Snapshots of the Literature | ||||||
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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. 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
.
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.
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.
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.
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. 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.
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