Human immunodeficiency virus and hepatitis C virus coinfection

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share the same parenteral, sexual and vertical routes of transmission (McNair et al. 1992). This common epidemiology explains the high frequency of combined infections by hepatotropic viruses in HIV-infected patients. The aim of the present review is to clarify some important issues dealing with the reciprocal interactions between HIV and hepatitis C virus infections. The main topics include epidemiology, virological markers of HIV-infection, histopathology, natural course and treatment of hepatitis C in HIV-infected individuals.     

Human immunodeficiency virus in otolaryngology

A new wound cleansing agent consisting of bead cellulose with covalently, firmly bound proteolytic enzyme, chymotrypsin, was prepared. It was found that this preparation can be applied in the treatment of suppurating wounds of all types with very good results.     

Human immunodeficiency virus type 1 proteinase resistance to symmetric cyclic urea inhibitor analogs

Resistant virus was isolated from virus propagated in cell culture in the presence of the human immunodeficiency virus type 1 (HIV-1) proteinase inhibitor DMP 323, Ro 31-8959, or A-75925. The proteinase gene of resistant virus was sequenced, and key mutations (G48V, V82A, I84V, L90M, and G48V/L90M) were introduced into clones used for the expression, purification, and further characterization of the enzyme. The mutant enzymes were all less active than the wild-type enzyme, as judged by k(cat) and k(cat)/Km values. L90M had a lower Km than the wild type, whereas the G48V/L90M double mutant had an increased Km compared with that of the wild type, contributing to a 10-fold reduction in the k(cat)/Km. Vitality values were used to show that the enzyme of the I84V mutant is the enzyme most resistant to the two cyclic urea inhibitors DMP 323 and AHA 008. Virus with the same mutation is also resistant, although the double mutation L10F/I84V confers even greater resistance. All of these mutants are more resistant to DMP 323 than to AHA 008. The resistance of the I84V mutant may be attributed to a loss of van der Waals interactions with the inhibitor, since the larger amino acid side chain involved in the interaction is replaced by a smaller side chain. This is supported by the lower level of resistance to AHA 008 that was observed. The phenyl groups of AHA 008 should protrude deeper into the S1 and S1' subsites than those of the smaller compound DMP 323, reducing the loss of interaction energy. These results reveal that small structural modifications of inhibitors that do not affect the inhibitory effect on wild-type virus can influence the inhibition of resistant strains. This is of importance for optimizing drugs with respect to their potency and resistance.     

Human immunodeficiency virus infection, Part I

Initially recognized in 1982, acquired immunodeficiency syndrome (AIDS) has been the leading cause of death among young adults in the United States for much of this decade, and it has had a devastating impact on people in the developing world. It is estimated that 42 million people worldwide have been infected with human immunodeficiency virus (HIV), the virus that causes AIDS, and that almost 12 million people have died from AIDS-related diseases through 1997. Among these 12 million are 3 million children. Two thirds of the more than 30 million people with HIV or AIDS reside in sub-Saharan Africa. In the United States, 641,086 patients have been diagnosed with AIDS through 1997, and at least 385,000 have died. However, for the first time, new highly active antiretroviral therapies that include multiple drugs that attack the virus at several sites have slowed the progression from HIV to AIDS and from AIDS to death for those infected with HIV. The cumulative effect of these changes has been a reduction in both AIDS incident cases and AIDS deaths. Recent epidemiologic trends indicate that the proportion of AIDS incident cases and new HIV infections are increasing among women, African-Americans, and Hispanics, and the infections are more likely to be acquired through heterosexual transmission. The clinical management of HIV infection and AIDS has become increasingly complex in recent years. In addition to complete medical and social histories and physical examinations, hematologic, biochemical, serologic, and immunologic laboratory tests are required to predict the likelihood that patients will develop opportunistic infections and other complications related to HIV infection. Among the most important laboratory tests are measurements of HIV in plasma (viral load) in conjunction with peripheral blood CD4+ helper T lymphocyte counts. These tests are potent predictors of disease progression and their results have become markers for clinical response to therapy. The development of highly active antiretroviral therapy has had a profound impact on the epidemiology of AIDS and on the lives of individual patients. Through combinations of antiretroviral drugs, especially protease inhibitors, viral suppression can be achieved. However, adherence to these complex medical regimens and drug interactions have been problems for many patients. In addition, numerous questions remain unanswered, most importantly those regarding the timing of the initiation of treatment, the durability of viral suppression and clinical response, and the optimal "salvage" regimens for patients failing therapy either clinically or virologically.     

