Polymorphisms at CYP enzymes, NR1I2 and NR1I3 in association with virologic response to antiretroviral therapy in Brazilian HIV-positive individuals.

Virologic failure of antiretroviral therapy (ART) may be explained by single nucleotide polymorphisms (SNPs) in drug absorption and metabolism genes. Here, we characterized the associations between polymorphisms in cytochrome P450 enzymes' genes CYP2B6 and CYP3A4/A5, nuclear receptor genes NR1I2/3, and initial ART efficacy among 203 HIV-positive individuals from Rio de Janeiro. Association between SNPs and virologic control was evaluated after 6 and 12 months of follow-up using Cox regression models. The SNP rs2307424 (NR1I3) was associated with increased virologic response after 12 months of treatment, while rs1523127 (NR1I2), rs3003596, and rs2502815 (NR1I3) were associated with decreased response. Increased virologic response after 12 months (adjHR = 1.54; p = 0.02) was also observed among carriers of the NR1I3 haplotype rs2502815G-rs3003596A-rs2307424A versus the reference haplotype G-A-G. Our results suggest that NR1I2 and NR1I3 variants are associated with virologic responses to ART among Brazilians.

Drug metabolism and transport gene polymorphisms and efavirenz adverse effects in Brazilian HIV-positive individuals.

Objectives: There are limited data regarding efavirenz pharmacogenetics in admixed populations. The Brazilian population is highly admixed. In a Brazilian cohort, we sought to characterize associations between efavirenz adverse effects (all-cause and CNS) and polymorphisms in seven genes known or suspected to affect efavirenz metabolism and transport. Methods: We studied 225 HIV-positive individuals who had been prescribed efavirenz-containing regimens at a hospital in Rio de Janeiro, Brazil. Eighty-nine cases had efavirenz adverse effects, including 43 with CNS adverse effects, while 136 controls had no adverse effect of any antiretroviral after treatment for at least 6 months. A total of 67 candidate polymorphisms in ABCB1, CYP2A6, CYP2B6, CYP3A4, CYP3A5, NR1I2 and NR1I3 genes were selected for association analysis. Admixture was assessed using 28 ancestry-informative polymorphisms previously validated for the Brazilian population. Associations were evaluated with logistic regression models adjusted for sex and genetic ancestry. Results: There was extensive African, European and Native American admixture in the cohort. Increased all-cause adverse effects were associated with the CYP2B6 genotype combination 15582CC-516TT-983TT (OR = 7.26, P = 0.003) and with the CYP2B6 slow metabolizer group 516TT or 516GT-983CT (OR = 3.10, P = 0.04). CNS adverse effects were nominally associated with CYP3A4 rs4646437 (OR = 4.63, P = 0.014), but not after adjusting for multiple comparisons. Conclusions: In a highly admixed Brazilian cohort, the CYP2B6 slow metabolizer genotype was associated with an increased risk of efavirenz adverse effects.

Prevalence of Hepatitis C Virus Infection in Patients With Renal-Cell Carcinoma.

BACKGROUND: Some studies have demonstrated that the prevalence of chronic hepatitis C virus (HCV) infection is increased in patients with renal-cell carcinoma (RCC). Brazil is considered a low prevalence area for HCV (1.38%). The aim of this study was to evaluate the prevalence of HCV infection in patients with RCC. PATIENTS AND METHODS: A cross-sectional study with retrospective data collection was carried out. Patients more than 18 years old with a histopathologic diagnosis of RCC and who underwent HCV serology were included. Sociodemographic, pathologic, and clinical characteristics were evaluated at the time of patient admission. A descriptive analysis of the data was performed using means accompanied by their respective standard deviations for the continuous variables, and absolute number and frequency for the categorical variables. Comparisons between means were performed by analysis of variance. A chi-square test was used to compare the frequency of categorical variables. P < .05 was considered statistically significant. RESULTS: The prevalence of HCV infection was 4.1% (95% confidence interval, 1.7-8.3). No significant differences in age, sex, ethnicity, schooling, and alcohol or tobacco consumption among HCV- and HCV-negative patients with RCC were observed. CONCLUSIONS: A 3-fold higher prevalence of HCV infection was identified among patients with RCC than in the general Brazilian population. Further studies are required to confirm these data.

