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Biomedical subjects

A R Lifson

Publications and source records attributed to A R Lifson.

At least 55 records · Page 3Linked to original sources

Concordance of polymerase chain reaction with human immunodeficiency virus antibody detection.

To evaluate the correlation of detection of human immunodeficiency virus (HIV) by polymerase chain reaction (PCR) with detection of HIV antibody, 271 simultaneous serum and peripheral blood mononuclear cell samples were examined from 242 persons whose activities placed them at increased risk for HIV infection: 142 from homosexual men, 86 from hemophilic men, and 43 from heterosexual partners of HIV-infected persons. PCR was performed using the gag region primer pair SK38/39 and the env region primer pairs SK68/69 and CO71/72. Amplified HIV DNA was detected using specific oligomer probes. Of 63 HIV antibody-positive samples, 58 (92%) had HIV DNA by PCR. Of 208 HIV antibody-negative samples, 7 (3.4%) had HIV DNA by PCR. On follow-up, 4 of the latter persons were seropositive when next tested; 2 were well and antibody- and PCR-negative; 1 had died of a stroke before retesting. Thus, PCR detects HIV in most antibody-positive persons; detection is increased by use of multiple primer pairs. PCR-positive antibody-negative specimens may indicate HIV infection in which antibody has not yet developed or may be false-positive PCR results. When PCR is discordant with HIV antibody, testing of additional specimens and clinical follow-up are necessary to assess HIV infection status.

Bisexuality↗

The role of human immunodeficiency virus infection in pneumococcal bacteremia in San Francisco residents.

Human immunodeficiency virus (HIV) is an important risk factor for invasive pneumococcal disease, but information on clinical course and infecting serotypes is limited. To help develop strategies to reduce the morbidity due to invasive pneumococcal disease, episodes of pneumococcal bacteremia were identified by retrospective review of microbiology records (November 1983-November 1987) at 10 San Francisco hospitals and, for patients 20-55 years old living in San Francisco, HIV antibody status was determined by review of medical records. Pneumococcal isolates from one hospital were serotyped. Of 294 patients with pneumococcal bacteremia identified, 32 (11%) had AIDS at the time pneumococcal bacteremia was diagnosed and another 43 (15%) were HIV-infected but did not have AIDS; 12 HIV-infected patients developed AIDS after the episode of pneumococcal bacteremia. The rate of pneumococcal bacteremia in AIDS patients was estimated to be 9.4/1000 patient-years. Serotypes of 27 (82%) of 33 pneumococcal isolates from HIV-infected patients and 107 (90%) from 119 patients without known HIV infection were among the 23 serotypes included in the currently available polysaccharide vaccine. The rate of pneumococcal bacteremia is approximately 100-fold greater in AIDS patients in San Francisco than rates reported before the AIDS epidemic, but more than half the episodes of pneumococcal bacteremia in HIV-infected patients occurred in patients without AIDS. Data on pneumococcal serotypes causing invasive disease in HIV-infected patients suggest that the current pneumococcal vaccine, if effective in this population, could provide significant protection against pneumococcal disease.

Acquired Immunodeficiency Syndrome↗

Risk factors for human immunodeficiency virus type 1 (HIV-1) infection in patients at a sexually transmitted disease clinic in New York City.

Patients who attended a sexually transmitted disease clinic in New York City in 1987 were offered enrollment in a nonblinded study to estimate human immunodeficiency virus type 1 (HIV-1) seroprevalence in adults with multiple sexual partners and to determine risk factors associated with HIV-1 infection. In addition, a blinded serosurvey of a representative sample of patients was performed to obtain an unbiased estimate of seroprevalence in clinic attendees. The seroprevalence in the blinded serosurvey was 7.5% (26/348), while the seroprevalence of the 1,201 volunteers for the nonblinded study was 11.2%. For men in the nonblinded study, the risk behaviors most strongly associated with HIV-1 infection were intravenous drug use, sexual contact with another man, and sexual contact with a female intravenous drug user. For women, intravenous drug use and sexual contact with a man at risk for HIV-1 infection (an intravenous drug user or a bisexual) were most important. The seroprevalence among persons who denied all high-risk behavior was 1% (7/723). The results of this study, conducted in a city with one of the nation's highest reported cumulative incidences of acquired immunodeficiency syndrome, suggest that HIV-1 infection in clinic attendees was primarily limited to intravenous drug users, homosexual/bisexual men, and the sexual partners of these two groups.

Acquired Immunodeficiency Syndrome↗

Kaposi's sarcoma in a cohort of homosexual and bisexual men. Epidemiology and analysis for cofactors.