Human immunodeficiency virus infection, Part II

The acceptance of highly active antiretroviral therapy (HAART) among patients and health care providers has had a dramatic impact on the epidemiology and clinical characteristics of many opportunistic infections associated with human immunodeficiency virus (HIV). Previously intractable opportunistic infections and syndromes are now far less common. In addition, effective antibiotic prophylactic therapies have had a profound impact on the risk of patients developing particular infections and on the incidence of these infections overall. Most notable among these are Pneumocystis carinii, disseminated Mycobacterium avium complex, tuberculosis, and toxoplasmosis. Nevertheless, infections continue to cause significant morbidity and mortality among patients who are infected with HIV. The role of HAART in many clinical situations is unquestioned. Compelling data from clinical trials support the use of these therapies during pregnancy to prevent perinatal transmission of HIV. HAART is also recommended for health care workers who have had a "significant" exposure to the blood of an HIV-infected patient. Both of these situations are discussed in detail in this article. In addition, although more controversial, increasing evidence supports the use of HAART during the acute HIV seroconversion syndrome. An "immune reconstitution syndrome" has been newly described for patients in the early phases of treatment with HAART who develop tuberculosis, M avium complex, and cytomegalovirus disease. Accumulating data support the use of hydroxyurea, an agent with a long history in the field of myeloproliferative disorders, for the treatment of HIV. Newer agents, particularly abacavir and adefovir dipivoxil, are available through expanded access protocols, and their roles are being defined and clarified.     

Human immunodeficiency virus infection and stroke in young patients

OBJECTIVE: To determine the association between human immunodeficiency virus (HIV) infection and stroke among young persons. DESIGN: Retrospective case-control study. SETTING: Large, inner-city public hospital. PARTICIPANTS: All patients aged 19 to 44 years with a diagnosis of stroke, whose HIV status was determined, admitted from January 1990 through June 1994. Controls matched for age and sex were selected from patients who were admitted during the same period for status asthmaticus whose HIV status was known. MAIN OUTCOME MEASURE: The associations of HIV infection with all strokes and with cerebral infarction, after adjustment for other cerebrovascular risk factors, were evaluated by Mantel-Haenszel stratified analyses. The subtypes and causes of stroke in HIV-infected patients were compared with HIV-seronegative patients. RESULTS: The HIV infection was associated with stroke (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.0-5.3) and cerebral infarction (OR, 3.4; 95% CI, 1.1-8.9), after adjustment for other cerebrovascular risk factors. Among patients with stroke, cerebral infarction was more frequent in HIV-infected patients than in HIV-seronegative patients (20 [80%] of 25 vs 48 [56%] of 88, P = .04). The frequency of cerebral infarctions associated with meningitis (P < .001) and protein S deficiency (P = .06) was higher in HIV-infected patients than in seronegative patients. CONCLUSIONS: Our study suggests that HIV infection is associated with an increased risk of stroke, particularly cerebral infarction in young patients. This risk is probably mediated by increased susceptibility of HIV-infected patients to meningitis and protein S deficiency.     

Human immunodeficiency virus (HIV) infection and arthritis

A variety of inflammatory arthritic conditions are observed in the setting of HIV infection. The epidemiology of these disorders is a point of current controversy, although it appears that several unique syndromes are clinically associated. The pathogenesis of these disorders remains unclear, but we hope that further work in this area will lend important insights into the mechanisms of both HIV-associated and non-HIV associated rheumatic disease. The overall management of such patients is based on recognizing the underlying HIV infection and the judicious use of antirheumatic drug therapy. Rheumatologists need to be aware of the natural history of HIV infection and its clinical manifestations.     

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.     

Human immunodeficiency virus status in facial fracture patients

A prospective study was performed to obtain an indication of the incidence of human immunodeficiency virus (HIV) among the population of facial fracture patients treated at a city hospital in Toronto, Ontario, Canada. This study was stimulated by the observation that a significant number of the patients treated at this unit were drug and alcohol abusers, inmates of a local penitentiary (where homosexual activity is believed not to be uncommon) or had no fixed address. In addition, the surgical treatment of these patients involved the use of sharp, high-powered motorized instruments e.g., saws, drills, wires, etc., and resulted in the spillage and aerosolization of considerable amounts of blood and other tissues. Operating room staff are exposed to these patients for 12 to 18 hours on many occasions. Accidental exposure to body fluids can occur easily. It was thus decided to obtain consented HIV testing of all facial fracture patients managed by the Plastic Surgery Team between July and December 1990. Fifty-two patients were seen, and 47 (90.4%) of them were tested for HIV. Results were obtained for 46 (97.8%) of those tested. One patient (2.2%) was found to be positive for HIV. This figure was smaller than anticipated considering the patient population demographics, but is not an insignificant number and thus it is advised that if any suspicion arises, consented HIV testing should be obtained and the necessary precautions taken.     

Human immunodeficiency virus infection in systemic lupus erythematosus

This report describes a female patient with systemic lupus erythematosus (SLE) who was infected with the human immunodeficiency virus (HIV). Using stored serum, the precise timing of HIV seroconversion was determined and the early effects of HIV infection on SLE examined. This infection resulted in clinical improvement and the disappearance of autoantibody production. A literature review of the association between HIV and SLE is provided.     

