Effect of oral beta-carotene supplementation on plasma human immunodeficiency virus (HIV) RNA levels and CD4+ cell counts in HIV-infected patients

We conducted a pilot, open-label study to assess the effect of short-term beta-carotene administration (180 mg/d with meals for 4 weeks) on the plasma human immunodeficiency virus (HIV) RNA levels and CD4+ lymphocyte counts in 21 HIV-infected patients. We found that plasma HIV RNA levels and CD4+ lymphocyte counts did not change following this short course of beta-carotene supplementation. Patients with lower serum concentrations of beta-carotene before supplementation were no more likely to have an increase in their CD4+ lymphocyte count or plasma HIV RNA copy number than were those with higher concentrations. No correlation was found between pre- or postsupplementation beta-carotene or vitamin A concentrations and pre- or postsupplementation CD4+ lymphocyte counts or plasma HIV RNA titers. This study provides no support for beta-carotene supplementation for HIV-infected subjects with normal baseline serum levels of beta-carotene and vitamin A.     

Interrelationship between the duration of HIV infection, viral load and CD4 positive lymphocyte count

BACKGROUND: The decline in CD4+ lymphocytes occurs at different rates in patients with HIV infection. A longer duration of HIV infection and a higher level of viral replication, represented by the viral load, are associated with a lower CD4+ lymphocyte count. However, the interelationship between these variables is still not well known. PATIENTS AND METHODS: 107 HIV-infected patients for whom the date of infection was known, were included in a transversal study, in which the CD4+ lymphocyte count and the plasma viral load were analysed, the last using an isothermal amplification method (NASBA). Patients were not receiving antiretroviral drugs or suffered intercurrent infections at the time of the study. RESULTS: The mean duration of HIV infection was 8.6 +/- 2.9 years. The mean CD4+ lymphocyte count was 366 +/- 264 x 10(6)/l. The mean plasma viraemia was 4.3 +/- 0.9 logs. In a linear regression model, the CD4+ lymphocyte count was explained in 21.7% of cases by the duration of HIV infection, meanwhile the viral load justified up to 36.2 of CD4+ cell variability. When both parameters were combined, up to 58.4% of CD4+ lymphocyte values were explained. In this model, changes of 1 log in viral load had a 4-fold higher effect on the CD4+ cell count than each year of HIV infection. CONCLUSIONS: The duration of HIV infection and, particularly the viral load strongly influences the current CD4+ lymphocyte count, although other variables should exist (virus with syncytium-inducing phenotype, age of the patient and his immunegenetic repertoire) influencing the different decline seen in CD4+ T-cells.     

A pilot study of hydroxyurea among patients with advanced human immunodeficiency virus (HIV) disease receiving chronic didanosine therapy: Canadian HIV trials network protocol 080

To assess the in vivo short-term antiretroviral effect of hydroxyurea in human immunodeficiency virus (HIV)-infected persons chronically treated with didanosine (ddI), 26 patients with CD4 cell counts between 100 and 350 were enrolled in a 12-week, open-label pilot study and randomly assigned to receive 500 or 1000 mg/day hydroxyurea. Clinical status, laboratory toxicities, CD4 lymphocyte count, and HIV RNA plasma virus load were assessed weekly. Median declines from baseline of 0.02 and 0.63 log10 HIV-1 RNA copies/mL of plasma were observed for the 500- and 1000-mg/day groups, respectively (P = .02). CD4 cell counts did not change significantly with the addition of hydroxyurea; however, a small but statistically significant decrease in counts was observed during the washout phase. Both doses of hydroxyurea were well-tolerated. These results demonstrate a substantial decrease in plasma virus load when 1000 mg of hydroxyurea is administered over 1 month as adjunctive therapy to ddI among HIV-infected persons with 100-350 CD4 cells/mm3.     

