Tenofovir disoproxil fumarate and emtricitabine maintenance strategy in virologically controlled adults with low HIV-1 DNA: 48 week results from a randomized, open-label, non-inferiority trial.

OBJECTIVES: Low HIV reservoirs may be associated with viral suppression under a lower number of antiretroviral drugs. We investigated tenofovir disoproxil fumarate/emtricitabine as a maintenance strategy in people living with HIV (PLHIV) with low HIV-DNA. METHODS: TRULIGHT (NCT02302547) was a multicentre, open-label, randomized trial comparing a simplification to tenofovir disoproxil fumarate/emtricitabine versus a triple regimen continuation (tenofovir disoproxil fumarate/emtricitabine with a third agent, control arm) in virologically suppressed adults with HIV-DNA <2.7 log10 copies/106 PBMCs and no prior virological failure (VF). The primary endpoint (non-inferiority margin 12%) was the percentage of participants with a plasma viral load (pVL) <50 copies/mL in ITT (Snapshot approach) and PP analyses at Week 48 (W48). RESULTS: Of the 326 participants screened, 223 (68%) were randomized to the tenofovir disoproxil fumarate/emtricitabine arm (n = 113) or control arm (n = 110). At W48, the tenofovir disoproxil fumarate/emtricitabine and control arms maintained a pVL < 50 copies/mL in 100/113 (88.5%) and 100/110 (90.9%) participants, respectively (ITT difference 2.4%, 95% CI -5.9 to 10.7; PP difference 3.4%, 95% CI -4.2 to 11.0). Six VFs occurred in the tenofovir disoproxil fumarate/emtricitabine arm (two with emerging mutations M184V and K65R) versus two in the control arm (ITT difference 3.5%, 95% CI -1.9 to 9.4). All VFs were resuppressed after treatment modification. CONCLUSIONS: Although non-inferiority was shown, simplification to tenofovir disoproxil fumarate/emtricitabine should not be used for most PLHIV because of a low risk of VF with resistance.

Immuno-virological and clinical impacts of treating cancer in patients living with HIV.

BACKGROUND: Patients living with HIV (PLHIV) are increasingly being affected by cancer. However, data evaluating the long-term impact of cancer treatment on HIV course are sparse. METHODS: To determine whether anticancer treatments detrimentally impact HIV course, we conducted a retrospective cohort study in seven hospitals in France. Adult PLHIV treated for haematological or solid malignancies were included and compared (1:1) with suitably matched (cancer-free) controls. The primary outcome was the risk of a ≥ 25% reduction in the absolute CD4+ count during follow-up. The risks for virological failure (i.e. a confirmed plasma viral load >50 copies/mL), incidental AIDS-related illnesses and death over time were also assessed. Multivariate Cox proportional-hazards regression analyses were used to identify the outcome predictors. RESULTS: One-hundred-and-ten patients with cancer and 110 controls were followed for a median of 4.4 years. In a Cox model, the CD4+ depletion was strongly predicted by external radiotherapy (ERT) exposure (HR = 5.1, 95% CI, 3.0-8.6, P < 0.0001) but not by chemotherapy. For patients exposed to ERT, the magnitude of the CD4+ depletion peaked 6 months after their cancer diagnosis (mean CD4+ drop at this time =  -283 ± 370 cells/mm(3)). Overall, the cancer patients were also more likely to experience virological failure than the controls (HR = 1.7, 95% CI, 1.1-2.7, P = 0.03). Finally, the incidence of AIDS-related illnesses was similar for both groups. CONCLUSIONS: In PLHIV, cancer treatment increased the risk for prolonged CD4+ depletion and virological failure but had no impact on AIDS-related events when appropriate prophylaxes were implemented.