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A controlled trial of itraconazole as primary prophylaxis for systemic fungal infections in patients with advanced human immunodeficiency virus infection in Thailand.

Cryptococcal meningitis and Penicillium marneffei infection are common serious fungal infections in patients infected with human immunodeficiency virus (HIV) in Southeast Asia. In a prospective, double-blind trial, 63 patients with HIV infection and CD4+ lymphocyte counts of <200 cells/microL were randomized to receive oral itraconazole (200 mg per day), and 66 similar patients received a matched placebo. Both groups were monitored for evidence of invasive fungal infections. Baseline characteristics and the CD4+ cell counts of the 2 groups were similar. In the intent-to-treat analysis, a systemic fungal infection developed in 1 patient (1.6%) assigned to receive itraconazole (P. marneffei) and in 11 patients (16.7%) given placebo (7 patients had cryptococcal meningitis, and 4 patients had P. marneffei infection; P=.003, by the log-rank test). The incidence of recurrent or refractory mucosal candidiasis was significantly reduced in the itraconazole group. The 2 groups did not differ with regard to adverse effects. Primary prophylaxis with oral itraconazole is well tolerated and prevents cryptococcosis and penicilliosis marneffei in patients with advanced HIV infection, especially those with CD4+ lymphocyte counts of <100 cells/microL. However, prophylaxis with itraconazole was not found to be associated with a survival advantage when it was given to patients with advanced HIV disease.

Administration, Oral↗

Anti-A60 immunoglobulin G in the serodiagnosis of tuberculosis in HIV-seropositive and seronegative patients.

OBJECTIVE: A60 is a high molecular weight mycobacterial antigen complex. The detection of immunoglobulin (Ig) G antibodies to A60 has been advocated as a reasonably sensitive and specific test for active tuberculosis (TB). We aimed to compare the sensitivity of this test among HIV-seropositive and HIV-seronegative patients with pulmonary TB. METHODS: The presence and concentration of anti-A60 IgG antibodies was assessed by enzyme-linked immunosorbent assay in 208 HIV-seropositive and 91 HIV-seronegative Zaïrian patients with smear-positive pulmonary TB. The relationship between anti-A60 IgG levels and HIV serostatus, CD4+ lymphocyte counts, presence of clinical AIDS, and tuberculin skin test results was verified. RESULTS: Only 36.5% of the HIV-seropositive, compared with 69.2% of the HIV-seronegative patients had a positive anti-A60 IgG test (P < 0.00001). Among HIV-seropositive patients, anti-A60 IgG levels did not differ according to CD4+ lymphocyte counts, presence of clinical AIDS, or tuberculin skin test results. CONCLUSIONS: Among patients with pulmonary TB, the sensitivity of testing for anti-A60 IgG was much lower among HIV-seropositive than among HIV-seronegative patients, even from the early stages of HIV-related immunodeficiency. This limits the utility of anti-A60 IgG-antibody testing in the diagnosis of TB among HIV-infected patients.

AIDS-Related Opportunistic Infections↗

Peptide T in the treatment of painful distal neuropathy associated with AIDS: results of a placebo-controlled trial. The Peptide T Neuropathy Study Group.

OBJECTIVE: To assess the safety and efficacy of Peptide T in the treatment of painful distal symmetrical polyneuropathy (DSP) associated with human immunodeficiency virus (HIV) infection. BACKGROUND: Painful DSP is a frequent complication of HIV infection, although its etiology and optimal treatment are unknown. Peptide T (D-(alpha 1)-Peptide T-amide) has been found in phase I trials and anecdotal reports to relieve neuropathic pain in AIDS patients. DESIGN/METHODS: In this multicentered, double-blind, randomized study, subjects received intranasal Peptide T 6 mg/day or placebo for 12 weeks. The primary outcome measure was change in the modified Gracely pain score. Secondary efficacy variables were results of neurologic examination, neuropsychological and electrophysiologic studies, global evaluation, and CD4 lymphocyte counts. RESULTS: Of 81 evaluable subjects, 40 received Peptide T and 41 received placebo. The change in pain scores was not significantly different (p = 0.32) in the Peptide T group (-0.24) as compared to placebo (-0.39). Group comparisons were not significantly different for change in any clinical examination or neuropsychologic measure, sural nerve amplitude or conduction velocity, or CD4 lymphocyte count. No significant drug-related adverse effects occurred in either group. CONCLUSION: Intranasal Peptide T is safe but ineffective in the treatment of painful DSP associated with AIDS.

