Plasma levels of clonidine following epidural bolus injection in children

PURPOSE: To describe dense vitritis as the primary manifestation of ocular syphilis in three human immunodeficiency virus (HIV)-positive patients and to determine the response of these patients to the established regimen for neurosyphilis. METHODS: Anti-Toxoplasma gondii IgM and IgG antibody titers, tuberculin skin test, chest radiograph, and serum angiotensin-converting enzyme level were obtained because tuberculosis, sarcoidosis, and toxoplasmosis were in the differential diagnosis. Two of the three patients were not known to have HIV infection at the time of initial examination and consented to HIV testing. Treponemal and nontreponemal tests were performed on serum and cerebrospinal fluid to establish a definitive diagnosis. Treatment for neurosyphilis was initiated, and daily ophthalmic examinations were performed, with careful attention to signs commonly associated with syphilitic eye disease. RESULTS: All three patients exhibited improvement in visual acuity and resolution of vitreous haze. There was no evidence of other signs of posterior uveitis. The one patient for whom there has been a 6-month follow-up showed no sequelae of his eye disease. CONCLUSIONS: Human immunodeficiency virus-positive patients with syphilis may present atypically dense vitritis. In these patients, vitritis may be the first manifestation of syphilis. The regimen for neurosyphilis provides effective therapy. Moreover, in some patients, syphilitic vitritis may be the initial manifestation of HIV disease.     

Resolution of serum and cerebrospinal fluid abnormalities after treatment of neurosyphilis. Influence of concomitant human immunodeficiency virus infection

BACKGROUND AND OBJECTIVES: Little is known about resolution of serum and cerebrospinal fluid abnormalities after neurosyphilis treatment, especially in patients infected with human immunodeficiency virus (HIV). GOAL: To examine the time course of resolution of these abnormalities. STUDY DESIGN: Case series of 22 patients with neurosyphilis (13 infected with HIV) with reactive cerebrospinal fluid Venereal Disease Research Laboratory test who underwent at least one lumbar puncture after treatment. RESULTS: Resolution of all serum and cerebrospinal fluid measures was slower in patients infected with HIV. Serum and cerebrospinal fluid abnormalities resolved in most patients not infected with HIV by 30 weeks, and all met Centers for Disease Control and Prevention criteria for cure. One patient infected with HIV failed therapy by Centers for Disease Control and Prevention criteria, and three others had persistent pleocytosis. CONCLUSIONS: HIV-infected patients with neurosyphilis have slower resolution of serum and cerebrospinal fluid abnormalities after therapy. This observation may suggest impaired clearance of Treponema pallidum from the central nervous system.     

Spectrum of immunodeficiency in HIV-1-infected patients with pulmonary tuberculosis in Zaire

Tuberculosis (TB) is the most common opportunistic infection in African patients who die from AIDS, yet the stage of immunodeficiency at which TB develops is uncertain. We studied the immune status of HIV-infected outpatients with pulmonary TB in relation to their clinical presentation in a cross-sectional study of 216 HIV-seropositive and 146 HIV-seronegative ambulatory incident cases of smear-positive and culture-positive pulmonary TB in Kinshasa, Zaire. HIV-seropositive and seronegative patients had median CD4 lymphocyte counts of 316.5/microL and 830.5/microL, respectively. Of the HIV-seropositive patients, 32.9% had less than 200 CD4 lymphocytes/microL, 37% between 200 and 499, and 30.1% 500 or more. Clinical AIDS, as defined by the WHO clinical case-definition or a modified version, was of similar limited use as a predictor of immunodeficiency. Among HIV-seropositive patients, oral candidosis, lymphopenia, a negative tuberculin purified protein derivative test, and cutaneous anergy were strongly associated with CD4 counts of less than 200/microL, and seemed to be better markers of immune dysfunction. We conclude that pulmonary TB develops across a broad spectrum of HIV-induced immunodeficiency and that a diagnosis of pulmonary TB is of limited use as a marker of stage of HIV disease in African HIV-infected outpatients.     

