The Hopkins HIV Report
A bimonthly newsletter for healthcare providers
Volume 8, Number 4, November 1996

Snapshots of the Literature

Detection of HIV-1 DNA and p24 Antigen in Breast Milk of HIV-1-Infected Ugandan Women and Vertical Transmission [Guay et al. Pediatrics 1996;98:438-444]: The authors determined the correlation between the detection of HIV in breast milk, the duration of breast feeding, and vertical transmission of HIV infection in Ugandan women. Expressed breast milk specimens were collected in a prospective study from 201 HIV-seropositive and 86 HIV-seronegative Ugandan women approximately 6 weeks after delivery. HIV DNA PCR was performed on the cellular fraction of the breast milk, and HIV p24 antigen was performed on the cell-free breast milk supernatant using p24 antigen enzyme immunoassay (EIA) after immune complex dissociation (ICD). The duration of breast feeding and the clinical status of the mothers and their children were recorded. Of the 201 HIV-infected women studied, 47 had HIV-infected children, 143 had children who seroreverted, and 11 had children of indeterminate status. Breast milk supernatants were available for ICD p24 antigen testing from 188 of the HIV-infected women and none had detectable p24 antigen. Breast milk cell pellets were available and contained amplifiable DNA in 125 of the HIV-infected women (20 transmitters, 104 nontransmitters, 1 indeterminate). HIV DNA was detected by PCR in 72% (75/104) of nontransmitters and 80% (16/20) of the transmitters. The duration of breast feeding by transmitter mothers (15.8 mos) was not significantly different from nontransmitter mothers (14.4 mos). The authors concluded that no correlation was found between the detection of HIV in breast milk or the duration of breast feeding and transmission of HIV infection in this study of Ugandan women. Although transmission of HIV from breast feeding has been documented to occur, these data suggest that the extent of postnatal HIV infection through breast milk may not be that significant.

By Brooks Jackson, M.D.

Effect of Mycobacterium tuberculosis on HIV Replication: Role of Immune Activation [Goletti D, et al. Journal of Immunology 1996;157:1271]: This is a collaborative study with the NIH, Hopkins, Einstein (New York) and the Catholic University in Rome. Quantitative HIV virology was studied sequentially in seven patients with HIV infection who developed active tuberculosis and compared with seven HIV-infected patients without TB. The mean HIV RNA copies increased 160-fold during the acute stage of tuberculosis. These results are consistent with the thesis that chronic immune activation promotes HIV progression. The investigators further noted that M. tuberculosis promoted HIV replication in vitro, presumably as a result of CD4 cell activation. These results have important implications regarding the need for diagnosis and effective treatment of concurrent infections that may apply to other pathogens as well. With respect to tuberculosis, WHO estimates that 5.6 million people worldwide and 80,000 in the U.S. are co-infected with HIV and M. tuberculosis .

By John G. Bartlett, M.D.

Coccidioidomycosis in Patients Infected with Human Immunodeficiency Virus: Review of 91 Cases at a Single Institution [Singh VR, et al. Clin Infect Dis 1996;23:563]: The authors from Maricopa Medical Center in Phoenix, Arizona retrospectively evaluated 91 patients with coccidioidomycosis and HIV infection. The most common presenting symptoms were fever, chills and weight loss; 24% had lymphadenopathy. Radiographic manifestations included reticulonodular infiltrates in 69%, focal infiltrates in 14% and normal chest x-rays in 16%. Of the 91 patients, 14 (15%) had meningitis. Extrapulmonary sites were less frequently involved and included lymph nodes, skin, liver, genitourinary system, eye, spleen, heart and larynx. The mean CD4 cell count in patients with diffuse pulmonary infiltrates was 55 cells/mm3, compared to 127 cells/mm3 for those with focal lung disease. Serologic tests were positive in 68% and negative in 23%. About two-thirds of the patients had positive cultures or cytology indicating C. immitis. The skin test was positive in only 2 of 30 (7%). Most of the patients were treated with amphotericin, with a mean dose of 1.3 gm followed by a prolonged course of oral ketoconazole or fluconazole. The mean survival was 246 days. The authors noted that the presenting findings and radiographic changes often mimicked other opportunistic infections such as PCP. As expected, the presence of diffuse pulmonary infiltrates and a CD4 cell count < 50 cells/mm3 were independent predictors of mortality. This large review of coccidioidomycosis in patients with AIDS calls attention to the importance of recognition in patients who have resided in or traveled to the endemic area.

By John G. Bartlett, M.D.

