HIV Pre-Exposure Prophylaxis (PrEP) in a Brazilian Clinical Setting: Adherence, Adverse Events, Sexual Behavior, and Sexually Transmitted Infections.

Tenofovir/emtricitabine (TDF/FTC) has been used as pre-exposure prophylaxis (PrEP) in preventing HIV infection. PrEP is an effective prevention tool as demonstrated in clinical trials and studies in clinical practice and was incorporated into the Brazilian public health system in December 2017. The present study was a prospective cohort that included 219 PrEP users monitored over a 10 month follow-up period in a capital city in Northeastern Brazil. Data were collected from the PrEP users' electronic medical records platform made available by the Brazilian Health Ministry. During the observation period, there was good user retention to the prevention program (84%) and there was high adherence to medication (90%). Almost half the users (49%) presented an adverse event, although these were mild and transient, 30 days after starting prophylaxis. There was a significant reduction in creatinine clearance (p < .001), from 104.9 to 83.5 mL/min; however, there was no need for drug discontinuation. Throughout the cohort, there was no significant change in the number of sexual partners, but the use of condoms during sexual intercourse decreased (p < .001). There was a non-significant increase in the incidence of syphilis (p = .08), and there was a 50% decrease in reporting signs and symptoms of sexually transmitted infections. No cases of HIV infection were observed. PrEP proved to be an effective tool in HIV prevention, presenting few complications of adverse events.

Dolutegravir: Virologic response and tolerability of initial antiretroviral regimens for adults living with HIV.

The integrase inhibitor dolutegravir was included in initial antiretroviral therapy in Brazil in January 2017. Studies have demonstrated that the efficacy and safety of antiretrovirals have improved with the introduction of new classes of antiretrovirals, such as integrase inhibitors. This study aimed to estimate the frequency of individuals with a virologic response by week 24 of antiretroviral treatment and to describe the adverse events of the regimen containing dolutegravir. This was a cohort of people living with HIV followed up at a referral hospital. Patients were included who had initiated their first treatment between January and August 2017. Data were obtained from medical records, the Drug Logistics Management System and from the Laboratory Tests Control System. Two hundred and twenty-two patients were included for the tolerability analysis and one hundred and thirty-seven for the virologic response analysis. The mean age was 34 years, the median time between diagnosis and initiating treatment was 1.9 months and the median time on antiretroviral therapy was 13.2 months. The frequency of adverse events was 10% (95% CI: 7% to 15.2%), of these, amongst the most frequent events, 91% presented gastrointestinal effects, and 47.8% neuropsychiatric. By week 24 the estimated incidence of virologic response was 89.1% (95% CI: 83% to 93.5%), with an increase during the first 6 months in the number of T-CD4 lymphocytes of 50.7 cells/mm 3 (95% CI: 42 to 59.3). Initial antiretroviral regimens containing dolutegravir were well tolerated and effective in viral suppression during the first 24 weeks after initiating treatment. The occurrence of adverse events was low, either mild or moderate.

Factors associated to modification of first-line antiretroviral therapy due to adverse events in people living with HIV/AIDS

ABSTRACT Antiretroviral therapy (ART) has modified the outcome of patients with HIV infection, providing virological control and reducing mortality. However, there are several reasons as to why patients may discontinue their antiretroviral therapy, with adverse events being one of the main reasons reported in the literature. This is a case-control nested in a cohort of people living with HIV/AIDS, conducted to identify the incidence of ART modification due to adverse events and the associated factors, in two referral services in Recife, Brazil, between 2011 and 2014. Of the modifications occurred in the first year of ART, 25.7% were driven by adverse events. The median time elapsed between initiating ART and the first modification due to adverse events was 70.5 days (95% CI: 26-161 days). The main adverse events were dermatological, neuropsychiatric and gastrointestinal. Dermatological events were the earliest to appear after initiating ART. Efavirenz was the most prescribed and most modified drug during the study period. The group of participants who used zidovudine, lamivudine, and efavirenz had a 2-fold greater chance (adjusted OR: 2.16 95% CI: 1.28-3.65) of switching ART due to adverse events when compared to the group that used tenofovir with lamivudine and efavirenz.

Factors associated to modification of first-line antiretroviral therapy due to adverse events in people living with HIV/AIDS.

