Development of H51Y and E157Q mutations for integrase inhibitor resistance in a patient undergoing treatment for pulmonary tuberculosis: A case report.

Background: Failure of first-line regimens with dolutegravir, a high genetic barrier antiretroviral of the integrase inhibitor class, although uncommon, tends to increase in prevalence due to broader use. Objective: To describe the clinical case of an HIV/Tuberculosis coinfected patient who developed Human Immunodeficieny Virus (HIV) treatment failure during dolutegravir therapy. Case report: Male, 29 years old, presented with a right cervical mass, dry cough, and hyporexia, which lasted 2 weeks. Diagnostic tests were positive for tuberculosis and HIV. The viral load was 437,927 cp/mL (Log = 5.64). Antiretroviral therapy was initiated with Tenofovir/Lamivudine and Dolutegravir (TDF/3TC and DTG), the latter at a dose of 50 mg/day, as was a regimen for tuberculosis. After 8 months, therapeutic failure was verified. Genotyping was requested, with detection of the H51Y and E157Q mutations in the integrase. Conclusion: Attention when determining the antiretroviral therapy treatment regimen of HIV/TB coinfected patients is paramount. Poor adherence to antiretroviral therapy and follow-up may have contributed to treatment failure and resistance.

Cytokines, chemokines, and cells growth factors in patients with mild to moderate SARS-CoV-2 infection: A case-control study.

Several biomarkers have been evaluated as predictors of severity or in directing the treatment of COVID-19, however there are no conclusive results. In this study, we evaluated serum levels of cytokines, chemokines, and cell growth factors in association with the pathobiology of mild to moderate SARS-CoV-2 infection. Serum levels of SARS-CoV-2 infected patients (n = 113) and flu symptoms individuals negative for SARS-CoV-2 (n = 58), tested by the RT-qPCR test-nasal swab were compared to healthy controls (n = 53). Results showed that the proinflammatory cytokines IL-1ß, MCP-3, TNF-α, and G-CSF were increased in symptomatic patients and the cytokines IL-6 and IL-10 were associated with patients positive for SARS-CoV-2 when compared to healthy controls. Symptoms associated with COVID-19 were fever, anosmia, ageusia, and myalgia. For patients without SARS-CoV-2 infection, their major symptom was sore throat. The pathobiology of mild to moderate SARS-CoV-2 infection was associated with increasing proinflammatory cytokines and a pleiotropic IL-6 and anti-inflammatory IL-10 cytokines compared to healthy controls. Thus, knowledge about the pathophysiology and the involvement of biomarkers in the mild to moderate profile of the disease should be evaluated. Monitoring these biomarkers in patients with mild to moderate disease can help establish adequate treatment and prevention strategies for long-term COVID-19.

Effectiveness of first-wave protease inhibitors in hepatitis C virus genotype 1 infection: a multicenter study in Brazil.

INTRODUCTION: In 2013, combination therapy using peginterferon, ribavirin, and boceprevir or telaprevir was introduced to treat hepatitis C virus genotype 1 infection in Brazil. The effectiveness of this therapy in four Brazilian regions was evaluated. METHODS: Clinical and virological data were obtained from patients of public health institutions in five cities, including sustained virological response (SVR) and side effects. Patients with advanced fibrosis (F3/4), moderate fibrosis (F2) for > 3 years, or extra-hepatic manifestations were treated according to Ministry of Health protocol. Treatment effectiveness was verified by using bivariate and multivariate analysis; p-values of < 0.05 were considered significant. RESULTS: Of 275 patients (64.7% men; average age, 57 years old), most (61.8%) were treatment-experienced; 53.9% had subgenotype 1a infection, 85.1% had advanced fibrosis, and 85.5% were treated with telaprevir. SVR was observed in 54.2%. Rapid virological response (RVR) was observed in 54.6% of patients (data available for 251 patients). Overall, 87.5% reported side effects and 42.5% did not complete treatment. Skin rash, severe infection, and death occurred in 17.8%, 2.5%, and death in 1.4% of cases, respectively. SVR was associated with treatment completion, RVR, and anemia. CONCLUSIONS: The effectiveness of hepatitis C virus triple therapy was lower than that reported in phase III clinical trials, possibly owing to the prioritized treatment of patients with advanced liver fibrosis. The high frequency of side effects and treatment interruptions observed supported the decision of the Brazilian authorities to suspend its use when safer and more effective drugs became available in 2015.