Performance Characteristics of a Rapid HIV Antibody Assay in a Hospital with a High Prevalence of HIV Infection [Irwin K, et al. Ann Intern Med 1996;125:471] The authors tested the utility of a rapid diagnostic test for HIV in 837 patients who were hospitalized or seen in the emergency department of the Bronx-Lebanon Hospital in New York City. The experimental test used fresh sera with the Genie HIV-1 and 2 assay (Genetic Systems, Seattle). This is a rapid synthetic peptide enzyme assay that can be performed in ten minutes and does not require special equipment. Results of the rapid test were compared with conventional serologic tests. Of the 837 patients tested, 45 (5.4%) had a positive conventional test. All 45 were positive with the rapid test, giving a sensitivity of 100% and a specificity of 99.1%. The negative predictive value was 100%, and the positive predictive value was 86.5%. Thus, as with prior studies using rapid tests, patients with negative results can be informed of the results without further testing. Patients with positive results should have confirmation of their results with routine serology. The practical application of this assay was demonstrated by the poor patient follow-up for results of conventional serologic testing in this study. Although patients were advised to return for test results, only 481 (57%) returned. Thus, rapid testing may be especially attractive for use in areas with high rates of HIV infection and clinical settings where follow-up is difficult to achieve.

By John G. Bartlett, M.D.

Weight Loss Associated with HIV Seroconversion Among Injection Drug Users [Marmor M, et al. J Acquir Immune Deficiency Synd 1996;12:514]: This is a longitudinal study of 366 injection drug users with evaluations at three month intervals. The authors noted 11 HIV seroconversions during a follow-up period of 622 person-years. Symptom histories of the seroconverters were compared with those of age-matched controls who remained seronegative. Among seroconverters, there was a significant association between seroconversion and weight loss exceeding 4.5 kg (7 of 11 cases) and oral ulcers (3 of 11 cases) during the three months before the first seropositive result. The authors concluded that a history of recent weight loss in this high risk population may indicate primary HIV infection.

By John G. Bartlett, M.D.

Eosinophilia in Patients Infected with Human Immunodeficiency Virus [Cohen AJ, et al. J Infect Dis 1996;174:615.] This is a review of differential blood cell counts in 855 HIV-infected patients examined over a four year period. There was an increase in eosinophils that was ascribed to two factors: a preservation of this cell line accompanied by a decrease in other cell lines, and/or absolute eosinophilia. The changes were more marked with progressive disease as indicated by CD4 cell count. The normal eosinophil count is < 400/mm3. Counts ex-ceeding 1500/mm3 were noted in 2.5% of HIV-infected patients compared to 0.7% in a control population. The absolute mean eosinophil count was 62% higher in patients with CD4 cell counts < 200 cells/mm3 compared to those with CD4 cell counts exceeding 200 cells/mm3. By contrast, other components of the CBC were significantly lower with later stage disease. No cause for eosinophilia could be determined in 19 of 22 cases reviewed; a possible drug effect was implicated in two; and adrenal insufficiency was implicated in one. None of these patients had parasitic infection. The authors suggest that with pro-gressive HIV infection, a shift to a Th2 response leads to production of IL-4 and IL-5, which promote develop- ment and terminal differentiation of eosinophils.

By John G. Bartlett, M.D.

Projecting Risks and Morbidity From HIV-Associated Sensory Neuropathy (SN) in the Multicenter AIDS Cohort Study (MACS) [Nance-Sproson TE, et al. Neuroscience of HIV Infection, Paris, March 6-9, 1996]; Cutaneous Innervation in Sensory Neuropathies: Evaluation by Skin Biopsy [McCarthy BG, et al. Neurology 45:1848-1855, 1995]: The cumulative lifetime risk of sensory neuropathy for people with HIV infection is approximately 20 percent, according to an analysis of 1323 gay men from the Multicenter AIDS Cohort Study (MACS). The risk increased as CD4 cell counts and hemoglobin levels decreased. The investigators calculated that the 24-month risk of neuropathy is 3% after the CD4 cell count falls below 500 cells/mm3, 11% below 200 cells/mm3, 14% below 100 cells/mm3, and 17% below 50 cells/mm3. Although sensory neuropathy is a common problem in people with HIV infection, clinicians have had to rely on subjective reports to gauge its severity. McCarthy's study suggests that deficiency may soon be remedied. The investigators used punch skin biopsies, which were characterized as minimally invasive and repeatable, to count the number of intraepidermal nerve fibers in 110 healthy volunteers, in nine HIV-negative persons with sensory neuropathy, and in three seropositive individuals with neuropathy. Biopsies from the back of the leg showed that the mean number of fibers in healthy volunteers was 13.7/mm3, compared to 3.43/mm3 in those with neuropathy (p<0.0001). The number of fibers also correlated with the clinical severity of the neuropathy. The technique, which is being used in a clinical trial of human nerve growth factor for neuropathy (ACTG 291), may prove useful in both confirming sensory neuropathy and in estimating its severity.

By Justin G. Bartlett, M.D.

This article is from The Johns Hopkins University AIDS Service,
The Hopkins HIV Report: A bimonthly newsletter for healthcare providers.