RT-PCR) (ANRS protocol). HIV1 RT-PCR and protease genotyping was performed when viral load were detectable (>400 copies/mL).

Results:  Overall, 113 patients were included, with a median age of 38 years (IQR 34 to 43) and a sex ratio male to female of 2 to 2. Switching to second-line regimen was decided upon immunological criteria alone (n = 35) or both immunological and virological criteria (n = 78). The median CD4 at switch was 68 (IQR 27 to 140) and median viral load was 4.8 Log₁₀ (IQR 4.0 to 5.3) with the presence of major resistances to both nucleoside reverse transcriptase inhibitors (NRTI) and non-NRTI (NNRTI). The most frequent second-line regimens used were didanosine (ddI)+lamivudine (3TC)+lopinavir (LPV)/ritonavir (r) (n = 47), ddI+zidovudine (AZT)+LPV/r (n = 21), tenofovir (TDF)+3TC+LPV/r (n = 16), ddI+abacavir (ABC)+LPV/r (n = 11), ddI+TDF+ LPV/r (n = 5), and AZT+3TC+LPV/r (n = 4). The median duration on second-line at the time of evaluation was 10.2 months (IQR 5.9 to 14.0). The viral load at evaluation was <400 copies/mL for 101 patients (89.4%), between 400 and 1000 copies/mL for 6 (5.3%), between 1000 and 10,000 for 2 (2.7%), between 10,000 and 100,000 for 1 (0.9%), and >100,000 for 3 (2.7%). Genotyping analysis did not find HIV-1 protease mutations. The median CD4 at 6 months (n = 105) was 180 cells/mL (IQR 115 to 274) and 277 (IQR 182 to 398) at 12 months (n = 59) of second-line treatment. Median CD4 gain was +105 (59 to 163) at 6 months and +180 (IQR 131 to 309) at 12 months.

Conclusions:  These first data in Cambodia outline the efficacy of Kaletra-based second-line ART in resource-limited settings and show the large extend of the immune reconstitution. They also reveal the short-term efficacy of empiric Kaletra-based second line given without virological examination. Second line antiretroviral molecules are urgently and widely needed at affordable prices in resource-limited countries.