Effectiveness of first-wave protease inhibitors in hepatitis C virus genotype 1 infection: a multicenter study in Brazil

Abstract INTRODUCTION: In 2013, combination therapy using peginterferon, ribavirin, and boceprevir or telaprevir was introduced to treat hepatitis C virus genotype 1 infection in Brazil. The effectiveness of this therapy in four Brazilian regions was evaluated. METHODS: Clinical and virological data were obtained from patients of public health institutions in five cities, including sustained virological response (SVR) and side effects. Patients with advanced fibrosis (F3/4), moderate fibrosis (F2) for > 3 years, or extra-hepatic manifestations were treated according to Ministry of Health protocol. Treatment effectiveness was verified by using bivariate and multivariate analysis; p-values of < 0.05 were considered significant. RESULTS: Of 275 patients (64.7% men; average age, 57 years old), most (61.8%) were treatment-experienced; 53.9% had subgenotype 1a infection, 85.1% had advanced fibrosis, and 85.5% were treated with telaprevir. SVR was observed in 54.2%. Rapid virological response (RVR) was observed in 54.6% of patients (data available for 251 patients). Overall, 87.5% reported side effects and 42.5% did not complete treatment. Skin rash, severe infection, and death occurred in 17.8%, 2.5%, and death in 1.4% of cases, respectively. SVR was associated with treatment completion, RVR, and anemia. CONCLUSIONS: The effectiveness of hepatitis C virus triple therapy was lower than that reported in phase III clinical trials, possibly owing to the prioritized treatment of patients with advanced liver fibrosis. The high frequency of side effects and treatment interruptions observed supported the decision of the Brazilian authorities to suspend its use when safer and more effective drugs became available in 2015.

CD38+CD8+ and CD38+CD4+ T Cells and IFN Gamma (+874) Polymorphism Are Associated with a Poor Virological Outcome.

The main objective of the work was to evaluate the use of CD38 on T lymphocytes, IFNγ (+874 A/T), and IL-10 (-1082 A/G) polymorphisms in HIV-infected patients under antiretroviral (ARV) therapy. Sixty-one patients were selected at the outpatient clinic for HIV infection at the Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil. The patients were classified into two groups, according to viral load after one year of ARV therapy. In the aviremic group (group I), a reduction of 35.5% of CD38+CD4+ T cells was observed (p = 0.02) and 49.3% of CD38+CD8+ T cells (p = 0.001). In the viremic group (group II), a reduction of 37.2% of CD38+CD4+ T cells (p = 0.067), and 21.4% of CD38+CD8+ T cells (p = 0.60) occurred. No association was found between IL-10 (-1082) polymorphism and the type of response to ARV therapy. Regarding the gene polymorphism on IFNγ (+874 T/A), 73.34% of group I and 33.3% of group II presented the AA genotype. The relative risk of the individuals carrying AA genotype or the A allele and not being able to suppress the viral load level after one year of ARV therapy was 3.44 (1.25-9.45; p = 0.014) or 2.35 (1.05-5.26; p = 0.027), respectively. Our data suggested that an augmented frequency of activated CD38+CD8+ T cells as well as the presence of the A allele of IFNγ polymorphism could contribute to a reduced virological suppression in patients under antiretroviral therapy.

Interleukin-10 gene polymorphism (-1082G/A) and allergy to efavirenz in patients infected with human immunodeficiency virus.

The aim of the present study was to investigate the association between polymorphism in the interleukin-10 gene promoter at position -1082 in human immunodeficiency virus-infected patients who had presented allergic reaction due to efavirenz. The study included 63 patients treated at the Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil. Twenty-one patients who had presented allergic reaction to efavirenz were compared to 42 patients with no allergic reaction following exposure to this drug. Blood samples were collected for DNA extraction and submitted to the restriction fragment length polymorphism - polymerase chain reaction technique. The -1082AA genotype was significantly more frequent in allergic patients as compared to non-allergic patients (p=0.019; χ(2)=5.534; OR=3.625; 95% CI=1.210-10.860). Likewise the allele IL-10 -1082A was identified significantly more often among efavirenz allergic patients than in the non-allergic group (p=0.009; χ(2)=6.787; OR=3.029; 95% CI=1.290-7.111). These findings suggest that the polymorphism in the interleukin-10 gene promoter -1082G/A can be related to the development of allergic reactions to efavirenz.