Gynaecological conditions associated with HIV infection in women who are partners of HIV-positive Thai blood donors

Women who were partners of HIV-positive blood donors were enrolled in a study of heterosexual HIV transmission between March 1992 and December 1996 and were interviewed and examined. Gynaecological conditions, including cervical dysplasia, human papillomavirus (HPV) infection, gonorrhoea, chlamydial infection, trichomoniasis, bacterial vaginosis, vaginal candidiasis and syphilis were assessed in addition to HIV status and CD4 level. Of 481 women enrolled, 224 (46.6%) were HIV seropositive. HIV-infected women were more likely to have abnormal vaginal discharge on physical examination (OR=2.6, P <0.01), HPV infection with a high-risk type (OR=6.9, P <0.01), and cervical dysplasia (OR=5.3, P <0.01). The prevalence of other gynaecological conditions detected at the enrolment visit did not differ by HIV status. History of prior STD (OR=2.0, P <0.01) was more common among HIV-infected women. The median CD4 count was 400 cells/microl among HIV-infected women. The prevalence of abnormal vaginal discharge and bacterial vaginosis increased significantly with decreasing CD4 count. The prevalence of ectopy, vaginal candidiasis, and cervical dysplasia increased with decreasing CD4 count, but these trends were not significant. We conclude that HIV-infected Thai women appear to have increased prevalences of abnormal vaginal discharge, squamous intraepithelial lesions and self-reported history of STD.     

Bacillary angiomatosis and bacillary peliosis in patients infected with human immunodeficiency virus: clinical characteristics in a case-control study

Clinical characteristics associated with bacillary angiomatosis and bacillary peliosis (BAP) in patients with human immunodeficiency virus (HIV) infection were evaluated in a case-control study; 42 case-patients and 84 controls were matched by clinical care institution. Case-patients presented with fever (temperature, > 37.8 degrees C; 93%), a median CD4 lymphocyte count of 21/mm3, cutaneous or subcutaneous vascular lesions (55%), lymphadenopathy (21%), and/or abdominal symptoms (24%). Many case-patients experienced long delays between medical evaluation and diagnosis of BAP (median, 4 weeks; range, 1 day to 24 months). Case-patients were more likely than controls to have fever, lymphadenopathy, hepatomegaly, splenomegaly, a low CD4 lymphocyte count, anemia, or an elevated serum level of alkaline phosphatase (AP) (P < .001). In multivariate analysis, a CD4 lymphocyte count of < 200/mm3 (matched odds ratio [OR], 9.9; P < .09), anemia reflected by a hematocrit value of < 0.36 (OR, 19.7; P < .04), and an elevated AP level of > or = 2.6 mukat/L (OR, 23.9; P < .05) remained associated with disease after therapy with zidovudine was controlled for. BAP should be considered an AIDS-defining opportunistic infection and should be included in the differential diagnosis for febrile, HIV-infected patients with cutaneous or osteolytic lesions, lymphadenopathy, abdominal symptoms, anemia, or an elevated serum level of AP.     

Estimation of the temporal probability of human immunodeficiency virus (HIV) dementia after risk stratification for HIV-infected persons

We developed a scheme using routinely available data to estimate the risk of human immunodeficiency virus (HIV) dementia in HIV-infected persons over time. We performed a longitudinal review of medical records from more than 100 medical facilities in 11 U.S. cities. A total of 19,462 HIV-infected persons without history of dementia enrolled in a multi-institution survey. The main outcome measure was the development of HIV dementia (1987 case definition) during the median follow-up period of 17 months (range, 1 to 72 months). Of 19,462 HIV-infected persons, HIV dementia developed in 880 persons (4.5%; 2.6% per person-year). The strongest predictors of HIV dementia were CD4+ T-lymphocyte count, anemia, and AIDS-defining infections or cancer. The 2-year probability of HIV dementia was highest for persons who had a CD4+ T-lymphocyte count of fewer than 100 cells/microL and an AIDS-defining illness or anemia or both (18.6 to 24.9%). Intermediate risk was observed in persons with CD4+ T-lymphocyte count of 100 to 199 cells/microL and an AIDS-defining illness or anemia or both or in persons with a CD4+ T-lymphocyte count of fewer than 100 cells/microL but without another risk factor (2-year probability, 10.4 to 15.2%). The 2-year probability that HIV dementia would develop was lowest (1.0%) for persons with CD4+ T-lymphocyte count of more than 200 cells/microL and no other risk factors. Risk stratification using routine clinical information provides information that may prove useful in patient care decisions.     