Serum beta-carotene deficiency in HIV-infected children

Representative levels of serum micronutrients specifically, beta-carotene and vitamins A and E, were studied in symptomatic human immunodeficiency virus (HIV)-infected children. The nutritional status of 23 symptomatic African-American and Hispanic HIV-infected children were compared with an appropriate control group comprised of 36 uninfected children matched for age and sex, using body mass index. Serum beta-carotene and vitamin A and E levels were randomly determined on 15 of the infected children. Beta-carotene concentration was 4.9-fold reduced in symptomatic HIV-infected children when compared with the control group. There was a 6.5-fold decrease in the serum level for children without acquired immunodeficiency syndrome (AIDS) and a 13-fold reduction in children with AIDS. No differences in the mean values for serum vitamins A and E were observed in the groups studied. Although the nutritional status of the symptomatic HIV-infected children was not different from that of the control population, their serum beta-carotene levels were profoundly deficient. This finding may have immunologic and clinical implications for children with rapidly progressing HIV disease.     

Comparative brain pathology of HIV-seronegative and HIV-infected drug addicts

Early stages of infection with human immunodeficiency virus (HIV) were studied in HIV-seropositive drug addicts. Since heroin users are immunocompromized even in the absence of HIV infection, the aim of the present study was to compare the morphological alterations present in HIV-seronegative and HIV-seropositive drug addicts. A total of 60 cases (32 HIV-seronegative subjects, 21 HIV-seropositive patients without signs of acquired immunodeficiency syndrome (AIDS), and 7 HIV-seropositive patients with signs of AIDS) were investigated macroscopically, histologically, and immunohistochemically HIV-seronegative patients presented more frequently with acute drug intoxication, died at a significantly younger age than HIV-seropositive patients, and were found to suffer more frequently from alcohol-related changes. These results indicated that HIV-seronegative and HIV-seropositive patients differed possibly in their drug consumption and also in their general conditions of life. In accordance with previous reports activated microglia and a diffuse astrogliosis in the white matter were detected at a significantly higher frequency and found to be more severe in HIV-seropositive subjects than in HIV-seronegative addicts. A lymphocytic meningitis was present in 6 of 21 HIV-seropositive patients but in none of the HIV-seronegative patients. Perivascular infiltrates consisting of lymphocytes and macrophages were detected at similar frequencies in HIV-seronegative and HIV-seropositive patients but were significantly more severe in patients suffering from lymphocytic meningitis or purulent encephalitis. Opportunistic infections were only demonstrated in 2 AIDS cases. In 10 of the HIV-seronegative patients and in 3 of the HIV-seropositive patients CD68-and Ham56-positive multinucleated cells were detected scattered in the subarachnoidal space exclusively over the frontal cortex.     

General paralysis of the insane and AIDS in old age psychiatry: epidemiology, clinical diagnosis, serology and ethics--the way forward

While the incidence of general paralysis of the insane (GPI) has declined, AIDS (acquired immune deficiency syndrome) has emerged as a new illness. Today, in England and Wales, as many elderly people die from AIDS as from neurosyphilis, although both diagnoses are rare in this age group. Both are serious medical conditions with psychiatric manifestations. For both, serological tests may identify the disease, and treatment may be of benefit, but there is considerable social stigma attached to the diagnoses. Ethical guidelines for serological testing for HIV (human immunodeficiency virus) have been available for over a decade. In view of the similarities between the diseases, it may be unethical to test patients for syphilis routinely. Epidemiology, risk factors, neurological and neuropsychiatric features and ethics must be considered before testing for both syphilis and HIV.     

Longitudinal assessment of growth in children born to mothers with human immunodeficiency virus infection

