El acceso universal al tratamiento antirretroviral no ha modificado las causas de internación y muerte en infectados por HIV en Buenos Aires / The universal high active antiretroviral treatment (HAART) did not chance the causes of admiission and death of HIV infected patients in Buenos Aires

Introducción: El tratamiento antirretroviral de alta eficacia (TARGA) ha desplazado a las infecciones oportunistas como principal causa de hospitalización en infectados por el HIV. Sin embargo, algunos autores hallaron que las causas de internación por HIV en Buenos Aires no cambiaron a pesar del acceso universal al TARGA desde 1996. Pacientes y Métodos. Para confirmar estos resultados revisamos todos los ingresos hospitalarios ocurridos durante tres años en un hospital general de la ciudad de Buenos Aires. Resultados: 57 pacientes (34 hombres) tuvieron 79 hospitalizaciones: 43 ingresaron sólo una vez y los 14 restantes tuvieron dos o más ingresos hasta totalizar 36 internaciones. La edad fue de 44.46 ± 11.55 años (promedio ± desvío estándard), 43 pacientes (75.45%) se sabían HIV + y 28 de ellos (65.12%) recibían TARGA al ingreso, 31 hospitalizaciones (39.24%) fueron causadas por enfermedades marcadoras de SIDA; 35 (44.30%) por infecciones no marcadoras de SIDA (INMS) y 13 (13.46%) por enfermedades no infecciosas. Tuberculosis fue el diagnóstico más frecuente (11 casos, 13.92%), seguida por meningitis a Cryptococcus neoformans en 9 (11.39%) y toxoplasmosis cerebral en 6 (7.59%). Entre las INMS, la neumonía fue la principal causa de hospitalización (13 pacientes, 16.46%). Discusión: Estos resultados confirman resultados previos comunicando que las causas de hospitalización en infectados por el HIV no cambiaron en respuesta al TARGA en Buenos Aires, lo que puede estar reflejando problemas de detección o adherencia, o puede estar relacionado con resistencia viral, razones sociales o cualquier combinación de estos factores (AU)

Introduction. High Active Antiretroviral Treatment (HAART) displaced opportunistic infections as the main cause of hospitalization in HIV infected patients. However, some authors found that causes for hospitalization in HiV infected patients did not changed at Buenos Aires although this country offers universal access to HAART since 1996. Patients and Methods. We analyzed all the HIV related admissions recorded during three years at a general hospital. Results. 57 patients (34 men) were hospitalized 79 times. 43 out of them were hospitalized only one time. The reaining 14 were hospitalized 36 times. Age was 44.46 ± 11.55 years (mean ± standard deviation). 43 patients (75.45%) had a previous diagnosis of HIV infection. 28 of them (65.12%) received HAART. 31 hospitalizations (39.24%) were caused by AIDS defining events. 35 (44.30%) related to non-AIDS-defining infections diseases (NADID), and 13 (13.46%) to non-infections diseases. Tuberculosis was the prevalent illness (11 cases, 13.92%), followed by cryptoccal meningitis in 9 (11.39%) and cerebral toxoplasmosis in 6 (7.59%). Among NADID, pneumonia was the main cause of admission (13 patientes, 16,46%). Discussion: These results confirm previous reports showing that causes of HIV related hospitalization remain unchanged in spite of HAART at Buenos Aires, which may be reflecting problems of detection and adherence, or may be related to local viral resistance, social reasons, or any combination of these factors (AU)

Causa inusual de meningitis en pacientes infectados por HIV-1 / Unusual cause of meningitis in HIV-1 infectedpatient6. Corredoira J, Garcia-Garrote F, Rabuñal R, et al. Association between bacteremia due to Streptococcus gallolyticus subsp. gallolyticus (S. bovis I) and colorectal neoplasia: a case-control study. Clin Infect Dis 2012; 55:491-967. Sheng WH, Chuang YC, Teng LJ, Hsueh PR. Bacteremia due to Streptococcus gallolyticus subspecies pasteuri