Antiretroviral therapy-induced paradoxical worsening of previously healed Mycobacterium haemophilum cutaneous lesions in advanced HIV infection.

Mycobacterium haemophilum is a nontuberculous mycobacterium that causes localized or disseminated disease, mainly in immunocompromised hosts. We report the case of a 35-year-old HIV-infected woman who presented with several enlarging cutaneous lesions over the arms and legs. Histopathological examination revealed the diagnosis of a cutaneous mycobacterial disease. Mycobacterial analyses unveiled M. haemophilum infection. Six months after completion of a successful antimycobacterial treatment, she developed an immune reconstitution inflammatory syndrome (IRIS). This paradoxical relapse presented as tenderness, redness and swelling at the precise sites of the healed lesions and took place in the setting of significant recovery of the CD4 cell count (from 05 to 318 cells/mm 3 ). Microbiological analyses of these worsening lesions were negative, and they spontaneously remitted without the initiation of a novel antimycobacterial treatment cycle. M. haemophilum infection should always be considered as a cause of skin lesions in immunocompromised subjects. Physicians should be aware of the possibility of IRIS as a complication of successful antiretroviral therapy in HIV-infected patients with M. haemophilum infection.

Prevalence of hepatitis C virus infection and its impact on the prognosis of head and neck cancer patients.

OBJECTIVE: Several studies have shown a higher prevalence of hepatitis C virus (HCV) infection among patients with head and neck cancer (HNC) compared to the general population. In Brazil, the prevalence of HCV infection is considered low (1.38%). The aim of this study was to determine HCV prevalence and how this can modify outcomes of patients with HNC. STUDY DESIGN: Retrospective cohort. METHODS: Patients with a diagnosis of malignant neoplasm in the head and neck (HN) region and who had serology performed for HCV were included. Patients were classified into two groups: head and neck squamous cell carcinoma (HNSCC) and other head and neck malignant neoplasms (OHNMN). Descriptive statistics were performed for all variables of interest. Means were compared using ANOVA and proportions using chi-square tests. Survival data were compared by Kaplan-Meier curves and log-rank test. RESULTS: Global HCV prevalence in patients with HNC was 7.8%, reaching 12.8% in HNSCC and 3.4% in OHNMN (p = 0.003). There was a higher risk of developing a second primary neoplasm in HNSCC compared to OHNMN patients (20.6% versus 4.6%; p = 0.001). The mean survival was not different between HCV-positive and HCV-negative patients (6.0 years versus 6.6 years, respectively, p = 0.516). CONCLUSION: The prevalence of HCV infection was higher in HNC patients compared to the general Brazilian population. It seems reasonable to consider that HCV infection is associated with an increased risk of HNC, but HCV infection does not worsens the prognosis of HNC patients.

Chlamydia trachomatis asymptomatic urethritis recurrence among males living with HIV-1.

