Virologic and immunologic effectiveness of darunavir-based salvage therapy in HIV-1-infected adults in a Brazilian clinical practice setting: results of a multicenter and retrospective cohort study

Background: Darunavir has been proven efficacious for antiretroviral-experienced HIV-1-infected patients in randomized trials. However, effectiveness of darunavir-based salvage therapy is understudied in routine care in Brazil. Methods: Retrospective cohort study of HIV-1-infected patients from three public referral centers in Belo Horizonte, who received a darunavir-based therapy between 2008 and 2010, after virologic failure. Primary endpoint was the proportion of patients with viral load <50 copies/mL at week 48. Change in CD4 cell count was also evaluated. Outcome measures were analyzed on an intent-to-treat basis applied to observational studies. Sensitivity analysis was conducted to evaluate the impact of missing data at week 48. Predictors of virologic failure were examined using rare-event, finite sample, bias-corrected logistic regression. Results: Among 108 patients, the median age was 44.2 years, and 72.2% were male. They had long-standing HIV-1 infection (median 11.6 years) and advanced disease (76.9% had an AIDS-defining event). All patients had previously received protease inhibitors and nucleoside reverse transcriptase inhibitors, 75% nonnucleoside reverse transcriptase inhibitors, and 4.6% enfuvirtide. The median length of protease inhibitor use was 8.9 years, and 90.8% of patients had prior exposure to unboosted protease inhibitor. Genotypic resistance profile showed a median of three primary protease inhibitor mutations and 10.2% had three or more darunavir resistance-associated mutations. Virologic success at week 48 was achieved by 78.7% (95% CI = 69.7–86%) of patients and mean CD4 cell count increase from baseline was 131.5 cells/μL (95% CI = 103.4–159.6). In multiple logistic regression analysis, higher baseline viral load (RR = 1.04 per 10,000 copies/mL increase; 95% CI = 1.01–1.09) and higher number of darunavir resistance-associated mutations (RR = 1.23 per each; 95% CI = 0.95–1.48) ...

Detección de resistencia primaria en pacientes chilenos infectados por VIH / Detection of primary antiretroviral resistance in Chilean patients recently infected with human immunodeficiency virus (HIV)

Background: In countries with universal access to antiretroviral therapy a progressive increase in the number of patients that are infected with resistant virus, is observed. Aim To detect the presence of primary resistance to antiretroviral drugs among patients with a recent diagnosis of HIV infection. Material and methods: Twenty five male patients aged 25 to 45 years, with a diagnosis of a recent HIV infection, done between 2004 and 2005, were studied. Genotypic resistance to antiretroviral drugs was studied using the Genetic Resistance Test TRUGENE® from Bayer. Results: Resistance mutations were detected in 10 patients. All had an university title or had university studies. All lived in northeastern Santiago and had risky sexual behaviors while traveling abroad. Seven mutations were detected in reverse transcriptase. Of these, three were associated to a high resistance level and four, to an intermediate or low resistance, were also detected. Conclusions: A high frequency of genotypic resistance was detected in this group of Chilean patients recently infected with HIV. A higher socioeconomic status and lifestyle could have influenced these results.