Antiretroviral pill count and clinical outcomes in treatment-naïve patients with HIV infection.

OBJECTIVES: Treatment guidelines recommend single-tablet regimens for patients with HIV infection starting antiretroviral therapy. These regimens might be as effective and cost less if taken as separate drugs. We assessed whether the one pill once a day combination of efavirenz, emtricitabine and tenofovir reduces the risk of disease progression compared with multiple-pill formulations of the same regimen. METHODS: We selected treatment-naïve patients starting one-, two- or three-pill formulations of this regimen in data from the Antiretroviral Therapy Cohort Collaboration. These patients were followed until an AIDS event or death or until they modified their regimen. We analysed these data using Cox regression models, then used our models to predict the potential consequences of exposing a future population to either a one-pill regimen or a three-pill regimen. RESULTS: Among 11 739 treatment-naïve patients starting the regimen, there were 386 AIDS events and 87 deaths. Follow-up often ended when patients switched to the same regimen with fewer pills. After the first month, two pills rather than one was associated with an increase in the risk of AIDS or death [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.01-1.91], but three pills rather than two did not appreciably add to that increase (HR 1.19; 95% CI 0.84-1.68). We estimate that 77 patients would need to be exposed to a one-pill regimen rather than a three-pill regimen for 1 year to avoid one additional AIDS event or death. CONCLUSIONS: This particular single-tablet regimen is associated with a modest decrease in the risk of AIDS or death relative to multiple-pill formulations.

Very low level viraemia and risk of virological failure in treated HIV-1-infected patients.

OBJECTIVES: The aim of the study was to investigate whether very low level viraemia (VLLV) (20-50 HIV-1 RNA copies/mL) was associated with increased risk of virological failure (VF) as compared with persistent full suppression (< 20 copies/mL). METHODS: From the VACH Cohort database, we selected those patients who started antiretroviral therapy (ART) after January 1997 and who achieved effective viral suppression [two consecutive viral loads (VLs) < 50 copies/mL] followed by full suppression (at least one VL <20 copies/mL). We carried out survival analyses to investigate whether the occurrence of VLLV rather than maintaining full suppression at < 20 copies/mL was associated with virological failure (two consecutive VLs > 200 copies/mL or one VL > 200 copies/mL followed by a change of ART regimen, administrative censoring or loss to follow-up), adjusted for nadir CD4 cell count, sex, age, ethnicity, transmission group, type of ART and time on effective suppression at < 50 copies/mL. RESULTS: Of 21 480 patients who started ART, 13 674 (63.7%) achieved effective suppression at < 50 copies/mL, of whom 4289 (31.4%) further achieved full suppression at < 20 copies/mL after May 2009. A total of 2623 patients (61.1%) remained fully suppressed thereafter, while 1666 had one or more episodes of VL detection > 20 copies/mL (excluding virological failure). A total of 824 patients had VLLV after suppression at < 20 copies/mL. VLLV was not associated with virological failure as compared with persistent full suppression [hazard ratio (HR) 0.67; 95% confidence interval (CI) 0.44-1.00], independently of the number of blips recorded (from one to 18). CONCLUSIONS: In our population of HIV-infected patients on ART who achieved viral suppression at < 20 copies/mL, the risk of virological failure was no different for patients who remained fully suppressed compared with those who experienced subsequent episodes of VLLV.

Late initiation of HAART among HIV-infected patients in Spain is frequent and related to a higher rate of virological failure but not to immigrant status.

PURPOSE: To determine whether immigrant status is associated with late initiation of highly active antiretroviral treatment (HAART) and/or poor response to antiretrovirals. METHODS: GESIDA 5808 is a multicenter, retrospective cohort study (inclusion period January 2005 through December 2006) of treatment-naïve patients initiating HAART that compares HIV-infected patients who are immigrants with Spanish-born patients. A late starter (LS) was defined as any patient starting HAART with a CD4+ lymphocyte count <200 cells/µL and/or diagnosis of an AIDS-defining illness before or at the start of therapy. The primary endpoint was time to treatment failure (TTF), defined as virological failure (VF), death, opportunistic infection, treatment discontinuation/switch (D/S), or missing patient. Secondary endpoints were time to treatment failure as observed data (TTO; censoring missing patients) and time to virological failure (TVF; censoring missing patients and D/S not due to VF). RESULTS: LS accounted for 56% of the patients. Lower educational and socioeconomic level and intravenous drug use (IVDU) were associated with categorization as LS, but immigrant status was not. Cox regression analysis (hazard ratio [HR]; 95% CI) between LS and non-LS patients showed no differences in TTF (0.97; 0.78-1.20) or TTO (1.18; 0.88-1.58), although it did reveal a difference in TVF (1.97; 1.18-3.29). CD4+ lymphocyte recovery was equivalent for both LS and non-LS patients (159 vs 173). CONCLUSIONS: In our cohort, immigrant status was not shown to be related to late initiation of HAART. Although LS patients did not have a longer TTF for any reason, TVF was significantly shorter. Despite universal free access to HAART in Spain, measures to ensure early diagnosis and treatment of HIV infection are necessary.

