Arelly Ornelas

Antiretroviral simplification with darunavir/ritonavir monotherapy in routine clinical practice: safety, effectiveness, and impact on lipid profile.

Background Simplification of antiretroviral treatment (ART) with darunavir/ritonavir (DRV/r) monotherapy has achieved sustained suppression of plasma viral load (pVL) in clinical trials; however, its effectiveness and safety profile has not been evaluated in routine clinical practice. Methodology/Principal Findings We performed a retrospective cohort analysis of HIV-1-infected patients who initiated DRV/r monotherapy once daily with a pVL <50 copies/mL under ART and at least 1 subsequent follow-up visit in our clinic. The primary study endpoints were the percentage of patients with virological failure (VF, defined as 2 consecutive pVL>50 copies/mL) at week 48, and time to VF. Other causes of treatment discontinuation and changes in lipid profile were evaluated up to week 48. Ninety-two patients were followed for a median (IQR) of 73 (57–92) weeks. The median baseline and nadir CD4+ T-cell counts were 604 (433–837) and 238 (150–376) cells/mm3, respectively. Patients had previously received a median of 5 (3–9) ART lines and maintained a pVL<50 copies/mL for a median of 76 (32–176) weeks before initiating DRV/r monotherapy. Nine (9.8%) patients developed VF at week 48; time to VF was 47.1 (IQR: 36.1–47.8) weeks among patients with VF. Other reasons for changing ART were gastrointestinal disturbances (n = 3), rash (n = 1), and impaired CD4 recovery (n = 2). Median low-density lipoprotein cholesterol levels increased from 116.1 mg/dL at baseline to 137.3 mg/dL at 48 weeks (p = 0.001). Conclusions/Significance Treatment simplification with DRV/r monotherapy seems safe and effective in routine clinical practice. Further research is needed to elucidate the effect of DRV/r monotherapy on cholesterol levels.

Pulse wave velocity as index of arterial stiffness in HIV-infected patients compared with a healthy population.

Background:Chronic HIV infection leads to premature atherosclerosis. Arterial stiffness is considered a subclinical marker of cardiovascular disease. Methods:Pulse wave velocity (PWV) was determined in 254 individuals (174 HIV-infected patients and 80 healthy controls, 2:1 matched by age and gender) to compare the prevalence of arterial stiffness and to identify associated factors. PWV was determined using noninvasive automated device (Complior). Factors associated with impaired PWV were assessed among cardiovascular risk factors, HIV infection parameters, and laboratory data. Logistic regression analyses were performed to determine differences between groups and factors associated to arterial stiffness. Results:Overall, 81.4% of participants were male, median age was 46.54 [interquartile range (IQR): 41–52] years. Higher percentages of HIV-infected subjects showed dyslipemia (P = 0.012) and smoking habit (P = 0.002). The median time from HIV diagnosis was 13 (IQR: 6–18) years and the median time on antiretroviral therapy was 11 (IQR: 5–15) years. Nearly, all patients were virologically suppressed (89.7%) at the time of PWV. Arterial stiffness in the global population was 20.5%, 18.9% in HIV-infected group, and 23.8% in controls (P = 0.405). High diastolic blood pressure and high levels of triglycerides at time of PWV were associated with increased PWV (P = 0.009 and P = 0.023, respectively). Conclusions:Virologically suppressed HIV-infected patients showed similar arterial elasticity to non–HIV-infected patients. HIV-related conditions were not associated with arterial stiffness, probably because of the good immunologic and virological status of this group. However, high diastolic pressure at the time of PWV and high levels of triglycerides were associated risk factors.

Pneumocystis jirovecii pneumonia in HIV-1-infected patients in the late-HAART era in developed countries.