Acquired Immunodeficiency Syndrome↗

Pregnancy, immunosuppression and reactivation of latent toxoplasmosis.

Toxoplasmosis is a chronic, latent infection which can be reactivated in the presence of immunosuppression. The critical question in obstetrics is whether toxoplasmosis may be reactivated in the presence of the physiological "immunosuppression" of pregnancy. Standard in vitro tests, done in 24 healthy pregnant women and compared with the literature, show no significant changes in humoral and cellular immunity during pregnancy. However, the fact that some infections occur more frequently and more severely than in non-pregnant women (e.g. those due to cytomegalovirus (CMV) and human papilloma virus (HPV) points to a degree of pregnancy-associated immunosuppression. Non-rejection of the semiallogenic fetus is achieved in presence of maternal immunocompetence and is explained mainly by local changes in immune function, mediated by inhibitors of decidual, placental and fetal origin, and by the absence of class II histocompatibility antigens at the fetomaternal interface. Immune status allowing reactivation of toxoplasmosis was studied in a selected group of (predominantly male) AIDS patients from the Swiss HIV Cohort study. Shortly before (cerebral) reactivation of toxoplasmosis, 92% of these patients had very low CD4 lymphocyte counts (mean 50 cells/microliters, i.e. lower than ever recorded in a normal uncomplicated pregnancy). In a larger population of 48 women receiving immunosuppressive therapy after organ transplantation, not a single case of cerebral toxoplasmosis was observed during pregnancy, while in the 105 HIV-positive women in the Swiss HIV and Pregnancy study, there was only one case of cerebral toxoplasmosis during pregnancy and the puerperium (20 CD4/microliters), even though some 17% of those sampled (18/105) had CD4 levels below 200 cells/microliters on at least one occasion during pregnancy. These findings explain why latent toxoplasmosis is not reactivated in normal pregnancy, and why it is only likely in an immunosuppressed mother when her CD4 lymphocyte count is very low (< 200 cells/microliters). In such cases, a prophylactic treatment to prevent maternal reactivation and vertical transmission of toxoplasmosis may be useful.

AIDS-Related Opportunistic Infections↗

[The prevention of Pneumocystis carinii pneumonia by pentamidine inhalation].

167 HIV-positive patients (155 men, 12 women; mean age 31 [18-61] years) with CD4 lymphocyte counts below 250/microliter every 4 weeks received 300 mg pentamidine per aerosol inhalation during out-patient visits, as prophylaxis against Pneumocystis carinii. 89 patients were clinically in the AIDS stage and 33 in the AIDS-related complex (ARC) stage. 29 patients had a lymphadenopathy syndrome, while 16 were asymptomatic. 130 patients received primary prophylaxis, while 37 who had previously had an attack of Pneumocystis carinii pneumonia were given pentamidine as secondary prophylaxis. During a mean observation period of 8 months three patients developed Pneumocystis carinii pneumonia (1.7%): their CD4 lymphocyte count was under 20/microliters. Pentamidine inhalation reduced the incidence of a first attack of pneumonia to 0.18% per month and recurrence to 0.32% per month. These figures confirm the great effectiveness of primary and secondary prophylaxis with pentamidine inhalation.

AIDS-Related Complex↗

Tine testing in HIV positive patients.