The relationship between antiretroviral prescription patterns and treatment guidelines in treatment-naïve HIV-1-infected patients.

BACKGROUND: Reports have shown that the publication of practice guidelines does not guarantee their use in clinical practice. The objective of this study was to evaluate the agreement between antiretroviral treatments (ARTs) prescribed in clinical practice and the recommendations in published guidelines. METHODS: A retrospective cohort study was carried out in ART-naïve adults of the Spanish Asociacion Medica Vach de Estudios Multicentricos (VACH) Cohort for the period from 2003 to 2006. RESULTS: A total of 945 patients initiated ART. Of these patients, 12.3% had a CD4 cell count above 350 cells/microL. A 'nonrecommended' antiretroviral regimen was prescribed to 5.3, 5.1 and 7.8% of patients with CD4 counts <200, 200-350 and >350 cells/microL, respectively. Multivariate analyses demonstrated that only a higher viral load was associated with the selection of a combination treatment that was recommended by the guidelines. CONCLUSIONS: Most patients were prescribed initial treatments in agreement with the recommendations. Appropriate routine data collection in databases can be used to evaluate the level of antiretroviral guideline compliance. We propose that routine evaluations of the guidelines must be part of quality assessment to improve medical care.

[Bacillary (epithelioid) angiomatosis with a nodular presentation and self-limited evolution]. / Angiomatosis bacilar (epitelioide) de presentación nodular y evolución autolimitada.

Bacillary angiomatosis (epithelioid) is a recently described clinicopathologic syndrome, principally associated to infection by the human immunodeficiency virus. The case of a patient who was seen for fever and the appearance of four painful, erythematous and indurated subcutaneous nodules on the anteroexternal face of the right lower extremity 15 days previously is presented. No microorganisms were observed by microbiologic and histologic techniques however the latter showed a vascular proliferation with prominent endothelium of epithelioid morphology and notable interstitial inflammatory reaction according to the pattern described as characteristic of epithelioid angiomatosis. The fever and the nodules disappeared spontaneously. The clinical and histopathologic characteristics of this disease as well as the recent contributions with respect to the identification of the possible causative bacillus are discussed.

[HIV infection and cervical cancer: a note of caution for clinicians and health planners]. / Infección por VIH y cáncer de cérvix: una llamada de atención para clínicos y planificadores.

BACKGROUND: To estimate the association between HIV infection and cervical intraepithelial neoplasia (CIN). PATIENTS AND METHODS: Cross-sectional study based on data from 251 women from a Sexually Transmitted Diseases clinic. Patients with CIN were compared with those without CIN in terms of HIV infection and exposure to other risk factors, calculating the corresponding adjusted odds ratio (ORA) by logistic regression. RESULTS: HIV infection (ORA = 7.5; CI 95%: 2.5-22.1), having previous cytologies with cellular changes associated with human papillomavirus infection (ORA = 3.6; CI 95%: 1.3-10.2) and history of condylomas (ORA = 3.2; CI 95%: 1.2-8.4) were associated with CIN. CONCLUSIONS: The strong association observed between HIV and CIN, shows that it is necessary for health services planners and clinicians caring for HIV infected women to ensure that the latter receive the appropriate care to guarantee its early detection.

[Risk of the development of dementia after interruption of zidovudine treatment]. / Riesgo de desarrollo de demencia tras la interrupción de un tratamiento con zidovudina.

BACKGROUND: Epidemiologic data suggest that zidovudine (ZDV) could prevent the AIDS dementia complex (ADC), but this hypothesis has been specifically studied. PATIENTS AND METHODS: We have reviewed the medical records of all patients with human immunodeficiency virus (HIV) infection admitted to our section between January 1990 and December 1993 who were diagnosed with ADC, and we have compared them to those of a control group with regard to the interruption of ZDV at least 3 months before. Controls were selected from the remaining HIV-related admissions, matched by calendar year, CD4-cell count and previous HIV-disease stage. RESULTS: Thirty-nine cases and 39 controls were available for analysis; twenty-nine (74%) and 25 (64%) were male. The median age was similar for both groups: 30. Thirty-one patients (79%) in each group had a previous diagnosis of AIDS, six (15%) in each group had an AIDS-related complex and in two (5%) the ADC was the first complication of their HIV disease. The median CD4-cell counts were 79.6 and 79.4 x 10(6)/l. Twenty-three patients in each group had taken ZDV. Six of these from the ADC had withdrawn treatment, as compared to 2 from the control group (odds ratio [OR] 3.36; 95% confidence interval [CI]: 0.54-35.76). On the other hand, 16 patients with ADC were still on ZDV at the time of diagnosis, as compared to 21 controls (OR: 0.66; 95% CI: 0.22-1.60). CONCLUSION: In this case-control study, the interruption of treatment with ZDV was not found to be a risk factor for the development of ADC.

