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L Zamora

Publications and source records attributed to L Zamora.

At least 19 recordsLinked to original sources

Presence of genotypic resistance in nucleoside analogue-treated HIV-1-infected patients with undetectable viral load.

Patients harbouring drug-resistance viruses usually suffer a rise in serum viraemia after a variable period of time. We have investigated the relationship between the appearance of resistant genotypes and the viral load of each patient after treatment. Our objective was to assess the association between human immunodeficiency virus (HIV) RNA plasma levels and the number of drug resistance-associated point mutations after treatment. A total of 150 patients from three reference centres in Spain (Madrid, Barcelona and Seville) from a previous study (Erase Study) were included. Patients had at that time undergone antiretroviral treatment with nucleoside analogues for at least 1 year (zidovudine/didanosine; zidovudine/zalcitabine; zidovudine/zalcitabine/lamivudine; zidovudine/didanosine/lamivudine). In this study, plasma viraemia in these patients was quantified and a line probe assay was used to determine the genotype of the virus. Viral load was significantly higher in patients harbouring virus with more than three mutations than in those individuals who harboured wild-type strains (P < 0.05). Surprisingly, when patients with viral load < 500 copies/ml (13/150) were analysed, only two carried wild-type strains, whereas three had virus with more than three point mutations. The viral load of six samples was assayed using an ultrasensitive test (detection limit < 20 copies/ml). Of the three samples where viral load was < 20 copies/ml, one patient harboured wild-type virus, whereas two carried mutant virus strains. These results suggest that even in patients with undetectable viral loads by conventional methods, viral replication may continue and mutations develop. Therefore, standard values of plasma viraemia for measuring the effectiveness of the treatment should be reconsidered when patients are on antiviral regimens of just two or three nucleoside analogues.

Acquired Immunodeficiency Syndrome

Prevalence of genotypic resistance to nucleoside analogues in antiretroviral-naive and antiretroviral-experienced HIV-infected patients in Spain.

OBJECTIVE: To determine the prevalence of genotypic resistance to nucleoside analogues (NA) in a large group of HIV-infected individuals in Spain, some of whom had no previous treatment with antiretroviral drugs (antiretroviral-naive) and some of whom had such experience (antiretroviral-experienced). SETTING: Cross-sectional study in out-patient clinics in three reference hospitals for HIV/AIDS located in Barcelona, Madrid and Seville, Spain. PATIENTS AND METHODS: Primary mutant genotypes were examined in plasma HIV RNA collected from 150 antiretroviral-naive subjects, half in 1993 and the other half in 1997. Furthermore, drug resistance mutations were analysed in plasma collected from another 150 antiretroviral-experienced patients who had received 2 NA for longer than 1 year, either in sequence as monotherapy or as combination therapy. A line probe assay was used for recognizing mutations conferring resistance to zidovudine (ZDV), didanosine (ddI), zalcitabine (ddC), and lamivudine (3TC). A point-mutation nested-PCR assay was used for examining a codon 151 mutation associated with multiple drug resistance. RESULTS: One or more mutations associated with primary resistance to NA were seen in 10 antiretroviral-naive (13.3%) patients in 1993 and in nine (12%) in 1997. In all but two cases, they were associated with ZDV resistance. In contrast, all but six (96%) of the antiretroviral-experienced subjects harboured drug-resistant mutant viruses. The codon 184 mutation (associated with resistance to 3TC) was detected in 92% of patients treated with 3TC, but also in 18% of those treated with only ddI or ddC. The codon 215 mutation was found in 67.3% of patients who had been exposed to ZDV; the codon 69 mutation was found in 15% of patients treated with ddC; and the codon 74 mutation was found in only 7.2% of patients treated with ddI. Finally, the codon 151 multidrug resistant mutation was found in four (2.7%) of 150 patients with a long-term exposure to NA. CONCLUSIONS: Overall, the prevalence of drug-resistant HIV-1 genotypes was 12.7% in antiretroviral-naive patients, most of whom had ZDV-resistant mutants. There is no evidence of an increase during the last 5 years. However, multidrug-resistant HIV genotypes are currently circulating in Spain.

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Curriculum

[Prophylaxis secondary to retinitis by CMV in patients with AIDS: the efficacy of an intermittent schedule of 3 days/week].

