Effectiveness, safety and discontinuation rates of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in people with HIV using real-world data: a systematic review and meta-analysis.

BACKGROUND: The use of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) is based on the results of robust clinical trials. OBJECTIVES: To assess the effectiveness and safety of BIC/FTC/TAF in treatment-naïve (TN) and treatment-experienced (TE) people with HIV using available real-world cohort studies. METHODS: Systematic review and meta-analysis of publications and communications identified via Boolean search in Medline, PubMed and Embase, and conference abstracts reporting retrospective real-world use of BIC/FTC/TAF, published until 31 January 2024. The primary endpoint was the proportion of TN and TE people with HIV with viral load (VL) < 50 copies/mL at 48 weeks while on treatment. RESULTS: Of the 38 identified publications and conference abstracts, for the present analysis we included 12 publications (comprising 792 TN and 6732 TE individuals). For the three publications including 507 TN participants reporting the primary outcome, VL suppression was 97% [95% confidence intervals (CI): 89-100]. For the nine publications including 4946 TE participants reporting the primary outcome, VL suppression was 95% (95% CI: 94-96), with suppression >93% in all studies. Total discontinuations at 48 weeks in TE individuals were 3% (95% CI: 2-5), 1% (95% CI: 0-2) due to side effects. A total of four publications with 151 TE individuals with previous presence of M184V substitution were identified, reporting a suppression rate at 48 weeks of 95% (95% CI: 88-100). CONCLUSIONS: Real-world studies demonstrate low discontinuation rates and high rates of virologic suppression in individuals treated with BIC/FTC/TAF, both TN and TE with and without previous detection of M184V substitution.

Efficacy and safety of raltegravir plus lamivudine maintenance therapy.

BACKGROUND: Decreasing medication burden with raltegravir plus lamivudine in virologically suppressed persons with HIV (PWH) maintained efficacy and was well tolerated at 24 weeks, but more comprehensive data over longer follow-up are required. METHODS: Prospective 48 week extension phase of the raltegravir plus lamivudine arm from a previous 24 week pilot randomized clinical trial in which virologically suppressed PWH were randomized 2:1 to switch to fixed-dose combination 150 mg lamivudine/300 mg raltegravir twice daily or to continue therapy. In this 48 week extension phase, raltegravir was dosed at 1200 mg/day and lamivudine 300 mg/day. Primary outcome was the proportion of PWH with treatment failure at Week 48. Secondary outcomes were changes in ultrasensitive plasma HIV RNA, HIV DNA in CD4 cells, serum IL-6, ultrasensitive C-reactive protein and sCD14, body composition, sleep quality, quality of life and adverse effects. RESULTS: Between May 2018 and June 2019, 33 PWH were enrolled. One participant experienced virological failure without resistance mutations and re-achieved sustained virological suppression without therapy discontinuation, and two others discontinued therapy due to adverse effects. Treatment failure was 9% (95% CI 2%-24%) and 3% (95% CI 0%-17%) in the ITT and on-treatment populations. There were significant changes between baseline and Week 48 in serum cytokines but not in other secondary outcomes. CONCLUSIONS: Switching to raltegravir and lamivudine in PWH with virological suppression maintains efficacy and is well tolerated. This maintenance regimen might be a cost-effective option for PWH at risk of drug-drug interactions or needing to avoid specific toxicities of certain antiretroviral drugs or their negative impact on comorbidities.

Clinical use and effectiveness of dolutegravir and lamivudine: a long-term, real-world, retrospective study.

BACKGROUND: The use of dolutegravir/lamivudine is based on solid clinical trials; however, real-world data remain limited. OBJECTIVES: To provide data on the clinical use and effectiveness of dolutegravir/lamivudine in persons with HIV in a real-world scenario. PATIENTS AND METHODS: Retrospective, single-centre and observational study. We included all adults starting dolutegravir/lamivudine since November 2014. We reported all demographic, virological and immunological variables at baseline and assessed effectiveness [on treatment (OT), modified ITT (mITT) and ITT in those persons who reached 6 and 12 month follow-ups (M6 and M12). RESULTS: Of the 1058 persons, 9 were treatment-naive; the final analysis included 1049 treatment-experienced people with HIV. Median (IQR) follow-up was 1 (0.3-1.6) years, with 81% and 63% persons reaching M6 and M12, respectively. The longest use of dolutegravir/lamivudine was 7.4 years. Per OT, mITT and ITT, HIV-RNA < 50 copies/mL was 97%, 92% and 81% (M6) and 98%, 90% and 80% (M12), respectively. Females [adjusted risk ratio, aRR (95% CI): 1.69 (1.19-2.40)]; immediate, previous PI-based regimen [aRR (95% CI): 1.67 (1.09-2.56)]; and viral load (VL) ≥ 50 copies/mL at dolutegravir/lamivudine initiation [aRR (95% CI): 3.36 (2.32-4.88)] were independently associated with lack of effectiveness at M12; other demographic, immunological and virological variables like previous M184V/I substitutions or virological failure, were unrelated. Of the total, 944 (90%) continued dolutegravir/lamivudine. The most frequent known reason for discontinuation was toxicity [48 (46%) cases]. CONCLUSIONS: In our real-world experience, virological suppression rates were high for treatment-experienced persons on dolutegravir/lamivudine; however, we identified subgroups with a higher risk of lack of effectiveness at M12, who may benefit from closer follow-ups.