OBJECTIVES: To describe and to evaluate the longitudinal growth of children born to mothers with human immunodeficiency virus (HIV) infection. DESIGN: Measurements of weight, length (measured in infants in a recumbent position) and height (measured in older children in an upright position), and head circumference were documented and evaluated longitudinally using generalized estimating equations in a group of children born to HIV-infected mothers. Children infected with HIV were compared with uninfected children and with National Center for Health Statistics standards. SETTING: Primary care clinic in an urban hospital devoted to the medical care of children born to HIV-infected mothers. PATIENTS: One hundred nine children born to HIV-infected mothers, 59 HIV-infected and 50 uninfected, between birth and 70 months of age. RESULTS: The mean birth weights of both groups were below the 50th percentile. While the mean weight-for-age curve of uninfected children attained the 50th percentile by age 24 months, the mean birth weight-for-age curve of HIV-infected children remained below the 50th percentile. Weight gain became significantly different between the two groups by age 36 months. The mean birth length-for-age curves of HIV-infected and uninfected children was also below the 50th percentile. The mean height-for-age curve of uninfected children attained the 50th percentile by age 40 months, while that of HIV-infected children remained well below the 50th percentile. Linear growth between HIV-infected and uninfected children diverged earlier than weight, becoming significantly different by age 15 months. CONCLUSIONS: Although children born to HIV-infected mothers are born with weight and length below the 50th percentile, uninfected children catch up, while HIV-infected children remain below the 50th percentile and experience an earlier and more pronounced decrease in linear growth (height-for-age) than in weight-for-age.     

The impact of HIV on Streptococcus pneumoniae bacteraemia in a South African population

OBJECTIVES: To determine the impact of HIV infection on Streptococcus pneumoniae bacteraemia in adults and children by analysing the prevalence and clinical features of such diseases and determining the prevalent serotypes/serogroups and susceptibility patterns of isolates. DESIGN: Patients were identified prospectively from January to October 1996. SETTING: Chris Hani Baragwanath Hospital, Soweto, a tertiary referral hospital treating adults and children, in an urban district near Johannesburg, South Africa. PATIENTS AND METHODS: All patients with S. pneumoniae isolated from blood culture by the Microbiology Department, Chris Hani Baragwanath Hospital were studied. Clinical and microbiological features were recorded. RESULTS: A total of 178 patients with S. pneumoniae were investigated as part of the study; 49 were aged < 13 years. HIV seroinfection was present in 25 (51%) children and 58 (45%) adults. The incidence of S. pneumoniae bacteraemia was 36.9-fold increased in HIV-seropositive children and 8.2-fold increased in HIV-seropositive adults compared with HIV-seronegative individuals. Both adult and paediatric HIV-seropositive patients with S. pneumoniae bacteraemia were significantly younger than HIV-seronegative patients. Pneumonia was a significantly more common presentation in HIV-seropositive children, otherwise the spectrum of disease and outcome were similar in HIV-seronegative and positive groups. Serotype 1 S. pneumoniae isolates were significantly less common in HIV-infected individuals (both adults and children). Resistance to penicillin was increased in S. pneumoniae isolates from HIV-infected patients (significant in adults). Patients with penicillin-resistant isolates did not have a poorer outcome. The potential coverage of serotypes/serogroups included in the proposed nine-valent conjugate pneumococcal vaccine was 88% in HIV-seronegative children and 83% in HIV-seropositive children. The potential coverage of the currently available 23-valent pneumococcal vaccine for adults was 98.2 and 100)% for HIV-infected and HIV-uninfected adults, respectively. CONCLUSION: The burden of bacteraemia due to S. pneumoniae in HIV-seropositive individuals admitted to our hospital is considerable. Differences in the S. pneumoniae serotypes/serogroups in HIV-infected patients have been demonstrated with resultant differences in antibiotic susceptibility patterns. Excellent potential for vaccine coverage was demonstrated for both HIV-seronegative and HIV-seropositive individuals. Further studies are necessary to test the clinical efficacy of pneumococcal vaccination of HIV-seropositive adults and children as a potential preventative measure against this prevalent disease.     

