Hepatitis C virus infection and spontaneous clearance in HTLV-1 and HIV co-infected patients in Salvador, Bahia, Brazil

Background: While 20–40% of patients with hepatitis C virus (HCV) monoinfection will spontaneously clear the virus, less is known regarding clearance with coinfections. HCV, human immunodeficiency virus (HIV), and human T-cell lymphotrophic virus 1 and 2 (HTLV-1/2) coinfection occurs due to shared routes of transmission and is prevalent in Brazil. Objectives: To compare the proportion of patients who have spontaneously cleared HCV in patients with HCV monoinfection to patients coinfected by HCV/HIV, or HCV/HIV/HTLV-1. Methods: Using medical records from two clinics in Salvador, Brazil, including demographic data and serological markers of HCV, HIV and HTLV-I/II, cross-sectional data was obtained from 197 patients. Patients who were anti-HCV positive and HCV RNA negative, and who did not receive HCV treatment were defined as having cleared infection. Results: Nineteen patients (9.5%) showed evidence of spontaneous HCV clearance; with clearance in 9 of 108 (8.3%) patients in the HCV monoinfected group, 5 of 68 (7.4%) patients with HCV/HIV, and 5 of 21 (23.8%) patients with HCV/HIV/HTLV. Demographic data were not associated with HCV clearance status. Patients coinfected with both HIV and HTLV-1 had increased odds (5.50; 95% CI 1.00, 30.17) of spontaneous clearance of HCV compared with patients who were HIV negative or of unknown HIV status. Conclusion: Our study found that patients coinfected with HIV and HTLV-1 were more likely to spontaneously clear hepatitis C virus than patients with HIV/HCV or HCV alone. The effects of HTLV coinfection on the immune response of such patients may be associated with these findings. Keywords: HTLV-1, HIV, Hepatitis C, Brazil, Spontaneous HCV clearanc

A randomized, pilot trial comparing full versus escalating dose regimens for the desensitization of AIDS patients allergic to sulfonamides

Sulfonamides are drugs extensively used in the management of AIDS patients. However, the use of sulfonamides is often associated with the development of allergic reactions, provoking the substitution of the drug (by another that may be less effective); alternatively attempts are made to desensitize the patient. OBJECTIVE: Compare two drug regimens (full vs. escalating doses) for the oral desensitization of AIDS patients allergic to sulfonamides. MATERIAL AND METHODS: AIDS patients with previous allergic reactions to sulfonamides and requiring prophylaxis against Pneumocistis carinii, central nervous system toxoplasmosis and diarrhea caused by Isospora belli were randomly assigned to a group receiving a routine dose of cothrimoxazole, or another that received escalating doses of an oral suspension of the same drug, initiating with 75mg/day of sulfamethoxazole that was doubled every 48 hours till the full dose was reached, if no allergic reaction occurred. Patients were monitored for at least 6 months after enrollment in the trial. The major end-point was the ability to maintain prophylactic treatment after that period of time. Plasma viral load (PVL) and CD4/CD8 counts were measured at baseline. Liver enzymes and hematological parameters were measured at baseline and after 1, 3 and 6 months. RESULTS: Eighteen patients were enrolled in the study (15 men and 3 women), with ages ranging from 30 to 57 years (mean 39.9). The mean CD4 counts were slightly higher for patients receiving a full dose; there was also a trend towards higher baseline CD8 counts among patients developing new reactions. The mean PVL was similar among the patients in both desensitization groups. The incidence of new allergic reactions was identical (40%) in the two groups. All adverse reactions were mild and no significant increase in liver enzymes were observed. CONCLUSON: Dose regimen is not a predictor of the development of new allergic reactions amongst patients challenged with sulfonamides after an initial allergic reaction

A randomized, pilot trial comparing full versus escalating dose regimens for the desensitization of AIDS patients allergic to sulfonamides