Tolerability of bictegravir/tenofovir alafenamide/emtricitabine versus dolutegravir/lamivudine as maintenance therapy in a real-life setting.

BACKGROUND: While both the burden of therapy and the individual drugs in bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) and dolutegravir/lamivudine differ, it is unclear whether their real-life tolerability may be also different. METHODS: Single-centre, clinical cohort analysis of all virologically suppressed persons with HIV (PWH) who were first prescribed bictegravir as BIC/TAF/FTC or dolutegravir as dolutegravir/lamivudine and had taken ≥1 dose of study medication. Major outcomes were discontinuations either for any reason or due to toxicity. Incidence was calculated as number of episodes per 100 person-years adjusted through propensity score analysis. RESULTS: Relative to persons treated with BIC/TAF/FTC (n = 1231), persons treated with dolutegravir/lamivudine (n = 821) were older and had more AIDS-defining conditions although better HIV control. After a median follow-up of 52 weeks, adjusted incidence rates for discontinuation were 6.68 (95% CI 5.18-8.19) and 8.44 (95% CI 6.29-10.60) episodes per 100 person-years for BIC/TAF/FTC and dolutegravir/lamivudine, respectively; adjusted incidence rate ratio for dolutegravir/lamivudine was 1.26 (95% CI 0.89-1.78) relative to BIC/TAF/FTC (P = 0.1847). Adjusted incidence rates for discontinuation due to toxicity were 3.88 (95% CI 2.70-5.06) and 4.62 (95% CI 3.05-6.19) episodes per 100 person-years for BIC/TAF/FTC and dolutegravir/lamivudine, respectively; adjusted incidence rate ratio for dolutegravir/lamivudine was 1.19 (95% CI 0.75-1.90) relative to BIC/TAF/FTC (P = 0. 4620). Adverse events leading to discontinuation were neuropsychiatric (n = 42; 2%), followed by gastrointestinal (n = 23; 1%), dermatological (n = 15; 1%) and weight increase (n = 15; 1%), without differences between regimens. CONCLUSIONS: Switching to BIC/TAF/FTC or dolutegravir/lamivudine showed no difference in the risks of overall or toxicity-related discontinuations or in the profile of adverse events leading to discontinuation.

Use of contraindicated antiretroviral drugs in people with HIV/HCV coinfections receiving HCV treatment with direct-acting antivirals-Results from the EuroSIDA study.

OBJECTIVES: Our objective was to determine whether antiretroviral drugs (ARVs) were used according to the European AIDS Clinical Society (EACS) guidelines for people with HIV/hepatitis C virus (HCV) coinfection treated with direct-acting antivirals (DAAs) between 30 November 2014 and 31 December 2019 in the pan-European EuroSIDA study. METHODS: At each publication date of the EACS guidelines, plus 3 and 6 months, we calculated the number of people receiving DAAs with potential and actual ARV contraindications ('red shading' in the EACS guidelines). We used logistic regression to investigate factors associated with using contraindicated ARVs. RESULTS: Among 1406 people starting DAAs, the median age was 51 years, 75% were male, 57% reported injected drug use as an HIV risk, and 76% were from western Europe. Of 1624 treatment episodes, 609 (37.5%) occurred while the patient was receiving ARVs with potential contraindications; among them, 38 (6.2%; 95% confidence interval [CI] 4.3-8.2) involved a contraindicated ARV (18 non-nucleoside reverse transcriptase inhibitors), 16 involved protease inhibitors, and four involved integrase strand transfer inhibitors. The adjusted odds of receiving a contraindicated ARV were higher (3.25; 95% CI 1.40-7.57) among participants from east/central east Europe (vs. south) and lower (0.22; 95% CI 0.08-0.65) for 2015-2018 guidelines (vs. 2014). In total, 29 of the 32 (90.6%) patients receiving a contraindicated ARV and 441 of the 461 (95.7%) with potential ARV contraindications experienced a sustained virological response ≥12 weeks after stopping treatment (SVR12; p = 0.55). CONCLUSION: In this large heterogenous European cohort, more than one-third of people with HIV/HCV coinfection received DAAs with potential ARV contraindications, but few received a contraindicated ARV. Use of contraindicated ARVs declined over time, corresponding to the increased availability of ARV therapy regimens without interactions with DAA across Europe. Participants who received a contraindicated DAA and ARV combination still had a high rate of SVR12.

