[New CCR5 inhibitor antiretroviral drugs and integrase inhibitors]. / Nuevos fármacos antirretrovirales: inhibidores del CCR5 y de la integrasa.

Two new antiretroviral drugs belonging to a new drug family have recently been marketed in Spain. These are maraviroc (CCR5 correceptor inhibitor) and raltegravir (integrase inhibitor). These have the advantage of not presenting crossed resistance with other previously administered antiretroviral drugs, converting them into the cornerstone of the rescue treatment in the patient infected by a multiresistant viral strain. The scientific evidence available on these two drugs is reviewed in this work and its indications in the HIV infected patient are discussed.

Nuevos fármacos antirretrovirales: inhibidores del CCR5 y de la integras / New CCR5 inhibitor antiretroviral drugs and integrase inhibitors

Recientemente se han comercializado en Españados fármacos antirretrovirales que pertenecen anuevas familias farmacológicas: maraviroc (inhibidordel correceptor CCR5) y raltegravir (inhibidor de laintegrasa). Tienen la ventaja de no presentarresistencia cruzada con otros fármacosantirretrovirales administrados previamente, lo quelos convierte en la piedra angular del tratamiento derescate en el paciente infectado por una cepa viralmultirresistente. En este trabajo se revisa laevidencia científica disponible de estos dosfármacos, y se comentan cuáles son sus indicacionesen el paciente infectado por el virus de lainmunodeficiencia humana (VIH)

Two new antiretroviral drugs belonging to a newdrug family have recently been marketed in Spain.These are maraviroc (CCR5 correceptor inhibitor)and raltegravir (integrase inhibitor). These have theadvantage of not presenting crossed resistance withother previously administered antiretroviral drugs,converting them into the cornerstone of the rescuetreatment in the patient infected by a multiresistantviral strain. The scientific evidence available onthese two drugs is reviewed in this work and its indications in the HIV infected patient are discussed (AU)

Nuevos fármacos antirretrovirales: inhibidores del CCR5 y de la integrasa / New CCR5 inhibitor antiretroviral drugs and integrase inhibitors

Recientemente se han comercializado en Españados fármacos antirretrovirales que pertenecen anuevas familias farmacológicas: maraviroc (inhibidordel correceptor CCR5) y raltegravir (inhibidor de laintegrasa). Tienen la ventaja de no presentarresistencia cruzada con otros fármacosantirretrovirales administrados previamente, lo quelos convierte en la piedra angular del tratamiento derescate en el paciente infectado por una cepa viralmultirresistente. En este trabajo se revisa laevidencia científica disponible de estos dosfármacos, y se comentan cuáles son sus indicacionesen el paciente infectado por el virus de lainmunodeficiencia humana (VIH)

Two new antiretroviral drugs belonging to a newdrug family have recently been marketed in Spain.These are maraviroc (CCR5 correceptor inhibitor)and raltegravir (integrase inhibitor). These have theadvantage of not presenting crossed resistance withother previously administered antiretroviral drugs,converting them into the cornerstone of the rescuetreatment in the patient infected by a multiresistantviral strain. The scientific evidence available onthese two drugs is reviewed in this work and its indications in the HIV infected patient are discussed (AU)

[Mortality and survival in a cohort of 1,115 HIV-infected patients (1989-97)]. / Estudio de la mortalidad y supervivencia en una cohorte de 1,115 pacientes con infección VIH (1989-97).

BACKGROUND: To study survival and HIV/AIDS-related mortality from 1989 through 1997. To analyze the effect of antiretroviral treatment and prophylaxis against P. carinii pneumonia (PCP-prophylaxis). PATIENTS AND METHODS: We retrospectively studied a cohort of 1,115 HIV (+) outpatients (331 with AIDS-defining criteria) seen in our specific HIV hospital unit from January 1989 through May 1997. We analyzed the effect of different antiretroviral treatments on annual mortality rate. In survival studies we used Cox regression analysis to analyze survival over time as well as the effect of different opportunistic events, adherence and changes in treatment during follow up. RESULTS: Mortality rate was 13.7 per 100 person-years in 1994. It went down to 4.2 during the first half of 1997 (p=0.001). Mortality rate decreased depending on treatment received: 53% (CI 95=34-65%) with monotherapy, 68% (CI 95=38-84%) with bitherapy, 86% (CI 95=40-96%) with triple therapy, and 49% (CI =29-64%) with PCP-prophylaxis. Patients with more than 100 CD4 had an increasing survival over time (p=0.002). In AIDS patients good adherence to antiretroviral treatment and PCP-prophylaxis were associated with a lower risk of death (RR=0.88; CI 95=0.63-1.22 and RR=0.72; CI 95=0.55-0.95 respectively). CONCLUSIONS: In recent years PCP-prophylaxis and antiretroviral treatment (especially combined therapy) have contributed to a decrease in AIDS-related mortality. Adherence to treatments relates to risk of death and survival.