BACKGROUND: The incidence of tuberculosis is increased in HIV positive patients. Purified protein derivative (PPD, tuberculin) testing has not been performed routinely on patients infected with HIV in the UK and its usefulness in diagnosing tuberculosis in these patients is unclear. METHODS: 198 HIV positive patients were Tine tested and a CD4+ lymphocyte count and chest radiograph were performed. Of the 179 male patients 164 were homosexual or bisexual, 11 were injecting drug users (IDUs), and four were both homosexual and IDUs. Of 19 women 14 were heterosexual and five were IDUs. Patients assessed their own skin reactions at 72 hours, recording the grade on a card which was returned by post. Patients with a grade 0 reaction were requested to have a second test one month later. RESULTS: Details were available on 168 of the 198 patients. Grade 0 reactions occurred in 89 of the 168 patients, requiring a second Tine test, and 73 completed Tine 2 results were received. Of 57 patients with CD4+ lymphocyte counts below 200/mm3, low grade PPD reactivity was seen in 18 on Tine 1 and nine on Tine 2. No history of BCG immunisation of tuberculosis was found in 33 Tine positive patients. Two patients treated for tuberculosis in the previous six months were PPD positive with CD4+ counts of 60/mm3 and 4/mm3 respectively. CONCLUSIONS: PPD reactivity may be maintained despite a CD4+ count of 100/mm3 or less when there is a history of tuberculosis or BCG immunisation.

AIDS-Related Opportunistic Infections↗

High levels of circulating RNA in patients with symptomatic HIV-1 infection.

OBJECTIVE: To evaluate the concentration of circulating RNA (viraemia) in patients with symptomatic primary HIV infection and relate it to sero-immunological parameters. METHODS: Semiquantitation of circulating HIV RNA and proviral HIV DNA was performed using the polymerase chain reaction. Circulating HIV RNA concentrations were expressed as virus equivalent (RNA copies/2) per ml serum. RESULTS: The mean CD4+ lymphocyte count for 19 patients with symptomatic primary HIV infection was 583 x 10(6)/l. Fifteen (79%) patients had detectable levels of p24 antigen (median 462 pg/ml). Circulating HIV RNA (median 2.3 x 10(7) virus equivalent/ml serum) and proviral HIV DNA (median 3630 copies/ml blood) were detected in all samples tested. Follow-up data for five patients (200-1600 days) showed a 1-3 log reduction in circulating RNA within 2 months. Later, circulating RNA concentrations were consistently greater than 10(3) virus equivalent/ml serum. Within 10 days no p24 antigen was detectable. Levels of CD4+ cells varied markedly from patient to patient during the follow-up and, in this small group, no evident correlation was observed between circulating RNA levels and CD4+ lymphocyte counts. CONCLUSIONS: High concentrations of circulating RNA (viraemia) were present in 19 patients with symptomatic primary HIV infection. Although a decrease in viraemia was observed during the following 2 months, viraemia persisted in all patients with long-term follow-up. This suggests that active viral replication is a continuous process in HIV-infected patients.

Adult↗

Clofazimine as prophylaxis for disseminated Mycobacterium avium complex infection in AIDS.

A randomized, prospective, open-label, treatment versus no treatment community-based clinical trial was conducted to evaluate the safety and efficacy of clofazimine as prophylaxis for disseminated Mycobacterium avium complex (MAC) infection in patients with human immunodeficiency virus (HIV) disease. Subjects were 110 patients with a first episode of Pneumocystis carinii pneumonia 2-4 months before enrollment or CD4 lymphocyte counts < or = 100/mm3; they were randomized to receive 50 mg of clofazimine daily or no treatment. Seven patients randomized to clofazimine developed disseminated MAC infection, compared with 6 patients receiving no treatment. Seventeen patients died: 9 in the treatment group and 8 receiving no treatment. Clofazimine at a dose of 50 mg/day is well tolerated by patients with HIV disease. Reduction in CD4 lymphocyte count to < 50/mm3 is a significant predictor of the development of disseminated MAC infection.

Acquired Immunodeficiency Syndrome↗

Coccidioidomycosis during human immunodeficiency virus infection: results of a prospective study in a coccidioidal endemic area.