Sex-based epidemiological and immunovirological characteristics of people living with HIV in current follow-up at a tertiary hospital: a comparative retrospective study, Catalonia, Spain, 1982 to 2020.

BackgroundEpidemiological and immunovirological features of people living with HIV (PLWH) can vary by sex.AimTo investigate, particularly according to sex, characteristics of PLWH who consulted a tertiary hospital in Barcelona, Spain, in 1982-2020.MethodsPLWH, still in active follow-up in 2020 were retrospectively analysed by sex, age at diagnosis, age at data extraction (December 2020), birth place, CD4+ cell counts, and virological failure.ResultsIn total, 5,377 PLWH (comprising 828 women; 15%) were included. HIV diagnoses in women appeared to decrease from the 1990s, representing 7.4% (61/828) of new diagnoses in 2015-2020. From 1997, proportions of new HIV diagnoses from patients born in Latin America seemed to increase; moreover, for women born outside of Spain, the median age at diagnosis appeared to become younger than for those born in Spain, with significant differences observed in 2005-2009 and 2010-2014 (31 vs 39 years (p = 0.001), and 32 vs 42 years (p < 0.001) respectively), but not in 2015-2020 (35 vs 42 years; p = 0.254). Among women, proportions of late diagnoses (CD4+ cells/mm3 < 350) were higher than men (significantly in 2015-2020: 62% (32/52) vs 46% (300/656); p = 0.030). Initially, virological failure rates were higher in women than men, but they were similar in 2015-2020 (12% (6/52) vs 8% (55/659); p = 0.431). Women ≥ 50 years old represented 68% (564/828) of women actively followed up in 2020.ConclusionsWomen still have higher rates of late HIV diagnoses than men. Among currently-followed-up women, ≥ 50 year-olds, who need age-adapted care represent a high percentage. Stratifying PLWH by sex matters for HIV prevention and control interventions.

Simplification from tenofovir disoproxil fumarate plus lamivudine or emtricitabine plus ritonavir-boosted protease inhibitor to ritonavir-boosted atazanavir plus lamivudine in virologically suppressed HIV-infected adults with osteopenia: a pilot study.

BACKGROUND: Tenofovir disoproxil fumarate, particularly when given with a ritonavir-boosted PI, reduces bone mineral density (BMD) and increases bone turnover markers (BTMs). Ritonavir-boosted atazanavir plus lamivudine is a feasible simplified option. We evaluated whether switching from a triple ritonavir-boosted PI plus tenofovir disoproxil fumarate to a two-drug regimen of lamivudine plus ritonavir-boosted atazanavir would improve BMD. METHODS: Single-arm pilot study. Virologically suppressed patients on tenofovir disoproxil fumarate plus lamivudine or emtricitabine plus ritonavir-boosted PI with low BMD, without previous resistance mutations and/or virological failure to study drugs were switched to 100/300 mg of ritonavir-boosted atazanavir plus 300 mg of lamivudine once daily. The primary endpoint was BMD change by DXA at Week 48. RESULTS: There were 31 patients, 4 (13%) female, and median age was 40 years. Seven participants (22.5%) had osteoporosis. At 48 weeks, mean (SD) changes in spine and hip BMD were +0.01 (0.03) (P = 0.0239) and +0.013 (0.03) g/cm2 (P = 0.0046), respectively. Mean (SD) T-score changes were +0.1 (0.23) (P = 0.0089) and +0.25 (0.76) (P = 0.0197), respectively. N-telopeptide and urine tenofovir disoproxil fumarate toxicity markers showed significant improvements. One participant withdrew from the study and two were lost to follow-up. There were no virological failures, or serious or grade 3-4 adverse events. CONCLUSIONS: Switching from a tenofovir disoproxil fumarate plus ritonavir-boosted PI triple therapy to a lamivudine plus ritonavir-boosted atazanavir two-drug regimen in virologically suppressed HIV-infected adults with low BMD was safe, increased low BMD and reduced plasma markers of bone turnover and urine markers of tenofovir disoproxil fumarate toxicity over 48 weeks.

Real-life experience with bictegravir/emtricitabine/tenofovir alafenamide in a large reference clinical centre.