Results of in vitro contracture tests for the diagnosis of malignant hyperthermia susceptibility in monozygote twins

In this retrospective study, we report 43 cases (41 males and 2 females) of human immunodeficiency virus (HIV) infection in the Singapore population aged 50 years and above at first presentation. We found an increasing proportion of these older individuals among our HIV-seropositive patients; from 4.8% in 1991 to 16.7% by mid-1996. The mean age at presentation was 59.2 years (range 50 to 75 years). They were mainly heterosexuals (93%) and the majority (79.1%) were previously or currently married. Thirty-six (83.7%) patients had multiple sexual exposures to commercial sex workers. Nearly all had acquired the infection through the sexual route. The majority (76.7%) were symptomatic at presentation. Common clinical presentations were weight loss (72%), respiratory symptoms (60%) and oral candidiasis (56%). More than half (58.1%) of the patients had acquired immunodeficiency virus (AIDS) at the time of first presentation with a low median CD4 count of 17 cells/mm3. Pneumocystis carinii pneumonia and tuberculosis were the common AIDS-defining diseases. Survival in patients presenting with AIDS (median survival 3 months) is poorer compared to younger HIV-seropositive patients (< 50 years; median survival 1 year). No increase in age-related infection or malignancy was seen. Common causes of death were pneumonia and septicaemia. Physicians should consider HIV infection in older patients particularly when he/she presents with unexplained weight loss, respiratory symptoms and oral candidiasis. A history of high-risk sexual behaviour must be sought in all patients, including the elderly.     

Human immunodeficiency virus seropositivity in adolescents with syphilis

OBJECTIVE: The purpose of this study was to assess the relationship between syphilis and human immunodeficiency virus (HIV) infection among inner-city, minority group adolescents. METHODS: From August 1989 through June 1990, serum from all positive serologic tests for syphilis, obtained from patients attending a comprehensive adolescent health center in an acquired immunodeficiency syndrome epicenter and its two school-based clinics, were frozen without patient identifiers and were subsequently screened for HIV by enzyme-linked immunosorbent assay with confirmatory Western blot for positives. In addition, a retrospective chart review was performed for all patients with a positive serologic test for syphilis during the study period. RESULTS: Of the 59 specimens with a positive syphilis serologic test, 9 (15.3%) were HIV seropositive. Of the patients with syphilis, 57.4% were black and 42.6% were Hispanic; 16.4% were male (mean age 18.1) and 83.6% were female (mean age 17.8). Only 1 subject (female) was an injection drug user; 4 of the male subjects self-identified as having had sex with other males. Of the subjects, 27.8% had primary, 19.7% had secondary, and 52.5% had latent syphilis at the time of diagnosis. A prior or concurrent sexually transmitted disease was present in 90% of the males and 80% of the females; gonorrhea was the most prevalent sexually transmitted disease in the males (89%) and chlamydia was most prevalent in the females (35%). A history of chancroid and/or herpes was present in 16.4% of the subjects. CONCLUSIONS: It is concluded that the diagnosis of syphilis in an adolescent is a risk factor for HIV infection. All sexually active adolescents should be routinely screened for syphilis, regardless of sexual practices. Those with syphilis should be specifically counseled about their increased risk for HIV infection and the importance of consistent condom use, and they should be referred for formal HIV pretest counseling.     

Gene therapy for primary immunodeficiency

The mechanisms by which monocytes from patients infected with human immunodeficiency virus (HIV) have reduced growth inhibitory activity against Cryptococcus neoformans was examined. Monocyte-enriched peripheral blood mononuclear cells from 12 HIV-seropositive donors with CD4 cell counts of 10-210 cells/mm3 (median, 85) and HIV-seronegative donors were compared in assays to determine the binding and phagocytosis of C. neoformans and the respiratory burst and degranulation in response to C. neoformans and zymosan. Monocytes from HIV-infected and uninfected persons bound and ingested C. neoformans equally well; however, generation of hydrogen peroxide and specific release of beta-glucuronidase in response to C. neoformans was significantly reduced in monocyte-enriched cells from the HIV-infected donors. The impaired anticryptococcal activity of monocytes from persons with HIV may be related to defects in both oxidative and nonoxidative effector pathways that occur after the binding and internalization of the organism.     

