Human T-cell Lymphotropic Virus Type III Research Articles

Frequency and Survival of T-Cell Lymphomas in Peru: Initial Report of a Peruvian Registry Experience

Introduction: T-cell lymphomas are a relatively rare and heterogeneous group of lymphoid neoplasms. Its incidence relies on viral infections incidence as Human T-cell lymphotropic virus type I-II (HTLV-I/II) and Ebstein Bar virus (EBV). Specifically, these viruses have a significantly higher incidence in Latin-American populations. Our objective was to calculate the incidence and survival of T-cell lymphomas in the largest Peruvian population based on a national registry. Methods: We conducted a multicenter, retrospective registry study of non-Hodgkin T cell lymphoma. The data was extracted from Instituto Nacional de Enfermedades Neoplasicas and Oncosalud-AUNA, Lima-Peru, from January 2010 to December 2019, a total of 948 patients who were diagnosed as mature T cell non-Hodgkin lymphoma based on the World Health Organization Classification 2008 were enrolled. T-lymphoblastic lymphoma/leukemia was excluded. Overall survival was calculated based on death dates from the Peruvian national identification registry (RENIEC).Results: The median age was 51 years (range, 1-94), and male and female patients were 512 (54%) and 436 (46%). Among the 948 patients enrolled, Peripheral T-cell lymphoma was the common neoplasm accounting for 23% (n=221), and Extra-Nodal NK T-lymphoma (22%, n=213), Adult T-cell lymphoma (22%, n=205), Anaplasic Large cell lymphoma (14%, n=131), Cutaneous T-cell lymphoma (14%, n=129) (Figure 1a). At the time of diagnosis, extranodal disease was found in 68.6% (650) of patients. By July 2021, only 15.3% of cases were in remission and 37% (350) were alive. Median global overall survival of T-cell lymphomas was 1 year (0.8-1.1), Cutaneous T-cell lymphoma had the highest survival and Adult T-cell lymphoma had the lowest survival (Table 1 and Figure 1b).Conclusion: This initial report shows a relatively high frequency of mature T-cell lymphomas in Latin-America real-world setting, and confirms that T-cell lymphomas patients had a dismal outcome. The clinical outcome for patients with T-cell lymphomas subtypes is poor with standard therapies, and novel agents and new modalities are needed to improve survival. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Clinical investigations of lymphadenopathy, including lymph node biopsies, in 24 homosexual men with antibodies to the human T-cell lymphotropic virus type III (HTLV-III).

The findings of 27 lymph node biopsies performed on 24 homosexual patients with lymphadenopathy are presented. Six had acquired immune deficiency syndrome (AIDS) and 18 lymphadenopathy only, of whom one subsequently developed AIDS. All these patients had antibodies to the human T-cell lymphotropic virus type III (HTLV-III) suggesting that HTLV-III is currently the commonest cause of lymphadenopathy in homosexual men. The histopathological findings of six of seven nodes from AIDS patients showed either follicular depletion alone or follicular and paracortical lymphocyte depletion. Nodes from four patients showed Kaposi's sarcoma, three of which also showed follicular hyperplasia. In two of these patients there were no cutaneous manifestations of this condition. One lymph node from a patient with persistent generalized lymphadenopathy (PGL) showed Mycobacterium tuberculosis. Six nodes from six other patients have had features of toxoplasmosis although there was no serological or clinical evidence of recent toxoplasma infection. The remaining 11 lymph nodes from patients with PGL and one node from a patient with transient lymphadenopathy, showed reactive follicular hyperplasia only. We conclude that homosexuals with lymphadenopathy who are HTLV-III antibody positive do not need a routine node biopsy unless an alternative diagnosis is strongly suspected.

Living With AIDS

The worldwide pandemic of the acquired immunodeficiency syndrome (AIDS), which was first manifest a scant 10 to 12 years ago, has assumed a kaleidoscope of identities. In one short decade, the name of the disease progressed from gay-related immune disease (GRID), to HTLV-III (human T-cell lymphotropic virus type III) infection, to HIV (human immunodeficiency virus) infection, and its stages of development added yet further acronyms: ARC (AIDS-related complex) and AIDS itself. Some of these terms, though obsolete, have become enshrined in the language of bureaucracy, which defines eligibility for social services and entitlement. The terminology of the AIDS social movement in the United States has also evolved. Social activists have rejected the pity and dependency that they believe are embodied in such terms as "AIDS victims" or even "AIDS patients." They prefer terms of empowerment and the neutral "people with AIDS" (PWAs). They eschew "innocent victims," often employed when describing

