ENF represented an important breakthrough. It was the first approved ARV agent belonging to a new drug class and hence cross-resistance with previous agents was not a problem. ENF is not used usually in HIV-naïve patients except among highly ARV-experienced patients who do not have another therapy option.

Our study provides additional published data describing the effectiveness and safety of ENF among ARV-experienced patients in a clinical setting. Therapy with ENF-based regimens was associated with high levels of HIV-1 RNA viral load suppression through 6 and 12 months follow-up, with 91% and 81% in highly treatment-experienced patients with viral load <400 copies/mL, and 65.8% and 55.5% <50 copies/mL, respectively, and was seems to be independent of genotypic sensitivity score according HIV Stanford database of OBR.

In addition, therapy with ENF was associated with a median increase in CD4+ cell counts after 6 months and even greater at 12 months, which is clinically relevant given the patients’ extensive treatment history and limited options for background therapy.

Because of the disparity of patient regimens, it is difficult to determine the contribution made by an individual agent within the regimen, although, in the mutations analysis, we can observe that PI score was highly compromised; then the role of ENF in reducing viral load in these patients was likely substantial given their large degree of baseline resistance to the alternative classes.

As predictors of therapeutic success we use GSS, predictor derived from viral genotype. Including genotype information into treatment outcome prediction is challenging because of the large number of observed mutations and the complexity of the genotype-phenotype relationship, in our study GSS value was not associated with failure but sample size is not enough for this analysis, and much less for the analysis by OBR groups.

In addition, the clinical efficacy of ENF has been demonstrated in several studies, in which it was shown to be superior with an optimized ARV background versus optimized background alone (T-20 vs. Optimized Regimen Only [TORO] studies) in highly treatment-experienced patients [5],[6]. Outside of clinical trials, there are few published studies with similar results of effectiveness, durability, and safety of ENF among ARV-experienced patients in clinical settings. Loutfy et al. found that therapy with ENF-based regimens for a minimum of 2 months was associated with a 2.53 log (10) viral load decrease through 12-month follow-up in a retrospective cohort of 67 treatment-experienced patients [11]. Belperio et al. described a cohort of treatment-experienced, older, HIV-infected patients who received ENF-based regimens: 41% and 55% achieved viral load <400 copies/mL at 6 months and 2 years, respectively (analysis of unique time period of ENF use before the availability of newer oral agents indicated for treatment experienced patients) [12]. In a retrospective monocentric cohort of 18 patients who started ENF and completed at least 3 months of therapy, 11 (61%) patients had HIV-1 RNA viral load <400 copies/mL, among whom eight (44%) patients had <50 copies/mL in the first 3 months. The median increase in CD4+ cell count was 159 cells/mm3 (range, 25 to 301) and the median decrease in HIV-1 RNA viral load was 2.5 ± 1.4 log (10) after 12 months of ENF-based regimen [13].

As to regimen tolerability, a mild increase in plasma lipid levels during the initial 24 weeks of treatment was not sustained at the final follow-up, at variance with reports elsewhere. Elevation of lipids at baseline may be attributed to those previous and currently exposure to PI-based regimens [7],[14].

For the injection site reaction, observed at 6 and 12 months, our findings are consistent with previous studies [15], although the percentages reported by Cohen et al. were higher [16].

ENF was fairly well tolerated by patients in this study. Although 19% of patients developed ISRs, it was not associated with discontinuation therapy. These data differ from those observed in the TORO studies, in which ISRs were observed in 98% of patients receiving ENF, leading to treatment discontinuation in 4.4% of the study participants [5],[6] and Loutfy et al. who reported 52% of their patients developed ISRs, and 14.1% of the entire cohort discontinued therapy as a result of ISRs [11].

Despite being a retrospective, descriptive design study with a small number of patients and lack of a control group or randomization, this Mexican study also demonstrates that ENF is a valuable therapy option in highly ARV-experienced HIV-1-infected patients who have advanced disease, resistance to traditional ARV drug classes, and clinical progression with very few or no treatment options.

Currently, there is no new different drugs families in HIV, regarding drugs with different mechanism of action and no cross-resistance mutations, some people with HIV multi-drug resistance has only integrase inhibitors and sometimes CCR5 antagonist or partial activity of a PI to integrate an OBR; then, ENF will continue as part of salvage therapy in highly ARV-experienced patients.

ENF has been successfully used to produce durable reductions in viremia even in patients with multi-drug resistance. The likelihood of a sustainable virologic and immunologic responses is maximized when the patient has at least 2 other active agents besides ENF in the OBR, CD4+ cells counts are greater than 100 cells/mm3, and RNA HIV-1 plasma viral load is less than 100,000 copies/ml.

Despite its adverse injection site effects, the addition of ENF to an optimized background antiretroviral regimen did not exacerbate toxicities associated with antiretroviral therapy, and patients treated with enfuvirtide experienced a significantly lower incidence of diarrhea and other gastrointestinal side effects.

In conclusion, our study provides clinically important evidence of the effectiveness and safety of ENF in highly ARV-experienced HIV-1-infected patients. These findings strengthen the results of previous randomized controlled trials with this agent.