A prevalence of 3.47% of asymptomatic Chlamydia trachomatis urethritis has been previously reported among males living with HIV infection in Brazil. This study aims to assess the recurrence of C. trachomatis urethritis three years later in the same cohort of patients and analyze associated risk factors. A total of 115 male patients diagnosed with HIV infection, with no symptoms of urethritis and observed since May of 2015 in followup visits were enrolled. They had urine samplers tested by PCR for C. trachomatis and N. gonorrhoeae between February and March 2018. Results: Three of the four patients who had asymptomatic C. trachomatis urethritis three years before were recurrently positive for C. trachomatis urethritis. Two new patients were diagnosed as positives, accounting for a total asymptomatic C. trachomatis urethritis prevalence of 4.34%. The prevalence during the whole study was 5.21%. The relative risk for a new urethritis episode among those previously diagnosed with urethritis is RR=41.62 (95% CI: 9.42-183.84), p < 0.01. Patients who presented asymptomatic urethritis anytime and who were recurrently positive for C. trachomatis had a lower mean age (p<0.01). Married individuals were protected regarding asymptomatic urethritis [p<0.01, OR = 0.04 (0.005-0.4)] and had lower risk to develop recurrence [p<0.01, RR = 0.86 (0.74-0.99)]. Illicit drugs users had risk associated to asymptomatic urethritis [p=0.02, OR= 5.9 (1.03-34)] and higher risk to develop recurrence [p<0.01, RR=1.1 (1-1.22)]. Conclusion: The recurrence of asymptomatic C. trachomatis urethritis after treatment among males living with HIV infection in Brazil can be considered high and should not be neglected.

Prevalence of asymptomatic urethritis by Chlamydia trachomatis and Neisseria gonorrhoeae and associated risk factors among males living with HIV-1.

OBJECTIVES: The increase in HIV transmissibility in non-ulcerative sexually transmitted infection is already well-established. It is estimated that symptomatic carriers of N. gonorrhoeae and C. trachomatis have a relative risk of 4.8-fold and 3.6-fold, respectively, for the sexual acquisition of HIV. This type of evaluation for asymptomatic urethritis is necessary to reinforce strategies to combat HIV transmission. This study aims to assess the prevalence of patients with asymptomatic urethritis among men diagnosed with HIV-1 and determine the risk factors associated with this infection. METHODS: We enrolled a total of 115 male patients aged 18 years or older who have been diagnosed with HIV infection and have no symptoms of urethritis or other sexually transmitted infections and who have been evaluated between May and August 2015 in a follow-up visit at the Immunology Outpatient Clinic of a Brazilian University Hospital. RESULTS: Four asymptomatic patients were positive for C. trachomatis and were considered asymptomatic carriers of urethritis. Prevalence was 3.47%. Patients who were positive for C. trachomatis urethritis had a lower mean age (p = 0.015). CONCLUSION: The presence of asymptomatic sexually transmitted infection is a challenge in clinical practice. We recommend that, in outpatient practice, the habit of inquiring on previous sexual behavior to obtain more information about risks and associations with asymptomatic sexually transmitted infection, a routine physical examination and complementary tests to detect STI pathogens should be performed to discard these conditions. The development of rapid tests for this purpose should also be encouraged.

Secondary syphilis presenting as leucoderma syphiliticum: case report and review.

Leucoderma syphiliticum (LS), originally described as syphilide pigmentaire, encompasses a spectrum of dyschromic lesions that emerge during the course of secondary syphilis. Very few case reports are available in modern biomedical databases. We present the case of a 57-year-old HIV-infected male patient who presented with several round to oval, non-scaling, slightly raised and well-demarcated hypochromic lesions scattered over the trunk, abdomen, dorsum, and arms. Prior non-treponemal tests were negative for syphilis, but novel studies yielded positive results at high titers. Skin lesions slowly regressed and the hypochromic areas repigmented a few weeks after benzathine penicillin G treatment. This is the first report of LS in an HIV-infected patient. A review of modern and ancient literature was performed. The present case report emphasizes the need for clinicians to have a heightened awareness of the varied and unusual clinical phenotypes of syphilis.

Facial botryomycosis-like pyoderma in an HIV-infected patient: remission after initiation of darunavir and raltegravir.

Botryomycosis is an uncommon, chronic, suppurative, bacterial infection that primarily affects the skin and subcutaneous tissues. It has long been associated with defects of cellular immunity. We report a 28-year-old woman who presented with a chronic, ulcerated lesion with draining sinuses in the right malar region. Predisposing factors were HIV infection with poor immunological control, alcoholism, and a previous trauma to the right cheek. Several courses of antimicrobial therapy provided only partial and temporary remission. Complete clinical remission was only achieved 5 years later when a novel antiretroviral regimen composed of darunavir and raltegravir was initiated.