Changes in CD4+ cell count and the risk of opportunistic infection or death after highly active antiretroviral treatment. Groupe d'Epidémiologie Clinique du SIDA en Aquitaine

OBJECTIVE: To study the relationship between the CD4+ cell response after initiation of protease inhibitors and the occurrence of opportunistic infections and survival. DESIGN: Prospective observational cohort study. METHODS: HIV-1-seropositive subjects followed-up in HIV centres of Bordeaux University Hospital, Southwest France who were prescribed at least one available protease inhibitor between January and December 1996 were included in this analysis. A Cox model estimated the independent effect of baseline covariates and CD4+ cell response, considered as a time-dependent covariate, on the occurrence of new AIDS-defining opportunistic infection, new AIDS-defining events, new AIDS-defining opportunistic infection or death. RESULTS: A total of 556 HIV-positive patients were prescribed at least one protease inhibitor: 34% saquinavir, 52% indinavir, and 14% ritonavir. Median CD4+ cell count at baseline was 95 x 10(6)/l and mean plasma HIV RNA was 5.0 log10 copies/ml. After a median follow-up of 230 days, 65 patients experienced a new episode of opportunistic infection, 79 patients experienced at least one AIDS-defining event, and 24 had died. On average, the increase in CD4+ cell count was 42 x 10(6)/l (SD, 74) after a median of 49 days. In the multivariate analysis of opportunistic infection or death, each 50% higher CD4+ cell count at baseline was associated with a 23% reduction [95% confidence interval (CI), 14-30] of risk. Each 50% increase in CD4+ cell count during follow-up was associated with a 9% reduction (95% CI, 2-15) of risk, adjusted for the presence of AIDS prior to protease inhibitor therapy (hazard ratio, 3.76 versus absence of AIDS; P < 0.01) and haemoglobin level (hazard ratio, 0.48 if > 11 g/dl versus <11 g/dl; P < 0.01). CONCLUSION: Our results show, at least indirectly, how protease inhibitors might produce clinical stabilization. This result may be due to improved functionality of CD4+ cells in patients started on protease inhibitors.     

Cytomegalovirus (CMV) viremia and the CD4+ lymphocyte count as predictors of CMV disease in patients infected with human immunodeficiency virus

We screened 192 patients infected with human immunodeficiency virus (HIV) to examine the relation between CD4+ lymphocyte counts and cytomegalovirus (CMV) viremia and the occurrence of CMV disease and subsequent duration of survival. When we stratified the viremic patients by CD4+ lymphocyte counts, the proportions were as follows: <50/mm3, 20 (25%) of 80 patients; 50-100/mm3, 2 (5.5%) of 36; 101-150/mm3, none of 14; and >150/mm3, 1 (1.5%) of 62. After a mean follow-up period of 8.5 months, 21 (11%) of 192 patients developed CMV disease. The probability of developing CMV disease at 6 months was 13% when the CD4+ lymphocyte count was <50/mm3, 3% when the CD4+ lymphocyte count was 50-100/mm3, and 0 when the CD4+ lymphocyte count was >100/mm3; this probability was 46% for viremic patients and 1% for nonviremic patients. In a multivariate analysis, CMV viremia was independently prognostic of CMV disease (relative risk, 22.03; 95% confidence interval, 6.49-78.97; P < .001), whereas a CD4+ lymphocyte count of <50/mm3 was not (P = .26). These results support the value of CMV viremia for predicting which HIV-infected patients are at risk of developing CMV disease and should therefore receive primary prophylaxis.     

Virological treatment failure of protease inhibitor therapy in an unselected cohort of HIV-infected patients

OBJECTIVE: To determine the rate of virological treatment failure with protease inhibitor therapy in unselected patients and to assess underlying risk factors. DESIGN AND SETTING: Retrospective study in two German tertiary care treatment centres. PATIENTS: A total of 198 HIV-infected patients treated with protease inhibitors in 1996. MAIN OUTCOME MEASURES: Levels of HIV RNA 1-6 months after start of treatment; definition of treatment failure of < 1 log10 reduction in plasma HIV RNA within 6 months after starting protease inhibitor therapy; multivariate analysis of risk factors for treatment failures. RESULTS: A total of 226 treatment episodes with protease inhibitors were evaluable (saquinavir, 83; ritonavir, 47; indinavir, 96). The rate of virological treatment failure was 44% (saquinavir, 64%; ritonavir, 38%; indinavir, 30%). In a multivariate analysis, the following independent risk factors for virological failure were found: CD4 cell count, pretreatment with antiretroviral drugs (number), and protease inhibitor (compound). The relative risk reduction for each CD4 cell count increase was 0.997 (P = 0.012), 2.64 for pretreatment with one or two drugs versus no drug (P = 0.05), 2.97 for pretreatment with more than two drugs versus no drug (P = 0.05), and 4.62 for treatment with saquinavir versus indinavir (P = 0.001). CONCLUSION: An unexpectedly high rate of virological treatment failure of protease inhibitor therapy was found in an unselected cohort of HIV-infected patients. Response to antiretroviral combination therapy in normal clinical practice may considerably differ from results of randomized clinical trials. Further studies are warranted to find optimal treatment strategies for both initial and salvage therapy.     