Estudio de la mortalidad y supervivencia en una cohorte de 1.115 pacientes con infección VIH (1989-97) / Mortality and survival in a cohort of 1,115 HIV-infected patients (1989-97)

Fundamento: Analizar la supervivencia y mortalidad por VIH/sida entre 1989 y 1997, y evaluar el impacto que sobre ellas han tenido el tratamiento antirretroviral y la profilaxis frente al Pneumocystis carinii (anti-NPC). Pacientes y métodos: Estudio de una cohorte retrospectiva de 1.115 pacientes (331 con sida) seguidos en una Unidad hospitalaria de VIH en Madrid entre enero de 1989 y mayo de 1997. Se analizó tasa anual de mortalidad y el efecto en la misma del régimen de tratamiento antirretroviral. La regresión de Cox fue utilizada en los estudios de supervivencia para analizar su evolución, la influencia de los distintos eventos oportunistas, el efecto de la adherencia a los tratamientos y del cambio de tratamiento antirretroviral durante el seguimiento. Resultados: La tasa de mortalidad fue de 13,7 por 100 personas-año en 1994 y descendió hasta 4,2 en el primer semestre del 1997 (p=0,001).La monoterapia se asoció a una disminución de la mortalidad del 53 por ciento [IC95=34 por ciento-65 por ciento], la biterapia del 68 por ciento [IC95=38 por ciento-84 por ciento], la triple terapia del 86 por ciento [IC95=40-96 por ciento] y la profilaxis anti-NPC del 49 por ciento [IC95=29 por ciento-64 por ciento]. En los pacientes con CD4>100/mm3la supervivencia mejoró a lo largo del tiempo (p=0,002). En los pacientes con sida, el buen cumplimiento del tratamiento antirretroviral y de la profilaxis antiNPC se asociaron con una disminución del riesgo de muerte (RR=0,88; IC95=0,63-1,22 y RR=0,72; IC95=0,55-0,95 respectivamente). Conclusiones: La profilaxis anti-NPC y el tratamiento antirretroviral, en especial la terapia combinada, han contribuido a disminuir la mortalidad por sida en los últimos años. El grado de adherencia a los tratamientos se relaciona con el riesgo de morir y la supervivencia (AU)

[Symptomatic hyperlactatemia associated with the use of antiretroviral agents]. / Hiperlactatemia sintomática en relación con el uso de antirretrovíricos.

Lactic acidosis has been reported as a rare but potentially fatal complication of anti-retroviral therapy in HIV-infected patients, mostly with nucleoside analogues. Two cases of lactic acidosis with a favorable prognosis are here reported. So far, no distinct risk factors associated with the development of lactic acidosis have been identified which were associated with the use of anti-retroviral agents, apart from female sex, obesity, and the prolonged use of necleoside reverse transcriptase inhibitors. Currently, there is no specific treatment for this condition, apart from drug discontinuation and hydro-electrolytic support. Several therapies based upon the pathophysiology of this entity have been tested, but none of them has been validated so far.

Hiperlactatemia sintomática en relación con el uso de antirretrovíricos / Symptomatic hyperlactatemia associated with the use of antiretroviral agents

La acidosis láctica en relación con el uso de antirretrovíricos, sobre todo con los análogos de nucleósidos, constituye una rara complicación, aunque potencialmente grave, de la terapia antirretrovírica. Presentamos en esta nota dos casos registrados en nuestro centro, ambos con resolución sin producir la muerte de los pacientes. No se han identificado factores de riesgo claros para el sufrimiento de acidosis láctica inducida por antirretrovíricos, salvo el sexo femenino, la obesidad y el uso prolongado de inhibidores de la transcriptasa inversa análogos de nucleósidos. No existe tratamiento específico, salvo la retirada de los fármacos y el sostén hidroelectrolítico. Se han ensayado tratamientos fundamentados en la fisiopatología del proceso, sin que hayan sido realmente validados. (AU)

[Prognostic factors of mortality during the episode of pneumonia due to Pneumocystis carinii in patients with HIV infection]. / Factores pronósticos de mortalidad durante el episodio de neumonía por Pneumocystis carinii en pacientes con infección por VIH.