Acquired immunodeficiency syndrome (AIDS) surveillance data for both the United States and San Francisco indicate that Kaposi's sarcoma is more common in homosexual and bisexual men with AIDS than in other adults with AIDS, and that the proportion of newly diagnosed AIDS cases presenting with Kaposi's sarcoma has been significantly declining over time. The changing epidemiology of Kaposi's sarcoma was analyzed in a well-characterized cohort of homosexual and bisexual men; laboratory and interview data from a sample of these men were evaluated for determinants of and cofactors associated with Kaposi's sarcoma. Among 1,341 men with AIDS, the proportion presenting with Kaposi's sarcoma declined from 79% in 1981 to 25% in 1989. Compared with other men with AIDS, men with Kaposi's sarcoma had a shorter interval from human immunodeficiency virus (HIV) seroconversion to AIDS diagnosis (median, 77 vs. 86 months). Men with and without Kaposi's sarcoma did not significantly differ with respect to number of sexual partners, history of certain sexually transmitted or enteric diseases, use of certain recreational drugs (including nitrite inhalants), or participation in certain specific sexual practices. The decline in Kaposi's sarcoma may at least partly be due to a shorter latency period from infection to disease. Although cofactors for the development of Kaposi's sarcoma may exist, many previously hypothesized agents were not supported by this analysis.

Acquired Immunodeficiency Syndrome↗

HIV seroconversion in two homosexual men after receptive oral intercourse with ejaculation: implications for counseling concerning safe sexual practices.

Seroconversion for HIV antibody occurred in two homosexual men who reported no anal intercourse for greater than or equal to 5 years and multiple episodes of receptive oral intercourse with ejaculation. Neither man reported intravenous drug use or receipt of blood products. The last antibody-negative specimen was also negative by the polymerase chain reaction and p24 antigen assays. All sexually active persons should be clearly counselled that receptive oral intercourse with ejaculation carries a potential risk of HIV transmission.

Adult↗

Relationship between AIDS latency period and AIDS survival time in homosexual and bisexual men.

We identified 277 homosexual and bisexual men diagnosed with acquired immune deficiency syndrome (AIDS) whose estimated human immunodeficiency virus (HIV) seroconversion dates, ranging from 1977-85, could be well approximated. These men were from a cohort of 6,705 homosexual and bisexual men originally recruited for studies of sexually transmitted hepatitis B in San Francisco in 1978-80. We compared the time from HIV seroconversion to the initial disease diagnostic of AIDS (AIDS latency period) with the time from first AIDS diagnosis to death (AIDS survival time) and found no significant overall correlation between latency period and survival time. Both Kaplan-Meier and Cox proportional hazard stepwise analyses found the initial AIDS diagnosis to be significantly associated with latency period, with individuals first diagnosed with Kaposi's sarcoma (KS) having a shorter latency but longer survival than those first diagnosed with Pneumocystis carinii pneumonia (PCP) or other AIDS diagnoses. Individuals with KS tended to be diagnosed earlier in the epidemic compared to those with PCP and other non-KS diagnoses. The AIDS survival time was significantly associated with the initial AIDS diagnosis but not with the estimated year of seroconversion, the year of first AIDS diagnosis, age at seroconversion, or racial/ethnic group. The information presented here on the relationship between the AIDS latency period and survival times suggests a model for the pathogenesis of HIV infection in which there is continual deterioration of the immune system. The wider use of antiviral and prophylactic therapies both preceding and following a diagnosis of AIDS may change this model as both latency and survival times are improved.

Acquired Immunodeficiency Syndrome↗

Kaposi's sarcoma among homosexual and bisexual men enrolled in the San Francisco City Clinic Cohort Study.

The changing epidemiology of Kaposi's sarcoma (KS) and possible explanations for this change were analyzed using data from a well-characterized cohort of homosexual and bisexual men. Among 1,341 men with AIDS, the proportion presenting with KS declined from 79% in 1981 to 25% in 1989. For 250 men whose date of HIV seroconversion could be well characterized, persons presenting with KS had a shorter interval from HIV seroconversion to AIDS diagnosis than other AIDS patients without KS (mean = 77 vs. 86 months). Among 182 men who were interviewed prior to a diagnosis of AIDS, men with and without KS did not significantly differ with respect to number of sex partners, a history of certain sexually transmitted or enteric diseases, use of certain recreational drugs (including nitrite inhalants), or participation in certain specific sexual practices. The decline in KS may at least partly be due to a shorter latency period from infection to disease. Although cofactors for the development of KS may exist, many previously hypothesized agents were not supported by this analysis.

