AIDS and Other Manifestations

of HIV Infections

Fourth Edition

Edited by

Gary P. Wormser, M. D.Department of Medicine

Division of Infectious Diseases

New York Medical College

Valhalla, New York

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expect that different primer pairs will have differentsensitivities concerning identiÞcation of HTLV-I andHTLV-II within given populations (380). Differences inPCR ampliÞcation efÞciency have been noted for HTLVprimer pairs SK 43/44 and SK 110/111 (B. McCreedy,unpublished observations). Primer set SK 43/44 and probeSK 45 appear to yield better results following ampliÞca-tion of low copy number HTLV DNA than does the primerpair SK 110/111 and probes SK 112 and SK 188. Furtherresearch is this area is necessary (380).

In addition, nucleotide sequence diversity and the issueof defective or incomplete retroviral elements may need tobe considered. Sequence diversity among HTLV-II isolateshas received recent attention (403Ð409). However, deletedHTLV-I proviruses have been shown to exist in freshleukemic cells of patients with adult T-cell leukemia-lymphoma syndrome (410,411). Hall and colleaguesfound deleted HTLV-I provirus in HTLV EIA seronegativepatients with mycosis fungoides (277). Some analyses ofHTLV EIA reactive cohorts by means of PCR have found12% to 24% of the HTLV infection non-typeable(401,412), although others found almost all specimens tobe typeable with the newer primers and probes (380). Theability to detect all HTLV-II infected individuals by EIAscreening assays, or to conÞrm infection by WB or PCR,may therefore be limited by sequence diversity andpossibly proviral deletions. Further characterization ofoptimal PCR primer pairs, EIA and WB capture antigens(388), and possible newer serological assays (such as theuse of synthetic peptides (395,396)) should be a target offuture research.

One study has linked sexual transmission of HTLV-Iwith the presence of anti-HTLV-I-tax antibody (413).Thus, selective assays may be important in further deÞningepidemiologic transmission characteristics. For HIV, stud-ies of speciÞc antibody have been controversial withrespect to prediction of transmission (122). More work inthis area for HTLV is also necessary.

Currently, multiple assays are necessary to deÞneaccurately the prevalence of HTLV-I and -II in a givenpopulation. Further work is required for the development

of assays that are highly sensitive and speciÞc. Recentstudies suggest that HTLV-II may have immunologic andhealth consequences (346,379,414Ð417), as does HTLV-I(18,418). SpeciÞc laboratory assays will be importanttools in further clarifying the epidemiology of HTLV-II.These newer approaches, in combination with an EIA thatincludes HTLV-II antigens, hold promise for improvingHTLV diagnostics.

The initial commercial HTLV WB that was commonlyused by blood banks to conÞrm repeat HTLV EIAreactivity was inadequate for conÞrmation of HTLV-IIinfection. Since counseling of donors by blood banks isdone when EIA results are conÞrmed, the sensitivity andspeciÞcity of the conÞrmatory tests are critical. Asdiscussed above, the conventional WB needs to bereplaced or supplemented by other easily performedassays, particularly in geographic regions where theprevalence of HTLV-II represents a signiÞcant proportionof the HTLV serologic reactivity (358,359,363,382).

CONCLUSIONS

The armamentarium of HIV and HTLV detectionsystems has continued to grow rapidly. Testing alternativeswill continue to move from the research bench to theclinical laboratory. The judicious choice of these tools willdepend upon an increased understanding of the dynamicsof retroviral infection, critical head-to-head comparisontesting, and cost-beneÞt decision analyses. Further devel-opment and evaluation are warranted for direct HIVdetection methods as well as other immunologic tests ofHIV exposure, and serologic detection and conÞrmation ofHTLV infection. The context within which any test is usedis of critical importance to its interpretation. No test, perse, should be the basis for diagnosis on its own, but rathera test is merely an aid in correct diagnosis. The practitionermust use test results in the context of a clinical picture toreach an accurate diagnosis.

FIG. 8.7. Paired Western Blot results comparingstandard Biotech/DuPont strips with the Cam-bridge Biotech strips containing addedrecombinant p21e protein The major bands repre-sented are p24 and p21e. Strips 3 and 11 wereincubated with HTLV-I positive control serum,strips 4 and 12 with HTLV-II postive control serum,and strips 5 and 13 with control serum negative forHTLV-I and HTLV-II. Al remaining pairs representindividuals from a study of intravenous drug usersin New Jersey who were both HTLV EIA (AbbottLaboratories) reactive and con rmed by PCR torepresent HTLV-II infection (380). Figure courtesyof Paul E. Palumbo, M.D., Steven S. Alexander,Ph.D., and Stanley H. Weiss, M.D.

168 Chapter 8