Abstract Background: In developed countries with free access to health care, primary chemoprophylaxis with co-trimoxazole, and antiretroviral treatment, Pneumocystis pneumonia (PCP) in HIV-infected subjects should be restricted to undiagnosed late presenters. Methods: We retrospectively identified confirmed PCP hospital admissions in HIV-1 patients (period 1986–2010) and examined their characteristics and factors associated with mortality. Results: Three hundred and twelve episodes (median CD4 27 cells/μl) were identified during 3 periods: pre-HAART (1986–1995), 49%; early-HAART (1996–1999), 17.3%; and late-HAART (2000–2010), 33.7%. PCP was the initial AIDS-defining diagnosis in only 86 (27.6%). Thirty-four (10.9%) patients died during their hospital stay, without a significant reduction in mortality in recent periods (p = 0.311). However, the 12-month mortality decreased through the periods (33.3% to 16.2%; p = 0.003). Drug users (p = 0.001) and those naïve to HAART (p < 0.001) decreased in the late-HAART era, while heterosexuals (p = 0.001), immigrants (p < 0.001), and HAART initiation before hospital discharge (p < 0.001) increased. A partial pressure of oxygen (PaO2) ≤ 55 (p = 0.04), intensive care admission (p < 0.001), and the absence of HAART initiation before discharge (p = 0.02) were correlated with mortality. Conclusions: The epidemiology and 12-month mortality of HIV-1-infected subjects with PCP have changed significantly in the late-HAART era, while mortality during hospital stay has remained unchanged. HIV diagnosed individuals lost to follow-up in care have emerged as the main driver of PCP in developed countries. Like HIV late presenters, they are more likely to have AIDS-defining illnesses, to be hospitalized, and to die. This finding has important implications for the design of better strategies to retain HIV-1-infected individuals in care.

Randomised Study to Assess the Efficacy and Safety of Once-Daily Etravirine-Based Regimen as a Switching Strategy in HIV-Infected Patients Receiving a Protease Inhibitor-Containing Regimen. Etraswitch Study

Background Etravirine (ETR) was approved for patients with virological failure and antiretroviral resistance mutations. It has also shown antiviral efficacy in antiretroviral-naïve patients. However, data on the switching from protease inhibitors (PI) to ETR are lacking. Methods HIV-1-infected patients with suppressed viral load (VL) during a PI-containing regimen (>12 months) and no previous virological failure were randomized to switch from the PI to ETR (400 mg/day, dissolved in water) (ETR group, n = 22) or to continue with the same regimen (control group, n = 21). Percentage of patients with VL≤50 copies/mL were assessed at week 48, as well as changes in CD4 T-cell counts and metabolic profile. Results We included 43 patients [72.9% male, 46.3 (42.2; 50.6) years]. Two patients receiving ETR (grade-1 diarrhea and voluntary discontinuation) and another in the control group (simplification) discontinued therapy early. No patients presented virological failure (two consecutive VL>50 copies/mL); treatment was successful in 95.2% of the control group and 90.9% of the ETR group (intention-to-treat analysis, missing = failure) (p = 0.58). CD4+ T-cell counts did not significantly vary [+49 cells/µL in the ETR group (p = 0.25) and −4 cells/µL in the control group (p = 0.71)]. The ETR group showed significant reductions in cholesterol (p<0.001), triglycerides (p = <0.001), and glycemia (p = 0.03) and higher satisfaction (0–10 scale) (p = 0.04). Trough plasma concentrations of ETR were similar to observed in studies using ETR twice daily. Conclusion Switch from a PI-based regimen to a once-daily combination based on ETR maintained undetectable VL during 48 weeks in virologically suppressed HIV-infected patients while lipid profile and patient satisfaction improved significantly. Trial Registration ClinicalTrials.gov NCT01034917

Ten-year safety with polyacrylamide gel used to correct facial lipoatrophy in HIV-infected patients

Long-term results (>5 years) for synthetic substances used to repair facial lipoatrophy have not been published. We performed a cross-sectional study to evaluate the 10-year safety of polyacrylamide hydrogel (Aquamid) among the 751 patients from our unit who received facial infiltrations at least 10 years ago. Epidemiological and clinical data such as complications and patient satisfaction were collected. We also identified those patients who presented a facial infection at any time after infiltration. A total of 104 patients had received Aquamid at least 10 years ago. Before infiltrations, 24.0%, 41.3%, and 34.7% presented very severe, severe, and moderate facial lipoatrophy, respectively. After a mean (SD) of 10.3 (0.5) years since the infiltrations, 19.2%, 47.7%, and 31.7% of patients reported moderate, mild, and no signs of facial lipoatrophy. The values reported by physicians for the same categories were 1.9%, 10.6%, and 87.5%. Indurations were detected in 6.7% of patients and nodules in 3.8%. Five patients (4.8%) had a local infection. A further 15 patients with a shorter follow-up (less than 10 years) presented local infections (overall incidence considering the 751 patients who received infiltrations of Aquamid, 2.7%); the product had to be withdrawn in three cases. The majority of patients were highly satisfied (74.8%) or satisfied (23.4%) with the cosmetic results; among patients with severe or very severe lipoatrophy at baseline, 31.4% were satisfied and 65.7% were highly satisfied. Infiltrations with polyacrylamide hydrogel (Aquamid) are a safe strategy for the treatment of facial lipoatrophy in the long term. The rate of severe complications was low, and patient satisfaction with the cosmetic results was high. However, facial infections may appear in the long term. Therefore, HIV-infected patients who received synthetic substances should be carefully monitored over time.