BACKGROUND: An approach of daily or 5 days per week treatment as maintenance therapy is mandatory among HIV patients with CMV retinitis. We evaluate the efficacy and tolerance of thrice weekly maintenance therapy for CMV retinitis in AIDS patients. METHODS: Sixty nine consecutive patients with CMV disease were eligible for a prospective open clinical trial. Thirty three completed the induction treatment of CMV retinitis, agreed on maintenance thrice weekly and were included. Twenty nine received Ganciclovir (10 mg/kg/day) and 4 foscarnet (100 mg/kg/day) thrice weekly. RESULTS: The mean age was 34 years. Twenty nine of the 33 (87%) were males and 13 (39%) drug addicts. Mean CD4+ lymphocyte count at inclusion was 44 cells per relapsed and 22 (66%) died. The median time to relapse, survival free of CMV retinitis and the median survival was 18, 14 and 34 weeks respectively. CONCLUSION: Since the outcome of our patients with thrice weekly maintenance therapy was similar to historical controls our study at least provides the rational for this hypothesis to be tested in a future randomised trial.

AIDS-Related Opportunistic Infections

[Disability in the private pension system in Chile].

BACKGROUND: The degree of disability of workers ascribed to the private allowances system in Chile, is judged by Medical Commissions that apply norms that establish percentages of incapacity, without considering prognosis. AIM: To communicate the causes of disability among Chilean workers ascribed to the private allowances system, their mortality and to correlate the causes of death with diagnoses. SUBJECTS AND METHODS: We analyzed 13,456 consecutive cases judged between August 1990 and April 1992. Mortality was registered up to 12 months after judgment. RESULTS: Total incapacity was determined in 4,158 cases (30.9%), partial incapacity in 1,340 (9.9%) and minor incapacity in 7,958 (59.1%). Osteoarticular diseases were the main cause of disability in 4,460 patients (33.1%) and 77.8% of patients with malignant tumors were considered as having total incapacity. Mortality was 17% among subjects with total incapacity, 1.5% among those with partial disability and 1% among those with minor disability. The cause of death was related to the main disabling disease in 94% of subjects with total incapacity and 66.6% of those with partial incapacity. CONCLUSIONS: Osteoarticular diseases are the main cause of inability among workers ascribed to a private pension system.

Chile

[Analysis of 1,187 consecutive cases of AIDS: variations and trends in time].

BACKGROUND: The characteristics of AIDS patients in Spain have already been described, as have the factors which may or may not be present at the time of AIDS diagnosis influence in the prognosis. The introduction of zidovudine and later other antiretroviral drugs have improved the prognosis versus historical controls. Nonetheless, advances in prevention, control and the treatment of opportunistic infections have provided the greatest influence in the development of clinical manifestations of AIDS: The aim of the present was to study the evolution of AIDS patients seen at the Hospital Clínic in Barcelona, Spain, from 1985 to 1992 and analyze the variations in the time of clinical manifestations and survival. METHODS: The clinical records of 1187 patients in the Hospital Clinic in Barcelona with HIV infection who developed AIDS (1985-1992) according to the CDC criteria of August 1987 were retrospectively reviewed. RESULTS: Out of the 1187 AIDS cases, the percentage of women rose from 8% to 25%. The route of HIV infection which has most varied over time has been that of heterosexual relations (68%). Despite being the most frequent form of AIDS presentation, opportunistic infection has decreased from 79% to 51%. Tuberculosis, pneumonia by Pneumocystis carinii and cerebral toxoplasmosis as forms of presentation have also decreased on performing routine primary prophylaxis for these opportunistic infections. A significant trend towards improvement in survival over time was observed, mainly due to better prognosis of patients in whom AIDS diagnosis was obtained due to pneumonia by P. carinii or Kaposi's sarcoma. CONCLUSIONS: There has been an increase in the percentage of women and heterosexual transmission in AIDS, as well as an important change in the form of AIDS presentation probably due to the systematic administration of primary prophylaxis for several opportunistic infections. There has also been a global improvement in survival.

AIDS-Related Opportunistic Infections

Prognostic factors influencing the outcome in pneumocystis carinii pneumonia in patients with AIDS.