Pre-AIDS mortality in the Edinburgh City Hospital HIV cohort

In this paper, we look at the incidence and predictive factors of pre-AIDS mortality among HIV-infected individuals, and injecting drug users (IDUs) in particular, and compare IDUs with non-IDUs. 627 patients (73 per cent IDUs) of the Edinburgh City Hospital HIV Cohort were enrolled pre-AIDS and followed up until September 1994. Analyses were performed using cumulative hazard and cumulative incidence estimators for a competing risks model, the Cox proportional hazards model and the non-parametric hazard estimator of Fusaro et al. (1993). The effects of age and CD4 T-lymphocyte cell count, progressively depleted during HIV progression, were investigated. 60 deaths occurred in AIDS-free patients during follow-up; 25 were drug-related deaths in IDUs. Pre-AIDS mortality was higher among IDUs than non-IDUs (p = 0.07). The cumulative incidences of pre-AIDS death after five years from enrollment were 11 per cent in IDUs and 6 per cent in non-IDUs; the cumulative AIDS incidences were, respectively, 19 per cent and 32 per cent. After eight years, cumulative pre-AIDS death incidence was 15 per cent among IDUs; cumulative AIDS incidence among IDUs was 35 per cent. Both groups had similar risks of medically-related (non-AIDS)-MRNA-death. Age and CD4 count were both individually predictive of MRNA death (relative risks (RRs); 2.1 per decade of life, p < 0.01; and 1.9 for each 100 cells per 100 microliters lost, p < 0.0001), although when used together age was less significant (RR 1.6, p = 0.07). Neither was statistically significant for drug-related mortality, although hazard may be lower in older individuals and may increase with falling CD4 count. The drug-related mortality was 1.1 per cent: 2.3 per cent in the first two years after enrollment, and 0.4 per cent thereafter. We conclude that older HIV-infected individuals are at greater risk of medically-related death before AIDS. This risk increases as CD4 count declines. Drug-related hazard may be greater in younger individuals and may increase as CD4 counts fall, but neither effect was formally significant.     

Human immunodeficiency virus replication in AIDS patients with Mycobacterium avium complex bacteremia: a case control study. California Collaborative Treatment Group

The development of opportunistic infections and the administration of vaccines have been associated with transient increases of human immunodeficiency virus (HIV) RNA plasma levels in HIV-infected patients. To determine the relationship between Mycobacterium avium complex (MAC) bacteremia and HIV RNA levels, HIV RNA levels in patients who developed MAC bacteremia (cases) were compared with levels in patients who remained free of MAC disease (controls). Cases and controls were matched for CD4 cell count, prophylaxis against MAC disease, antiretroviral therapy, and duration of follow-up. Mean baseline HIV RNA levels were 4.8 log10 copies/mL in cases and 4.6 log10 copies/mL in controls (P = 0.22). HIV RNA levels increased by a median of 0.4 log in cases but not controls at the time of MAC bacteremia (P = 0.01). In AIDS patients, the onset of MAC bacteremia is associated with a modest but significant increase in serum HIV RNA levels. Increased HIV replication may contribute to the higher mortality associated with MAC bacteremia.     