BACKGROUND: The use of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) is mainly based on robust, pivotal clinical trials. OBJECTIVES: To provide data on clinical use of BIC/FTC/TAF in real life. PATIENTS AND METHODS: This was an observational, retrospective and single-centre study. We included all adult, treatment-naive (TN) and treatment-experienced (TE) people living with HIV (PLWH) starting BIC/FTC/TAF from 8 June 2018. We evaluated effectiveness [on treatment (OT), modified intention-to-treat (mITT) and intention-to-treat (ITT)], tolerability and safety in those patients who reached 6 months of follow-up (M6). RESULTS: We included 1584 PLWH [213 TN (13%) and 1371 TE (87%)]. The median (IQR) follow-up was 16 (7-21) months, with 81% and 53% of PLWH reaching M6 and M12, respectively. By OT, mITT and ITT, HIV-RNA <50 copies/mL was 77%, 70% and 62% at M6 and 92%, 77% and 63% at M12 for TN PLWH and 94%, 89% and 83% at M6 and 93%, 85% and 78% at M12 for TE PLWH, respectively. In PLWH carrying an M184V/I substitution, OT RNA <50 copies/mL was 89.5% at M6. The median CD4 cell count increased from 329 to 511/µL in TN PLWH and from 630 to 683/µL in TE PLWH at M6. Of the total, 1148 (88%) PLWH continued on BIC/FTC/TAF at M6. The most frequent known reason for discontinuation was toxicity [42 (69%) cases]; only 7 cases were considered virological failures (0.6% of the total OT cohort at M6), with no emerging resistance substitutions. CONCLUSIONS: In real life, BIC/FTC/TAF showed high rates of virological suppression and also in PLWH carrying lamivudine/emtricitabine resistance substitutions. The tolerability and safety of BIC/FTC/TAF were good, with high persistence observed for patients on this regimen at M6.

Chemsex Practices in PrEP: Beyond Addiction and Risk Toward a Healthy Sex Life-Baseline Experiences from a Hospital-Based PrEP Program in Barcelona, Spain.

Pre-exposure prophylaxis (PrEP) is a biomedical intervention that has demonstrated efficacy in HIV prevention in individuals at high-risk, among them chemsex users. Out of 190 PrEP users followed at Hospital Clinic of Barcelona until October 2020, 89% reported drug use, and 63% disclosed that they had engaged in chemsex practices, initiated in 64% of cases within the past year. Twenty-one percent used 3 or more drugs simultaneously, being GHB/GBL, nitrites, sildenafil, and methamphetamine the most prevalent combination. Eight percent reported slamming. Forty-one percent described having had negative experiences and 8% did not remember the last time they had sober sex. Methamphetamine, mephedrone, GHB/GBL, and having had open relationships, group sex, double penetration, and fisting were significantly more prevalent. Forty-nine percent admitted being worried about chemsex use, and 18% said they needed help. A comprehensive, interdisciplinary approach is mandatory to enable the attainment of a healthy approach to one's sex life.

RESUMEN: La PrEP es una intervención biomédica eficaz en la prevención del VIH en personas con alto riesgo, entre ellas las personas que practican chemsex. De los 190 usuarios de PrEP seguidos en el Hospital Clínic de Barcelona hasta octubre de 2020, el 89% refirió utilizar drogas y el 63% en contexto de chemsex, iniciando el consumo el 64% durante el último año. El 21% refería policonsumo, siendo GHB/GBL, nitritos, sildenafilo y metanfetamina la combinación más prevalente. El 8% reportó slamming. El 41% describió haber tenido experiencias negativas y el 8% no recordaba la última vez que tuvo sexo sobrio. Metanfetamina, mefedrona, GHB/GBL y haber tenido relaciones abiertas, sexo en grupo, doble penetración y fisting fueron significativamente más frecuentes. El 49% refirió estar preocupado por la práctica de chemsex y el 18% necesitar ayuda. Un abordaje integral e interdisciplinar mejoraría el acompañamiento global de la sexualidad en estas personas.

Factors associated with the use and composition of two-drug regimens in a large single-centre HIV cohort.

