Acquired Immunodeficiency Syndrome: Laguna F

Rubio R, Berenguer J, Miró JM, Antela A, Iribarren JA, González J, Guerra L, Moreno S, Arrizabalaga J, Clotet B, Gatell JM, Laguna F, Martínez E, Parras F, Santamaría JM, Tuset M, Viciana P. · Hospital 12 Octubre, Madrid, Spain. · Enferm Infecc Microbiol Clin. · Pubmed #12084354 links to  free full text

Abstract: OBJECTIVE: To provide an update of recommendation on antiretroviral treatment (ART) in HIV-infected adults.Methods. These recommendations have been agreed by consensus by a committee of the spanish AIDS Study Group (GESIDA) and the National AIDS Plan. To do so, advances in the physiopathology of AIDS and the results on efficacy and safety in clinical trials, cohort and pharmacokinetics studies published in biomedical journals or presented at congresses in the last few years have been reviewed. Three levels of evidence have been defined according to the data source: randomized studies (level A), case-control or cohort studies (level B) and expert opinion (level C). Whether to recommend, consider, or not to recommend ART has been established for each situation. RESULTS: Currently, ART with combinations of at least three drugs constitutes the treatment of choice in chronic HIV infection. In patients with symptomatic HIV infection, initiation of ART is recommended. In asymptomatic patients initiation of ART should be based on the CD41/mL lymphocyte count and on the plasma viral load (PVL): a) in patients with CD41 lymphocytes < 200 cells/mL, initiation of ART is recommended; b) in patients with CD41 lymphocytes between 200 and 300 cells/mL, initiation of ART should, in most cases, be recommended; however, it could be delayed when the CD41 lymphocyte count remains close to 350 cells/mL and the PVL is low, and c) in patients with CD41 lymphocytes > 350 cells/mL, initiation of ART can be delayed. The aim of ART is to achieve an undetectable PVL. Adherence to ART plays a role in the durability of the antiviral response. Because of the development of cross-resistance, the therapeutic options in treatment failure are limited. In these cases, genotypic analysis is useful. Toxicity limits ART. The criteria for ART in acute infection, pregnancy and postexposure prophylaxis and in the management of coinfection with HIV and hepatitis C and B virus are controversial. CONCLUSIONS: The current approach to initiating ART is more conservative than in previous recommendations. In asymptomatic patients, the CD41 lymphocyte count is the most important reference factor for initiating ART. Because of the considerable number of drugs available, more sensitive monitoring methods (PVL) and the possibility of determining resistance, therapeutic strategies have become much more individualized.

Miró JM, Antela A, Arrizabalaga J, Clotet B, Gatell JM, Guerra L, Antonio Iribarren J, Laguna F, Moreno S, Parras F, Rubio R, Santamaría JM, Viciana P, Anonymous00076. · Hospital Clínic Universitari, Barcelona. · Enferm Infecc Microbiol Clin. · Pubmed #11153204 links to  free full text