PURPOSE: To determine the incidence of active coccidioidomycosis among subjects infected with the human immunodeficiency virus (HIV) living in an area endemic for coccidioidomycosis and to identify factors associated with the development of active coccidioidomycosis in these patients. PATIENTS AND METHODS: This was a prospective cohort analysis of HIV-infected subjects living in an area endemic for coccidioidomycosis in Arizona. On entry and at approximately 4-month intervals, subjects were interviewed and examined, and had spherulin skin testing and CD4 lymphocyte counts performed along with other tests. During each interval, it was determined whether the subject had developed active coccidioidomycosis according to established criteria. RESULTS: One hundred seventy subjects entered the study. Median follow-up was 11.3 months (range: 0 to 44 months). Thirteen subjects developed active coccidioidomycosis, with an estimated cumulative incidence of 24.6% by 41 months (95% confidence limits 8.2% and 41.1%). Risk factors associated with the development of active coccidioidomycosis in the cohort were a CD4 lymphocyte count of less than 0.250 x 10(9)/L and a diagnosis of acquired immunodeficiency syndrome. Factors associated with prior coccidioidal infection, including a positive spherulin skin test, length of residence in the endemic area for more than 25 months, and a prior history of coccidioidomycosis, were not associated with the development of active infection. CONCLUSION: Active coccidioidomycosis among individuals infected with HIV is common in the coccidioidal endemic area. Immunodeficiency appears to be the major risk factor for the development of disease. Evidence of prior coccidioidomycosis, including a positive spherulin skin test, does not appear to predict the development of active infection.

Acquired Immunodeficiency Syndrome↗

Soluble receptors for tumour necrosis factor: a putative marker of disease progression in HIV infection.

OBJECTIVE: To assess the value of concentrations of soluble receptors for tumour necrosis factor (sTNFR) as markers for disease progression in HIV infection. DESIGN: We measured concentrations of sTNFR in the serum of 32 HIV-infected male patients in various stages of disease and in 12 healthy male control subjects. Correlations between the levels of sTNFR and CD4+ lymphocyte counts were calculated. RESULTS: Serum levels of sTNFR p55 and p75 were elevated in parallel with severity of clinical stage. sTNFR p55 levels were higher at later stages of HIV infection (Centers for Disease Control stage IV) with or without concurrent illness, whereas sTNFR p75 was already elevated in asymptomatic carriers, compared with controls. There was an inverse correlation between sTNFR concentrations and CD4+ lymphocyte counts. CONCLUSIONS: Our results suggest that sTNFR concentrations could be potential markers for disease progression in HIV infection.

Acquired Immunodeficiency Syndrome↗

Anti-F(ab')2 antibody in HIV type 1 infection: relationship to hypergammaglobulinemia and to antibody specific to the V3 loop region of glycoprotein 120.

As HIV infection and autoimmune disease share certain similarities, it has been suggested that HIV may disrupt control of humoral immunity by the antiidiotype network, and that this may be evident as increased IgG antibody to F(ab')2. When anti-F(ab')2 was quantified by ELISA in sera of randomly chosen HIV-infected versus uninfected donors, some HIV-infected sera did contain increased anti-F(ab')2, resulting in a median amount twofold higher than in uninfected sera. Moreover, when data were grouped by blood CD4 lymphocyte count, anti-F(ab')2 in HIV+ groups appeared to rise as CD4 lymphocytes declined. However, increased anti-F(ab')2 mirrored the elevation in serum IgG closely, and normalization of anti-F(ab')2 to serum IgG concentration equalized the groups so that no relationship to CD4 lymphocytes remained. Hypergammaglobulinemia is therefore strongly implicated as a cause of variation in anti-F(ab')2. After dissociation of immune complexes, anti-F(ab')2 activity per microgram of monomeric IgG was slightly increased over normal only in the HIV-infected group with fewest CD4 lymphocytes, without statistical significance. In contrast, the proportion of IgG antibody to the V3-neutralizing determinant in HIV-1 decreased significantly as disease advanced. The same was true for 12 HIV+ individuals studied longitudinally for 500-1300 days. The data suggest that measuring serum anti-F(ab')2 is misleading when immune complexes are present: apparent increases as disease progresses are due to increased IgG and, possibly, to related technical artifacts. During HIV infection, the proportion of antiidiotypic IgG in fact remains unaltered or falls, making this an unlikely cause of suppressed humoral immunity to HIV-1.

Acquired Immunodeficiency Syndrome↗

Limited immune restoration after 3 years' suppression of HIV-1 replication in patients with moderately advanced disease.