OBJECTIVES: We aimed to assess the clinical characteristics associated with the use of two-drug regimens (2DRs) and the factors associated with specific antiretrovirals in 2DRs in a large single-centre HIV cohort. METHODS: Retrospective analysis of demographics, HIV characteristics and AIDS events, antiretroviral prescription, virological failure and genotypic resistance testing, and laboratory results from all adult people with HIV (PWH) prospectively followed at the Hospital Clinic of Barcelona who were receiving a 3DR or a 2DR in January 2020. We assessed factors associated with the probability of receiving 2DRs relative to three-drug regimens (3DRs) using a logistic regression model, controlling for age, sex and year of HIV diagnosis. The same methodology was applied to identify factors associated with the prescription of integrase inhibitor-based regimens or PI-based regimens among PWH receiving 2DRs. RESULTS: There were 3432 (88%) PWH receiving 3DRs and 463 (12%) receiving 2DRs. In the final adjusted model, ≥2 previous virological failures, previous resistance mutations, previous AIDS diagnosis, longer time on current regimen, higher total cholesterol or triglycerides and lower baseline haemoglobin were independent factors associated with 2DRs. The majority of 2DRs included an integrase inhibitor or/and a PI. We identified independent factors associated with the inclusion of integrase inhibitors (lower HDL cholesterol) or PIs (prior AIDS, prior genotypic resistance mutations and lower CD4/CD8 ratio) in the 2DR. CONCLUSIONS: In this large single-centre HIV cohort, a worse cardiometabolic status or more archived resistance were key factors associated with inclusion of integrase inhibitors or PIs, respectively, in 2DRs.

Low risk of hepatitis B reactivation in patients with severe COVID-19 who receive immunosuppressive therapy.

A significant proportion of patients infected with SARS-CoV-2 develop severe respiratory symptoms due to an excessive immune response. Treatment of this condition may include immunosuppressive therapies, such as IL-6 receptor antagonists and corticosteroids, which pose a risk for patients with active or past hepatitis B virus (HBV) infection. In this prospective cohort study, we analysed the risk of HBV reactivation in patients with severe COVID-19 and resolved HBV infection undergoing immunosuppressive therapy. From 15th March to 30th April 2020, 600 patients with severe COVID-19 were admitted to our hospital and treated with immune modulators. Data regarding HBV infection were available in 484, of whom 69 (14%) were HBsAg negative/anti-HBc positive. For these patients, HBV reactivation prophylaxis with entecavir was strongly recommended. Complete follow-up was available in 61 patients: 72% were male, median age was 67 years, and anti-HBs was >10 IU/mL in 72%. The immunosuppressive drug most used was tocilizumab (72%). Despite HBV prophylaxis recommendation, 38 (62%) patients received entecavir and 23 (38%) did not. Baseline features of both groups were similar. At follow-up, we found no cases of HBsAg seroreversion and only 2 (3%) patients (no prophylaxis group) had detectable serum HBV-DNA (<15 IU/mL). Both were anti-HBs negative and had normal aminotransferase levels. Our data show that the risk of HBV reactivation in patients with severe COVID-19 and resolved HBV infection undergoing immunosuppressive treatment is low. However, if a systematic follow-up after hospital discharge is unfeasible in patients without anti-HBs, a short course of antiviral prophylaxis may be a safe option.

Elimination of hepatitis C virus infection from a hemodialysis unit and impact of treatment on the control of anemia.

INTRODUCTION: In the interferon era, the treatment of hepatitis C virus (HCV) infection in patients on haemodialysis (HD) was limited due to the significant number of treatment-related adverse events (AEs). Direct-acting antivirals (DAAs) have demonstrated their efficacy and safety in the treatment of HCV in patients with advanced chronic kidney disease on haemodialysis. The objective of the study was to evaluate the success in eliminating HCV infection from our dialysis unit using DAAs, and to assess the impact of HCV elimination on clinical and analytical outcomes. PATIENTS AND METHODS: This is a prospective, interventional, single-center study at Hospital Clínic de Barcelona. All HCV-RNA positive patients who received antiviral therapy with DAAs within a 3-year period (2014-2017) were analyzed (n=20). Data on virologic response, adverse events, and biochemical and hematological parameters during and after DAA therapy were analyzed. RESULTS: All patients achieved sustained virologic response (SVR) and only 40% of patients presented with mild AEs. None of the patients presented with HCV reinfection after a 1-year follow-up period, and thus HCV was eliminated from our HD unit. SVR was associated with a significant increase in hemoglobin and hematocrit, and a tendency toward the need for lower doses of iron supplementation with no changes in darbepoetin dose. CONCLUSION: HCV infection can be safely eliminated from HD units with the use of DAAs, preventing new infections in patients and healthcare staff. In the short term, the achievement of SVR is associated with an improvement in the control of anemia.

Efficacy and safety of direct antiviral agents in a cohort of cirrhotic HCV/HIV-coinfected patients.