Using action research to facilitate organisational change in mental health service delivery

OBJECTIVE: To evaluate human immunodeficiency virus (HIV)-1 RNA burden in paired plasma and cervicovaginal lavage specimens and to assess the relation of plasma HIV-1 RNA level, CD4 cell count, and antiretroviral therapy with cervicovaginal HIV-1 viral load. METHODS: Paired blood and cervicovaginal lavage specimens were collected from 72 HIV-infected women. Quantitation of HIV-1 RNA from plasma and cervicovaginal lavage specimens was performed by using the nucleic acid sequence-based amplification assay. Analyses examined relations between cervicovaginal HIV-1 RNA and plasma HIV-1 RNA level, CD4 count, and antiretroviral therapy. RESULTS: Plasma HIV-1 RNA was detectable in 61 of 72 women (85%), with copy numbers ranging from 330 to 1,600,000 copies/mL. Twenty-eight of 72 (39%) had detectable HIV-1 RNA in cervicovaginal lavage specimens, ranging from 320 to 440,000 copies/mL. The cervicovaginal lavage HIV-1 RNA level was detectable in 9%, 29%, 52%, and 53% of the women with plasma HIV-1 RNA of less than 400, 400-9999, 10,000-100,000, and more than 100,000 copies, respectively (P = .043). Among women with CD4 counts of less than 200, 200-500, and greater than 500/mm3, cervicovaginal lavage HIV-1 RNA was detected in 67%, 32%, and 25% of subjects, respectively (P = .018). Among women receiving antiretroviral therapy, cervicovaginal lavage revealed HIV-1 RNA in 67%, 31%, and 25% with CD4 cell counts of less than 200, 200-500, and more than 500/mm3, respectively (P = .042). CONCLUSION: The presence of HIV-1 RNA in cervicovaginal lavage correlates significantly with the level of HIV-1 RNA in plasma and negatively with CD4 cell count.     

The effect of triclabendazole (Fasinex) in children with fasciolosis

In this study, baseline plasma from 619 persons with acquired immunodeficiency syndrome (AIDS) (median CD4+ lymphocyte count -21/microl) who participated in a trial to determine the efficacy of oral ganciclovir for cytomegalovirus (CMV) disease prevention were evaluated for CMV DNA load by qualitative and quantitative polymerase chain reaction (PCR), and correlated with the development of CMV disease and survival. For participants without detectable plasma CMV DNA, the 12-mo Kaplan-Meier CMV disease event rate was 14% and 1% for the placebo and ganciclovir groups, respectively (P < 0.001). For PCR positive participants, CMV disease developed in 43% of placebo and 26% ganciclovir recipients (P < 0.017). Among placebo recipients, CMV PCR positivity was associated with a 3.4-fold increased risk of developing CMV disease (P < 0.001) whereas CD4+ lymphocyte count was not a useful predictor (P = 0.47). A positive plasma CMV DNA PCR was also associated with a 2.5-fold increased risk of death. Each log10 increase in baseline CMV DNA load was associated with a 3.1-fold increase in CMV disease (P < 0.001) and a 2.2-fold increase in mortality (P < 0.001). These data indicate that the risk of developing CMV disease and death in persons with advanced AIDS is directly related to the quantity of CMV DNA in plasma, and is a better predictor than CD4+ lymphocyte count in this population.     

Treatment response and durability of a double protease inhibitor therapy with saquinavir and ritonavir in an observational cohort of HIV-1-infected individuals

OBJECTIVE: To evaluate treatment response, durability and tolerance of a four-drug regimen including saquinavir and ritonavir in combination with either zidovudine/lamivudine or stavudine/lamivudine. DESIGN: Observational cohort of HIV-positive individuals. METHODS: Viral load, CD4+ and CD8+ T lymphocyte counts were assessed at intervals of 1-3 months in subjects commencing therapy between July 1996 and November 1996. Adverse events were evaluated as well as risk factors for therapeutic failures. RESULTS: A group of 56 male patients were included and followed for 48 weeks. Of these, 66% had already taken a protease inhibitor. Viral load dropped by a median 1.98 log10 HIV RNA copies/ml from baseline (interquartile range: 1.49-2.46) and became undetectable (< 400 copies/ml) in 68% of patients. Response varied: 9% were non-responders (HIV RNA reduction < 0.5 log10 copies/ml) and 23% were incomplete responders (nadir of HIV RNA > 400 copies/ml). After 48 weeks, viral load remained undetectable in 49%. Median CD4+ T lymphocyte count increased from 191 x 10(6) to 418 x 10(6) cells/l (range, 241-537 x 10(6) cells/l). Although protease inhibitor and nucleoside pretreatment selected for drug-resistant viral mutants, only the protease inhibitor experience was identified as a risk factor for therapeutic failure. Adverse events occurred in 73% of patients and led to a change of therapy in 9%. CONCLUSION: Despite advanced HIV disease and pretreatment with multiple antiretroviral drugs, a strong initial treatment response to this drug regimen was observed. However, virological failure occurred in 51% of patients after 48 weeks and frequent adverse events complicated therapy.     