OBJECTIVE: To describe the magnitude of immune restoration after long-term control of HIV-1 replication. DESIGN Prospective study of immune restoration in patients starting highly active antiretroviral therapy (HAART). METHODS: Patients with moderately advanced HIV-1 infection (CD4 cells between 100 x 10 and 300 x 10 /l) who enrolled in a trial of HAART and who had suppression of HIV-1 replication during 3 years of therapy were evaluated for phenotypic and functional indices of immune restoration. RESULTS: Almost all immune restoration achieved occurred during the first year. The median CD4 lymphocyte count increased by 159 x 10 cells/l during the first year (P < 0.001); CD4 lymphocyte rises during the second and third years were not significant. Most decreases in activation antigen expression (CD38/HLA-DR) on CD4 and CD8 lymphocytes occurred during the first year, and after 3 years, patient lymphocytes were still abnormally activated. The proportion of CD4 lymphocytes expressing CD28 increased during the first and second years, but even after 3 years, CD28 expression on CD4 cells remained abnormally low. Lymphocyte proliferative responses to normalized during the first 12 weeks of HAART while responses to tetanus increased only after immunization and enhanced responses to HIV-1 p24 antigen were not observed. CONCLUSIONS: Immune restoration was incomplete in patients who started HAART with moderately advanced HIV-1 disease and most changes occurred during the first year. These data suggest that this degree of suppression of HIV-1 replication alone will not suffice to restore immune competence. The clinical significance of incomplete reconstitution of CD4 lymphocyte number, phenotype, and proliferative function in HIV-1 infection remains to be determined.

Adult↗

Zalcitabine compared with zidovudine in patients with advanced HIV-1 infection who received previous zidovudine therapy.

OBJECTIVE: To evaluate the safety and efficacy of zalcitabine (also known as dideoxycytidine [ddC]) in patients with advanced human immunodeficiency virus (HIV) infection. DESIGN: Open-label, randomized study. SETTING: AIDS Clinical Trials Units, university-affiliated medical centers, and private practice groups. PATIENTS: Patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex who had tolerated zidovudine for 48 weeks or more. INTERVENTION: Fifty-nine patients received zidovudine (500 to 1200 mg/d) and 52 patients received zalcitabine (2.25 mg/d). MEASUREMENTS: The primary end points were survival and time to an AIDS-defining event or death. RESULTS: Because significantly more patients withdrew from zidovudine therapy, the median duration of treatment was greater in the zalcitabine group than in the zidovudine group (279.0 days compared with 174.5 days; P = 0.001). The estimated 12-month, event-free probabilities were 53% for the zalcitabine group and 57% for the zidovudine group (relative risk, 1.02; 95% CI, 0.5 to 2.2). The estimated 12-month survival rates were 81% for the zalcitabine group and 75% for the zidovudine group (relative risk, 1.39; CI, 0.5 to 3.8). The rate of decline in CD4 lymphocyte counts was significantly slower in the zalcitabine group than in the zidovudine group (-0.08 cells/day compared with -0.17 cells/day). Patients in the zalcitabine group had gained an average of 0.5 kg at week 20 and 0.4 kg at week 24, whereas patients in the zidovudine group had lost an average of 1.8 kg at week 20 and 2.4 kg at week 24 (P = 0.04 and P = 0.05, respectively). Moderate to severe peripheral neuropathy and ulcerative stomatitis occurred in 10 and 9 patients, respectively, in the zalcitabine group. CONCLUSIONS: The sample size for this study was smaller than planned, and no differences in survival and clinical end points were found. Slower rates of decline in CD4 lymphocyte counts and weight, however, were noted for the zalcitabine group.

Adult↗

HIV infection/acquired immunodeficiency syndrome at Siriraj Hospital, 2002: time for secondary prevention.