Background: New direct-acting antiviral agents (DAAs) have shown great efficacy and tolerability in clinical trials and real-life cohorts. However, data are scarce regarding efficacy and safety in cirrhotic HCV/HIV-coinfected patients. Methods: A multicentre prospective analysis was performed in 13 Spanish hospitals, including all cirrhotic HCV/HIV-coinfected patients starting DAA combinations from January to December 2015. Sustained virological response 12 weeks after treatment (SVR12) was analysed. Withdrawal due to toxicity and/or hepatic decompensation and change in liver stiffness measurement (LSM) after HCV treatment were evaluated. Results: Patients (n = 170) were mostly male (n = 125; 74.3%) with the following HCV genotype (Gt) distribution: Gt-1a, 68 (40%); Gt-1b, 21 (12.4%); Gt-4, 47 (27.6%); and Gt-3, 26 (15.3%). Baseline median LSM was 20.6 kPa (IQR 16.1-33.7) and log10 HCV-RNA 6.1 IU/mL (IQR 5.7-6.5). Most patients had a Child-Pugh class A score (n = 127; 74.7%) and 28 (16.5%) had prior hepatic decompensation. There were 89 (52.4%) pretreated patients with 40.4% (n = 36) of null responders. Preferred regimens were as follows: sofosbuvir/ledipasvir + ribavirin, 43 (25.3%) patients; sofosbuvir + simeprevir + ribavirin, 34 (20%); sofosbuvir/ledipasvir, 26 (15.3%) and sofosbuvir + daclatasvir + ribavirin, 25 (14.7%). Overall SVR12 was 92.9% (158/170), without differences between genotypes. Pretreated patients had lower SVR12 rates compared with naive (88.8% versus 97.5%; P = 0.026). Treatment failures were as follows: 7 (4.1%) relapses; 2 (1.2%) lost to follow-up; 1 (0.6%) toxicity-related discontinuation; 1 (0.6%) hepatic decompensation; and 1 (0.6%) viral breakthrough. On-treatment hepatic decompensation was recorded in four (2.4%) patients (encephalopathy and ascites, two each). Paired LSM in 33 patients showed a decrease of 5.6 kPa (95% CI 1.8-9.2; P = 0.004). Conclusions: In our cohort of cirrhotic HCV/HIV-coinfected patients, DAAs were highly safe and efficacious. Viral eradication was associated with a significant decrease in liver stiffness.

Tolerability of integrase inhibitors in a real-life setting.

Background: Integrase inhibitors have shown better tolerability than other drugs in clinical trials, but some post-marketing data have suggested potential differences among them. Aims: We compared rates and reasons for discontinuation of raltegravir-, elvitegravir- and dolutegravir-based regimens in a large cohort of HIV-infected patients. Methods: Retrospective analysis of a prospectively followed cohort including all antiretroviral-naive and all virologically suppressed antiretroviral-experienced patients prescribed a first regimen containing raltegravir, elvitegravir or dolutegravir with at least one follow-up visit. Major outcomes were early discontinuation (≤1 year) due to any reason and more specifically due to toxicity. Incidence was calculated as number of episodes per 1000 person-years. Risk factors for discontinuation were assessed by multivariate Cox models. Results: Early discontinuations due to any reason were 271 (raltegravir), 168 (elvitegravir) and 264 (dolutegravir) per 1000 patient-years ( P = 0.0821). Early discontinuations due to toxicity were 76 (raltegravir), 103 (elvitegravir) and 81 (dolutegravir) per 1000 patient-years ( P = 0.6792). Overall, the most common toxicities leading to discontinuation were neuropsychiatric, osteomuscular or digestive. Most frequent neuropsychiatric manifestations reported at discontinuation were insomnia, dizziness, headache and anxiety irrespective of the integrase inhibitor. Among discontinuations due to toxicity, neuropsychiatric effects were more common with dolutegravir than with raltegravir or elvitegravir ( P = 0.0046). Age (HR 1.04, 95% CI 1.02-1.07, P = 0.0007) was the only independent risk factor for early discontinuation due to toxicity. Conclusions: Discontinuations due to any reason tended to be less common with elvitegravir, but discontinuations due to toxicity did not differ among integrase inhibitors. Neuropsychiatric toxicity leading to drug discontinuation was more frequent with dolutegravir.

IFN-free therapy for HIV/HCV-coinfected patients within the liver transplant setting.

OBJECTIVES: IFN-based therapy against hepatitis C recurrence after liver transplantation (LT) has poor effectiveness and tolerability. In HIV/HCV-coinfected liver transplant recipients, the results are even poorer. Here, we report our experience using direct antiviral agents (DAAs) in 11 consecutive coinfected patients within the LT setting. METHODS: Four patients with compensated cirrhosis and hepatocellular carcinoma were treated while awaiting LT and seven patients received antiviral therapy due to severe hepatitis C recurrence after LT [fibrosing cholestatic hepatitis (n = 1), fibrosis stage ≥F3 (n = 2) and decompensated cirrhosis (n = 4)]. Patients were treated with different sofosbuvir-based regimens with or without ribavirin for 12 or 24 weeks. RESULTS: Sustained virological response (SVR) was achieved in all patients. Two of the four patients treated while awaiting LT reached the time of transplant with undetectable HCV-RNA that remained undetectable 12 weeks after LT, one patient had detectable HCV-RNA at the time of transplant but achieved SVR after completing 12 weeks of therapy after LT and the last patient is still on the waiting list. Seven patients with severe post-LT hepatitis C recurrence were treated within 11-120 months after LT. In these patients, viral eradication was associated with an improvement in liver function and clinical decompensation. Tolerance to antiviral therapy was good and only four patients reported mild adverse events. CONCLUSIONS: IFN-free regimens are effective and well tolerated in HIV/HCV-coinfected patients within the LT setting, but more data are needed to confirm our promising results and to establish the best treatment option in this population.

