2nd National Conference Human Retroviruses and Related Infections


Washington, D.C. - January 29 - February 2, 1995

Cite as: Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: abstract no. xx

Session 6—Opportunistic Infections I
1 EVALUATION OF NEUROSYPHILIS IN PERSONS WITH AND WITHOUT CONCURRENT HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 1)
S. Gordon*, M. Eaton, J. Kuypers, S. Thompson, C. Marra, S. Lukehart
We conclude that the serum serologic response and neurologic involvement by T. pallidum may be affected by concurrent HIV infection in adult pts with symptomatic neurosyphilis. The PCR assay appeared to be a specific but not a sensitive means of detecting T. pallidum in CSF in adult pts with neurosyphilis.
2 A RANDOMIZED, DOUBLE-BLIND STUDY OF THE EFFICACY AND SAFETY OF ORAL GANCICLOVIR FOR THE PREVENTION OF CYTOMEGALOVIRUS DISEASE IN HIV-INFECTED PERSONS
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 2)
S.A. Spector*, G. McKinley, W.L. Drew, M.J. Stempien for the Syntex Ganciclovir Study Group
This study demonstrates that oral ganciclovir can significantly reduce the incident of, and time to, CMV disease and may improve survival in HIV-infected persons. The final analysis of this study will be presented.
3 RISK FACTORS FOR FLUCONZAOLE-RESISTANT CANDIDIASIS (FRC) IN HIV-INFECTED PATIENTS
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 3)
Maenza JR, Keruly JC, Moore RD, Chaisson RE, Gallant JE
Compared to patients with susceptible candidiasis, patients who develop FRC have more advanced HIV disease and greater exposure to oral azoles, Relatives importance of disease severity and azole exposure is not yet known.
4 IMPROVED OUTCOMES IN A COHORT OF HIV-INFECTED PATIENTS WITH MULTI-DRUG-RESISTANT TUBERCULOSIS ENROLLED IN A DIRECTLY OBSERVED THERAPY TUBERCULOSIS PROGRAM
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 1d)
Salomon N, Perlman DC
Bacteriologic response and survival of HIV+ person with MDR- TB can exceed that previously reported when treated with effective agents with adherence assured by DOT.
5 TWICE WEEKLY INH VS RIF AND PZA FOR TB PROPHYLAXIS IN HIV INFECTED ADULTS
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 5)
Halsey N, Coberly J, Losikoff P, Atkinson J, Moulton L, Cantave M, Johnson M, Chaisson R, Geiter L, Huebner R
Twice weekly INH chemoprophylaxis for 6 months provides effective prevention against TB in HIV infected adults during the treatment period, but the optimal duration of prophylaxis has not been determined. The differences in the rates of breakthrough TB appear to be related primarily to the different durations of prophylaxis.
6 A PHASE II/III TRIAL OF RIFAMPIN (RIF) CIPROFLOXACIN (CIPRO), CLOFAZIMINE (CLOF), ETHAMBUTOL (ETH), ± AMIKACIN (AK) IN THE TREATMENT (RX) OF DISSEMINATED MYCOBACTERIUM AVIUM (MA) INFECTION IN HIV-INFECTED INDIVIDUALS (PTS).
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 1f)
Parent D, Ellner J, Hafner R, Williams M, Jacobs P, Hojczyk P, and ACTG 135 Protocol Team
The proportion of negative cultures increased in similar fashion. 13 PTS died within the first 12 wks, 24 during the remainder of study, 10 after study discontinuation. There was no difference between RX arms in after study discontinuation. There no was difference between RX arms in survival distributions (logrank test p=0.83). The addition to AK to this four-drug oral regimen did not provide additional clinical or microbiological benefit.
