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Biomedical subjects

M Markowitz

Publications and source records attributed to M Markowitz.

117 records · Page 7Linked to original sources

HIV-1 drug resistance in newly infected individuals.

CONTEXT: There is concern that the widespread use of antiretroviral drugs to treat human immunodeficiency virus 1 (HIV-1) infection may result in the increased transmission of drug-resistant virus. OBJECTIVE: To determine the prevalence of drug resistance-conferring mutations and phenotypic resistance to antiretroviral agents in a cohort of individuals newly infected with HIV-1. DESIGN: Case series with genetic analyses of the HIV-1 plasma-derived pol gene using reverse transcriptase polymerase chain reaction followed by direct sequencing of polymerase chain reaction products. Phenotypic analysis was performed with a recombinant virus assay. SETTING AND PATIENTS: Eighty individuals referred, on average, 1.7 months after infection with HIV-1 to the Aaron Diamond AIDS Research Center between July 1995 and April 1999. Subjects were from large urban areas (65 from New York, NY; 11 from Los Angeles, Calif); 60 (75%) were white, and 75 (93.8%) were homosexual men. MAIN OUTCOME MEASURES: Prevalence of known resistance-conferring genotypes and reduced susceptibility to individual antiviral agents by phenotype. RESULTS: Thirteen individuals (16.3%) had genotypes associated with drug resistance to any antiretroviral agent. Virus with known resistance-conferring mutations to any nucleoside reverse transcriptase inhibitors was found in 10 individuals, to any nonnucleoside reverse transcriptase inhibitors in 6 subjects, and to any protease inhibitors in 2 cases. Multidrug-resistant virus was identified in 3 individuals (3.8%). Extensive polymorphism in the protease gene was identified. Interpretation of genotypes and phenotypes was concordant in 57 (85%) of the 67 cases in which both studies were performed. CONCLUSION: The prevalence of HIV-1 variants with known resistance-conferring genotypes to any antiretroviral agent in this cohort of 80 newly infected individuals is 16.3%. These data support expanded use of resistance testing in the setting of primary HIV-1 infection. Clinical trials should be initiated to establish whether therapy guided by resistance testing, compared with the use of empirical triple combination antiretroviral therapy, provides additional virological and immunological benefit when treating primary HIV-1 infection. Further efforts to expand the study of transmission of drug-resistant HIV-1 variants, particularly in cohorts with different epidemiological profiles, are indicated.

Adult↗

Management of streptococcal pharyngitis reconsidered.

Adequate treatment of GABHS pharyngitis with penicillin shortens the course of illness, reduces the spread of streptococci and prevents suppurative complications. It has also been a major factor in the markedly accelerated decline in the incidence of acute rheumatic fever in this country. Difficulties in the clinical diagnosis of GABHS pharyngitis make bacteriologic confirmation highly desirable. Currently a properly performed throat culture is the best way to obtain this bacteriologic confirmation. However, it is possible that rapid antigen detection tests will replace the throat culture in the future. These diagnostic tools should be used more selectively and only in conjunction with clinical and epidemiologic data. Greater selectivity will help control costs and will increase the chances of identifying patients who are truly infected and are not merely streptococcal carriers. Penicillin is still the drug of choice and an oral preparation given twice daily is as effective as more frequent doses. Patients at risk for noncompliance should be treated with a single injection of benzathine penicillin combined with procaine penicillin to lessen the local discomfort. Routine follow-up cultures of asymptomatic patients should be abandoned. Persistence of GABHS following a course of treatment may no longer be an important risk factor for the development of rheumatic fever. However, there are exceptional cases, as noted in the text, in which eradication of GABHS carriage with a short course of rifampicin may be desirable.

Administration, Oral↗

Long-acting penicillins: historical perspectives.

For the more than three decades since benzathine penicillin G was discovered it remains unique as the only antibiotic formulation that can provide serum drug concentrations for several weeks following a single intramuscular injection. Benzathine penicillin G has withstood the test of time as the ideal drug to treat early, infectious syphilis and to prevent and treat Group A streptococcal infections. It has proved to be extraordinarily effective for the prevention of rheumatic fever recurrences and is a major reason for the marked reduction in the morbidity and mortality in countries where carefully monitored prophylaxis programs have been established.

Administration, Oral↗