An unusual case of bacillary angiomatosis in the oral cavity of an AIDS patient who had no concomitant tegumentary lesions - case report and review.

Bacillary angiomatosis (BA) is an angioproliferative disease of immunocompromised patients that usually presents as vascular tumors in the skin and subcutaneous tissues. It is caused by chronic infections with either Bartonella henselae or B. quintana. Oral cavity BA is exceedingly rare and even rarer without simultaneous cutaneous disease. We report herein the case of a 51-year-old HIV-infected man who presented severe odynophagia and an eroded lesion on the hard palate that progressed to an oronasal fistula. No cutaneous lesions were recorded. Doxycycline led to complete resolution. To the best of our knowledge, only six previous cases of oral BA without tegumentary disease have been previously reported and none of them progressed to fistula.

Association between antiretrovirals and thyroid diseases: a cross-sectional study.

OBJECTIVE: This study aims to estimate the prevalence of thyroid diseases and anti-TPO status. We searched for an association among presence of immune reconstitution and use of stavudine, didanosine and protease inhibitors with thyroid diseases. MATERIALS AND METHODS: A cross-sectional study was performed to analyze the records of 117 HIV-infected patients who had their CD4+ cell count, viral load, anti-TPO, TSH and free T4 levels collected on the same day. Immune reconstitution was considered in those whose T CD4+ count was below 200 cells/mm3, but these values increased above 200 cells/mm3 after the use of antiretrovirals. The odds ratio obtained by a 2x2 contingency table and a chi-square test were used to measure the association between categorical variables. RESULTS: The prevalence of thyroid disease was 34.18%; of these, 4.34% were positive for anti-TPO. There was an association of risk between stavudine use and subclinical hypothyroidism (OR = 4.19, 95% CI: 1.29 to 13.59, X2 = 6.37, p = 0.01). Immune reconstitution achieved protection associated with thyroid disease that was near statistical significance OR = 0.45, 95% CI: 0.19 to 1.04, X2 = 3.55, p = 0.059. CONCLUSION: The prevalence of thyroid disease in the sample studied was higher than what had been found in the literature, with a low positive anti-TPO frequency. The historical use of stavudine has an association of risk for the presence of subclinical hypothyroidism, and immune reconstitution has trends towards protection for the presence of thyroid diseases.

Pyoderma Gangrenosum Simulating Necrotizing Fasciitis.

Pyoderma gangrenosum received this name due to the notion that this disease was related to infections caused by bacteria in the genus Streptococcus. In contrast to this initial assumption, today the disease is thought to have an autoimmune origin. Necrotizing fasciitis was first mentioned around the fifth century AD, being referred to as a complication of erysipelas. It is a disease characterized by severe, rapidly progressing soft tissue infection, which causes necrosis of the subcutaneous tissue and the fascia. On the third day of hospitalization after antecubital venipuncture, a 59-year-old woman presented an erythematous and painful pustular lesion that quickly evolved into extensive ulceration circumvented by an erythematous halo and accompanied by toxemia. One of the proposed etiologies was necrotizing fasciitis. The microbiological results were all negative, while the histopathological analysis showed epidermal necrosis and inflammatory infiltrate composed predominantly of dermal neutrophils. Pyoderma gangrenosum was considered as a diagnosis. After 30 days, the patient was discharged with oral prednisone (60 mg/day), and the patient had complete healing of the initial injury in less than two months. This case was an unexpected event in the course of the hospitalization which was diagnosed as pyoderma gangrenosum associated with myelodysplastic syndrome.

Paradoxical reaction to the treatment of tuberculosis uncovering previously silent meningeal disease.

