CD4 cell recovery following first line combination antiretroviral treatment (cART) is known to be poorer in HIV-2 than in HIV-1 infected patients (Matheron et al AIDS 2006; Drylewicz et al AIDS 2008) but has not been studied yet in large datasets while adjusting for plasma viral load (pVL) and other characteristics at cART initiation.
Adult patients from two European multi-cohort collaborations, COHERE (HIV-1) and ACHIeV2e (HIV-2) were included, if they were treatment-naïve and started first line cART (NNRTI-containing regimens excluded) from 1997 to 2011, had ≥1 CD4 cell measure before and after start of cART, and a pretreatment pVL. Evolution of CD4 cell count was studied using linear mixed models adjusting for pre-treatment pVL, age, sex, geographic origin, HIV transmission route, previous AIDS diagnosis, cART regimen, period of cART initiation, and pre-treatment CD4 cell counts. We did several sensitivity analyses considering pVL as a binary variable (with different cut-offs), as a continuous and as a time dependent covariable.
We included 159 HIV-2 and 42,735 HIV-1 infected patients with a median age of 46 (IQR): 36; 52) and 37 (IQR: 32; 44) years, respectively. Median pre-treatment CD4 cell counts/mm3 were 182 (IQR: 83-285) and 224 (IQR: 100-352) in HIV-2 and HIV-1 infected patients, respectively. The median observed CD4 cell counts at 12 months were 276 (171; 416) in HIV-2 and 382 (244; 550) in HIV-1 infected patients. Adjusted estimated mean CD4 cell increases within the first year of cART were overall significantly lower in HIV-2 compared to HIV-1 infected patients: 31 CD4 cells/mm3/12 months less (95% CI: 12; 51; P = 0.002).
In sensitivity analyses (Figure) similar differences between HIV-2 and HIV-1 have been found. In stratified analysis, differences in CD4 cell increases for HIV type were not modified by the initial cART regimen (interaction test: P=0.93). Patients receiving a boosted lopinavir or darunavir containing cART HIV-2 infected patients had a slower CD4 cell increase than HIV-1 infected patients (33 cells/mm3/12 months less (95% CI: 3-62; P=0.03)).
Poorer CD4 cell increase following first-line cART in HIV-2 infected patients was consistent in all analyses and independent of pre-treatment pVL, as well as of age, cART regimen and other covariables adjusted for. Our results are in favour of early treatment of HIV-2 infection and the need to identify the most potent drugs against HIV-2.