BACKGROUND: Despite a steady decrease in its incidence, pneumonia caused by Pneumocystis carinii (PCP) are still diagnosed, and they occur frequently in patients unaware of being infected with the human immunodeficiency virus (HIV). Since it is a disease with a high mortality risk, its early diagnosis and therapy would allow these patients to benefit from the advantages afforded Pneumocystis carinii, neumonía, infecciones oportunistas relacionadas con el sida, pronóstico.by anti-retroviral therapy. PATIENTS AND METHODS: Retrospective study, in which all adult HIV infected patients with microbiologically demonstrated PCP diagnosed at two tertiary-level hospitals in our country between 1985 and 1996 were included. The clinical records of patients were used as information source. The relative risks (RR) of death were estimated by the multivariant logistic regression. RESULTS: PCP was the first AIDS indicating disease in approximately 70 % of cases. Thirteen percent of patients died during the episode. Patients aged over 45 years had a death RR during the episode of 3.15 (95 % CI from 0.8 to 12.2); patients previously diagnosed of AIDS had a death RR of 3.4 (95 % CI from 1.3 to 9), and those with an alveolar-arterial oxygen gradient (pA-aO2) > 50 mmHg, a death RR of 3 (95% CI from 1.1 to 8). CONCLUSIONS: Factors independently related to survival to the PCP episode are age below 45 years, not to have had another AIDS indicating disease, and to have a pA-aO2 below 50 mmHg at diagnosis.

Factores pronósticos de mortalidad durante el episodio de neumonía por Pneumocystis carinii en pacientes con infección por VIH / Prognostic factors of mortality during the episode of pneumonia due to Pneumocystis carinii in patients with HIV infection

Fundamento. A pesar de un claro descenso en su incidencia, se siguen diagnosticando neumonías por Pneumocystis carinii (NPC), presentándose con frecuencia en pacientes que ignoran su situación de infectados por el VIH. Puesto que se trata de una enfermedad con un riesgo elevado de mortalidad, su rápido reconocimiento y tratamiento les permitirá beneficiarse a posteriori de las ventajas aportadas por el tratamiento antirretrovírico. Pacientes y métodos. Estudio retrospectivo en el que se incluyeron todos los pacientes adultos con infección por VIH y NPC confirmada microbiológicamente, diagnosticados en dos hospitales terciarios de nuestro país entre 1985 y 1996. Las historias clínicas de los pacientes se utilizaron como fuente de información. Los riesgos relativos (RR) de muerte se estimaron mediante regresión logística multivariable. Resultados. La NPC fue la primera enfermedad indicadora de sida en aproximadamente el 70 por ciento de los casos. Un 13 por ciento de los pacientes fallecieron durante el episodio. Los pacientes mayores de 45 años tienen un RR de muerte durante el episodio de 3,15 (índice de confianza [IC] 95 por ciento: 0,8, 12,2); aquellos que habían sido previamente diagnosticados de sida tienen un RR de muerte de 3,4 (índice de confianza [IC] 95 por ciento: 1,3, 9) y los que presentan un gradiente alveolo-arterial de oxígeno (pA-a O2) > 50 mmHg, un RR de muerte de 3 (IC 95 por ciento: 1,1,8).Conclusiones. Los factores relacionados de forma independiente con la supervivencia al episodio de NPC son la edad menor de 45 años, el no haber tenido con anterioridad otra enfermedad indicadora de sida y presentar en el momento del diagnóstico un pA-a O2 inferior a 50 mmHg. (AU)

[Diastolic dysfunction in human immunodeficiency virus infection]. / Disfunción diastólica en la infección por el virus de la inmunodeficiencia humana.

AIMS: We sought to determine the prevalence and characteristics of echocardiographic abnormalities (systolic and/or diastolic dysfunction, pericardial effusion) in patients with human immunodeficiency virus infection (HIV) with no symptoms or previous history of cardiac disease, and compare them with a healthy control group. PATIENTS AND METHOD: Transthoracic echocardiography was performed in 125 patients (73% male, mean age 33.2 +/- 6.6 years) with HIV infection without cardiac involvement and 47 age and sex-matched healthy volunteers (78% male, 31.6 +/- 7.3 years). The immunologic situation was determined by CD4 lymphocyte counts. RESULTS: Abnormal left ventricular relaxation and filling patterns (E/A relation 1.31 +/- 0.35 in HIV group, 1.66 +/- 0.38 in control group, p < 0.001; pressure half-time 57.5 +/- 13 in HIV group, 50.6 +/- 6.6 in control group, p < 0.001), segmental wall-motion abnormalities (15%) and pericardial effusion (7.2%) were found in patients with HIV infection. Systolic function (EF 64.8 +/- 8.3) and left ventricular dimension (diastolic diameter 4.94 +/- 0.55, systolic diameter 3.17 +/- 0.51) showed normal patterns and did not significantly differ from those of the control group. CONCLUSIONS: Silent echocardiographic abnormalities in patients with HIV infection are frequent suggesting a direct myocardial effect of the virus. The development of diastolic dysfunction is directly related to a worse immunologic situation. Prospective studies are needed to clarify the clinical prognosis of these asymptomatic abnormalities.

