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D Havlir

Publications and source records attributed to D Havlir.

28 records · Page 2Linked to original sources
PubMed1995

Early versus delayed treatment of HIV infection. Zidovudine should be given before symptoms develop.

An understanding of the virology and pathogenesis of HIV infection provides a rationale for initiating early intervention with antiretroviral drugs. Even at the earliest stages of infection when HIV-infected patients are asymptomatic, viral replication is ongoing, particularly in lymphoid tissues. Initiation of antiretroviral therapy can reduce viral replication and delay disease progression. A possible objection to early intervention therapy with zidovudine is the risk of selecting out resistant isolates of HIV, which would be difficult to treat. In practice, zidovudine-resistant isolates occur significantly less frequently in patients with early-stage disease compared with those with late-stage HIV infection, thus supporting the early use of zidovudine; in addition, alternative therapies, active against zidovudine-resistant isolates, are available. Clinical trials with zidovudine in asymptomatic patients have differed in terms of length of follow-up, patient inclusion criteria, dosages and end-points. However, a number of conclusions are possible based on the results obtained: early intervention delays the progression of AIDS, delays the onset of symptomatic disease, has a favourable effect on surrogate markers of HIV infection and is well tolerated; it does not, however, seem to produce any benefit in terms of survival. It is this last point that has given rise to much of the controversy regarding early intervention with zidovudine in asymptomatic patients. Since the disease is progressive in nature with persistent and high levels of viral replication and as prolonging the period of relative health and quality of life when the patient is asymptomatic is desirable, the choice to treat before symptoms develop would appear to be the optimal therapeutic strategy.

CD4 Lymphocyte Count↗
PubMed1994

The individual microbiologic effect of three antimycobacterial agents, clofazimine, ethambutol, and rifampin, on Mycobacterium avium complex bacteremia in patients with AIDS.

The individual antibacterial activities of clofazimine, ethambutol, and rifampin in the treatment of Mycobacterium avium complex bacteremia in patients with AIDS were determined. Sixty human immunodeficiency virus 1-infected patients who had at least one blood culture positive for M. avium complex were randomized to receive either clofazimine (200 mg), ethambutol (15 mg/kg), or rifampin (600 mg) once daily for 4 weeks. Only ethambutol resulted in a statistically significant reduction in the level of mycobacteremia. The median change in individual baseline colony counts was -0.60 log10 cfu/mL after 4 weeks of ethambutol (P = .046). In contrast, median changes in individual baseline colony counts were -0.2 log10 cfu/mL and +0.2 log10 cfu/mL for clofazimine and rifampin, respectively (both, P > .4). Ethambutol had greater antibacterial activity, as determined by changes in the level of mycobacteremia, than either rifampin or clofazimine, supporting its continued use in combination with other agents in the treatment of M. avium infection.

AIDS-Related Opportunistic Infections↗
PubMed1994

Transient bacteremia due to Mycobacterium avium complex in patients with AIDS.

It is generally assumed that Mycobacterium avium complex (MAC) bacteremia, once it develops, is unremitting. On the basis of this presumption, changes in the level of mycobacteremia are used to gauge therapeutic response. In 7 (12%) of 60 patients enrolled in a prospective trial of MAC bacteremia and AIDS, bacteremia became undetectable before the initiation of antimycobacterial therapy. Patients with transient bacteremia reported fewer and shorter symptoms and survived longer than those with sustained bacteremia (59 vs. 31 weeks; P = .022). There was no difference in the duration of AIDS, CD4+ cell count, hematocrit, or body weight between groups. Two additional patients with transient bacteremia were identified outside this study setting. Despite disappearance of detectable mycobacteremia and subsequent administration of antimycobacterial agent(s), bacteremia once again became detectable in 6 patients 4-45 weeks after their negative pretreatment cultures. Patients with disseminated MAC may have fluctuating levels of mycobacteremia that become undetectable in the absence of antimycobacterial therapy.