7 MYCOBACTERIUM AVIUM COMPLEX (MAC) DISEASE IN HIV-INFECTED PATIENTS IS A UNIFORM INFECTION OF BONE MARROW THAT DOES NOT CORRELATE WITH THE LEVEL OF INFECTION IN BLOOD
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 7)
DATRI 007 Study Group
In this group of patients, we found a high correlation in MAC load from bilateral bone marrow specimens, suggesting that MAC is uniformly distributed in the bone marrow. MAC load was several logs higher in bone marrow than blood. However, the correlation between MAC and blood load was poor, suggesting that baseline blood culture results are a poor indicator of tissue load.
8 TREATMENT OF DISSEMINATED MYCOBACTERIUM AVIUM COMPLEX (DMAC) WITH CLARITHROMYCIN DECREASES TRANSFUSIONAL REQUIREMENTS
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 8)
Burman W, Rietmeijer C, Reves R
Treatment of DMAC with a clarithromycin-based regimen was superior to a rifampin-based regimen as judged by a marked decrease in transfusional requirements. Anemia is a prominent effect of DMAC, and changes in transfusional /EPO requirements may be a valuable clinical endpoint for clinical trials of DMAC therapy.
Session 7—Epidemiology
9 ESTIMATED RISK OF HIV TRANSMISSION BY SCREENED BLOOD IN THE UNITED STATES
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 9)
Lackritz EM1, Satten GA1, Raimondi VP2, Aberle-Grasse J3, Dodd RY3, Lewis WF3, Petersen LR1
The estimated risk of HIV transmission by screened blood in the United States is small and is lower than earlier estimates.
10 HIV INCIDENCE AMONG YOUNG URBAN STREET-RECRUITED CRACK COCAINE SMOKERS
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 10)
Brian RE1, Word CO2, McCoy CB3, Faruque S4, Dushku JC1, Holmberg SD1, and the Multicenter Crack Cocaine and HIV Infection Study Team
These HIV incidence rates are among the highest ever reported in the United States. HIV is being rapidly transmitted heterosexually among young adults in these inner city areas, particularly among crack smokers, and especially among women who exchange sex for money or drugs.
11 EFFICACY OF ANTENATAL ZIDOVUDINE IN REDUCING HIV-1 PERINATAL TRANSMISSION
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 11)
Matheson P, Thomas P, Abrams EJ, Hernan MA, Thea DM, Lambert G, Krasinski K, Bamji M, Rogers MF, Heagarty M, and the New York City Perinatal HIV Transmission Collaborative Study
The reduction in mother-to-child transmission of HIV-1 associated with antenatal ZDV use alone raises the possibility that the success of the ACTG 076 ZDV regimen may result primarily from maternal oral treatment. Further investigation of the efficacy of the other two treatment components (maternal intravenous intrapartum ZDV and newborn oral ZDV) is warranted. Pregnant women with high levels of immunosuppression who are at higher risk of transmission may also benefit from antepartum ZDV treatment.
12 CIRCUMSTANCES OF CAESAREAN DELIVERIES RELEVANT TO MATERNAL-INFANT HIV TRANSMISSION
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 12)
Kuhn L, Bobat R, Coutsoudis A, Moodley D, Coovadia HM, Tsai WY, Stein Z
If a caesarean section was undertaken with membranes intact, fewer infants were infected than if the procedure was undertaken following prior spontaneous rupture of membranes, although differences are not significant. The circumstances surrounding caesarean deliveries may influence the risk of maternal-infant HIV transmission.
13 INTERVENTIONS AMONG THAI CONSCRIPTS MAY REDUCE HIV INCIDENCE
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 13)
Celentano DD, Bond KC, Chiang MC, Vaddhanaphuti C, Eiumtrakul S, Nelson KE
Preliminary data obtained through August 1994 demonstrates that there may be an intervention effect on HIV incidence. Incidence in the first two cohorts was 3.4 per 100 person-years. Incidence for the first intervention cohort was 0.87 per 100 person- years, with no seroconversions in the second half-year.