Virologic and immunologic effectiveness at 48 weeks of darunavir-ritonavir-based regimens in treatment-experienced persons living with HIV-1 infection in clinical practice: a multicenter Brazilian cohort.

INTRODUCTION: Published data addressing the effectiveness of darunavir-ritonavir (DRV/r)-based therapy for multiexperienced patients in developing countries are scarce. This study evaluated the 48-week virologic and immunologic effectiveness of salvage therapy based on DRV/r for the treatment of multidrug-experienced HIV-1-infected adults in Brazil. MATERIALS AND METHODS: A multicenter retrospective cohort study was carried out with multidrug-experienced adults who were on a failing antiretroviral therapy and started a DRV/r-based salvage therapy between 2008 and 2010. The primary effectiveness end point was the proportion of patients with virologic success (plasma HIV-1 RNA <50 copies/mL at week 48). RESULTS: At 48 weeks, 73% of the patients had HIV-RNA <50 copies/mL and a mean increase of 108 CD4 cells/mm(3). Higher baseline viral load, lower baseline CD4 count, younger age, and 3 or more DRV/r-associated resistance mutations were significantly predictive of virologic failure. Concomitant use of raltegravir was strongly associated with virologic success. CONCLUSION: The use of DRV/r-based regimens for salvage therapy is an effective strategy in the clinical care setting of a developing country.

Factors determining changes in initial antiretroviral therapy.

OBJECTIVE: To investigate factors determining changes in initial antiretroviral therapy (ART) in patients attended to in an AIDS tertiary care hospital in Ceará, Brazil. METHODS: This descriptive and exploratory study used the analysis of request to initiate or change treatment forms in the year of 2008, and the changes in therapy were followed through the first year of treatment. Data were analyzed with SPSS and EpiInfo by using ANOVA and the exact test of the coefficient of contingency, with significance at p < 0.05. RESULTS: From 301 patients initiating ART, 22.1% (n = 68) needed a change in the first year. These patients were mostly males, aged 20 to 39 years; with only one ART changed needed in 86.8% of the cases (n = 59). Reports of two or three changes in regimen were observed. Zidovudine was the drug most often changed, followed by lopinavir/ritonavir and efavirenz. A significant association was found between changes in initial regimens and the report of adverse reactions (p < 0.001). CONCLUSION: The main factor determining changes in the initial ART was an adverse reaction report. Most patients had one change in the initial ART over the first year of treatment. ART monitoring contributed to a better control of the specific drug therapy.

Fatores determinantes para modificações da terapia antirretroviral inicial / Factors determining changes in initial antiretroviral therapy

OBJETIVO: Investigar os fatores determinantes das mudanças da terapia antirretroviral (TARV) inicial dos pacientes assistidos em hospital de referência em AIDS do Ceará. MÉTODOS: O estudo descritivo e exploratório utilizou a análise dos formulários de solicitação de início ou modificação de tratamento do ano de 2008, acompanhando as mudanças de terapia durante o primeiro ano de tratamento. Os dados foram analisados nos programas Statistical Package for the Social Sciences (SPSS) e Epi Info, utilizando ANOVA e teste exato do coeficiente de contingência, com significância de p < 0,05. RESULTADOS: Dos 301 pacientes que iniciaram TARV, 22,1% (n = 68) realizaram troca no primeiro ano. Os pacientes eram, na maioria, do sexo masculino, de idade entre 20 e 39 anos, e fizeram apenas uma mudança da TARV (86,8%; n = 59). Registros de duas ou três mudanças de esquema foram observados. A zidovudina foi o fármaco mais substituído, seguido por lopinavir/ritonavir e efavirenz. Existiu associação significante entre as trocas dos esquemas iniciais com o relato de ocorrência de reações adversas (p < 0,001). CONCLUSÃO: O principal fator determinante para as mudanças de TARV inicial foi o relato de ocorrência de reações adversas. A maioria dos pacientes fez somente uma mudança na TARV inicial durante o primeiro ano de tratamento. O monitoramento da TARV contribuiu para melhor controle da farmacoterapia específica.