Switching from a ritonavir-boosted PI to dolutegravir as an alternative strategy in virologically suppressed HIV-infected individuals.

Background: Switching from PIs to dolutegravir in virologically suppressed HIV-infected individuals has not been assessed. Objectives: The principal aim was to assess the evolution of bone mineral density (BMD) when switching from a ritonavir-boosted PI to dolutegravir in HIV-infected patients with osteopenia or osteoporosis. The secondary objective was to assess the antiviral efficacy and safety of the switch therapy. Methods: This randomized, multicentre study assessed changes in BMD, bone turnover markers, and antiviral efficacy and safety in 73 virologically suppressed patients with osteopenia/osteoporosis taking a ritonavir-boosted PI plus abacavir/lamivudine who were randomized to switch from PI to dolutegravir (DOLU group, n = 37) or continue with a PI (PI group, n = 36). Clinical Trials: NCT02577042. Results: One and three patients from the DOLU and PI groups, respectively, withdrew prematurely (unrelated to treatment). At 48 weeks, 97.3% versus 91.7%, respectively, maintained viral suppression (snapshot analysis, ITT, M = F). No significant differences were seen between the groups in percentage change from baseline to week 48 in femoral (P = 0.56) and lumbar spine (P = 0.29) BMD, although lumbar spine BMD improved by 1.43% (–1.36; 2.92) in the DOLU group [0.12% (–2.83; 2.89) in the PI group]. Bone marker values did not vary significantly. At week 48, triglycerides were lower (P < 0.001) and HDL cholesterol higher (P = 0.027) in the DOLU group. Conclusions: Dolutegravir + Kivexa® was safe and well-tolerated in virologically suppressed patients receiving a PI-based regimen. The lipid profile was better, albeit without significant changes in BMD, probably because of the short follow-up.

Implications of Unisex Assumptions in the Analysis of Longevity for Insurance Portfolios

Since the Court of Justice of the European Union (EU) imposed a rule that insurance prices cannot be different for men and women, it is relevant to look into insights of mortality rate calculation and its implications. We already know that mortality curves are distinct between men and women, mainly in youth ages. However we are interested in the longevity risk, therefore we studied elderly ages. We start the analysis describing mortality rates for each sex and age. The data used come from INEGI and CONAPO in Mexico. For each 5-year period, the number of deaths and the number of living people by age and sex are available. We assume possible scenarios of gender proportion in mortality tables. Using survival analysis we estimated the parameters of a Weibull distribution, moreover we calculated the value at risk at different confidence levels. We emphasize the limitations of using unisex mortality tables to estimate longevity risk if the proportion of male and female is not equilibrated in the insurance portfolio. The actuarial modeling is necessary even when regulatory circumstances impose rules on the use of risk factors such as gender for tarification.

Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia.

Background Switching subjects with persistently undetectable HIV-1 viremia under antiretroviral treatment (ART) to once-daily tenofovir/emtricitabine (or lamivudine) + nevirapine is a cost-effective and well-tolerated strategy. However, the effectiveness of this approach has not been established. Methods We performed a retrospective study evaluating the rates of treatment failure, virological failure (VF), and variables associated, in all subjects initiating this switch combination in our clinic since 2001. Analyses were performed by a modified intention to treat, where switch due to toxicity equalled failure. The main endpoint was plasma HIV-RNA < 50 copies/mL. Results 341 patients were treated for a median of 176 (57; 308) weeks. At week 48, 306 (89.7%) subjects had HIV-1 RNA <50 copies/mL, 10 (2.9%) experienced VF, and 25 (7.4%) discontinued the treatment due to toxicity. During the whole follow-up 23 (6.7%) individuals (17 on lamivudine, 6 on emtricitabine; p = 0.034) developed VF and treatment modification due to toxicity occurred in 36 (10.7%). Factors independently associated with VF in a multivariate analysis were: intravenous drug use (HR 1.51; 95%CI 1.12, 2.04), time with undetectable viral load before the switch (HR 0.98; 0.97, 0.99), number of prior NRTIs (HR 1.49; 1.15, 1.93) or NNRTIs (HR 3.22; 1.64, 6.25), and previous NVP (HR 1.54; 1.10, 2.17) or efavirenz (HR 5.76; 1.11, 29.87) unscheduled interruptions. VF was associated with emergence of usual nevirapine mutations (Y181C/I/D, K103N and V106A/I), M184V (n = 16; 12 with lamivudine vs. 4 with emtricitabine, p = 0.04), and K65R (n = 7). Conclusions The rates of treatment failure at 48 weeks, or long-term toxicity or VF with this switch regimen are low and no unexpected mutations or patterns of mutations were selected in subjects with treatment failure.