HTLV-I/II Infection in Women With Acute Pelvic Inflammatory Disease

To the Editor.— We studied the seroprevalence of human T-cell lymphotropic virus type I/II (HTLV-I/II) antibody in 333 women admitted to San Francisco General Hospital with acute pelvic inflammatory disease between January 1985 and December 1988. Testing was limited to banked serum samples from women who had enrolled in antibiotic research studies, representing 45% of women admitted with acute pelvic inflammatory disease during this period. Antibody to chromatographically purified (C91/PL) HTLV-I was detected by immunoblot; reactivity with p24 and p19 was confirmed by two separate observers. Seroprevalence of HTLV-I/II was 3.0% (95% confidence interval, 1.2% through 4.8%). There was no evidence of increasing prevalence of infection during the 4-year time span: 2 (12.5%) of 16 patients in 1985, 4 (3.9%) of 103 in 1986,4 (4.2%) of 95 in 1987, and 0 (0%) of 119 in 1988. In this same sample, seroprevalence of human immunodeficiency virus type 1 was 4.2% (95%

Antibody to the AIDS Virus in Kaposi’s Sarcoma in Nigeria

The present study has investigated whether Kaposi's sarcoma (KS) in Nigeria is associated with infection with the AIDS virus variously called human T-cell lymphotropic virus type III (HTLV-III), lymphadenopathy/AIDS virus (LAV), and AIDS-associated retrovirus (ARV). Serum samples from 40 KS patients, 30 patients with malignant melanoma of the foot (contemporaneous controls), and 50 normal nontumour-bearing controls were tested for anti-AIDS virus antibody by enzyme-linked immunosorbent assay (ELISA). The assay consistently and reproducibly failed to show seropositivity in all the patients and controls. These results show that Kaposi's sarcoma in Nigeria is not associated with infection with the AIDS virus and that the virus is not endemic in this region.

Envelope sequences of two new United States HIV-1 isolates

One of the striking molecular aspects of the human T-cell lymphotropic virus type III (HTLV-III) (now called HIV-1) is an unusually large variability in the env genes of different isolates. These differences are clustered primarily within the coding sequences for the large envelope protein and are interspersed among regions within the env gene of relative constancy. Differences among the envelopes of isolated from Africa are so far greater than those among U.S. isolates, but few U.S. isolates have been characterized to date. We report the sequence of the env gene of two U.S. isolates [HTLV-III(MN) and (SC)] and compare them with previously characterized isolates. These two isolates differ substantially from all previously described isolates, especially in the region coding for the large envelope proteins. The env genes of the two new HIV-1 isolates contain conserved and hypervariable regions similar to what has been reported for other isolates, helping to further define those regions. A comparison of the envelope sequences of all the U.S. isolates shows that the similarity between any two ranges from 81 to 85% [except for LAV(BRU) and HTLV-III(BH10) which are 97% similar]. Similar analyses of the African (Zairean) isolates give significantly lower values [71 to 78%, except for 88% between LAV(ELI) and Z6]. This suggests that the African isolates diverged earlier than the U.S. isolates or that transmission of the virus has been more rapid in Africa. Two previous presumptive Haitian isolates are similar to each other and to the U.S. isolates to the same degree as are other U.S. isolates, but differ more markedly from the African isolates, suggesting a common lineage of Haitian and U.S. HIV-1 isolates.

Effects of heat inactivation on HIV antibody screening and confirmatory test systems.

In order to evaluate the effect of heat inactivation on serum undergoing testing for HIV antibody, 100 heat-inactivated and nonheat-inactivated serum samples were tested by two modifications of Abbott's screening assays for human T-cell lymphotropic virus type-III (lot numbers 1037 and 3036) and by two confirmatory assays (Cambridge BioScience CBre3-EIA; Damon Corporation Western blot). The samples consisted of 75 HIV antibody-negative and 25 HIV antibody-positive sera. The specimens were divided into two equal aliquots. One set was not subjected to heat inactivation, while the others were subjected to heat inactivation at 56 degrees C for 30 min. Heat inactivation had no significant effect on the HIV-position sera; however, heat-inactivated, negative sera evaluated by Abbott lot numbers 1037 and 3036 resulted in false-positive rates of 8% and 7%, respectively. No false positives were generated by the two confirmatory assays; however, the CBre3-EIA recombinant envelope protein assay had a significantly increased optical density reading following heat inactivation of the negative sera. The Western blot procedure used in the study was not affected by heat inactivation.

Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides.