OBJECTIVE: To investigate factors determining changes in initial antiretroviral therapy (ART) in patients attended to in an AIDS tertiary care hospital in Ceará, Brazil. METHODS: This descriptive and exploratory study used the analysis of request to initiate or change treatment forms in the year of 2008, and the changes in therapy were followed through the first year of treatment. Data were analyzed with SPSS and EpiInfo by using ANOVA and the exact test of the coefficient of contingency, with significance at p < 0.05. RESULTS: From 301 patients initiating ART, 22.1% (n = 68) needed a change in the first year. These patients were mostly males, aged 20 to 39 years; with only one ART changed needed in 86.8% of the cases (n = 59). Reports of two or three changes in regimen were observed. Zidovudine was the drug most often changed, followed by lopinavir/ritonavir and efavirenz. A significant association was found between changes in initial regimens and the report of adverse reactions (p < 0.001). Conclusion: The main factor determining changes in the initial ART was an adverse reaction report. Most patients had one change in the initial ART over the first year of treatment. ART monitoring contributed to a better control of the specific drug therapy.

Impact of the number of failed therapeutic regimes on the development of resistance mutations to HIV-1 in northeast Brazil.

Highly-potent antiretroviral therapy is necessary to avoid viral replication in HIV patients; however, it can favor the appearance of resistance mutations. The mutations 41L, 67N, 70R, 210W, 215Y/F, 219E/Q, 44D and 118I are defined as nucleoside analogous mutations (NAMs), because they affect the efficacy of all nucleoside reverse transcriptase inhibitors (NRTI). The mutation most frequently associated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) is 103N. 33W/F, 82A/F/L/T, 84V and 90M are called protease inhibitor resistance-associated mutations (PRAM), because they are associated with resistance to several protease inhibitors (PI). This study evaluated the development of resistance mutations and examine the susceptibility of HIV with these mutations to antiretrovirals in HIV-1 patients who have failed one or more therapy regimes. Analyses were made of 101 genotypic tests of patients with therapeutic failure to 2 or 3-drug regimens with NRTI, NNRTI or PI. We used the Stanford database to define the susceptibility profile of the viruses. The samples were divided into three treatment-failure groups: first (F), second (S) and multi-failure (MF) to antiretroviral regimens, and we correlated these groups with resistance profiles and principal mutations. There was a significant increase in resistance mutations V82A/F/L/T, I84V, L90M, M41L, K70R, L210W, T215Y/F and K219Q/E in MF. We also found significantly higher resistance to zidovudine, didanosine, stavudine and abacavir in MF. There was no increase in resistance to tenofovir (p=0.28) and lopinavir (p=0.079) in MF. A high degree of resistance to NNRTIs was observed in all groups. Increased resistance mutations will affect future therapeutic options for HIV patients in Brazil because it results in a significant increase in resistance to antiretroviral drugs.

Impact of the number of failed therapeutic regimes on the development of resistance mutations to HIV-1 in northeast Brazil

Highly-potent antiretroviral therapy is necessary to avoid viral replication in HIV patients; however, it can favor the appearance of resistance mutations. The mutations 41L, 67N, 70R, 210W, 215Y/F, 219E/Q, 44D and 118I are defined as nucleoside analogous mutations (NAMs), because they affect the efficacy of all nucleoside reverse transcriptase inhibitors (NRTI). The mutation most frequently associated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) is 103N. 33W/F, 82A/F/L/T, 84V and 90M are called protease inhibitor resistance-associated mutations (PRAM), because they are associated with resistance to several protease inhibitors (PI). This study evaluated the development of resistance mutations and examine the susceptibility of HIV with these mutations to antiretrovirals in HIV-1 patients who have failed one or more therapy regimes. Analyses were made of 101 genotypic tests of patients with therapeutic failure to 2 or 3-drug regimens with NRTI, NNRTI or PI. We used the Stanford database to define the susceptibility profile of the viruses. The samples were divided into three treatment-failure groups: first (F), second (S) and multi-failure (MF) to antiretroviral regimens, and we correlated these groups with resistance profiles and principal mutations. There was a significant increase in resistance mutations V82A/F/L/T, I84V, L90M, M41L, K70R, L210W, T215Y/F and K219Q/E in MF. We also found significantly higher resistance to zidovudine, didanosine, stavudine and abacavir in MF. There was no increase in resistance to tenofovir (p=0.28) and lopinavir (p=0.079) in MF. A high degree of resistance to NNRTIs was observed in all groups. Increased resistance mutations will affect future therapeutic options for HIV patients in Brazil because it results in a significant increase in resistance to antiretroviral drugs.

Genotype testing and antiretroviral resistance profiles from HIV-1 patients experiencing therapeutic failure in northeast Brazil.