Abstract: OBJECTIVE: To update the recommendations for antiretroviral therapy (ART) in adult HIV-infected persons according to the new scientific advances and the existence of new antiretroviral drugs in the last two years. METHODS: The ART recommendations have been condensed by a panel of experts from the Spanish AIDS Study Group (Grupo de Estudio de Sida-GESIDA) of the Spanish Infectious Diseases and Clinical Microbiology Society (SEIMC) and from the Clinical Advisory Panel (CAP) of the Secretariat of the Spanish National Plan on AIDS (SPNS) of the Ministry of Health. Three levels of evidence have been established depending if the data came from randomized and controlled studies, from cohort or case-control studies or from descriptive studies and expert opinions, for that purpose we have reviewed the advanced in HIV pathophysiology and results of efficacy (clinical, virologic and immunologic) and security (toxicity) from clinical trials involving ART lasting at least 12 months, from cohort studies and pharmacokinetic and security data of antoiretrovírico drugs, presented in international conferences or published in biomedical journals in the last two years. In each situation we have established either to recommend or to consider or not recommend ART. RESULTS: Nowadays, ART consistent of at least three drugs constitutes the election therapy for chronic HIV infection, since it delays clinical progression, increases significantly the survival and diminishes hospital admissions and associated costs. The decision to start ART must be based upon three elements: presence or absence of symptoms, plasma vírica load and CD4+ cells counts. Thus, in asymptomatic cases with a high CD4+ cells count (> 500/microliter) and low vírica load (< 10,000 copies/ml by branched DNA bDNA or < 20,000 copies/ml by reverse-transcription polymerase chain reaction [RT-PCR] or nucleic acid sequence based amplification [NASBA]) we recommend to delay ART. In symptomatic patients we recommend to start it, and in asymptomatic patients, we could recommend or consider ART initiation depending on the risk of progression, established by the vírica load and the CD4+ cells count. In any case, if therapy is started, the objective must be to reach an indetectable vírica load (< 50 copies/ml). The adherence to ART plays a key role for its initial moment and for the duration of the antiviral response. ART can achieve a restoration of cellular immunity inb the advanced patients. There are few therapeutic options in failing patients due to cross-resistance. Resistance studies can be useful in this setting. The toxicity (lypodistrophy) is a new and limiting factor of ART which requires to look for new therapeutic options. ART criteria for acute infection, pregnancy, post-exposure prophylaxis and when to use resistance testing are discussed. CONCLUSIONS: In this moment, there is a more conservative attitude towards starting ART than in previous recommendations in which a virus eradication was considered. On the other hand, the high number of disposable drugs, the more sensitive monitorization methods (plasma vírica load) and the possibility of performing resistance studies make therapeutic strategies more dynamic and individualized for each patient and situation. In any case, it is mandatory to ensure a perfect adherence to ART from the patients.

Miró JM, Antela A, Arrizabalaga J, Clotet B, Gatell JM, Guerra L, Iribarren JA, Laguna F, Moreno S, Parras F, Rubio R, Santamaría JM, Viciana P. · Hospital Clínic Universitari, Barcelona. · Enferm Infecc Microbiol Clin. · Pubmed #11109725 links to  free full text

Abstract: OBJECTIVE: To update the recommendations for antiretroviral therapy in adult HIV-infected persons according to the new scientific advances and the existence of new antiretroviral drugs in the last two years. METHODS: The antiretroviral therapy recommendations have been condensed by a panel of experts from the Spanish AIDS Study Group (Grupo de Estudio de sida-GESIDA) of the Spanish Infectious Diseases and Clinical Microbiology Society (SEIMC) and from the Clinical Advisory Panel of the Secretariat of the Spanish National Plan on AIDS (SPNS) of the Ministry of Health. Three levels of evidence have been established depending if the data came from randomised and controlled studies, from cohort or case-control studies or from descriptive studies and expert opinions. For that purpose we have reviewed the advances in HIV pathophysiology and results of efficacy (clinical, virologic and immunologic) and security (toxicity) from clinical trials involving antiretroviral therapy lasting at least 12 months, from cohort studies and pharmacokinetic and security data of antiretroviral drugs, presented in international conferences or published in biomedical journals in the last two years. In each situation we have established either to recommend or to consider or not recommend antiretroviral therapy. RESULTS: Nowadays, antiretroviral therapy consisting of at least three drugs constitutes the election therapy for chronic HIV infection, since it delays clinical progression, increases significantly the survival and diminishes hospital admissions and associated costs. The decision to start antiretroviral therapy must be based upon three elements: presence or absence of symptoms, plasma viral load and CD4+ cells counts. Thus, in asymptomatic cases with a high CD4+ cells count (> 500/microL) and low viral load (< 10,000 copies/ml by branched DNA [bDNA] or < 20,000 copies/ml by reverse-transcription polymerase chain reaction [RT-PCR] or nucleic acid sequence based amplification [NASBA]) we recommend to delay antiretroviral therapy. In symptomatic patients we recommend to start it, and in asymptomatic patients, we could recommend or consider antiretroviral therapy initiation depending on the risk of progression, established by the viral load and the CD4+ cells count. In any case, if therapy is started, the objective must be to reach an undetectable viral load (< 50 copies/ml). The adherence to antiretroviral therapy plays a key role for its initial moment and for the duration of the antiviral response, antiretroviral therapy can achieve a restoration of cellular immunity in the advanced patients. There are few therapeutic options in failing patients due to cross-resistance. Resistance studies can be useful in this setting. The toxicity is a new and limiting factor of antiretroviral therapy which requires to look for new therapeutic options. Antiretroviral therapy criteria for acute infection, pregnancy, post-exposure prophylaxis and when to use resistance testing are discussed. CONCLUSIONS: In this moment, there is a more conservative attitude towards starting antiretroviral therapy than in previous recommendations in which a virus eradication was considered. On the other hand, the high number of disposable drugs, the more sensitive monitorization methods (plasma viral load) and the possibility of performing resistance studies make therapeutic strategies more dynamic and individualised for each patient and situation. In any case, it is mandatory to ensure a perfect adherence to antiretroviral therapy from the patients.