Antiretroviral therapy (ART) has modified the outcome of patients with HIV infection, providing virological control and reducing mortality. However, there are several reasons as to why patients may discontinue their antiretroviral therapy, with adverse events being one of the main reasons reported in the literature. This is a case-control nested in a cohort of people living with HIV/AIDS, conducted to identify the incidence of ART modification due to adverse events and the associated factors, in two referral services in Recife, Brazil, between 2011 and 2014. Of the modifications occurred in the first year of ART, 25.7% were driven by adverse events. The median time elapsed between initiating ART and the first modification due to adverse events was 70.5 days (95% CI: 26-161 days). The main adverse events were dermatological, neuropsychiatric and gastrointestinal. Dermatological events were the earliest to appear after initiating ART. Efavirenz was the most prescribed and most modified drug during the study period. The group of participants who used zidovudine, lamivudine, and efavirenz had a 2-fold greater chance (adjusted OR: 2.16 95% CI: 1.28-3.65) of switching ART due to adverse events when compared to the group that used tenofovir with lamivudine and efavirenz.

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

INTRODUCCIÓN: Estudios recientes confirman un aumento de la incidencia de infección aguda por el virus de la hepatitis C (HAC) en hombres que tienen sexo con hombres (HSH) infectados o no por el VIH. El tratamiento temprano con interferón-alfa, solo o asociado a ribavirina, reduce significativamente el riesgo de evolución a la cronicidad. MÉTODOS: Estudio retrospectivo que incluye todos los pacientes VIH diagnosticados de HAC en nuestro centro desde junio del 2003 a marzo del 2013, definida la HAC por la seroconversión de anticuerpos contra el VHC y la detección de ARN-VHC sérico. RESULTADOS: Se diagnosticaron 93 episodios de HAC en 89 pacientes. Excepto en 3 casos todos eran HSH con antecedentes de prácticas sexuales de riesgo. Treinta y 7 (40%) pacientes presentaban otra enfermedad de transmisión sexual asociada. El 29% (27) presentaron algún síntoma sugestivo de HAC. El genotipo 4 del VHC fue el más frecuente (41%), seguido del genotipo 1. En 70 casos se inició tratamiento con interferón-alfa y ribavirina ajustada a peso. En la actualidad 46 han finalizado el tratamiento y el seguimiento, alcanzando 26 de ellos (56,5%) una respuesta viral sostenida. CONCLUSIONES: La incidencia de HAC en los pacientes VIH HSH de nuestro centro ha aumentado de forma exponencial en los últimos años, siendo la transmisión sexual la vía principal de infección. El tratamiento precoz con interferón-alfa y ribavirina consigue una respuesta moderada en estos pacientes

BACKGROUND: Recent studies suggest an increased incidence of acute infection with hepatitis C 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 genotype 1. 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

[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.

Effectiveness of ritonavir-boosted protease inhibitor monotherapy in the clinical setting: same results as in clinical trials? The PIMOCS Study Group.

OBJECTIVES: Ritonavir-boosted protease inhibitor monotherapy (PIMT) is a maintenance strategy that prevents nucleoside reverse transcriptase inhibitor toxicity and reduces costs. Some trials compare PIMT with combined antiretroviral therapy, but restricted selection criteria and low sample size hamper data extrapolation to routine practice. Here, we analyse the effectiveness and safety of PIMT in clinical practice. METHODS: This was a retrospective, observational, multicentre study. Adult HIV-1 patients receiving PIMT with darunavir or lopinavir were included. A Cox regression model identified independent predictors for virological failure (VF). RESULTS: A total of 664 patients (435 on darunavir/ritonavir and 229 on lopinavir/ritonavir) [74% male, median age of 54 years, one-third with previous protease inhibitor VF, CD4 nadir 189 cells/mm(3) and 42% coinfected with hepatitis C virus (HCV)] were analysed. After a median follow-up of 16 months, 78% of patients (95% CI 74%-81%) remained free from therapeutic failure (TF) (change between ritonavir-boosted PIs not considered failure). At 12 months, by intention-to-treat analysis (change between ritonavir-boosted PIs equals failure), 83% of patients were free from TF (87% darunavir/ritonavir versus 77% lopinavir/ritonavir, P = 0.001). Regarding VF, 88% of patients maintained viral suppression at 12 months (93% darunavir/ritonavir versus 88% lopinavir/ritonavir, P = not significant). CD4 nadir <200 cells/mm(3) [hazard ratio (HR) 1.58, 95% CI 1.01-2.49] and undetectable viral load prior to PIMT <24 months (HR 1.86, 95% CI 1.20-2.91) were independent predictors for VF. Prior protease inhibitor failure, HCV coinfection and the protease inhibitor/ritonavir used were not associated with PIMT outcome. A total of 158 patients stopped PIMT, 6% due to adverse events. Two patients developed encephalitis. CONCLUSIONS: PIMT effectiveness was consistent with data from clinical trials. Viral suppression duration prior to PIMT and CD4 cell count nadir were independent predictors for PIMT outcome.