Genotype testing for HIV-1 drug resistance is useful for selecting antiretroviral drug regimens for patients experiencing therapeutic failure, but the optimal means for interpreting the test results is unknown because many HIV-1 protease and reverse transcriptase (RT) mutations contribute to drug resistance. This study identified common combinations of resistance mutations related to antiretroviral resistance profiles. From April 2002 to March 2004, 101 protease and RT sequences were determined for HIV-1 isolates from patients who were failing antiretroviral therapy. The resistance profile was evaluated using the Stanford Database program. Male patients predominated (76.2%), the median age was 38 years, the average CD4 count was 279.21 cells/mm(3) and the average viral load was 4.49 log. In relation to protease inhibitors (IP) 31 mutation patterns were detected, 49 mutation patterns were detected in Nucleoside RT Inhibitors (NRTI), and 17 patterns were found in the Non Nucleoside RT Inhibitors (NNRTI). K65R was detected in 5.9% of the isolates. The most frequent mutations were: L90M, M184V and K103N related to PI's, NRTI's and NNRTI's, respectively. The best antiretroviral susceptibility was found to be Lopinavir in the PI class and Tenofovir in the NRTI class. The top six mutation patterns accounted for 49% of the resistance to PI's, for 38.5% of NRTI resistance, and the top two mutation patterns accounted for 40.9% of resistance to NNRTI's.

Genotype testing and antiretroviral resistance profiles from HIV-1 patients experiencing therapeutic failure in northeast Brazil

Genotype testing for HIV-1 drug resistance is useful for selecting antiretroviral drug regimens for patients experiencing therapeutic failure, but the optimal means for interpreting the test results is unknown because many HIV-1 protease and reverse transcriptase (RT) mutations contribute to drug resistance. This study identified common combinations of resistance mutations related to antiretroviral resistance profiles. From April 2002 to March 2004, 101 protease and RT sequences were determined for HIV-1 isolates from patients who were failing antiretroviral therapy. The resistance profile was evaluated using the Stanford Database program. Male patients predominated (76.2 percent), the median age was 38 years, the average CD4 count was 279.21 cells/mm³ and the average viral load was 4.49 log. In relation to protease inhibitors (IP) 31 mutation patterns were detected, 49 mutation patterns were detected in Nucleoside RT Inhibitors (NRTI), and 17 patterns were found in the Non Nucleoside RT Inhibitors (NNRTI). K65R was detected in 5.9 percent of the isolates. The most frequent mutations were: L90M, M184V and K103N related to PI's, NRTI's and NNRTI's, respectively. The best antiretroviral susceptibility was found to be Lopinavir in the PI class and Tenofovir in the NRTI class. The top six mutation patterns accounted for 49 percent of the resistance to PI's, for 38.5 percent of NRTI resistance, and the top two mutation patterns accounted for 40.9 percent of resistance to NNRTI's.

Dermatite Seborreica da Face Tratada com Pimecrolimus Creme em Quatro Pacientes HIV positivos / Facial Seborrheic Dermatitis Treated with Pimecrolimus Cream in four patients HIV positive

Quatro pacientes HIV positivos com perfil imunologico diferente e portadores de dermatite seborreica(DS) da face forma tratados exclusivamente com pimecrolimus creme, um imunomodulador macrolactamico. O pimecrolimus inibe a calcineurina atraves do complexo droga-macrofilina-12 e desta maneira inibe a ativacao e maturacao das celulas T, bloqueia a ativacao da transccricao dos genes das linfocinas, evita a degranulacao mastocitaria e iniube a funcao das celulas de Langerhans. Nao promove atrofia, estria, foliculite, exacerbacao de acne/rosacea, telangiectasia ou toxicidade ocular permitindo o uso seguro em areas criticas com a face. Os pacientes usaram na face o pimecrolimus 1,0porcento creme duas vezes por dia por sete dias consecuti9vos havendo desaparecimento total das lesoes apos este periodo.