Mutations in the protease gene associated with virological failure to lopinavir/ritonavir-containing regimens

OBJECTIVES To assess the most frequent resistance-associated mutations (RAMs) to lopinavir/ritonavir in a cohort of patients attended in daily practice. METHODS We retrospectively identified 195 multitreated subjects with virological failure. Patients were classified as follows: (i) 71 (36.4%) never received lopinavir/ritonavir (lopinavir/ritonavir naive); (ii) 75 (38.5%) had previously failed on lopinavir/ritonavir; and (iii) 49 (25.1%) were on lopinavir/ritonavir at failure. RAM patterns were assessed. Medians, IQRs, percentages, Kruskal-Wallis, χ(2) or Fishers exact test, and multinomial logistic regression were used whenever appropriate. RESULTS L10I/F, K20R, L24I, L33F, M36I, M46I/L, I47V, G48V, F53L, I54V, A71V, G73S, V82A, I84V and L90M (all with P ≤ 0.037) were protease RAMs overexpressed in patients with lopinavir/ritonavir failure. L10I, M36I, M46I, I54V, L63P, A71V, V82A, I84V and L90M were the most common in lopinavir/ritonavir-naive patients. Other IAS-USA RAMs for lopinavir/ritonavir (L10R/V, K20M, V32I, I47A, I50V, I54L/A/M/T/S, A71T, L76V and V82F/T/S) were not associated with previous or current failure to lopinavir/ritonavir. Lopinavir/ritonavir failure was associated with the number of protease RAMs (OR = 1.146, 95% CI = 1.287, 1.626), higher exposure to protease inhibitors, and the presence of E44D, L33F, I54V and I84V. CONCLUSIONS In multitreated patients with previous or current lopinavir/ritonavir failure, some protease mutations are selected at significantly greater rates. L10I, M36I, I54V, L63P, A71V, V82A and L90M were found in >50% of cases. Thus, their presence should be expected when genotypic testing results are not available. The number of protease RAMs and higher prior exposures to protease inhibitors were significantly associated with lopinavir/ritonavir failure.

Effectiveness of physically ablative and pharmacological treatments for anal condyloma in HIV-infected men

Background There is limited information on the effectiveness of available treatments for anal condyloma acuminata in HIV-1-infected men. Aim To provide data on the effectiveness of electrosurgical excision, infrared coagulation and pharmacological (imiquimod) treatments for anal condyloma acuminata (peri-anal and/or intra-anal) in HIV-1-infected men based on authors’ practice. Methods Single-center, retrospective descriptive analysis of HIV-1-infected men, 18 years or older treated for anal condyloma acuminata. Standard treatments were offered: electrosurgery excision, infrared coagulation and topical imiquimod. Effectiveness was evaluated by the recurrence rate at 1 year after treatment. Recurrence was defined as any anal condyloma acuminata diagnosed after 3 months of condyloma-free survival post-treatment. Anal cytology and human-papillomavirus-infection (HPV) was assessed. Results Between January 2005 and May 2009, 101 men were treated for anal condyloma acuminata: 65 (64%) with electrosurgery, 27 (27%) with infrared coagulation and 9 (9%) with imiquimod. At 1 year after treatment, the cumulative recurrence rate was 8% (4/65, 95%CI: 2–15%) with electrosurgery excision, 11% (3/27, 95%CI: 4–28%) with infrared coagulation and 11% (1/9, 95%CI: 2–44%) with imiquimod treatment. No predictive factors were associated with recurrence. Anal HPV-6 or HPV-11 was detectable in 98 (97%) patients and all had high-risk HPV genotypes, and 89 (88%) patients had abnormal anal canal cytology. Limitations: this was a retrospective descriptive analysis; limited to a single center; it cannot know if the recurrence is related to new infection. Conclusion Recurrence of anal condyloma after any treatment was common. Abnormal anal cytology and high-risk HPV-infection were highly prevalent in this population, therefore at high-risk of anal cancer, and warrants careful follow-up.