HIV infection in non-pregnant women: a review of current knowledge

HIV infection has become an important health problem among American women. The natural history of HIV infection and AIDS appears to be similar for women and men, and preliminary studies demonstrate similar survival and clinical events for both sexes. The natural history and presentation of common gynecologic infections and conditions may be altered by HIV. Most is known about cervical dysplasia. The risk of cervical dysplasia appears to be increased in women with HIV infection, progression of cervical dysplasia may be more rapid, severity of disease increased, particularly for women with HIV-related immunocompromise. Recently, the Centers for Disease Control and Prevention added invasive cervical cancer as an AIDS-defining condition. Vulvovaginal candidiasis, sexually transmitted diseases, including syphilis, herpes, and cytomegalovirus, and pelvic inflammatory disease are also common in HIV-infected women. Preliminary data suggest that these conditions may be more severe and more difficult to treat in HIV-infected women than uninfected women. Women who are HIV-infected should have thorough evaluation and follow up of all gynecologic conditions, particularly as they become immunosuppressed.     

Increased transmission of vertical hepatitis C virus (HCV) infection to human immunodeficiency virus (HIV)-infected infants of HIV- and HCV-coinfected women

The transmission of perinatal hepatitis C virus (HCV) infection was studied retrospectively in 62 infants born to 54 HCV- and human immunodeficiency virus (HIV)-coinfected women enrolled in a prospective natural history study of HIV transmission. Infant HCV infection was assessed by nested RNA polymerase chain reaction. The overall rate of vertical HCV transmission was 16.4% (9/62). Most HCV-infected children did not develop antibodies to HCV. The rate of HCV infection was higher among HIV-infected infants (40%) than among HIV-uninfected infants (7.5%; odds ratio, 8.2; P = .009). This difference in transmission was not related to differences in maternal HCV load, as measured by branched DNA assay, or mode of delivery. Why HIV-infected infants of HCV- and HIV-coinfected women have significantly higher rates of perinatal HCV transmission remains to be elucidated. The rate of HCV transmission in HIV-uninfected infants of HCV- and HIV-coinfected women is similar to that reported for infants born to HIV-seronegative mothers.     

Cost of care for patients with human immunodeficiency virus infection. Patterns of utilization and charges in a public health care system

BACKGROUND: The increasing impact of human immunodeficiency virus (HIV) infection on the health care delivery system requires surveillance of current patterns of HIV-related health care utilization to adequately plan for future needs. Most studies to date have concentrated on inpatient care for patients with the acquired immunodeficiency syndrome (AIDS). Outpatient utilization has been less well studied and there are few data regarding HIV-infected patients without a diagnosis of AIDS. METHODS: Denver Health and Hospitals is a public system delivering comprehensive health care to mostly indigent residents of the city and county of Denver. Patients with HIV infection in this system were identified through multiple surveillance sources, and billing system records for these patients were analyzed. RESULTS: During 1990, 812 patients with HIV infection of 13 years or more were accessed in the Denver Health and Hospitals. During that year, the total HIV-related health care charges were $7,858,690, of which 57% were for inpatient care and 43% for ambulatory care. Patients with AIDS (34% of patients) accounted for 62% of all charges, and patients with HIV infection but without a diagnosis of AIDS (66% of patients) for 38% of charges. Compared with national predictions, patients with AIDS in our system had lower inpatient and higher outpatient utilization. CONCLUSIONS: These results are consistent with a shift from inpatient to outpatient health care services in patients with AIDS. A significant proportion of HIV-related health care costs are incurred by patients who have not yet developed AIDS.     

Endoscopic plantar fascia release: a cross-sectional anatomic study

BACKGROUND AND OBJECTIVES: Neurocognitive impairment is common in human immunodeficiency virus (HIV)-infected subjects. The relationship of sexually transmitted diseases to neurocognitive changes is unknown. GOAL: To establish whether HIV-infected patients with a history of syphilis or gonorrhea have a higher rate of neurocognitive dysfunction. STUDY DESIGN: Neurocognitive function was measured by a battery of quantitative tests in a 453-person HIV-infected cohort and a 219-person HIV-seronegative control group. Neurocognitive function was then correlated with histories of either syphilis or gonorrhea to assess for possible relationships between these sexually transmitted diseases and neurologic impairment. RESULTS: Human immunodeficiency virus-infected subjects with a history of either syphilis or gonorrhea tended to perform worse on neurocognitive testing than their counterparts. This difference could not be explained by educational attainment, age, race or CD4 cell count, and was not noted in the HIV-uninfected control subjects. CONCLUSIONS: Sexually transmitted diseases in HIV-infected subjects are correlated with neurocognitive impairment through an unidentified mechanism.     