[Pneumocystis carinii pneumonia and HIV infection: diagnosis and treatment]. / Neumonía por Pneumocystis carinii e infección por el VIH: diagnóstico y tratamiento.

Pneumocystis carinii pneumonia (PCP) is one of the leading complications among HIV-infected patients. Recent advances in PCP prophylaxis, diagnosis and treatment have caused a decrease in PCP-related morbidity and mortality. Despite these advances, PCP continues to be frequent in patients not known to be HIV-infected and in those patients with poor adherence to prophylactic regimens or severe immunosuppression. In typical cases diagnosis may be suspected by the patient's clinical presentation. Clinicians are frequently faced with the differential diagnosis between PCP, bacterial pneumonia, pulmonary tuberculosis, and other specific respiratory disorders HIV-associated. Definitive diagnosis of PCP requires demonstration of Pneumocystis carinii (PC) in respiratory secretions or lung tissue. Conventional techniques, immunofluorescence using monoclonal antibodies and molecular techniques are highly specific, but sensitivity varies depending on the PC load present in the sample. Best diagnostic yield is obtained analyzing samples obtained by bronchoalveolar lavage. PC diagnosis using highly sensitive PCR in sputum-induced samples might allow noninvasive diagnosis in most HIV-infected patients suffering from PCP but PCR techniques remain to be standardized. Like in PCP prophylaxis, trimethoprim-sulphametoxazole (TS) is the drug of choice for PCP treatment. In severe case, TS is given intravenously. If patient is intolerant to TS, i.v. pentamidine or i.v. trimetrexate with folinic acid can be used. TS has a dose-dependent toxicity. In cases of hypersensitivity to TS, drug-desensitization should be tried. In severe documented PCP adjunctive corticosteroid therapy is effective and safe. In mild to moderate PCP, TS can be given orally. Best alternatives to TS in this situation are dapsone-pyrimethamine or clindamycin-primaquine (CP). Other effective options are oral atovaquone, aerosolize pentamidine and i.v. pentamidine.

[Efficacy and safety of zidovudine in monotherapy in patients with HIV infection]. / Eficacia y tolerancia del tratamiento con zidovudina (ZDV) en monoterapia en pacientes con infección VIH.

BACKGROUND: To study the efficacy and the tolerance of the zidovudine (ZDV) in monotherapy for the treatment of a cohort of patients with HIV infection, most of them injection-drug users (IDU). METHODS: Retrospective study of a historic cohort of 350 patients, from January 1988 to December 1994. The clinic progression, the immunologic deterioriation and the survival after the ZDV administration were evaluated, like the toxicity of the drug. RESULTS: The estimated progression time to AIDS for the 25% of the cohort was 29 months for the initially asymptomatic patients and 22 months for the subjects who showed symptoms. After 26 months half of the patients showed CD4 cell counts less to 50% of the basals. The cumulative survival probability after a year was 99%, 97% and 85% for the groups A, B y C of the CDC classification, and 94%, 87% and 58% after two years for these groups. The predictive factors associated with the survival were the clinic and immunologic status, ESR, LDH, and beta 2-microglobulin levels at the beginning of the treatment. The 35% of the patients suffered adverse events, mainly hematologic effects, although they only forced to suspend the treatment in the 5% of the cases. The only predictive factor associated with the toxicity was a neutrophile count less than 1.500 cells/mm3 previous to the treatment (p < 0.001). CONCLUSION: The ZDV use in monotherapy in a cohort of patients majority IDU shows the same efficacy and safety as the treatment in other patients with HIV infection.

[Past, present and future of zidovudine, the first antiretroviral drug]. / Pasado, presente y futuro de la zidovudina, el primer antirretroviral.

The zidovudine (ZDV) was the first drug approved to treat the VIH infection. The ZDV prescriptions have been changing throughout the years. Actually it's known that its efficacy is limited over time, and same substances have been discovered which inhibtes more strongly the VIH replication. However the ZDV appears in majority the combined therapy regimens as a first line drug. Even in same special situations there is no existence of another antiretroviral drugs which have showed utility. In this essay it s revised the mainly studies which have provided new knowledge about the ZDV treatment and it s also considered the possibilities of this drug in the more new therapies against the VIH.