BACKGROUND: Studies attempting to identify the prognostic factors that influence the outcome of Pneumocystis carinii pneumonia (PCP) in patients with AIDS using a multivariate analysis are few. In order to identify those prognostic factors amenable to medical intervention, univariate and multivariate analyses were performed on 102 patients with AIDS suffering a first episode of PCP. METHODS: One hundred and two consecutive patients with AIDS (51% drug abusers, 45% homosexuals, and 4% with other HIV risk factors) admitted to our institution between 1986 and 1989 whose respiratory infection was diagnosed by bronchoalveolar lavage were studied prospectively. RESULTS: The overall mortality was 28%, rising to 79% in those patients who required mechanical ventilation. According to univariate analysis the following variables were related to a poor prognosis: age > 35 years; risk factor for HIV infection other than drug abuse; and AIDS diagnosis confirmed before 1988; PaO2 < 8 kPa at admission; severe acute respiratory failure on admission (PaO2/FIO2 < 20 kPa); mechanical ventilation; antibiotic therapy for PCP other than trimethoprim-sulphamethoxazole; multiple microbial pulmonary infection; serum lactate dehydrogenase (LDH) > 22.5 mukat/l on admission; serum albumin level < 30 g/l. Multivariate analysis showed that only mechanical ventilation was independently associated with a poor outcome. CONCLUSIONS: The mortality of AIDS patients presenting with a first episode of PCP before 1990 was high (28%). The main prognostic factor associated with poor outcome was the requirement for mechanical ventilation due to severe acute respiratory failure.

AIDS-Related Opportunistic Infections

[CD4+ lymphocytes and opportunistic infections and neoplasms in patients with human immunodeficiency virus infection].

BACKGROUND: The CD4+ lymphocytes are the principal target cell for the human immunodeficiency virus (HIV). Their depletion originates a very severe cell immunosuppression, which conditions the appearance of opportunistic infections and neoplasms characteristic of AIDS. The aim of this study was to evaluate whether there is a relation between the degree of cell immunosuppression and the type of opportunistic infections and neoplasms which these patients develop in Spain. METHODS: The CD4+ lymphocyte counts in 400 adults with HIV infection who developed opportunistic infections or neoplasms were retrospectively reviewed (1987-1991). This determination was carried out during between two months prior to diagnosis of AIDS (CDC, 1987) to one month after such diagnosis. RESULTS: The results allowed opportunistic infections to be classified into three groups according to the grade of immunosuppression: 1) opportunistic infections with more than 0.2 x 10(9) CD4+ lymphocytes/l (45-60% of cases of tuberculosis, esophageal candidiasis and enteritis by Isospora belli); 2) opportunistic infections with 0-0.2 x 10(9) CD4/l (87-100% of the cases of pneumonia by Pneumocystis carinii, encephalic toxoplasmosis, visceral leishmaniasis and enteritis by Cryptosporidium); 3) opportunistic infections with 0-0.1 x 10(9) CD4 lymphocytes/l (70-100% of the cases of systemic cryptococcosis, retinitis by cytomegalovirus, progressive multifocal leukoencephalopathy and infection by Mycobacterium avium-intracellulare). With respect to the neoplasms, Kaposi's sarcoma was observed in patients with different degrees of immunosuppression. Seventy-five and 80% of the patients with non Hodgkin's lymphoma and primary cerebral lymphoma had less than 0.2 x 10(9)/l and less than 0.1 x 10(9)/l CD4+ lymphocytes, respectively. CONCLUSIONS: The CD4 lymphocyte counts may predict the type of opportunistic infections which patients with the human immunodeficiency virus infection may develop.

AIDS-Related Opportunistic Infections

[Incidence of enteropathogens in patients with human immunodeficiency virus infection].

BACKGROUND: To establish the incidence of diarrhea and its evolution over time, the causal microorganisms, recurrence and associated mortality in patients with AIDS or severe immunologic alterations (CD4 lymphocytes lower than 0.5 x 10(9)/l). METHODS: A prospective longitudinal study was carried out from 1984 to 1992. The following patients were included in the study: 1) all those patients with diarrhea in whom a pathogenic microorganism was identified in the stools, and 2) patients with fever and positive blood cultures for enteropathogenic bacteria. The patients belonged to a series of 1,456 patients with infection by HIV. RESULTS: Of the 1,456 controlled patients, 253 (17%) had infection by enteropathogenic microorganisms. The incidence was greater in homosexual patients (26%) than in drug addicts (12%). The most frequent germs were Cryptosporidium, in 104 episodes and Salmonella sp. in 78 episodes (31 as isolated bacteria). The mortality in the 15 days following isolation was 2%, the referred microorganisms being the most frequent responsible for the deaths. The mean of CD4 lymphocytes in the patients with enteropathogens was 0.17 x 10(9)/l). SD 0.14 x 10(9)/l). In patients with infection by Cryptosporidium the CD4 lymphocyte count was lower than that observed in the cases of infection by Isospora belli. Prior to 1988, 21% of the patients had infection by enteropathogenic bacteria and 23% by parasites, those percentages being 3% and 6%, respectively in 1991. CONCLUSIONS: Infections by enteropathogenic microorganisms in patients with infection by the human immunodeficiency virus in an advanced stage are frequent, particularly, in homosexuals. The patients with enteritis by Cryptosporidium have a greater grade of immunosuppression (CD4 lymphocytes lower than 0.1 x 10(9)/l) than patients with infection by other enteropathogenic microorganisms. In the last few years, the incidence of enteropathogenic bacteria, especially Salmonella sp. and protozoa has decreased [corrected].