[Acute severe hepatic insufficiency caused by carbamazepine]. / Insuficiencia hepática aguda grave por carbamacepina.

Acute liver toxicity caused by carbamazepine is a well known though infrequent event. Severe toxicity with hepatocellular insufficiency is even more rare. A case is presented of a patient who suffered of partial epilepsy on treatment with valproate and carbamazepine, who was admitted because of severe acute liver insufficiency attributable to carbamazepine. He had started treatment with the latter drug two weeks earlier, when he developed fever, jaundice, rash and signs of encephalopathy in association with elevation in serum transaminases levels and a decrease in prothrombin index (24%). Discontinuation of both antiepileptic drugs, together with the usual supportive measures, was followed by a complete resolution. Valproate was restarted without complications. Liver biopsy suggested acute hepatitis of drug-related origin. Granulomas or steatosis were not found. The histologic picture together with the relation between carbamazepine administration and the development of hepatotoxicity allow us to dismiss valproate as the possible causal agent of this patient's disease. Therefore, we believe it was an acute hepatocellular failure secondary to carbamazepine.

Once-daily antiretroviral therapy: Spanish Consensus Statement.

BACKGROUND: Administration of antiretroviral therapy (ART) once daily is creating extraordinary interest among the members of the scientific community and also among those who receive the therapy. However, in clinical practice, some doubts remain about its use. OBJECTIVES: This document examines the characteristics and possibilities of treatment administered once daily. METHODS: Consensus of 248 Spanish experts in the field. RESULTS: Once-daily dosing is considered an added value which could favour adherence and, therefore, efficacy, as well as the quality of life of certain patients, however, the objective of adequate adherence in the long term is often difficult to achieve regardless of the treatment used. In theory, any patient can receive once-daily therapy, although some patients could particularly benefit from it, e.g. those with unfavourable social or personal circumstances, including drug users, patients whose treatment must be supervised, patients receiving multiple medications, or those who need rescue therapy after multiple treatment failures. At present, it is possible to design once-daily ART using some of the combinations of drugs considered as first-choice in national and international recommendations for antiretroviral therapy, but the options are still limited. The marketing of new drugs with this characteristic could allow us to increase the number and types of patient who can benefit from once-daily regimens, including those patients who need rescue therapy. CONCLUSIONS: Once-daily ART is a good alternative to regimens administered several times each day when a potent combination of active drugs is available.

[Pneumonia caused by non-opportunistic bacteria in patients infected with HIV. Incidence and evaluation of a non-invasive approach]. / Neumonía por bacterias no oportunistas en pacientes infectados por VIH. Incidencia y valoración de una aproximación no invasiva.

BACKGROUND: Pneumonia due to pathogenic bacteria is common in HIV infected patients. However, a global overview has not been yet performed and also the effectiveness of a non-invasive approach has not been tested. PATIENTS AND METHODS: An open study was conducted in 1989 including all HIV infected patients with a presumptive or definite diagnosis of bacterial pneumonia. Fiberoptic bronchoscopy procedures were used only in patients with a difficult diagnosis and/or problems in their clinical evolution. Clinical and biological data were compared among different etiologic groups, and their evolution was also recorded in relation with the use of non-invasive procedures. RESULTS: Among a total of 302 admissions of HIV infected patients, 113 developed a primary or secondary respiratory tract infection. Forty-three of those were bacterial pneumonia episodes. Etiologic diagnosis was achieved with non invasive methods in 18 cases (42%). Blood cultures were the most effective method used. Streptococcus pneumoniae was the most frequently identified microorganisms (9 cases, 21%). The identification of other bacteria was linked with more severe forms of disease regarding immunologic (leukopenia, p less than 0.001; T4 lymphopenia, p less than 0.05), and respiratory parameters (hypoxemia, p less than 0.05). Two deaths were directly related with pneumonia of known etiology. CONCLUSIONS: Bacterial pneumonia is the most frequent respiratory infection in HIV infected patients. An initial non-invasive approach yields a reasonable percentage of etiologic diagnosis and is not related with a poorer outcome.