[Predictive factors of non-compliance with anti-tuberculosis treatment in patients infected with the human immunodeficiency virus]. / Factores predictivos del abandono del tratamiento antituberculoso en pacientes infectados por el virus de la inmunodeficiencia humana.

A study was conducted to know the rate of non-compliance of antituberculosis therapy among HIV-infected patients, the factors associated with non-compliance and the evolution of these patients. The therapy compliance in 276 tuberculous HIV infected patients diagnosed in two Madrid hospitals was analyzed. Fifty-one patients (18%) were not included in the analysis (6 died without therapy, 6 were lost and 39 died during therapy). Out of the 225 evaluable patients, 36 (16%, 95% CI, 11.6-21.6) did not comply with therapy. The only factor associated with a higher therapy non-compliance was the antecedent of drug use (20% of non-compliance; relative risk: 10, 95% CI, 1.4-71). Patients using drugs at tuberculosis diagnosis had higher risk for non-compliance (31%; RR, 3.1; 95% CI, 1.6-6.3). The incidence of tuberculosis reactivation after leaving therapy was 78.8/100 patient-years. Therapy non-compliance increased death risk associated with tuberculosis (RR, 9.8; 95% CI, 4.6-21). Programs for controlling antituberculous therapy should give priority to active drug users, as this is the group with the highest risk for non-compliance.

[Reactivity of serologic tests for the detection of syphilis in patients infected with the human immunodeficiency virus]. / Reactividad de las pruebas serológicas para detección de sífilis en pacientes infectados por el virus de la inmunodeficiencia humana.

BACKGROUND: The coexistence of syphilis and infection by the human immunodeficiency virus (HIV) appears to modify the natural history of both diseases. The aim of this study was to know the prevalence of syphilis in a population of patients with HIV infection, the possible association with certain risk practices and the validity of the reaginic test in such patients. METHODS: Three hundred sixty-seven patients with HIV infection who went for the first time to a monographic clinic of a university hospital were studied. Syphilis serology was carried out: rapid plasma reaginic (RPR) and hemagglutination (MHA-TP) tests. RESULTS: Out of all the patients 26 (7.1%) had positive MHA-TP. The proportion of homosexuals was greater among those who had a positive treponemic test (69%) than among those who were negative (6.4%; odds ratio [OR] = 32.6; confidence interval 95%: 16.2-65.4). The positivity of MHA-TP was more frequent among those presenting criteria of the acquired immunodeficiency syndrome (AIDS) at the diagnosis (18% versus 5.6%; OR = 3.6 [1,5-8,9]). Seventy-four false positive reactions were observed with the RPR (20%) corresponding almost exclusively (96%) to intravenous drug users who presented false positivity in 25% of the cases. CONCLUSIONS: The prevalence of syphilis detected by treponemic serology among subjects with infection by the human immunodeficiency virus is related with homosexuality as the principal practice of risk. One quarter of the intravenous drug users with infection by the human immunodeficiency virus presented false positive results to the reaginic test thus leading to the recommendation that therapeutic measures should not be initiated without confirmation with a treponemic test.

[Mycobacterium avium-intracellulare disseminated infection in patients with AIDS]. / Infección diseminada por Mycobacterium avium-intracellulare en pacientes con SIDA.

BACKGROUND: Disseminated infection by Mycobacterium avium-intracellulare is almost exclusively produced in individuals with HIV infection. The incidence of this infection in Spain is unknown. METHODS: The clinical and microbiologic registries of 30 patients with AIDS and disseminated infection by Mycobacterium avium are reviewed. METHODS: Twenty-three percent of the patients with AIDS had, at some time in their evolution, disseminated infection by M. avium. The clinical picture included prolonged fever, digestive symptoms, weight loss and appearance of lymph node enlargement. This infection appeared in patients with severe alteration of cellular immunity (mean CD4 lymphocytes: 0.19 x 10(9)/l). Although medium term prognosis was bad the causes of death of the patients were other opportunistic diseases related with the immunodeficiency. CONCLUSIONS: Infection by Mycobacterium avium is frequent among the population of individuals with HIV infection. With the appearance of prolonged fever in a patient with HIV infection and CD4 lymphocyte count lower than 0.2 x 10(9)/1 appropriate microbiologic studies including blood cultures for mycobacteria should be initiated.