La infección por HIV suele ser un campo propicio para la aparición de complicaciones de causas inusuales, entre ellas, las infecciones por gérmenes extremadamente infrecuentes. Las distintas subespecies de Streptococcus bovis suelen presentarse como bacteriemias o endocar-ditis asociadas, con mucha frecuencia, a tumores benignos o malignos de las regiones colorrectal, gástrica, pancreática o hepatobiliar.Se presenta un caso raro de meningitis por Streptoccocus gallolyticusen un paciente adulto infectado por HIV, sin evidencia alguna de las asociaciones o localizaciones mencionadas y con características clíni-cas y licuorales que pueden inducir a pensar en diagnósticos distintos y, por ende, a tratamientos no apropiados.Un sistema inmunológico deteriorado suele ser el escenario determi-nante para la emergencia de estas raras complicaciones

HIV infectionis, usually, a favorable field for the development of complications from unusual causes including infections with extremely raregerms. The different subspecies of Streptococcus bovis often present as bacteriemias or endocarditis, most frequently associated with benign or malignant tumors of the colorectal, gastric, pancreatic or hepatobiliary regions.A rare case of meningitis due to Streptoccocus gallolyticus in an adult patient infected by HIV is presented without any evidence of associations or mentioned locations and with clinical and the cerebrospinal fluid features that induce to other diagnoses and subsequent inappropriate treatment.A deteriorated immune system is the determining factor for the emergence of these rare complications

Short-term monotherapy with IDX184, a liver-targeted nucleotide polymerase inhibitor, in patients with chronic hepatitis C virus infection.

IDX184 is a liver-targeted prodrug of 2'-methylguanosine (2'-MeG) monophosphate. This study investigated the safety, tolerability, antiviral activity, and pharmacokinetics of IDX184 as a single agent in treatment-naïve patients with genotype-1 chronic hepatitis C virus (HCV) infection. Forty-one patients with baseline HCV RNA ≥ 5 log(10) IU/ml, alanine aminotransferase (ALT) ≤ 2.5× the upper limit of normal, and compensated liver disease were dosed. Sequential cohorts of 10 patients, randomized 8:2 (active:placebo), received 25, 50, 75, and 100 mg of IDX184 once daily for 3 days, with a 14-day follow-up. There were no safety-related treatment discontinuations or serious adverse events. The adverse events and laboratory abnormalities observed for IDX184- and placebo-treated patients were similar. At the end of the 3-day treatment period, changes from baseline in HCV RNA levels (means ± standard deviations) were -0.5 ± 0.6, -0.7 ± 0.2, -0.6 ± 0.3, and -0.7 ± 0.5 log(10) for the 25-, 50-, 75-, and 100-mg doses, respectively, while viral load remained unchanged for the pooled placebo patients (-0.05 ± 0.3 log(10)). Patients with genotype-1a and patients with genotype-1b responded similarly. Serum ALT levels decreased, especially at daily doses ≥ 75 mg. During the posttreatment period, plasma viremia and serum aminotransferase levels returned to near pretreatment levels. No resistance mutations associated with IDX184 were detected. Plasma exposure of IDX184 and its nucleoside metabolite 2'-MeG was dose related and low. Changes in plasma viral load correlated with plasma exposure of 2'-MeG. In conclusion, the results from this proof-of-concept study show that small doses of the liver-targeted prodrug IDX184 were able to deliver significant antiviral activity and support further clinical evaluation of the drug candidate.

Pilot, randomized study assessing safety, tolerability and efficacy of simplified LPV/r maintenance therapy in HIV patients on the 1 PI-based regimen.