Dual therapy with etravirine plus raltegravir for virologically suppressed HIV-infected patients: a pilot study.

BACKGROUND: Clinical use of protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs) may be hampered by toxicity, interactions or resistance issues. Simple and effective antiretroviral regimens avoiding both drug classes may be needed for selected patients. METHODS: This was a prospective cohort study. Virologically suppressed patients on PI or NRTI regimens, with problems of tolerability, safety concerns due to comorbidities or risk of drug interactions for both PIs and NRTIs, were given the opportunity to switch their regimen to etravirine plus raltegravir. Patients were required not to have prior virological failure to raltegravir and if there was prior non-nucleoside reverse transcriptase inhibitor (NNRTI) virological failure, only patients in whom efficacy of etravirine could be anticipated through the Stanford Drug Resistance Database were included. Follow-up was scheduled for at least 48 weeks, unless the patient was lost to follow-up or discontinued therapy. RESULTS: Twenty-five patients were included. Their median age was 54 years; they had a median of 16 years on antiretroviral therapy and a median of nine previous regimens; 21 (84%) patients had previous virological failure; and 15 (60%) patients had a genotypic test that showed three or more NRTI mutations in 9 (36%), four or more PI mutations in 11 (44%) and at least one NNRTI mutation in 8 (32%) patients. At 48 weeks efficacy was 84% (95% CI 65.3%-93.6%) by intent-to-treat analysis and 91.3% (95% CI 73.2%-97.6%) by per-protocol analysis. One (4%) patient died, two (8%) discontinued due to intolerance and one (4%) experienced virological failure. The CD4/CD8 ratio and plasma lipids improved. CONCLUSIONS: Dual therapy with etravirine plus raltegravir was well tolerated and maintained durable viral suppression in selected virologically suppressed patients for whom both PI and NRTI therapy was challenging.

Creatine kinase elevation in HIV-1-infected patients receiving raltegravir-containing antiretroviral therapy: a cohort study.

OBJECTIVES: To evaluate the incidence and risk factors for significant creatine kinase elevation in HIV-1-infected patients who were prescribed a raltegravir-containing antiretroviral therapy. DESIGN: A retrospective analysis of a prospectively collected cohort involving all consecutive patients who were prescribed a raltegravir-containing antiretroviral regimen between June 2005 and December 2010. METHODS: Significant creatine kinase elevation was defined as an elevation of at least 3-fold from the upper limit of normal (ULN) (grade 2, WHO classification) while receiving raltegravir. Blood analysis at each visit included at least creatine kinase, as well as plasma HIV-1 RNA and CD4 cell count. RESULTS: There were 475 patients who had been exposed to raltegravir for a median of 11.5 (IQR 8.2-15.2) months. An increase of creatine kinase ≥ 3-fold ULN was detected in 53 (11.2%) patients, representing an incidence of 3.8/100 person-years. Symptoms were reported by seven patients (1.5%), they showed either grade 1 (n = 3) or 2 (n = 4) creatine kinase increases. The median duration of raltegravir therapy before creatine kinase elevation was 5.9 (IQR 3.3-9.3) months. Evidence of creatine kinase elevation prior to raltegravir therapy [hazard ratio (HR) 3.30; 95% CI 1.59 ± 6.86; P = 0.001], abnormal baseline creatine kinase (HR 3.24; 95% CI 1.63 ± 6.45; P = 0.001) and male gender (HR 4.17; 95% CI 1.33 ± 1.27; P = 0.001) were identified as independent risk factors for creatine kinase elevation during raltegravir treatment. CONCLUSIONS: Although ≈ 1 in 10 patients on raltegravir therapy developed significant creatine kinase elevation as defined in this study, symptoms were uncommon, not severe and occurred in patients with easily identifiable risk factors.