Seroconversion for human herpesvirus 8 during HIV infection is highly predictive of Kaposi's sarcoma

BACKGROUND: The finding of antibodies against human herpesvirus 8 (HHV-8) is associated with the occurrence of Kaposi's sarcoma in persons infected with HIV. However, the predictive value of HHV-8 antibodies for Kaposi's sarcoma in HIV infection is unknown. METHODS: The Amsterdam Cohort Studies on HIV infection and AIDS started in 1984 for homosexual men and in 1985 for injecting drug users. Serum samples from 1459 homosexual men and 1167 drug users were tested for antibodies to recombinant HHV-8 lytic-phase capsid (ORF65) antigen and latent-phase nuclear (ORF73) antigen. Individuals were retrospectively identified as HHV-8-positive or HHV-8-negative at enrolment or HHV-8 seroconverter during the study. Kaposi's sarcoma-free survival time was compared between HIV-infected men who were positive for HHV-8 at enrolment and those who later seroconverted for HHV-8. Hazard ratios were estimated for Kaposi's sarcoma, lymphoma, and opportunistic infection according to the HHV-8 serostatus. RESULTS: The incidence of HHV-8 seroconversion among drugs users was 0.7 per 100 person-years based on 31 seroconversions, whereas an incidence of 3.6 was found among homosexual men based on 215 seroconversions. The hazard ratio for Kaposi's sarcoma was 3.15 (95% CI: 1.89-5.25) in HIV-infected individuals if HHV-8 antibodies were present either at enrolment or at HIV seroconversion. In HIV-infected persons who later seroconverted to HHV-8, Kaposi's sarcoma developed more rapidly: hazard ratio of 5.04 (95% CI: 2.94-8.64), an additional risk of 1.60 (95% CI: 1.01-2.53; P = 0.04). Time-dependent adjustment for CD4+ cell count and HIV RNA had no impact on the additional risk, although the CD4+ cell count was an independent risk factor for Kaposi's sarcoma. HHV-8 infection did not increase the risk of AIDS-related lymphoma or opportunistic infections. CONCLUSIONS: The incidence of HHV-8 infection is higher in homosexual men than in drug users. The presence of HHV-8 antibodies in HIV-infected persons increases the risk of Kaposi's sarcoma. Among HIV-infected persons, those who subsequently seroconvert for HHV-8 are at highest risk. These results strongly confirm the causal role of HHV-8 in Kaposi's sarcoma and emphasize the clinical relevance of HHV-8 seroconversion before and after the HIV infection.     

Correspondence and personal contact between donor families and organ recipients: one OPO''s procedure and experience

OBJECTIVE: To determine the frequency of disseminated Mycobacterium avium-complex infections (MAC) and the impact of MAC disease on overall survival in patients with HIV disease and AIDS. METHODS: Prospective study of HIV infected patients with a CD4 lymphocyte count < 150/microliter or patients with AIDS over a 7-year period. Blood cultures of all patients presenting symptoms and signs suggestive of disseminated MAC infection were grown. Only patients who deceased at our clinic (n = 427) were included in the final analysis in order to calculate MAC disease-free survival and overall survival after first CD4 lymphocyte count < 100/microliter. RESULTS: 101 out of 427 patients (24%) developed disseminated MAC disease: The median time between first CD4 lymphocyte count < 100/microliter and MAC disease was 441 days (range 16 to 1560). The actuarial risk of MAC disease for the entire patient population was 12%, 28%, and 42% after 1, 2, and 3 years, respectively. When comparing overall survival after first CD4 lymphocyte count < 100/microliter, there was no statistically significant difference between patients who subsequently developed disseminated MAC infection and those who did not. CONCLUSION: MAC disease is a very frequent opportunistic infection in advanced AIDS, mostly in patients with less than 50 CD4 cells/microliter. In contrast to reports from the US, only 24% of our patients developed MAC disease. Survival time between patients with and without MAC infection did not differ.