OBJECTIVES: To compare the efficacy and safety of an individualized treatment-simplification strategy consisting of switching from a highly-active anti-retroviral treatment (HAART) with a ritonavir-boosted protease inhibitor (PI/r) and 2 nucleoside reverse-transcriptase inhibitors (NRTIs) to lopinavir/ritonavir (LPV/r) monotherapy, with intensification by 2 NRTIs if necessary, to that of continuing their HAART. METHODS: This is a one-year, randomized, open-label, multi-center study in virologically-suppressed HIV-1-infected adults on their first PI/r-containing treatment, randomized to either LPV/r-monotherapy or continue their current treatment. Treatment efficacy was determined by plasma HIV-1 RNA viral load (VL), time-to-virologic rebound, patient-reported outcomes (PROs) and CD4+T-cell-count changes. Safety was assessed with the incidence of treatment-emergent adverse events (AE). RESULTS: Forty-one patients were randomized to LPV/r and 39 to continue their HAART. No statistically-significant differences between the two study groups in demographics and baseline characteristics were observed. At day-360, 71(39:LPV/r;32:HAART) patients completed treatment, while 9(2:LPV/r;7:HAART) discontinued. In a Last Observation Carried Forward Intent-to-Treat analysis, 40(98%) patients on LPV/r and 37(95%) on HAART had VL<200 copies/mL (P = 0.61). Time-to-virologic rebound, changes in PROs, CD4+ T-cell-count and VL from baseline, also exhibited no statistically-significant between-group differences. Most frequent AEs were diarrhea (19%), headache (18%) and influenza (16%). Four (10%) patients on LPV/r were intensified with 2 NRTIs, all regaining virologic control. Eight serious AEs were reported by 5(2:LPV/r;3:HAART) patients. CONCLUSION: At day-360, virologic efficacy and safety of LPV/r appears comparable to that of a PI+2NRTIs HAART. These results suggest that our individualized, simplified maintenance strategy with LPV/r-monotherapy and protocol-mandated NRTI re-introduction upon viral rebound, in virologically-suppressed patients merits further prospective long-term evaluation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00159224.

Health-related quality of life in HIV patients switching to twice-daily indinavir/ritonavir regimen or continuing with three-times-daily indinavir-based therapy.

OBJECTIVE: To evaluate health-related quality of life (HRQoL) changes in patients treated with indinavir three-times daily after switching to a twice-daily indinavir/ritonavir regimen or continuing with the same regimen. METHODS: Patients on HAART including indinavir three-times-daily with undetectable viral load were randomly assigned to continue with this therapy or to change to a twice-daily indinavir/ritonavir (800/100 mg) regimen. The Medical Outcomes Study HIV Health Survey (MOS-HIV) questionnaire was used as the HRQoL measure. RESULTS: A total of 118 patients participated in the study, of which 59 (50%) were randomly assigned to continue with the three-times-daily regimen. Patients had a mean age of 39 years and 80% of them were male. At baseline, subjects included in the three-times-daily group presented a significantly greater number of symptoms than subjects in the twice-daily group, but no statistically significant differences were observed in MOS-HIV scores between the groups. In the intention-to-treat (ITT) analysis, a reduction in HRQoL scores was observed in both groups, which was greater in the twice-daily group. In the per protocol analysis, reduction of HRQoL was minimal. CONCLUSIONS: A HRQoL deterioration, greater in the twice-daily group, was observed in this study in the ITT analysis, while HRQoL remained stable in both groups in patients who continued with and tolerated the allocated regimen.

Continued indinavir versus switching to indinavir/ritonavir in HIV-infected patients with suppressed viral load.