Berenguer J, Miralles P, Arrizabalaga J, Ribera E, Dronda F, Baraia-Etxaburu J, Domingo P, Márquez M, Rodriguez-Arrondo FJ, Laguna F, Rubio R, Lacruz Rodrigo J, Mallolas J, de Miguel V, Anonymous00321. · Infectious Diseases Service of Hospital Gregorio Marañón, 28007, Madrid, Spain. · Clin Infect Dis. · Pubmed #12684918 No free full text.

Abstract: We analyzed survival rates, neurologic function, and prognostic factors for 118 consecutive patients with acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy (PML) treated with highly active antiretroviral therapy (HAART) in 11 hospitals throughout Spain. Seventy-five patients (63.6%) remained alive for a median of 114 weeks (2.2 years) after diagnosis of PML. Neurologic function of the survivors was categorized as cure or improvement in 33, stabilization or worsening in 40, and unknown in 2. The baseline CD4+ cell count was the only variable found with prognostic significance. The odds ratio of death was 2.71 (95% confidence interval, 1.19-6.15) for patients with CD4+ cell counts of <100 cells/microL, compared with patients who had CD4+ cell counts of > or =100 cells/microL. One-third of patients with PML died despite receipt of HAART; neurologic function improved in approximately one-half of the survivors. A CD4+ cell count of <100 cells/microL was associated with higher mortality.

Morales MA, Cruz I, Rubio JM, Chicharro C, Cañavate C, Laguna F, Alvar J. · World Health Organization Collaborating Centre for Leishmaniasis, Servicio de Parasitología, Centro Nacional de Microbiología, Madrid, Spain. · J Infect Dis. · Pubmed #11992294 No free full text.

Abstract: In the Mediterranean basin, Leishmania infantum is a major opportunistic parasite in people with acquired immunodeficiency syndrome (AIDS), and up to 9% of the patients with AIDS suffer from newly acquired or reactivated visceral leishmaniasis. Distinguishing between reinfections and relapses in these patients is important because some apparent treatment failures occur in patients with new rather than reactivated infections. Isoenzyme characterization is limited for use in determining relapsed versus newly acquired leishmaniasis in human immunodeficiency virus (HIV)-infected patients because of the variability of L. infantum and the predominance of the MON-1 zymodeme in people coinfected with HIV. A seminested polymerase chain reaction (PCR) was used to amplify L. infantum minicircle kinetoplast DNA, and, after digestion, the restriction fragment-length polymorphism (RFLP) profiles showed that 3 (7.5%) of 40 patients coinfected with L. infantum and HIV had a new infection, whereas isoenzyme characterization indicated that all 40 patients had infection relapses. These results suggest the utility of this PCR-RFLP analysis in detecting leishmaniasis reinfection in HIV-positive patients.