High-dose intravenous immunoglobulins in the treatment of adolescent and adult HIV-infected hemophiliacs

In children infected with human immunodeficiency virus (HIV) placebo-controlled trials with intravenous immunoglobulins have resulted in a significant reduction in morbidity; however, the results of small trials in adolescents and adults have been inconsistent. In this study 17 HIV-infected hemophiliacs aged 9-30 years were treated with monthly intravenous immunoglobulins for an average of 32 months. At the end of the study, 8 years after the HIV infection, three patients (18%) had progressed to the acquired immunodeficiency syndrome (AIDS), and the average decrease in CD4 cells was 81 cells/microliter per year. The natural history of HIV infection in hemophiliacs in this age group shows a manifestation rate of AIDS between 11% and 26% 6-8 years after seroconversion and an average yearly decrease in CD4 lymphocytes of 68-110 cells/microliters. In conclusion, we observed no difference either in the manifestation rate of AIDS or in prognostic markers in this small cohort of HIV-infected hemophiliacs treated for more than 30% of their latency period with intravenous immunoglobulins compared to the well-documented natural history of HIV-infected hemophiliacs. However, none of the patients developed severe bacterial infections during the study period.     

Plasma lipoprotein(a) levels in patients with hyperthyroidism

Thyroid function and regulation were studied in 14 consecutive male outpatients with asymptomatic human immunodeficiency virus (HIV) infection (CDC II/III, n = 8) or AIDS (CDC IV, n = 6) who were free of concomitant infections and hepatic dysfunction, and in eight healthy, age- and weight-matched male controls. Blood was sampled every 10 minutes over 24 hours for measurement of thyrotropin (TSH). Thereafter, thyroid hormones and TSH responsiveness to thyrotropin-releasing hormone (TRH) were measured. Triiodothyronine (T3) and thyroxine (T4) did not differ between HIV-infected patients and controls, but HIV patients had lower thyroid hormone-binding index ([THBI] HIV patients, 1.01 +/- 0.02; controls, 1.11 +/- 0.03; P < .02), free thyroxine (FT4) index (94 +/- 3 v 110 +/- 4, P < .01), FT4 (11.8 +/- 0.4 v 14.3 +/- 0.4 pmol/L, P < .01), and reverse triiodothyronine (rT3) values (0.18 +/- 0.01 v 0.26 +/- 0.02 nmol/L, P < .001) and higher thyroxine-binding globulin ([TBG] 20 +/- 1 v 16 +/- 1 mg/L, P < .02) values. Mean 24-hour TSH levels were increased in HIV patients (2.39 +/- 0.33 v 1.44 +/- 0.16 mU/L, P < .05), associated with increased mean TSH pulse amplitude and TSH responsiveness to TRH. No differences were observed between asymptomatic HIV-seropositive and AIDS patients. In conclusion, there is a hypothyroid-like regulation of the pituitary-thyroid axis in stable HIV infection, which differs distinctly from the euthyroid sick syndrome in non-HIV-nonthyroidal illnesses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential responses by psychosocial subgroups of fibromyalgia syndrome patients to an interdisciplinary treatment