A randomized clinical trial comparing ritonavir-boosted lopinavir versus raltegravir each with tenofovir plus emtricitabine for post-exposure prophylaxis for HIV infection.

OBJECTIVES: The objective of this study was to assess post-exposure prophylaxis (PEP) non-completion at day 28, comparing two regimens. METHODS: A prospective, open, randomized clinical trial was conducted at a tertiary hospital in Barcelona, Spain. Individuals attending the emergency room because of potential sexual exposure to HIV were randomized to tenofovir disoproxil/emtricitabine (245/200 mg) plus either ritonavir-boosted lopinavir (400/100 mg) or raltegravir (400 mg). The primary endpoint was PEP non-completion at day 28. Secondary endpoints were adherence, adverse events and rate of seroconversions. This study was registered in ClinicalTrials.gov: NCT01576731. RESULTS: One-hundred-and-twenty-one individuals were randomized to receive ritonavir-boosted lopinavir and 122 to raltegravir (n = 243). PEP non-completion at day 28 was 43% with no significant difference between arms. We performed a modified ITT analysis including only those patients who attended on day 1 (n = 191). PEP non-completion in this subgroup was higher in the ritonavir-boosted lopinavir arm than in the raltegravir arm (34.6% versus 20.4%, P = 0.04), as was the number of patients lost to follow-up at day 28 (32.6% versus 21.6%, P = 0.08) and the proportion of patients with low adherence (49.2% versus 30.8%, P = 0.03). Adverse events were significantly more common in the ritonavir-boosted lopinavir arm (73.4% versus 60.2%, P = 0.007). There was an HIV seroconversion at day 90 in the raltegravir arm in a patient who had multiple potential sexual risk exposures before and after receiving PEP. CONCLUSIONS: Although we found no differences between arms regarding PEP non-completion, poor adherence and adverse events were significantly higher in patients allocated to tenofovir disoproxil/emtricitabine plus ritonavir-boosted lopinavir. These data support the use of raltegravir as the preferred third drug in current PEP recommendations.

A randomized clinical trial comparing ritonavir-boosted lopinavir versus maraviroc each with tenofovir plus emtricitabine for post-exposure prophylaxis for HIV infection.

OBJECTIVES: The objective of this study was to assess post-exposure prophylaxis (PEP) non-completion at day 28, comparing ritonavir-boosted lopinavir versus maraviroc, both with tenofovir disoproxil/emtricitabine as the backbone. METHODS: We conducted a prospective, open, randomized clinical trial. Individuals attending the emergency room because of potential sexual exposure to HIV and who met criteria for receiving PEP were randomized to one of two groups: tenofovir disoproxil/emtricitabine (245/200 mg) once daily plus either ritonavir-boosted lopinavir (400/100 mg) or maraviroc (300 mg) twice daily. Five follow-up visits were scheduled for days 1, 10, 28, 90 and 180. The primary endpoint was PEP non-completion at day 28. Secondary endpoints were adherence, adverse events and rate of seroconversions. This study was registered in ClinicalTrials.gov: NCT01533272. RESULTS: One-hundred-and-seventeen individuals were randomized to receive ritonavir-boosted lopinavir and 120 to maraviroc (n = 237). PEP non-completion at day 28 was 38% (n = 89), with significant differences between arms [ritonavir-boosted lopinavir 44% (n = 51) versus maraviroc 32% (n = 38), P = 0.05]. We performed a modified ITT analysis including only those patients who attended on day 1 (n = 182). PEP non-completion in this subgroup was also significantly higher in the ritonavir-boosted lopinavir arm (27% versus 13%, P = 0.004). The proportion of patients with low adherence was similar between arms (52% versus 47%, P = 0.56). Adverse events were reported by 111 patients and were significantly more common in the ritonavir-boosted lopinavir arm (72% versus 51%, P = 0.003). No seroconversions were observed during the study. CONCLUSIONS: PEP non-completion and adverse events were both significantly higher in patients allocated to ritonavir-boosted lopinavir. These data suggest that maraviroc is a well-tolerated antiretroviral that can be used in this setting.