Sulfonamides are drugs extensively used in the management of AIDS patients. However, the use of sulfonamides is often associated with the development of allergic reactions, provoking the substitution of the drug (by another that may be less effective); alternatively attempts are made to desensitize the patient. OBJECTIVE: Compare two drug regimens (full vs. escalating doses) for the oral desensitization of AIDS patients allergic to sulfonamides. MATERIAL AND METHODS: AIDS patients with previous allergic reactions to sulfonamides and requiring prophylaxis against Pneumocistis carinii, central nervous system toxoplasmosis and diarrhea caused by Isospora belli were randomly assigned to a group receiving a routine dose of cothrimoxazole, or another that received escalating doses of an oral suspension of the same drug, initiating with 75mg/day of sulfamethoxazole that was doubled every 48 hours till the full dose was reached, if no allergic reaction occurred. Patients were monitored for at least 6 months after enrollment in the trial. The major end-point was the ability to maintain prophylactic treatment after that period of time. Plasma viral load (PVL) and CD4/CD8 counts were measured at baseline. Liver enzymes and hematological parameters were measured at baseline and after 1, 3 and 6 months. RESULTS: Eighteen patients were enrolled in the study (15 men and 3 women), with ages ranging from 30 to 57 years (mean 39.9). The mean CD4 counts were slightly higher for patients receiving a full dose; there was also a trend towards higher baseline CD8 counts among patients developing new reactions. The mean PVL was similar among the patients in both desensitization groups. The incidence of new allergic reactions was identical (40%) in the two groups. All adverse reactions were mild and no significant increase in liver enzymes were observed. CONCLUSON: Dose regimen is not a predictor of the development of new allergic reactions amongst patients challenged with sulfonamides after an initial allergic reaction

Evaluation of viral resistance to Reverse Transcriptase Inhibitors (RTI) in HIV-1-infected patients before and after 6 months of single or double antiretroviral therapy

We evaluated samples of peripheral blood mononuclear (PBMC) cells from 46 AIDS patients, before starting therapy with HIV-1 reverse transcriptase inhibitors (RTI), and after 6 months of drug use. PBMC were stored and tested by a Line Probe Assay (LiPA), in order to assess the frequency of RT mutations in this population. Six patients were taking AZT before initial blood collection (1 to 16 weeks of drug use) and 40 patients had no prior therapy. After baseline evaluation, 19 patients received AZT, 23 AZT plus DDI, 3 started AZT only with DDI added after 3 months, and 3 received a combination of AZT plus 3TC. Detection of at least one mutation was found in 33% (15/46) of patients at baseline, and 83% (38/46) had at least 1 mutation after 6 months of therapy. In the majority of cases, samples presented with the wild type and variants of HIV, simultaneously. Patients receiving monotherapy had a higher frequency of mutations (L41 and F214, Y215) than did patients receiving double-drug therapy (19 vs. 10). No specific mutation associated with DDI was identified in 26 patients so treated. Despite the finding of a mean increase in CD4 count and a mild decrease in viral load, patients tended to have an inverse correlation between the CD4 variation and number of mutations detected after 6 months, suggesting potential loss of drug efficacy in the presence of these genotypic changes

Evaluation of the genotypic pattern of HIV-1 resistance in AIDS patients failing antiretroviral therapy

We analyzed the first 96 patients tested for HIV resistance to antiretroviral therapy in three Brazilian states. The HIV-1 reverse transcriptase (RT) and protease (PR) were sequenced by using the ABI ViroSeq system. The drugs previously used for each patient were recorded and correlated with the mutations found in the samples. Viral load (VL) and CD4 count were also recorded. Only one patient had the wild type sequence. The most prevalent mutations were: 184V (59%), 41L (47.9%), 63P (53%), 215Y (50%), 36I (46%), 10I (35%), 67N (42%), 77I (37%), 90M (36%) and 210W (33%). A positive correlation between the number of previously used ARVs and the number of mutations was observed (p<0.05). Associations between mutations and ARV drugs were identified at positions 69, 118, 184 and 215 with previous exposure to NRTI, mutations at positions 98, 100, 103, 181 and 190 with previous NNRTI use and at positions 10, 20, 30, 46, 53, 54, 71, 73, 82, 84, 88 and 90 with previous PI therapy (p<0.05). Previous exposure to ARV drugs was associated with previous genotypic resistance to specific drugs, leading to treatment failure in HIV patients. Genotypic resistance was clearly associated with virological and immunological failure