14 PRIMARY HIV-1 INFECTION IN TRINIDAD: CLINICAL, IMMUNOLOGIC AND VIROLOGIC CORRELATES
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 14)
Cleghorn F, Jack N, Greenberg M, Weinhold K, Edwards J, Murphy J, Paul R, Mahabir B, O'Brien T, Bartholomew C
Severe symptoms of HIV-1 seroconversion are rare in this cohort. ADCC not neutralizing antibody correlate with down modulation of viral expression and CD4 recovery.
15 MARKERS OF HIV-1 INFECTION AND RAPID PROGRESSION TO AIDS
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 3d)
Farzadegan H, Lack C, Henrard D, Rinaldo C, Saah A, Detels R, Munoz A, Margolick J, Phair J
The data suggest that an insufficient immune response to HIV gag-gene products occurring very early in the course of HIV infection may contribute to rapid progression of HIV-mediated immune system destruction. The role that intensive high-risk sexual behavior prior to seroconversion may play in the development of rapid disease progression remains unclear.
16 THE EFFECT OF CIGARETTE SMOKING ON SELECTED MEDICAL CONDITIONS ASSOCIATED WITH HIV INFECTION
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 16)
Conley LJ1, Bush TJ1, Buchbinder SP2, Penley KA3, Judson FN3, Holmberg SD1
Cigarette development of HIV-associated oral candidiasis, hairy leukoplakia, and bacterial pneumonia.
Session 8—Pathogenesis I
17 ABSENCE OF INTACT NEF SEQUENCES IN A LONG-TERM NONPROGRESSING SURVIVOR OF HIV-1-INFECTION
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 17)
Kirchhoff F1, Greenough TC2, Brettler DB3, Sullivan JL1, Desrosiers RC1
The clinical and virologic characteristics of the HIV-1 infection in this individual are strikingly similar to the characteristics of rhesus monkey infection with a strain of SIV deleted in nef. These results suggest that infection with nef-defective, attenuated forms of HIV-1 may be responsible for the lack of disease progression in some individuals. The results also provide further justification for considering use of HIV-1 deletion mutants as live-attenuated vaccines.
18 NON-PROGRESSIVE HIV-1 INFECTION IS ASSOCIATED WITH LOW VIRAL BURDENS AND DETECTABLE PRIMARY CYTOTOXIC T LYMPHOCYTE RESPONSES IN INDIVIDUALS WITH HEMOPHILIA
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 18)
Greenough T1, Brettler D2, Forsberg A2, Sullivan JL1
These studies show that individuals with normal CD4 counts despite more than ten years of infection with HIV-1 have remarkably low viral burdens in circulation. That these individuals maintain activated circulating CTL indicates ongoing viral antigen expression.
19 VIRAL DYNAMICS IN HIV-1 INFECTION
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 19)
Shaw G1, Wei X1, Ghosh S1, Taylor M1, Kilby JM JR1, Johnson V1, Emini E2, Lifson J3, Hahn B1, Saag M1
The short t½ of virus in plasma and the rapidity of viral population turnover indicate that ongoing de novo infection of, and virus production by, a relatively short-lived lymphocyte and/or macrophage cell population plays a far greater role in viral pathogenesis than previously recognized. These results, and the methods described here to assess viral population turnover, have broad application in studies of viral pathogenesis, drug resistance, and immune surveillance.
20 HLA CLASS I AND CLASS II, AND TAP GENES STRONGLY INFLUENCE THE COURSE OF HIV INFECTION
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 20)
Kaslow RA, Mann D, Apple R, Carrington M, Munoz A, Park L, Detels R, Rinaldo C, Phair J, Goedert J, Saah A, for the Multicenter AIDS Cohort Study (MACS) and the DC Gay Cohort (DCG)
Specific combinations of interacting HLA class I, class II and TAP gene products appear to impact heavily on the course of HIV-1 infection. Confirmation of these effects on the natural history will have broad implication for care and vaccine development.
