Updates By Carol A. Kemper, MD, FACP
Diagnosing Primary HIV
Source:Daar ES, et al. Ann Intern Med. 2001;134:25-29.
Daar and colleagues assessed the use of the p24 antigen and PCR HIV RNA test results in the diagnosis of acute primary HIV-1 infection, and whether any specific sign or symptom, or complex of symptoms, could be used to target screening for primary HIV. A total of 436 patients with signs and/or symptoms consistent with possible primary HIV infection were evaluated as part of 3 separate cohort studies performed between 1993 and 1999. The majority of the subjects were male (89%); 77% were homosexual, 18% were heterosexual, and 4% were intravenous drug users. Primary HIV was diagnosed in 54 patients (12.4%), all of whom had undetectable HIV antibody or an indeterminate Western blot, with documented seroconversion within 1 month. Eighteen percent were found to have chronic HIV infection with positive Western blot, and 69.5% had no evidence of HIV infection.
For the purposes of this study, Daar et al assumed that PCR for plasma HIV RNA had a sensitivity of 100% (the lower limit of detection ranged from 50 copies/mL to 500 copies/mL, depending on the cohort). Patients with negative HIV RNA on repeated testing and who did not seroconvert were considered to have initial false-positive HIV RNA results. The sensitivity and specificity of p24 antigen was 88.7% and 100%, respectively, whereas the specificity for HIV RNA was 97.4%. Five patients had detectable HIV RNA with high levels of HIV RNA but negative p24 antigens. Eight of 303 uninfected patients (2.6%) had false-positive HIV RNA tests (mean concentration 269; range, 52-1950 copies/mL).
Patients with primary HIV infection typically presented with symptoms common to most viral infections, including fever (87.5%), malaise (72.5%), myalgia (60%), rash (57.5%), headache (55%), night sweats (50%), and sore throat (42.5%). However, while patients with primary HIV were significantly more likely to report fever, myalgia, arthralgia, rash, or night sweats than persons without primary HIV (P < .05 in each case), no single sign or symptom, or complex of symptoms, was clinically predictive of acute HIV infection. Patients with primary HIV infection were more likely to be homosexual and to report a specific exposure to an HIV-infected person.
PCR assays for HIV RNA are more sensitive than those for p24 antigen in the diagnosis of acute HIV infection, but are associated with lower specificity and can lead to false-positive results, especially if the pretest probability is low (Kemper CA. Infectious Disease Alert 1999;18:80). False-positives are unlikely to occur at values less than 10,000 particles/mL of whole blood, and true-positive test results in primary HIV generally exceed 10,000 particles/mL. It is important to keep in mind that the interpretation of these test results depends on the clinical situation, the patient’s risk factors, and confirmation of subsequent seroconversion.
Increasing Pneumococcal Resistance
Source: Whitney CG, et al. N Engl J Med. 2000;343:1917-1924.
Whitney and colleagues from the Active Bacterial Core Surveillance program of the Centers for Disease Control assessed 3475 isolates of Streptococcus pneumoniae obtained from patients with invasive infection in the United States during 1998. Overall, 24% of isolates were resistant to penicillin (PCN), up from 21% in 1995. During this 3-year period, overall resistance to cefotaxime increased from 10% to 14%, to erythromycin from 11% to 15%, and to trimethoprim-sulfamethoxazole from 25% to 29%. As has been previously reported, PCN-resistant isolates were more common in children younger than 5 years of age, and in whites compared with blacks. Georgia and Tennessee had the highest rates of PCN resistance (34%) compared with New York and California, which had the lowest (14.6%).
PCN-sensitive isolates generally remained sensitive to other antibacterial agents. In contrast, isolates with high-level PCN resistance were increasingly more likely to demonstrate high-level resistance to other agents (in descending order of frequency of resistance): cefuroxime (100%), trimethoprim-sulfamethoxazole (92%), erythromycin (61%), cefotaxime (42%), tetracycline (26%), chloramphenicol (14%), clindamycin (12%), and levofloxacin (0.7%).
These data don’t look too different from earlier surveys—patterns of resistance are similar, but there’s more of it. About one-third of all pneumococcal isolates are now resistant to at least 1 antimicrobial agent, and 14% are resistant to the 3 most heavily used agents in children for the treatment of otitis (amoxicillin, erythromycin, and trimethoprim-sulfamethoxazole). Resistance to clarithromycin and azithromycin, which was not specifically examined, can be extrapolated from these data.
Nearly 91% of the PCN-resistant isolates fell into 7 serotypes (6A, 6B, 9V, 14, 19A, 19F, and 23F), all of which should be covered by the 23-valent polysaccharide vaccine. However, clinicians should note that the new pediatric 7-valent conjugate vaccine would cover only 78% of the PCN-resistant isolates in this survey. Children who have received this vaccine are at significantly lower risk of invasive pneumococcal infection, but PCN-resistant invasive disease is still possible.
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