Comparacao da resposta terapeutica na "Vida Real" entre esquemas de resgate contendo RTV/SQV versus NVP/NFV / Comparison of therapeutic response to salvage therapy with RTV/SQV and NVP/NFV

A terapia anti-retroviral para pacientes que falham a esquemas iniciais e menos efetiva, devido a menor sensibilidade do virus aos medicamentos e a maior complexidade dos esquemas propostos, que acarretam menor adesao. Com o objetivo de comparar a resposta terapeutica na "vida real" entre esquemas de resgate contendo RTV/SQV (400/400BID) e NVP/NFV (200BID/750TID) analisamos, retrospectivamente, prontuarios de 64 pacientes (35 em uso de RTV/SQV - grupo 1 e 29 em uso de NVP/NFV - grupo 2). Os grupos nao diferiram quanto a sexo, idade, media de CD4 e Carga Viral (NASBA) basal, tempo medio de exposicao a terapia anti-retroviral previa e tempo de tratamento com o esquema de resgate (p>0,05). Nao houve diferenca significativa na melhora imunologica (aumento de CD4), que ocorreu em 37, 1 porcento no grupo 1 e 41,4 porcento no grupo 2, nem no ganho medio de CD4 que foi de 85,7 cel. e 52,9 cel., respectivamente(p>0,05). Da mesma forma, em relacao a resposta virologica, nao houve diferenca significativa na comparacao entre os grupos. Esse beneficio foi evidenciado em 54,3 porcento e 48,3 porcento dos pacientes nos grupos 1 e 2 (p>0,05). Tambem nao houve diferenca em relacao a magnitude da diminuicao de Carga Viral (1,5 log e 1,1 log) nem no numero de pacientes com Carga Viral indetectavel apos inicio do Resgate (17 porcento e 3,5 porcento) nos grupos 1 e 2 (p>0,05). Neste estudo nao houve diferenca quanto a resposta terapeutica entre os esquemas de resgate com RTV/SQV e NVP/NFV

Resposta terapeutica a esquema anti-retroviral inicial contendo efavirenz ou nelfinavir, na "Vida Real" / Therapeutic response in inicial antiretroviral therapy with efavirenz or nelfinavir

Comparameos resposta terapeutica, virologica e imunologica, em estudo na "vida real" entre esquemas de terapia inicial contendo ITRNN - Efavirenz (EFV) ou IP - Nelfinavir (NFV), por analise retrospectiva de 58 prontuarios (32 com EFV e 26 com NFV), de janeiro/1999 a outubro/2001. Os grupos nao diferiram quanto a sexo, idade media, tempo entre o diagnostico do HIV e inicio da terapia, tempo de avaliacao com a terapia em estudo e media de carga viral (CV) inicial. A media de CD4 inicial foi 258,6 cel/mm3 para EFVe 156,7 cel/mm3 para NFV (p=0,038). Dos pacientes com CD4 inicial <100 cel/mm3 (31 porcento do total), 27,7 porcento pertenciam ao grupo do EFV e 72 porcento ao do NFV(p=0,005). Apenas 25 porcento dos pacientes em EFV e 11,5 porcento com NFV apresentaram CV indetectavel durante a terapia. Resposta virologica foi percebida em 94,4 porcento no grupo EFV e 61,9 porcento no NFV(p=0,029), com diminuicao media da CV de 3,11 log para o grupo EFV e 1,85 log para NFV(p=0,02). Resposta imunologica foi alcancada em 96,8 porcento no grupo EFV e 79,1 porcento no NFV (p=0,033) com ganho medio de CD4 = 75 cel/mm3 para EFV e 96 cel/mm3 para NFV (p=0,0019). Nosso estudo evidenciou diferenca quanto a resposta virologicae imunologica entre os grupos EFV e NFV, em beneficio da primeira droga; assim como o grupo EFV apresentou maior numero de pacientes com Carga Viral indetectavel durante a terapia (25 porcento contra 11,5 porcento)

Clinical evaluation of the efficacy and tolerability of ritonavir in combination with two reverse transcriptase inhibitors

A retrospective study of 76 patients was carried out using ritonavir in an antiretroviral regimen combined with two reverse transcriptase inhibitors to treat outpatients from July, 1996, to April, 1998, with the objective of evaluating clinical efficacy and tolerability,. Seventy-six percent of the patients had been diagnosed with AIDS, an average number of CD4 cells =233.7 cells/mmü and viral load = 144,084 RNA copies/mmü. The majority of patients (76.3 percent) were antiretroviral treatment-experienced, 21.4 percent having taken protease inhibitors. A positive clinical response was found in 86.7 percent (including an average weight gain of 4.41kg in 58.5 percent), an average CD4 count increase of 169.5 cells/mmü in 83.3 percent and an average viral load decrease of approximately 2.28 log in 75 percent of patients. A high percentage of adverse effects (76.3 percent) was detected, with most slight or moderate, but they significantly impacted adherence to treatment as 31.6 percent stopped taking the drug as a result. We conclude that this antiretroviral regimen has good clinical efficacy, but relatively poor tolerability.