The development of paradoxical clinical worsening following initiation of tuberculosis treatment may complicate the clinical course of both HIV-infected and uninfected patients. We report a severe manifestation of the so called paradoxical reaction to the treatment of tuberculosis that unmasked previously silent meningeal disease in a 34-year-old HIV-infected male patient.

First case of autochthonous human visceral leishmaniasis in the urban center of Rio de Janeiro: case report.

Visceral leishmaniasis is an anthropozoonosis that is caused by protozoa of the genus Leishmania, especially Leishmania (Leishmania) infantum, and is transmitted to humans by the bite of sandflies of the genus Lutzomyia, such as Lutzomyia longipalpis. There are many reservoirs, including Canis familiaris. It is a chronic infectious disease with systemic involvement that is characterized by three phases: the initial period, the state period and the final period. The main symptoms are fever, malnutrition, hepatosplenomegaly, and pancytopenia. This article reports a case of a patient diagnosed with visceral leishmaniasis in the final period following autochthonous transmission in the urban area of Rio de Janeiro. The case reported here is considered by the Municipal Civil Defense and Health Surveillance of Rio de Janeiro to be the first instance of autochthonous visceral leishmaniasis in humans in the urban area of this city. The patient was discharged and is undergoing a follow-up at the outpatient clinic, demonstrating clinical improvement.

Conventional and liquid-based cytology (Liqui-PREP™) anal findings in male HIV anoreceptive patients in a referral University hospital in Rio de Janeiro, Brazil / Achados de citologia convencional e de citologia em base líquida (Liqui-PREP®) anal em pacientes masculinos HIV soropositivos anorreceptivos, em um hospital universitário de referência do Rio de Janeiro, Brasil

Introduction: The anal lesions seem to have a natural history that closely resembles cervical lesions, with signs that precede the invasion. Cytological changes of anal epithelium induced by HPV can be detected through cytology, as it is considered an effective screening method. Objective: To identify the frequency of atypical epithelial conventional cytology results by comparing anal samples through Liqui-PREPTM technology in HIV-positive men. Methods: Cross-sectional descriptive and analytical study of 33 men who have sex with men (MSM), HIV-positive and anoreceptive attended at the Gaffrèe and Guinle University Hospital (HUGG), Rio de Janeiro, from June to July, 2016. Collection of anal samples for the conventional cytology and Liqui-PREPTM cytology was carried out. For significance of findings, Fisher exact test with 95% confidence interval was used and cytological Kappa index was employed for concordance between the two cytological methods. Results: The age ranged from 23 to 60 years (mean=39.06). The CD4 cell count was between 200 to 500/mm3 on 16 (48.5%) and 13 (39.4%), and 50% was diagnosed with HIV for more than 6 years. In conventional cytology one case was considered unsatisfactory (3%). Among the cases considered satisfactory, 9 (28.1%) were diagnosed with ASC-US; 4 (12.5%) LSIL; 2 (6.3%) ASC-H, and 2 (6.3%) HSIL. Through Liqui-PREPTM method, 7 cases were considered unsatisfactory (21.2%). Among the satisfactory cases, 7 showed ASC-US (26.9%); 4 (15.4%) ASC-H; 2 (7.7%) LSIL; and 2 (7.7%) HSIL. The difference of unsatisfactory cases between both methods, although higher for Liqui-PREPTM, was not statistically significant (p=0.054). The correlation was moderate (0503; p<0.006 [0.1765­0.8298]). Conclusion: The cytologic atypia is common among MSM HIV (+), and the anal conventional cytology and liquid by Liqui-PREPTM cytology are equivalent, although they are more unsatisfactory in the latter technique.