SETTING: TB Treatment Centre, Kampala, Uganda. OBJECTIVE: To evaluate the impact of human immunodeficiency virus (HIV) co-infection on the bacteriologic and radiographic presentation of pulmonary tuberculosis (TB) in Uganda, a nation with high rates of Mycobacterium tuberculosis and HIV infection. DESIGN: To compare baseline characteristics among HIV-infected and non-HIV-infected adults with initial newly-diagnosed episodes of culture-confirmed pulmonary TB screened for participation in a randomized prospective TB treatment trial. RESULTS: Negative and paucibacillary (very scanty or scanty) sputum acid fast bacilli (AFB) smears were more frequent in HIV-infected patients presenting with pulmonary TB (P = 0.007). More HIV-infected individuals also had sputum cultures that required 7-8 weeks incubation until positivity than non-HIV-infected patients (P < 0.01). Lower lung field and diffuse pulmonary infiltrates were more frequent among HIV-infected patients. Rates of atypical X-ray presentations and cavitary disease were comparable between HIV-seropositive and -seronegative patients; however, atypical disease was more frequent in HIV-infected patients with small tuberculin reactions or tuberculin anergy (PPD = 0 mm). CONCLUSION: HIV co-infection was associated with a higher frequency of negative and paucibacillary sputum AFB smears. The differences in the diagnostic yields of microscopy and culture between HIV-infected and non-HIV-infected individuals were small and do not, in our opinion, significantly affect the utility of these important diagnostic tests in developing countries. Examining more than one sputum specimen and monitoring cultured specimens for a full 8 weeks may assist in optimizing the diagnostic yield. Upper lobe infiltrates and cavitary disease are still the most frequent radiographic presentations of pulmonary TB in HIV-infected and non-HIV-infected adults in countries with a high prevalence of TB.     

Inhibition of apoptosis in chlamydia-infected cells: blockade of mitochondrial cytochrome c release and caspase activation

Current clinical gene therapy protocols for the treatment of human immunodeficiency virus type 1 (HIV-1) infection often involve the ex vivo transduction and expansion of CD4+ T cells derived from HIV-positive patients at a late stage in their disease (CD4 count <400). These protocols involve the transduction of T cells by murine leukemia virus (MLV)-based vectors encoding antiviral constructs such as the rev m10 dominant negative mutant or a ribozyme directed against the CAP site of HIV-1 RNA. We examined the efficiency and stability of transduction of CD4+ T cells derived from HIV-infected patients at different stages in the progression of their disease, from seroconversion to AIDS. CD4+ T cells from HIV-positive patients and uninfected donors were transduced with MLV-based vectors encoding beta-galactosidase and an intracellular antibody directed against gp120 (sFv 105) or Tat. (sFvtat1-Ckappa). The expression of marker genes and the effects of the antiviral constructs were monitored in vitro in unselected transduced CD4+ T cells. Efficiency and stability of transduction varied during the course of HIV infection; CD4+ T cells derived from asymptomatic patients were transducible at higher efficiencies and stabilities than CD4+ T cells from patients with acquired immunodeficiency syndrome (AIDS). Expression of the anti-tat intracellular antibody was more effective at stably inhibiting HIV-1 replication in transduced cells from HIV-infected individuals than was sFv 105. The results of this study have important implications for the development of a clinically relevant gene therapy for the treatment of HIV-1 infection.     

The noninfectious respiratory complications of infection with HIV

Infection with HIV was first recognized through a clustering of unusual respiratory infections. The lung has been a major target manifesting many of the infectious complications of the immunodeficiency. Noninfectious pulmonary complications in HIV-infected individuals are also common and have been recognized since the advent of the AIDS epidemic. Malignancies involving the respiratory system, specifically Kaposi's sarcoma and non-Hodgkin's lymphoma, are epidemiologically linked to infection with HIV. Although other cancers have been identified in patients with HIV, these malignancies have a relationship to HIV infection that is unknown. Nonetheless, all cancers in the HIV-infected individual appear to follow a very deadly course. Interstitial pneumonitis and an alveolitis are also seen in individuals infected with HIV. Their relationship to the virus is unknown but may involve the lung's immune response to HIV. Pneumothorax and bullous lung disease are the sequela of pulmonary infections in the HIV-infected host. Pulmonary hypertension has been reported in HIV-infected patients, and like the other noninfectious respiratory complications, the link between the disease process and HIV is unknown. Bronchiectasis is now commonly recognized in AIDS patients who have survived prolonged immunosuppression and infection. Bronchoscopists have accumulated a collection of endobronchial lesions uncommonly seen in non-HIV-related pulmonary consultation. In the following review, we discuss the epidemiology, pathology, pathogenesis, clinical features, diagnostic findings, prognosis, and therapeutic options available for each noninfectious pulmonary complication. As the life expectancy for HIV-infected patients increases, the incidence of noninfectious pulmonary complications will rise.