OBJECTIVE: To compare continued indinavir (IDV) 8-hourly (q8h) with switching to indinavir/ritonavir (IDV/RTV) 12-hourly (q12h) in HIV-positive patients having suppressed viral load with IDV q8h plus two nucleoside reverse transcriptase inhibitors (NRTI). DESIGN: Multicentre, international, randomized, open-label study enrolling HIV-1 infected patients on IDV 800 mg q8h plus two NRTI with CD4 cell counts > or = 100 x 106/l and plasma HIV RNA < 500 copies/ml for > or = 3 months. METHODS: Patients were randomized to continue on the same regimen or to switch to IDV plus liquid RTV (IDV/RTV 800 mg/100 mg q12h). Primary endpoint was the proportion of patients remaining < 500 copies/ml at 48 weeks. RESULTS: A total of 323 patients (IDV/RTV, 162; IDV, 161) were evaluable. At 48 weeks, the proportions of patients with plasma HIV RNA < 500 copies/ml were 93%, 88% and 58% in the IDV/RTV arm versus 92% (P = 1), 86% (P = 0.87) and 74% (P = 0.003) in the IDV arm using on-treatment (OT) and intent-to-treat (ITT) [switches included (ITT, S = I) and switches = failure (ITT, S = F)] analyses respectively. Mean increase in CD4 cell count was 88 x 106/cells/l (IDV/RTV arm) and 60 x 106 cells/l (IDV arm) (P = 0.08). More patients discontinued study medication due to adverse events in the IDV/RTV arm than in the IDV arm (P < 0.001). CONCLUSIONS: Equivalence of continuing IDV q8h versus switching to IDV/RTV (liquid) q12h in suppressed stable patients was demonstrated by OT and ITT S = I analyses. However, the IDV q8h arm performed better when discontinuations were classified as failures. IDV/RTV q12h can be convenient and equally effective for patients able to tolerate it.

A randomized clinical trial comparing nelfinavir or nevirapine associated to zidovudine/lamivudine in HIV-infected naive patients (the Combine Study).

BACKGROUND: Non-nucleoside reverse transcriptase inhibitor-containing regimens may be a valid alternative to protease inhibitor-containing regimens for initial antiretroviral therapy, but to date few studies comparing these two strategies have been performed. OBJECTIVE: To evaluate the efficacy and safety of nelfinavir or nevirapine associated to zidovudine/lamivudine in HIV-infected naive patients. DESIGN: Randomized, open-label, multicentre trial. SETTING: Twelve centres in Spain (9) and Argentina (3). PATIENTS: One hundred and forty-two HIV-infected naive patients without AIDS. INTERVENTIONS: Patients received combivir (zidovudine 300 mg/lamivudine 150 mg, twice-daily) plus either nelfinavir (1250 mg) twice-daily (zidovudine/lamivudine/nelfinavir, n=70) or nevirapine (200 mg) twice-daily (zidovudine/lamivudine/nevirapine, n=72), and were followed for 12 months. The primary endpoint was the proportion of patients with a plasma HIV-1 RNA (pVL) of less than 200 copies/ml by PCR at 12 months. pVL of less than 20 copies/ml (PCR), changes in CD4 counts, clinical progression and adverse events were also evaluated. Efficacy was assessed using intent-to-treat (ITT) (missing=failure) and on-treatment analysis. RESULTS: At 12 months in the ITT analysis the proportion of patients with pVL below 200 copies/ml was 60% (95% CI 48.5-71.5) in the zidovudine/lamivudine/nelfinavir arm and 75% (95% CI 65-85) in the zidovudine/lamivudine/nevirapine arm (P=0.06), and the proportion below 20 copies/ml was 50% (95% CI 38.3-61.7) and 65% (95% CI 54.2-76.2), respectively (P=0.06). No differences were found when comparing the subgroup of patients with baseline pVL of more than 100,000 copies/ml. A gain of +173 and +162 CD4 cells/mm3, respectively, was observed. Zidovudine/lamivudine/nelfinavir was discontinued in 21% of patients, and zidovudine/lamivudine/nevirapine in 25%, due to toxicity (P>0.2). CONCLUSIONS: Our results suggest that zidovudine/lamivudine/nevirapine is at least as effective as zidovudine/lamivudine/nelfinavir as first-line therapy for HIV disease.