Introdução: As lesões anais parecem ter uma história natural, que se assemelha às de lesões de colo uterino, com sinais que precedem a invasão. As alterações citológicas do epitélio anal induzidas pelo HPV podem ser detectadas por citologia, um método de rastreio considerado efetivo. Objetivo: Identificar a frequência de atipias epiteliais nos resultados da citologia convencional comparando amostras anais pela tecnologia Liqui-PREP® em homens HIV positivos. Métodos: Estudo transversal, descritivo e analítico de 33 homens que fazem sexo com homens (HSH), HIV positivos e anorreceptivos atendidos no Hospital Universitário Gaffrèe e Guinle (HUGG), Rio de Janeiro, no período de junho a julho de 2016. Os pacientes foram submetidos à coleta de amostras anais para citologia convencional e citologia Liqui-PREP®. Para significância de achados, foi usado o teste exato de Fisher com intervalo de confiança de 95%, e para concordância entre os dois métodos citológicos, foi utilizado o índice de Kappa. Resultados: A idade variou de 23 a 60 anos (média=39,06). A contagem de células CD4 foi entre 200 e 500/mm3 para 16 (48,5%) e 13 (39,4%) dos casos analisados, e 50% tinham o diagnóstico de HIV há mais de seis anos. Na citologia convencional, um caso foi considerado insatisfatório (3%). Entre os casos considerados satisfatórios, 9 (28,1%) foram diagnosticados como células escamosas atípicas de significado indeterminado possivelmente não neoplásicas (ASC-US); 4 (12,5%) como lesão intraepitelial de baixo grau (LSIL); 2 (6,3%) como células escamosas atípicas não sendo possível excluir lesão intraepitelial de alto grau (ASC-H) e 2 (6,3%) como lesão intraepitelial de alto grau (HSIL). Pelo método Liqui-PREP®, 7 casos foram considerados insatisfatórios (21,2%). Entre os casos satisfatórios, 7 como ASC-US (26,9%); 4 (15,4%) como ASC-H; 2 (7,7%) como LSIL e 2 (7,7%) como HSIL. A diferença de insatisfatório entre os métodos, embora maior para Liqui-PREP®, não foi estatisticamente significativa (p=0,054). A concordância foi moderada (0,503; p<0,006 [0,1765­0,8298]). Conclusão: É frequente a atipia citológica entre HSH HIV (+), e as citologias anal convencional e em meio líquido pela técnica Liqui-PREPTM se equivalem, embora sejam mais insatisfatórias na técnica citológica Liqui-PREP®.

Facial botryomycosis-like pyoderma in an HIV-infected patient: remission after initiation of darunavir and raltegravir

Abstract Botryomycosis is an uncommon, chronic, suppurative, bacterial infection that primarily affects the skin and subcutaneous tissues. It has long been associated with defects of cellular immunity. We report a 28-year-old woman who presented with a chronic, ulcerated lesion with draining sinuses in the right malar region. Predisposing factors were HIV infection with poor immunological control, alcoholism, and a previous trauma to the right cheek. Several courses of antimicrobial therapy provided only partial and temporary remission. Complete clinical remission was only achieved 5 years later when a novel antiretroviral regimen composed of darunavir and raltegravir was initiated.

Severe shoulder tendinopathy associated with levofloxacin.

Fluoroquinolone (FQ)-associated tendinopathy and myopathy are uncommon but well recognized complications of the use of this class of antibacterial agents. The case of a 63-year-old previously asymptomatic female patient who developed severe left shoulder tendinopathy after surreptitiously doubling the prescribed dose of levofloxacin for the treatment of community-acquired pneumonia is reported here. Surgical stabilization with suture anchors and subacromial decompression were needed.

Acute gouty arthritis as a manifestation of immune reconstitution inflammatory syndrome after initiation of antiretroviral therapy.

Immune reconstitution inflammatory syndrome (IRIS) in HIV-infected subjects initiating antiretroviral therapy most commonly involves new or worsening manifestations of previously subclinical or overt infectious diseases. Reports of non-infectious IRIS are much less common but represent important diagnostic and treatment challenges. We report on a 34-year-old HIV-infected male patient with no history of gout who developed acute gouty arthritis in a single joint one month after initiating highly active antiretroviral therapy.