21 EARLY PATTERN OF HIV REPLICATION DETERMINES THE COURSE OF DISEASE PROGRESSION IN VERTICALLY INFECTED INFANTS
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 21)
Dickover R, Kwok S, Christopherson C, Wei L, Bryson Y
Our results indicate that rapid HIV replication early in vertical infection is associated with rapid disease progression. RNA PCR may prove useful for identifying infants who should be targeted for early antiretroviral therapy prior to the loss of CD4 cells.
22 VIRAL LOAD AND IMMUNOPHENOTYPE OF CELLS OBTAINED FROM LYMPH NODES BY FINE NEEDLE ASPIRATION COMPARED TO PERIPHERAL BLOOD CELLS IN HIV-INFECTED PATIENTS
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 22)
Meylan PR, Burgisser P, Weyrich SC, Spertini F
The minimum number of LNC necessary to cause a positive coculture ranged from 103 to >105 (median 104) while the corresponding number for PBMC ranged from 103 to >106 (median: 5×105). In patients selected for palpable LN, LNC could be obtained by FNA in a majority of patients. This methodology should allow to monitor the effect of antiviral therapy on the viral load in the lymphoid tissue in a non invasive manner.
23 DENDRITIC CELLS BIND HIV TO THEIR SURFACE AND INFECT UNSTIMULATED CD4 POSITIVE T CELLS: A MODEL FOR THE INITIATION OF HIV INFECTION
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 23)
Weissman D, Li Y, Barker T, Daucher J, Fauci AS
These conjugates of DC and T cells are easily infectable with small amounts of virus. A model where DC bind HIV at mucous membranes, travel to lymphoid organs alone or bound to T cells, migrate to the paracortical regions, and initiate active viral replication will be discussed.
24 HTLV-1 ENCEPHALOMYELOPATHY WITH DIRECT INFECTION OF BRAIN AND SPINAL CORD
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 24)
Isaacson SH, Al-Attar A, Gajdusek DC, Gibbs CJ Jr
Direct infection of the CNS may play a role in HTLV-1 associated neurological disease. Immunohistochemistry is being used to precisely identify infected neuroglia.
Session 9—Virology I
25 HIV TAT PROTEINS SPECIFICALLY ASSOCIATE WITH A CELLULAR PROTEIN KINASE (TAK) THAT HYPERPHOSPHORYLATES THE CARBOXYL- TERMINAL DOMAIN OF RNA POLYMERASE II: CANDIDATE FOR A TAT COFACTOR
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 25)
Herrmann CH, Rice AP
Phosphorylation of the CTD has been proposed to trigger the transition from initiation to active elongation and also to influence later stages during elongation. Together, these results implicate TAK as a very promising candidate for a cellular factor that mediates Tat transactivation. We are currently attempting to purify TAK and investigate its role in Tat function.
26 THE HIV-1 VPU PROTEIN SPECIFICALLY BINDS TO THE CD4 CYTOPLASMIC DOMAIN: IMPLICATIONS FOR THE MECHANISM OF CD4 DEGRADATION
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 26)
Bour S, Schubert U, Strebel K
Taken together, these results indicate that Vpu binding is necessary to trigger CD4 degradation. However, the binding to target molecules is not sufficient per se to cause degradation. Interaction between CD4 and Vpu is thus likely to be an early event critical in triggering a multi-step process leading to CD4 degradation. We also clarified the post-binding events of Vpu-mediated degradation of CD4 by examining the requirement of ATP in this process and are currently investigating the identity of the protease activities involved.
27 ENHANCEMENT OF VIRAL INFECTIVITY BY HIV-1 NEF
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 27)
Chowers M, Spina C, Richman D, Guatelli J
The hypothesis that CD4 downregulation by Nef is unrelated to the more rapid growth of wild-type virus was supported by growth curve studies using cells that express a truncated CD4 molecule lacking the cytoplasmic domain. These results suggest that the attenuation in vitro of nef-negative HIV-1 is due to post-entry events that lead to the establishment of the provirus and is unrelated to CD4 downregulation.
