Incidence and causes of death in HIV-infected persons receiving highly active antiretroviral therapy compared with estimates for the general population of similar age and from the same geographical area.

BACKGROUND: Since the introduction of highly active antiretroviral therapy (HAART), the incidence of death in HIV-infected patients has dramatically decreased, and causes of death other than those related to HIV infection have increased, although it is unclear how these parameters compare with those in the age-matched general population living in the same geographical region. METHODS: Consecutive HIV-infected adults who were prescribed HAART in our hospital were prospectively followed from January 1997 to December 2004 or until death, loss to follow-up or discontinuation of HAART. Estimations of the annual incidence and causes of death in the general population of similar age in Catalonia per calendar year in the study period were obtained and compared with those in the HIV-infected cohort. RESULTS: There were 235 deaths among the 4471 patients on HAART (5%). The incidence of mortality decreased over time in HIV-infected patients (P<0.001; chi(2) test for trend), although it has remained approximately five times higher than that for the age-matched general population. AIDS-related events were the most common cause of death (n=95; 40%), although they significantly decreased over time (P<0.001; chi(2) test for trend), whereas liver diseases (P<0.001; chi(2) test for trend) and non-AIDS-defining infections (P=0.008; chi(2) test for trend) significantly increased over time. Infections in general (33 times higher), liver diseases (11 times higher) and non-Hodgkin lymphoma (5 times higher) were overrepresented as causes of death in the HIV-infected cohort compared with the age-matched general population. CONCLUSIONS: Non-AIDS-defining infectious diseases, liver diseases, and non-Hodgkin lymphoma represent specific targets for efforts to further decrease mortality in HIV-infected patients receiving HAART.

Impact of switching from human immunodeficiency virus type 1 protease inhibitors to efavirenz in successfully treated adults with lipodystrophy.

We prospectively followed 20 consecutive patients with human immunodeficiency virus type 1 (HIV-1) with viral loads of <200 RNA copies/mL. These patients had been treated with 2 nucleoside reverse transcriptase inhibitors and > or =1 HIV-1 protease inhibitor for > or =3 months; they developed body changes consistent with lipodystrophy and requested they be switched from protease inhibitor to efavirenz. At baseline and every 3 months, we assessed the following: body mass index, waist-to-hip ratio, regional fat thickness (assessed by sonography), fasting total and high-density lipoprotein cholesterol, triglycerides, glucose, insulin, CD4(+) cells, and viral load. At baseline, hypertriglyceridemia (> or =200 mg/dL) was present in 17 (85%) patients, hypercholesterolemia (> or =200 mg/dL) in 14 (70%), and impaired fasting glucose (> or =110 mg/dL) in 8 (40%); CD4(+) T cells were 280x10(6) cells/L (range, 64-942x10(6) cells/L). HIV-1 RNA had been at <200 copies/mL for a median of 14 months (range, 3-24 months). Six months after switching to efavirenz, there was a reduction in triglyceride levels (a decrease of 31%; P=.03) and fasting insulin resistance index (a decrease of 28%; P=.03), but total and high-density lipoprotein cholesterol and glucose did not change. Waist-to-hip ratio decreased from 0.92 to 0.87 (P=.06). Subcutaneous fat thickness did not change. CD4(+) cells remained stable (363x10(6) cells/L; range, 102-741x10(6) cells/L; P=.65). Nineteen patients (95%) had HIV-1 RNA levels that remained at <200 copies/mL. Although CD4(+) response and viral suppression remained preserved after 6 months of switching from protease inhibitor to efavirenz, the benefits of this approach on the evolution of lipodystrophy were limited, and our findings do not support its routine recommendation to treat lipodystrophy.

High incidence of herpes zoster in patients with AIDS soon after therapy with protease inhibitors.

A high incidence of herpes zoster was noticed among patients with AIDS, shortly after addition of a protease inhibitor to their baseline treatment with nucleoside analogue reverse-transcriptase inhibitors. Within a median follow-up of 64 weeks (range, 34-103 weeks), 14 patients (7%) had a first episode or a recurrence of herpes zoster (6.2 episodes per 100 patient-years). No episodes of zoster were diagnosed before week 4. Twelve episodes (86%) occurred between weeks 4 and 16. The risk of zoster was independent of age, sex, type of protease inhibitor, and CD4+ lymphocyte count and viral load at baseline and month 1. A CD8+ lymphocyte proportion at baseline of > 66% (hazard ratio [HR], 10.6; 95% confidence interval [CI], 3.4-33.1) and an increase in CD8+ lymphocyte proportion at month 1 of > 5% (HR, 32; 95% CI, 8.1-126.4) were independently associated with the risk of herpes zoster. These data might be clinically useful for determining transient prophylaxis for those patients at high risk.

[Prophylaxis secondary to retinitis by CMV in patients with AIDS: the efficacy of an intermittent schedule of 3 days/week]. / Profilaxis secundaria de la retinitis por citomegalovirus en pacientes con sida: eficacia de una pauta intermitente de 3 días por semana.

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.

[Analysis of 1,187 consecutive cases of AIDS: variations and trends in time]. / Análisis de 1.187 casos consecutivos de sida: variaciones y tendencias en el tiempo.

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.

[CD4+ lymphocytes and opportunistic infections and neoplasms in patients with human immunodeficiency virus infection]. / Linfocitos CD4+ e infecciones oportunistas y neoplasias en pacientes con infección por el virus de la inmunodeficiencia humana.

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.

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.

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.