The authors retrospectively reviewed the medical records of HIV/AIDS patients who were admitted to the medical service, Siriraj Hospital from January 1, 2002 through December 31, 2002. Demographics, CD4 lymphocyte counts, discharge diagnoses, the incidence of Pneumocystis carinii pneumonia (PCP), cerebral toxoplasmosis and cryptococcosis in patients who received and did not receive appropriate chemoprophylaxis against those opportunistic infections when indicated, and outcome of the patients were collected. Three hundred medical records of 286 HIV/AIDS patients were available for review. One hundred and seventy two patients (60.1%) were male. Mean age of the patients was 36.8 +/- 9.91 years (range 14-74). The mean CD4 lymphocyte count that was determined in 165 patients was 74.7 +/- 134.21 cells/mm3 (range 0-894). Of the 300 admissions, 36 per cent were newly diagnosed HIV infection. Only 23 (7.7%) patients had received antiretroviral drugs at the time of hospitalization. The leading HIV-related diseases were tuberculosis (29.3%), Pneumocystis carinii pneumonia (18.7%), and cryptococcosis (15.7%). The rest of them included cytomegalovirus diseases (6.3%), lymphoma (6.3%), Salmonella bacteremia (6%), cerebral toxoplasmosis (5.7%), cryptosporidiosis (5.3%), disseminated Mycobacterium avium complex infection (1.0%), extrapulmonary histoplasmosis (1.0%), Candida esophagitis (1.0%), progressive multifocal leukoencephalopathy (1.0%), and rhodococcosis (0.7%). Among those for whom HIV infection was established and chemoprophylaxis for PCP, cerebral toxoplasmosis and cryptococcosis were indicated, 9.8 per cent vs 28.2 per cent, 3.6 per cent vs 5.1 per cent, and 10 per cent vs 15.2 per cent of whom received and did not receive the appropriate chemoprophylaxis developed PCP, cerebral toxoplasmosis and cryptococcosis respectively. One hundred and ninety (63.3%) patients were alive at discharge, 84 (28.0%) had died, 21 (7%) were referred to other hospitals, and 5 (1.7%) left hospital against medical advice. The mortality rate in newly diagnosed HIV and in known HIV without antiretroviral treatment were comparable but much lower in known HIV-infected patients who received antiretroviral therapy. Secondary prevention by detection of HIV-infected patients while they are asymptomatic and providing them with appropriate chemoprophylaxis against specific opportunistic infections as well as appropriate antiretroviral treatment would decrease morbidity, mortality, and improve the quality of life of HIV-infected patients in Thailand.

AIDS-Related Opportunistic Infections↗

A trial of integrated buprenorphine/naloxone and HIV clinical care.

BACKGROUND: Untreated opioid dependence adversely affects the care of human immunodeficiency virus (HIV)-positive patients. Buprenorphine, a partial opioid agonist, is available for maintenance treatment of opioid dependence in HIV specialty settings. We investigated the feasibility and efficacy of integrating buprenorphine, along with 2 levels of counseling, into HIV clinical care. METHODS: HIV-positive, opioid-dependent patients were enrolled in a 12-week pilot study and randomized to receive daily buprenorphine/naloxone treatment along with either brief physician management or physician management combined with nurse-administered drug counseling and adherence management. Primary outcomes included treatment retention; illicit drug use, assessed by urine toxicology test and self-report; CD4 lymphocyte counts; and log(10) HIV type 1 (HIV-1) RNA levels. RESULTS: Of the 16 patients who received at least 1 dose of buprenorphine, 13 (81%) completed 12 weeks of treatment. The proportion of opioid-positive weekly urine test results decreased from 100% at baseline to 32% (month 1), 20% (month 2), and 16% (month 3). Only 4 patients reported any opioid use (in the prior 7 days) during the 12-week study. CD4 lymphocyte counts remained stable over the course of the study. The mean log(10) HIV-1 RNA level (+/- standard deviation) declined significantly, from 3.66+/-1.06 log(10) HIV-1 RNA copies/mL at baseline to 3.0+/-0.57 log(10) HIV-1 RNA copies/mL at month 3 (P<.05). No significant differences based on counseling intervention were detected. All 13 patients who completed the study continued to receive treatment in an extension phase of at least 0-15 months' duration. CONCLUSIONS: We conclude that it is feasible to integrate buprenorphine into HIV clinical care for the treatment of opioid dependence. Patients experienced good treatment retention and reductions in their opioid use. HIV biological markers remained stable or improved during buprenorphine/naloxone treatment.

Administration, Sublingual↗

Ureaplasma urealyticum colonization in the vaginal introitus and cervix of human immunodeficiency virus-infected women.