28 PROTEIN KINASE ACTIVITY IN IMMUNOPRECIPITATES CONTAINING NEF PROTEIN OF SIVmac239
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 28)
Lang SM, Jung JU, Desrosiers RC
The 34 kDa protein that was the target of phosphorylation products were observed in COS cells using transient expression of nef from SIVmac239. These results, and the recent report of Sawai et al. (Proc. Natl. Acad. Sci.91:1539-1543,1994), suggest that nef may activate cellular protein kinases. Progress on identification of the cellular protein kinase will be presented.
29 STRUCTURAL AND FUNCTIONAL STUDIES ON HIV-1 Vpr SUGGEST THE IMPORTANCE OF A PREDICTED ALPHA-HELICAL AMINO-TERMINAL DOMAIN
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 29)
Di Marzio P1, Choe S1, Connor RI1, Knoblauch R2, Ebright M2, Isakoff S2, Landau NR1,2*
These experiments also showed, in agreement with a recent report, that Vpr appears to overlap in function with the matrix nuclear localization sequence in allowing infection of nondividing cells. In monocytes, Vpr appears to have an additional role subsequent to nuclear import.
30 GENETIC DISSECTION OF HIV-1 Vpr REVEALS DISTINCT FUNCTIONAL DOMAINS
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 30)
Mahalingam S1, Khan SA2, Jabbar MA3, Monken C1, Collman R4, Srinivasan A1
The role of Vpr in HIV-1 replication was also investigated using primary macrophages. Alteration at the Cys residue in Vpr, despite exhibiting virion incorporation function, showed a biological phenotype similar to Vpr-virus. These studies provide evidence for the presence of distinct functional domains in Vpr controlling different biological properties.
31 TARGETING FOREIGN PROTEINS TO HUMAN IMMUNODEFICIENCY VIRUSES TYPES 1 AND 2 VIA FUSION WITH VPR AND VPX
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 31)
Wu X1, Liu H1, Xiao H1, Kim J1, Seshaiah P2, Natsoulis G3, Boeke JD2, Hahn BH1, Kappes JC1
These results demonstrate the feasibility of incorporating foreign proteins into HIV virions by expression as gene fusions with vpr and vpx. Such findings may suggest potential application of virion-associated accessory proteins to gene therapy based approaches for limiting the spread of HIV by specific delivery/targeting of virus-toxic molecules.
32 EXAMINATION OF THE ROLE OF THE P6 GAG PROTEIN IN HIV-1 PARTICLE RELEASE
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 32)
Huang M, Martin MA, Freed EO
A mutation was introduced into the protease gene of the PTAP mutants to study further the role of p6 in virus particle production. Interestingly, the PTAP mutations did not reduce virus particle production in the context of the protease-defective proviral clone. These results suggest that Gag precursor processing by the viral protease might be linked, mechanistically, to virus release defect observed with p6 mutants.
Session 15—HIV-1: Regulatory Elements
33 EFFECTS OF DIFFERENT TYPES OF RADIATION ON HIV PROMOTER-DRIVEN GENE EXPRESSION
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 33)
Libertin CR, Panozzo J, Groh K, Chang-Liu CM, Schreck S, Woloschak G
When microwave exposure was carried out in low volumes of medium (so that excessive heat was generated) induction of HIV-LTR transcription was evident. Electromagnetic field exposures had no effect on expression of HIV-LTR. These results demonstrate that not all types of radiation and not all DNA-damaging agents are capable of inducing HIV. We hypothesize that inducing of HIV transcription may be mediated by several different signals after exposure to radiation.
34 TAR- AND TAT- INDEPENDENT REPLICATION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 IN HUMAN LIVER CELLS
Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 34)
Zhu M, Duan L, Pomerantz RJ
This alternative regulatory pathway of TAR- and Tat- independent viral production may be important in certain cell-types, for therapies which seek to perturb Tat-TAR binding as a strategy to interrupt the viral lytic cycle.
Session 16—HIV-1: Latency, Tropism and Envelope — Cellular Interactions