Acquired Immunodeficiency Syndrome

[Otoneurologic examination of patients with AIDS].

The influence of the HIV virus on the central nervous system tracts has been definitively shown. Over the past year we have affected otoneurologic tests based on elicited auditive potentials and tests of oculomotility on a total of 30 patients affected by stages II and III of the disease. The results show that around 27 percent of cases present alterations in the provoked auditory potentials and 20 percent in the oculomotility tests. The results are compared with those of previous studies.

Acquired Immunodeficiency Syndrome

[Therapeutic alternatives for cases of cerebral toxoplasmosis in patients with AIDS: clarithromycin and atovaquone].

BACKGROUND: Cerebral toxoplasmosis is the most common opportunistic infection of the central nervous system in AIDS patients. Its rate varies between 3-40% according to the prevalence of toxoplasmosis in the different geographic areas. Conventional treatments used for this pathology are: sulphadiacin or clindamycin plus pyrimethamine, but all can occasionally produce severe side effects. Therefore, the search for new alternative therapies is recommended. METHODS: Two cases of encephalic toxoplasmosis in AIDS patients who developed severe toxicity to conventional treatment with pyrimethamine and sulphadiacin and later to clindamycin are described. RESULTS: The first patient had a complete clinical and neuroradiological curation using clarithromycin 2 g/day and pyrimethamine 50 mg/day for 6 weeks. At 22 months follow up with a maintenance dose of 1 g/day of clarithromycin, the patient still remains asymptomatic. The second patient was successfully treated with atovaquone (750 mg/6 h) for 8 weeks and at 12 months of follow up with a maintenance dose of 750 mg/8 h remains asymptomatic. CONCLUSIONS: The authors believe that clarithromycin and atovaquone may constitute valid alternatives for the treatment of cerebral toxoplasmosis. Nonetheless, their use may, at present, be recommended only as an alternative for the cases of therapeutic failure or severe intolerance when the usual schedules are used.

AIDS-Related Opportunistic Infections

A prospective study of the risk of tuberculosis among HIV-infected patients.

OBJECTIVE: To evaluate the risk of developing active tuberculosis (TB) in a cohort of HIV-1-infected patients. METHODS: Prospective longitudinal follow-up of 839 HIV-infected patients, of whom 505 (60%) were parenteral drug users and 269 (32%) homosexual men. Tuberculin skin tests were performed at baseline and annually thereafter. Prophylaxis with isoniazid (300 mg daily for 9 months) was offered to those with a positive tuberculin test (induration > or = 5 mm). Diagnosis of TB was accepted if it could be confirmed microbiologically (acid-fast bacilli seen in Ziehl-Neelsen stains or grown in Lowenstein-Jensen cultures) or pathologically (presence of caseating granulomas) and patients had consistent clinical manifestations. RESULTS: Active TB developed in 23 out of the 733 (3.1%) patients with a negative tuberculin skin test after a mean follow-up of 16 +/- 11 months (range, 2-52 months), with an estimated cumulative probability of 1.5 and 7% after 1 and 3 years, respectively (or 2.4 per 100 patient-years). None of the 87 patients with a negative tuberculin test but a positive Multitest developed TB. Conversely, 106 patients had a positive tuberculin skin test (97 at baseline and nine who converted during follow-up). Active TB developed in seven out of the 26 not receiving prophylaxis or in whom prophylaxis had to be discontinued (16.2 per 100 patient-years), in four out of 61 patients 3-27 months after having completed 9 months of prophylaxis with isoniazid (8.9 per 100 patient-years) and in none of the 19 still receiving isoniazid. When TB was diagnosed, the mean CD4 lymphocyte count of the 34 patients who developed it during follow-up was 77 +/- 103 x 10(6)/l (range, 1-400 x 10(6)/l). CONCLUSIONS: Among HIV-infected patients in whom the tuberculin skin test is negative, the risk of developing active TB is sufficient to consider prophylaxis if the CD4 count falls below 400 x 10(6)/l, at least in those patients with skin anergy living in high-risk geographical areas such as Spain. When the tuberculin skin test was positive, isoniazid (9 months) provided a 45% protection beyond the period of its administration.

AIDS-Related Opportunistic Infections

Primary prophylaxis for Pneumocystis carinii pneumonia: a randomized trial comparing cotrimoxazole, aerosolized pentamidine and dapsone plus pyrimethamine.