Ureaplasma urealyticum colonization was examined in paired cervical and introital specimens from 56 untreated HIV-seropositive women. Specimens were tested for U. urealyticum by polymerase chain reaction (PCR). Peripheral blood was examined for CD4 lymphocyte counts and HIV RNA concentration. U. urealyticum was detected in the cervix of 38 (69.1%) women. Introital U. urealyticum was present in 16 (28.6%) women, all of whom were cervical-positive. Cervical motion pain was present in 40.0% of women with U. urealyticum in the introitus and cervix, 23.8% of those with only cervical U. urealyticum and 5.9% of women negative for this organism (P=0.03). There was no relation between U. urealyticum colonization and CD4 lymphocyte count. However, 64.3% of women with introital U. urealyticum had circulating HIV RNA levels > 10,000 copies per ml as compared with 28.6% of women with only cervical U. urealyticum and 7.1% of women negative for this organism (P < 0.01).

Cervix Uteri↗

Reduction of viral load and immune complex load on CD4+ lymphocytes as a consequence of highly active antiretroviral treatment (HAART) in HIV-infected hemophilia patients.

BACKGROUND AND OBJECTIVES: Human immunodeficiency virus (HIV)-induced immune complex load on circulating CD4+ blood lymphocytes is associated with dysfunction and depletion of CD4+ lymphocytes and with increased monocyte/macrophage function. It was investigated whether HAART reduces both the viral load in plasma and the number of immune complex-coated CD4+ lymphocytes in the blood, and whether CD4+ counts are associated with viral load and/or immune complex load. MATERIALS AND METHODS: Twelve HIV+ hemophilia patients before and after conversion to HAART (group 1); eight HIV+ hemophilia patients without antiretroviral therapy (group 2). HIV-1 RNA copies in plasma using NASBA/Nuclisens kits; CD4+ lymphocytes coated in-vivo with immune complexes using flowcytometry on whole blood samples; in-vitro responses of immune complex-coated T lymphocytes in cell culture assays. RESULTS: After conversion to HAART there was a significant reduction of viral load, CD4+ gp120+, CD4+ IgM+, and CD4+ IgG+ circulating blood lymphocytes and plasma neopterin, paralleled by a significant increase of CD4+ and CD8+ counts. The percentage of immune complex-coated CD4+ lymphocytes of converted patients was significantly associated with CD4+ counts, in-vitro responses to concanavalin A (Con A), pokeweed mitogen (PWM), phytohaemagglutinin (PHA), anti-CD3 and pooled allogeneic stimulator cells, and with plasma neopterin levels. CONCLUSION: HAART reduces viral load and HIV-induced immune complex load on circulating CD4+ blood lymphocytes. The results of this study can be interpreted to suggest that HAART increases CD4+ lymphocyte counts in part by counteracting HIV-induced autoimmune phenomena.

Anti-HIV Agents↗

[Cardiac involvement within the scope of HIV-1 infection: preliminary results of echocardiography study].

The results of one- and two-dimensional echocardiography in 128 patients (117 males, 11 females; median age 37 years) who were seropositive for HIV-1 were analyzed in addition to clinical, electrocardiographic, and laboratory data. Follow-up controls are available for 51 patients over an observation period of 1 to 24 months, median 9.5 months. Probably HIV-related echocardiographic abnormalities were identified in 36 patients (28%): small to moderate pericardial effusions (n = 34) and left ventricular dilation (n = 5). Pericardial effusions resolved in seven patients during follow-up, in three cases after tuberculostatic chemotherapy. Compared to patients without cardiac involvement patients with HIV-related echocardiographic abnormalities showed lower CD4-lymphocyte counts (143 +/- 138 vs 289 +/- 219/microliters, p less than or equal to 0.01), and left ventricular endsystolic dimensions were increased (34.2 +/- 4.5 vs 32.6 +/- 3.0 mm, p less than or equal to 0.05). Cardiac involvement occurred predominantly in the advanced stages of the HIV-1 infection with unclear etiology in the majority of cases, even though active concomitant diseases could be frequently demonstrated. The clinical course of some patients might be consistent with intercurrently completed perimyocarditis, probably of viral genesis. CD4-lymphocyte counts less than or equal to 100/microliters could be identified as a risk factor for the development of cardiac manifestations. The significance of a demonstrated involvement of the heart with regard to therapeutic consequences and prognosis appeared to be slight. Use of echocardiography as a routine method for the detection of cardiac involvement in HIV-1 infection has proved to be valuable, since indicative clinical symptoms were lacking in almost all cases.

Adult↗