Human immunodeficiency virus and risk of porphyria cutanea tarda: a possible association examined in a large hospital.

BACKGROUND: Human immunodeficiency virus (HIV) infection has been reported to be a risk factor for porphyria cutanea tarda (PCT). PURPOSE: To assess the strength of the association between HIV infection and PCT in a large hospital setting. METHODS: All patients (N = 210) diagnosed of PCT between 1990 and 2014 were retrospectively investigated for HIV infection and co-precipitating factors. High-performance liquid chromatography was used to assess the appearance of pre-PCT urinary porphyrin abnormalities among a group (N = 22) of HIV-infected patients without PCT using the urine of patients co-infected with hepatitis C virus (HCV) without PCT for comparison. RESULTS: Twenty-six HIV-infected patients (19 males and seven females) were diagnosed of PCT. During the same interval of time, ~8000 different patients infected with HIV were attended in the hospital of infectious diseases department. Examination of risk factors showed that 25 out of 26 of the PCT patients with HIV were co-infected with HCV. No chromatographic abnormalities were found in the urine of non-PCT-HIV-infected patients, whereas 39% co-infected patients showed urinary porphyrin abnormalities. CONCLUSIONS: In our large hospital series, the appearance of PCT among HIV-infected patients is low (<1%) and most present co-infection with HCV. Therefore, in most HIV-infected patients with PCT, hepatitis C and not HIV may induce uroporphyrinogen decarboxylase deficiency.

Pegylated interferon plus ribavirin in HIV-infected patients with recurrent hepatitis C after liver transplantation: a prospective cohort study.

BACKGROUND & AIMS: The aim of this study was to evaluate the results of treatment with pegylated interferon and ribavirin for the recurrence of hepatitis C after liver transplantation in HCV/HIV-coinfected patients. METHODS: This was a prospective, multicentre cohort study, including 78 HCV/HIV-coinfected liver transplant patients who received treatment for recurrent hepatitis C. For comparison, we included 176 matched HCV-monoinfected patients who underwent liver transplantation during the same period of time at the same centres and were treated for recurrent hepatitis C. RESULTS: Antiviral therapy was discontinued prematurely in 56% and 39% (p = 0.016), mainly because of toxicity (22% and 11%, respectively; p=0.034). Sustained virological response (SVR) was achieved in 21% of the coinfected patients and in 36% of monoinfected patients (p = 0.013). For genotype 1, SVR rates were 10% and 33% (p = 0.002), respectively; no significant differences were observed for the other genotypes. A multivariate analysis based on the whole series identified HIV-coinfection as an independent predictor of lack of SVR (OR, 0.17; 95% CI, 0.06-0.42). Other predictors of SVR were donor age, pretreatment HCV viral load, HCV genotype, and early virological response. SVR was associated with a significant improvement in survival: 5-year survival after antiviral treatment was 79% for HCV/HIV-coinfected patients with SVR vs. 43% for those without (p = 0.02) and 92% vs. 60% in HCV-monoinfected patients (p < 0.001), respectively. CONCLUSIONS: The response to pegylated interferon and ribavirin was poorer in HCV/HIV-coinfected liver recipients, particularly those with genotype 1. However, when SVR was achieved, survival of coinfected patients increased significantly.

[Acute outbreak of hepatitis C in human immunodeficiency virus-infected patients]. / Brote epidémico de hepatitis aguda C en pacientes infectados por el virus de la inmunodeficiencia humana.

BACKGROUND: Recent studies suggest an increased incidence of acute infection with hepatitisC virus (AHC) in men who have sex with men (MSM) co-infected with HIV. Early treatment with interferon-alpha, alone or in combination with ribavirin, significantly reduces the risk of chronic evolution. METHODS: This retrospective study includes all HIV patients with AHC in our centre from 2003 to March 2013. AHC was defined by seroconversion of HCV antibodies and detection of serum HCV RNA. RESULTS: 93 episodes of AHC were diagnosed in 89 patients. All but three were MSM with a history of unprotected sex. Thirty-seven (40%) patients had other associated sexually transmitted disease. The 29% (27) had any symptoms suggestive of AHC. HCV genotype 4 was the most common (41%), followed by genotype1. Seventy patients started treatment with interferon-alfa and weight-adjusted ribavirin. Currently 46 have completed treatment and follow-up, reaching 26 of them (56.5%) sustained viral response. CONCLUSIONS: The incidence of AHC in HIV MSM patients from our centre has increased exponentially in recent years; sexual transmission remains the main route of infection. Early treatment with interferon-alpha and ribavirin achieved a moderate response in these patients.