Acquired Immunodeficiency Syndrome↗

Duration of human immunodeficiency virus infection before detection of antibody.

To estimate the duration and frequency of the period of HIV infection without detectable antibody, modelling techniques were applied to results of detection of HIV DNA by means of the polymerase chain reaction (PCR) and to data from cases in published reports. PCR was carried out with gag and env region primers on samples from 27 homosexual and 12 haemophilic men for whom stored samples were available from before and after seroconversion; serum was also tested for p24 antigen by antigen-capture enzyme immunoassay. HIV DNA was detectable before seroconversion in 4 men; in all 4 PCR was positive only in the seronegative sample taken closest to the time of seroconversion. In 3 men antigen was detected before seroconversion; in each case HIV DNA was also detected. By a Markov model, the time from infection with HIV (as assessed by detection of HIV DNA) to first detection of HIV antibody was estimated to be 2.4 (SE 2.1) months for the median individual. Modelling of cases of HIV infection with known exposure in published reports gave a median estimate of 2.1 (0.1) months from exposure to antibody detection, and 95% of cases would be expected to seroconvert within 5.8 (0.6) months. HIV infection for longer than 6 months without detectable antibody seems uncommon.

Acquired Immunodeficiency Syndrome↗

Neurological and neuropsychological manifestations of HIV-1 infection: association with AIDS-related complex but not asymptomatic HIV-1 infection.

To determine whether neurological and neuropsychological abnormalities are associated with clinical manifestations of human immunodeficiency virus type 1 (HIV-1) infection in men who do not have acquired immunodeficiency syndrome (AIDS), we performed a historical prospective and cross-sectional study. One hundred HIV-1 seropositive homosexual or bisexual men, of whom 26 had AIDS-related complex, 31 had generalized lymphadenopathy, and 43 had no signs or symptoms of HIV-1 infection, and 157 HIV-1 seronegative men were enrolled from a cohort of 6,701 men who were originally recruited between 1978 and 1980 for studies of hepatitis B virus infection. Evaluation included medical history, physical examination, and neuropsychological tests. Of 26 HIV-1 seropositive subjects with AIDS-related complex, 11 (42%) reported neurological, cognitive, or affective symptoms compared with 30 (19%) of 157 HIV-1 seronegative subjects (relative risk = 2.2, p = 0.02). On neuropsychological testing, subjects with AIDS-related complex performed at a significantly lower level than the HIV-1 seronegative group (p = 0.001). A significantly higher percentage of subjects with AIDS-related complex (8[31%]of 26) than HIV-1 seronegative subjects (19 [12%] of 157) had abnormal results on two or more neuropsychological tests (rate ratio = 2.5, p = 0.03). Symptoms and impairment on neuropsychological tests were correlated only within the group who had AIDS-related complex. Subjects with generalized lymphadenopathy and subjects who had no signs or symptoms of HIV-1 infection were not different from HIV-1 seronegative subjects with respect to symptoms or performance on neuropsychological tests.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Dementia Complex↗

Phase I study of low-dose zidovudine and acyclovir in asymptomatic human immunodeficiency virus seropositive individuals.

PURPOSE: The combination of zidovudine and acyclovir has shown in vitro antiretroviral activity and led to short-term improvement in patients with symptomatic human immunodeficiency disease (HIV) disease. We performed a phase I study of zidovudine (500 mg/day) plus acyclovir (2 or 4 g/day) in asymptomatic HIV-seropositive men to investigate pharmacokinetics, safety, tolerance, and immunologic effects of the combination. SUBJECTS AND METHODS: Fifty HIV-seropositive homosexual or bisexual men from the San Francisco City Clinic Cohort Study were recruited for the study; of these, 20 met the eligibility criteria. Treatment with zidovudine and acyclovir was open label. Pharmacokinetic, virologic, immunologic, and clinical data were collected periodically over a 24-week period. RESULTS: Pharmacokinetic analysis showed no drug interaction. The combination was generally well tolerated, and hematologic parameters remained stable through 24 weeks. There were no significant changes in total lymphocytes, T4 lymphocytes, overall skin test reactivity, or ability to culture virus from peripheral blood. CONCLUSION: This combination of agents is safe in this population for at least six months. Conclusions about long-term tolerance and efficacy await the results of larger trials with longer follow-up.

Acyclovir↗

Prevalence, incidence, and progression of human immunodeficiency virus infection in homosexual and bisexual men in hepatitis B vaccine trials, 1978-1988.