OBJECTIVE: To compare the efficacy and tolerance of monthly aerosolized pentamidine versus cotrimoxazole versus dapsone plus pyrimethamine to prevent the initial episodes of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients. DESIGN: An open randomized clinical trial. PATIENTS AND METHODS: HIV-infected patients (n = 331) with CD4 cell counts < 200 x 10(6)/l or with AIDS but without a history of PCP or cerebral toxoplasmosis (CT) were randomized to receive pentamidine (300 mg every 4 weeks), cotrimoxazole (160/800 mg 3 days a week) or dapsone plus pyrimethamine (100 and 25 mg weekly). If immunoglobulin G (IgG) antibodies to Toxoplasma were present, patients in the first two groups were randomized further to 25 mg pyrimethamine per week or to no treatment. RESULTS: The mean follow-up was 313 days (range, 30-670 days). The three groups were homogeneous for age, sex, risk group for HIV infection, initial CD4 cell count and mean follow-up. PCP developed in 16 patients, with an estimated cumulative probability of 5.3% at 1 year of follow-up. The PCP rate per year of observation, using an intention-to-treat analysis, was 5.6% [95% confidence interval (CI), 0.9-10.3], 3% (95% CI, 0-6.3) and 8.3% (95% CI, 2.8-13.8) in the groups treated with pentamidine, cotrimoxazole and dapsone plus pyrimethamine, respectively (P > 0.05). Moderate or severe side-effects were observed in one patient on pentamidine, 10 on cotrimoxazole and nine on dapsone plus pyrimethamine (P < 0.05); the study drug had to be discontinued in no, 10 and six patients, respectively (P < 0.05). Neither cotrimoxazole alone nor pyrimethamine combined with dapsone or cotrimoxazole prevented initial episodes of toxoplasmosis among patients with IgG antibodies to Toxoplasma gondii. CONCLUSIONS: Low-dose thrice-weekly cotrimoxazole or weekly dapsone plus pyrimethamine was not significantly worse (differences > 15% would have been detected with 90% certainty) than monthly aerosolized pentamidine in preventing a first episode of PCP in patients at high risk, but aerosolized pentamidine was better tolerated.

AIDS-Related Opportunistic Infections

Influence on survival of p24 antigen levels in patients with AIDS or advanced AIDS related complex treated with zidovudine.

In a prospective study sixty-eight patients consecutively diagnosed as having AIDS or advanced ARC who were started on zidovudine therapy were followed up for a median period of 725 days. In the 20 patients who had a baseline p24 antigen level above 20 pg/ml, there was a statistically significant trend towards reduction of the p24 antigen levels after the first month of treatment. The median time of survival of the 68 patients was 702 days and the median symptom-free period was 510 days. Treatment with zidovudine significantly reduced the p24 antigen levels. However, the life expectancy and the symptom-free period were not statistically different in the patients with p24 antigen levels always below or with levels always above two arbitrarily chosen cut-off points of 20 pg/ml and 50 pg/ml, respectively.

AIDS-Related Complex

Influence of treatment with zidovudine (ZDV) on the long-term survival of AIDS patients.

The influence of treatment with zidovudine (ZDV) and other factors on long-term survival of AIDS patients was analyzed in a cohort of 629 adults. A total of 434 (69%) were diagnosed before ZDV became routinely available in Spain (December 1987) or refused the drug, while the remaining 195 (31%) received ZDV (starting at a dose of 750-1,200 mg/day). A total of 412 (65.5%) were parenteral drug addicts and 217 (34.5%) male homosexuals. Two hundred thirty-two (36.9%) presented with a tuberculosis, 303 (48.2%) with other opportunistic infections, 69 (11%) with Kaposi's sarcoma, and the remaining 25 (4%) with a lymphoma. By December 1990, 251 (39.9%) of the 629 have already died with a cumulative survival probability of 50.6% after 2 years (45.3-55.9%; 95% confidence interval). When patients receiving ZDV were compared with those untreated, the estimated survival probability was significantly (p less than 0.0001) higher (89% vs. 59% after 1 year, 69% vs. 48% after 2 years, and 55% vs. 40% after 3 years). Moreover, treatment with ZDV (p less than 0.0001) together with being less than 45 years old (p less than 0.0001), being a parenteral drug addict (p = 0.016), and presenting with tuberculosis (p less than 0.0001) were the factors selected by the multivariate analysis as independently improving the prognosis. In conclusion, adult AIDS patients (homosexual or drug addicts) may benefit from treatment with ZDV, at least during 3 years.

Acquired Immunodeficiency Syndrome