Human immunodeficiency virus inhibits multilineage hematopoiesis in vivo

Human immunodeficiency virus type 1 (HIV-1)-infected individuals often exhibit multiple hematopoietic abnormalities reaching far beyond loss of CD4(+) lymphocytes. We used the SCID-hu (Thy/Liv) mouse (severe combined immunodeficient mouse transplanted with human fetal thymus and liver tissues), which provides an in vivo system whereby human pluripotent hematopoietic progenitor cells can be maintained and undergo T-lymphoid differentiation and wherein HIV-1 infection causes severe depletion of CD4-bearing human thymocytes. Herein we show that HIV-1 infection rapidly and severely decreases the ex vivo recovery of human progenitor cells capable of differentiation into both erythroid and myeloid lineages. However, the total CD34+ cell population is not depleted. Combination antiretroviral therapy administered well after loss of multilineage progenitor activity reverses this inhibitory effect, establishing a causal role of viral replication. Taken together, our results suggest that pluripotent stem cells are not killed by HIV-1; rather, a later stage important in both myeloid and erythroid differentiation is affected. In addition, a primary virus isolated from a patient exhibiting multiple hematopoietic abnormalities preferentially depleted myeloid and erythroid colony-forming activity rather than CD4-bearing thymocytes in this system. Thus, HIV-1 infection perturbs multiple hematopoietic lineages in vivo, which may explain the many hematopoietic defects found in infected patients.     

Human immunodeficiency virus testing and counseling: nuts and bolts

The human immunodeficiency virus poses an increasing health hazard to women. Physicians must recognize this risk and evaluate their patients for human immunodeficiency virus. Because of general increased awareness and the recommendations that all prenatal patients be offered human immunodeficiency virus testing and counseling, more and more women will be tested, yet counseling has not become a routine aspect in the evaluation of patients. This article reviews the key components of human immunodeficiency virus testing and counseling, including test interpretation, risk assessment, risk reduction, and pretest and posttest counseling. Familiarity with these areas should enable the practitioner to feel comfortable in providing this service.     

Human immunodeficiency virus and hepatitis B virus seroprevalence in an urban trauma population

OBJECTIVE: To determine the seroprevalence of the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV) in patients of an urban level I trauma center. DESIGN: Prospective, blinded point prevalence study of serum HIV and HBV antibody and antigen. SETTING: An urban level I trauma center that participates in a trauma system serving three million people. PATIENTS: The study included 994 (94.8%) of 1049 consecutive trauma service patients treated between June 6, 1988 and September 22, 1988. The patients were 82.2% male and 73.1% black, with a mean age of 28.8 +/- 12.3 years. Blunt trauma was seen in 65.4% of patients, 5.2% were in shock, and 96.2% survived their trauma. MAIN OUTCOME MEASURES: HIV and HBV seroprevalence, using both antibody and antigen testing. RESULTS: HIV infection was seen in 43 patients (4.3%); 41 (95.3%) were HIV Ab+ and two (4.7%) were HIV Ab-/HIV Ag+. Infection with the HBsAg was seen in 31 patients (3.1%). Infection with either virus was seen in 70 patients (7%); four patients (0.4%) were infectious for both viruses. Infection was related to age 20 to 49 years, i.v. drug use, a hepatitis or sexually transmitted disease history, prior HIV testing, shock, and death (p < 0.05). Penetrating trauma was not predictive of infection. In a logistic regression model, IV drug use was the single significant predictor of infection (p < 0.05). CONCLUSIONS: Young urban trauma patients, because of drug-related intentional violence, are 15.3 to 17.6 times more likely to be HIV infected and 3.9 to 7.9 times more likely to be infectious for HIV or HBV than the trauma population overall. The 12 to 21% infection rates in critically injured patients who require shock resuscitation and/or die reinforces the need for mandated universal precautions and for clear policies which govern the performance of procedures by physicians in training. Primary HIV infection in critically injured patients may worsen their outcome and may adversely affect the exposed health care worker. Emergency departments and trauma units should develop a referral system to HIV primary care services (HIV counselling and testing) for high risk patients and for adversely exposed health care workers.     

Human immunodeficiency virus induction of corticotropin in lymphoid cells

Disruption of the linkage among the immune, nervous, and endocrine systems may contribute to the pathology and symptoms of acquired immunodeficiency syndrome (AIDS). We investigated the role of human immunodeficiency virus (HIV) in altering these linkages via induction of corticotropin (ACTH) by lymphocytes. Cultured T lymphocytes (H9 cell line) were infected with HIV-1, after which ACTH production was measured and characterized at various time intervals by immunofluorescence and Western blotting. We report a coordinate expression of ACTH and p24 HIV core protein in H9 cells. Also, the kinetics of HIV-induced ACTH production by H9 T lymphoma cells are demonstrated using three different strains of HIV as well as UV-inactivated HIV. ACTH production corresponded with the appearance of p24 antigen and was maximal 35 days after infection. UV-inactivated HIV and the viral envelope protein, gp120, were also able to induce ACTH production in these cells, indicating that viral replication was not required for the ACTH induction. The HIV-induced ACTH was synthesized de novo and had the size and biological activity of pituitary ACTH. Inhibition of ACTH in HIV-infected lymphocyte cultures by anti-ACTH antiserum enhanced viral p24 expression. The significance of lymphocyte ACTH in AIDS is not clear, but these results suggest that it may restrict HIV replication and possibly infection.