Between 1978 and 1980, 359 hepatitis B seronegative homosexual and bisexual men were recruited from the San Francisco municipal sexually transmitted disease clinic for hepatitis B vaccine trials. Of the 359 participants, 320 (89%) consented to have their stored blood samples tested for human immunodeficiency virus antibodies. The prevalence of human immunodeficiency virus infection in these 320 vaccine trial participants rose from 0.3% in 1978 to 50.9% in 1988. The annual incidence of human immunodeficiency virus infection showed that seroconversion peaked in 1980-1982, dropped significantly in 1983, and has remained low. Men less than 30 years old on entry into the study seroconverted earlier in the epidemic and had higher incidence rates than men 30 years or older (p = 0.07). No statistical difference in seroconversion rates was found for other demographic variables. Using a Kaplan-Meier survival curve of the cumulative proportion of men without acquired immunodeficiency syndrome by duration of human immunodeficiency virus infection, an estimated 39% (95% confidence interval 27%-51%) will develop acquired immunodeficiency syndrome within 9.2 years of infection. Cox proportional hazard stepwise analysis showed no correlation between age at seroconversion, race, or year of seroconversion and progression to acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Do alternate modes for transmission of human immunodeficiency virus exist? A review.

Transmission of human immunodeficiency virus (HIV) is known to occur perinatally, through sexual contact, and after exposure to infected blood or blood products. The possibility that breast milk may transmit HIV continues to be evaluated. There is no epidemiologic evidence that contact with saliva, tears, or urine has resulted in HIV infection. However, because HIV has (in some cases rarely) been isolated from these body fluids, guidelines have been developed to reduce more extensive exposures to such secretions. Laboratory and epidemiologic data strongly indicate that HIV is not transmitted through immune globulin preparations, the hepatitis B vaccine, or contact with insects. Increasing evidence from many studies also indicates that HIV is not transmitted through casual contact. All individuals need to be aware of how HIV is and is not transmitted, to reduce high-risk behaviors and to avoid unnecessary fears and actions.

Acquired Immunodeficiency Syndrome↗

Investigations of AIDS patients with no previously identified risk factors.

Through Sept 30, 1987, two thousand fifty-nine patients with acquired immunodeficiency syndrome (AIDS) and no recognized risk factors were reported to the Centers for Disease Control. Risk history was incomplete or unobtainable for 921 (45%) of them. Risk factors were ultimately identified for 825 (72%) of the remaining 1138. Another 32 persons (3%) did not meet the case definition for AIDS. Risk factors could not be identified for the remaining 281 patients (25%), despite additional information. Of these, 178 (63%) were interviewed with standard questionnaires; 38% reported sexually transmitted diseases and 34% of the men reported sexual contact with prostitutes. There was no evidence for new transmission modes. Although the proportion of AIDS patients with undetermined risk factors has increased significantly during the past year, the adjusted proportion shows no significant change over time. Thus, follow-up of AIDS patients with no apparent risk factors suggests that modes of transmission for human immunodeficiency virus have remained stable.

Acquired Immunodeficiency Syndrome↗

The natural history of human immunodeficiency virus infection.

Although much is known about the natural history of HIV infection, many issues remain unresolved and require additional study. At least four major questions require further investigation. (1) Current data suggest that most HIV-infected persons will eventually develop AIDS. The proportion of all infected persons who will eventually develop AIDS, as well as the average and maximum incubation periods, have not yet been conclusively defined. (2) Certain clinical signs (such as oral candidiasis) or laboratory test results (such as a depressed T4 count) may indicate a poorer prognosis. However, the predictive value of such indicators for a specific patient and in an individual situation varies. Combinations of clinical and laboratory data may help refine estimates of the likelihood of developing AIDS or other HIV-related diseases. (3) Why some HIV-infected persons develop disease and others do not is not completely understood. The role of cofactors for disease progression needs additional investigation. There may be no one universal cofactor for progression but, rather, various agents that cause immune stimulation and reactivation of latent HIV. Therefore, exposure to a variety of infectious or environmental agents (such as through sexually transmitted diseases or injection of iv drugs) may accelerate progression to disease in HIV-infected persons. (4) It is not established whether antiviral agents will prevent or reduce the likelihood of disease progression in asymptomatic HIV-infected persons. If beneficial, should they be given to all HIV-infected persons or only to those whose clinical and laboratory evaluation suggests an increased likelihood of progression? Given these uncertainties, how should the physician or other health care worker evaluate, treat, and counsel the HIV-infected patient? Such patients should receive a comprehensive medical evaluation for both diagnostic and staging purposes; the details of such an evaluation are beyond the scope of this review and have been well described. A few brief points, however, should be emphasized.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