AIDS-Related Opportunistic Infections↗
PubMed1994

Nevirapine resistance mutations of human immunodeficiency virus type 1 selected during therapy.

Drug susceptibility and mutations in the reverse transcriptase (RT) gene were analyzed with 167 virus isolates from 38 patients treated with nevirapine, a potent nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) RT. Resistant isolates emerged quickly and uniformly in all patients administered nevirapine either as monotherapy or in combination with zidovudine (AZT). Resistance developed as early as 1 week, indicating rapid turnover of the virus population. The development of resistance was associated with the loss of antiviral drug activity as measured by CD4 lymphocyte counts and levels of HIV p24 antigen and RNA in serum. In addition to mutations at amino acid residues 103, 106, and 181 that had been identified by selection in cell culture, mutations at residues 108, 188, and 190 were also found in the patient isolates. Sequences from patient clones documented cocirculating mixtures of populations of different mutants. The most common mutation with monotherapy, tyrosine to cysteine at residue 181, was prevented from emerging by coadministration of AZT, which resulted in the selection of alternative mutations. The observations documented that, under selective drug pressure, the circulating virus population can change rapidly, and many alternative mutants can emerge, often in complex mixtures. The addition of a second RT inhibitor, AZT, significantly altered the pattern of mutations in the circulating population of HIV.

Antiviral Agents↗
PubMed1993

Reproducibility of lysis-centrifugation cultures for quantification of Mycobacterium avium complex bacteremia.

While quantitative mycobacterial blood cultures have been accepted as the standard for evaluating response to various Mycobacterium avium complex (MAC) treatment regimens, variability in this methodology has not been evaluated in a rigorous fashion. We thus studied the reproducibility of quantitative MAC cultures by a lysis-centrifugation culture system within and among five institutions. To measure the intralaboratory variation in mycobacterial colony counts, colony counts from duplicate blood specimens collected from 52 AIDS patients with MAC bacteremia were determined. Colony counts ranged from 0 to 50,000 CFU/ml. Nonparametric analyses revealed there was no significant difference in colony counts between the 52 duplicate specimens. The agreement between the intralaboratory paired specimens, as measured by the intraclass correlation coefficient, was 0.997. To measure the interlaboratory variation, multiple 10-ml aliquots from 12 patients were distributed to five institutions and processed within 24 to 32 h by lysis-centrifugation. For the 12 specimens distributed to the five laboratories, two-way analysis of variance for repeated measures revealed no significant difference in an individual patient's colony counts between laboratories (P > 0.2). We conclude that quantitation of mycobacterial colony counts by the lysis-centrifugation system is reproducible within and between institutions. Clinical trials evaluating response to therapeutic interventions for MAC can use multiple laboratories for quantitation of mycobacteremia. Furthermore, a 24- to 32-h delay in processing appeared to have no impact on reproducibility.

AIDS-Related Opportunistic Infections↗
PubMed1989

Do not resuscitate discussions in a hospital-based home care program.

Discussion of code status of a patient is usually raised in the inpatient setting, when patients are unable to participate because of their critical condition. In order to increase patient participation, code status was discussed in the homes of 37 chronically ill patients enrolled in a hospital-based home care program. Twenty patients or conservators did not want resuscitation performed in case of cardiac arrest. In this small, select group, outpatient code discussions benefited the patients, families, and health care providers.

Aged↗
PubMed1987

Biochemical and clinical aspects of amyloidosis.

These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from transcriptions, they are prepared by Drs Homer A. Boushey, Associate Professor of Medicine, and David G. Warnock, Associate Professor of Medicine, under the direction of Dr Lloyd H. Smith, Jr, Professor of Medicine and Associate Dean in the School of Medicine. Requests for reprints should be sent to the Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA 94143.

Amyloid↗
PubMed1982

Typhoid fever.

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Amoxicillin↗