A synthetic peptide (SP-10-IIIB) with an amino acid sequence [Cys-Thr-Arg-Pro-Asn-Asn-Asn-Thr-Arg-Lys-Ser-Ile-Arg-Ile-Gln-Arg-Gly-Pro -Pro-Gly-(Tyr); amino acids 303-321] from the human immunodeficiency virus (HIV) isolate human T-cell lymphotropic virus type III (HTLV-III) HTLV-IIIB envelope glycoprotein gp120 was coupled to tetanus toxoid and used to raise goat antibodies to HIV gp120. Goat anti-SP-10-IIIB serum bound to the surface of HTLV-IIIB-infected CEM T cells but not to the surface of HTLV-IIIRF-infected or uninfected CEM T cells. Anti-SP-10-IIIB antibodies also selectively bound to gp120 from lysates of HTLV-IIIB cells in immunoblot assays. Twenty-one percent of sera (28 of 175) from patients seropositive for HIV contained antibodies that reacted with SP-10-IIIB in RIA. Human anti-SP-10-IIIB antibodies affinity purified from acquired immunodeficiency syndrome (AIDS) patient serum bound to HTLV-IIIB-infected cells and immunoprecipitated gp120. Goat antibodies to SP-10-IIIB neutralized HTLV-IIIB (80% neutralization titer of 1/600), inhibited HTLV-IIIB-induced syncytium formation, but did not neutralize HIV isolates HTLV-IIIRF or HTLV-IIIMN or inhibit syncytium formation with these isolates. Also, goat antiserum to an homologous synthetic peptide [SP-10-IIIRF(A), (Cys)-Arg-Lys-Ser-Ile-Thr-Lys-Gly-Pro-Gly-Arg-Val-Ile-Tyr] from gp120 of HIV isolate HTLV-IIIRF inhibited syncytium formation by HTLV-IIIRF, but did not inhibit syncytium formation by HTLV-IIIB or by HTLV-IIIMN. Thus, the amino acid sequences of SP-10-IIIB and SP-10-IIIRF(A) define homologous regions of gp120 that are important in type-specific virus neutralization. The identification of these type-specific neutralizing epitopes should facilitate the design of a polyvalent, synthetic vaccine for AIDS.

Antibody to the AIDS virus in Kaposi's sarcoma in Nigeria.

The present study has investigated whether Kaposi's sarcoma (KS) in Nigeria is associated with infection with the AIDS virus variously called human T-cell lymphotropic virus type III (HTLV-III), lymphadenopathy/AIDS virus (LAV), and AIDS-associated retrovirus (ARV). Serum samples from 40 KS patients, 30 patients with malignant melanoma of the foot (contemporaneous controls), and 50 normal nontumour-bearing controls were tested for anti-AIDS virus antibody by enzyme-linked immunosorbent assay (ELISA). The assay consistently and reproducibly failed to show seropositivity in all the patients and controls. These results show that Kaposi's sarcoma in Nigeria is not associated with infection with the AIDS virus and that the virus is not endemic in this region.

Neurologic disease as the presenting manifestation of acquired immunodeficiency syndrome.

Neurologic disease was the harbinger of the acquired immunodeficiency syndrome (AIDS) in 26 (20%) of 132 patients and ultimately developed in 83 (63%). The most common neurologic disorder heralding AIDS was toxoplasmic encephalitis (17 cases) followed by cryptococcal meningitis (six), retinitis (three), progressive multifocal leukoencephalopathy (two), neuropathy (one), myopathy (one), and subacute "viral" encephalitis (one). In four patients, more than one neurologic disorder coexisted at presentation. Recognition of underlying human T cell lymphotropic virus type III (HTLV-III) infection may allow a more expedient determination of the cause of the neurologic disease. Our study emphasizes the importance of testing for the presence of HTLV-III antibody and assessing the immunologic status of all patients at risk for AIDS who have neurologic illness.

Oral Hairy Leukoplakia

Oral hairy leukoplakia (HL) is a newly described lesion occurring principally on the lateral borders of the tongue in immunosuppressed homosexual men infected with human T-cell lymphotropic virus type III (HTLV-III). Clinically, HL appears as a slightly raised, poorly demarcated lesion with a corrugated or "hairy" surface. Histologically, the lesion is characterized by keratin projections on the surface (which often resemble hairs), parakeratosis, and acanthosis. In addition, large pale-staining cells with pyknotic nuclei are seen in the upper stratum malpighii, which appear similar to the koilocytes described in uterine condylomata. Candida organisms are frequently observed on the lesion surface. Little, if any, subepithelial inflammation is present. Human papillomavirus and Epstein-Barr virus have been identified in biopsy specimens from lesions of oral HL. The association of this lesion in patients with HTLV-III infection has been established. We saw a patient with HTLV-III infection and HL, in whom the immunochemical and ultrastructural findings revealed the presence of a mixed viral infection. Because oral HL may be of diagnostic value as an early indicator of HTLV-III infection, awareness of its characteristic clinical, histologic, immunochemical, and ultrastructural features is important.

Autologous Blood Transfusion

To the Editor.— Report H of the American Medical Association's Council on Scientific Affairs1will assist greatly in establishing regular usage for autologous blood transfusions. The idea of using your own blood for yourself has long appealed to the prospective recipient and has been advocated by blood bankers. The involvement of the clinician in using the service is necessary for success. There is correction needed in the COUNCIL REPORT about the most practical option, ie, predeposit autologous blood. The Council advocates that donated blood undergo ABO and Rh group testing, antibody screening, and screening for hepatitis B surface antigen and human T-cell lymphotropic virus type III (HTLV-III) antigen. The last words are in error, since testing for the HTLV-III antigen is not done. The available blood bank test of the donor blood is for the antibody to the HTLV-III antigen, not the antigen itself. In addition, the Council has

Evaluation of Heterosexual Partners, Children, and Household Contacts of Adults With AIDS

Forty-five adults with the acquired immunodeficiency syndrome (AIDS) and their 45 spouses, 109 children, and 29 household contacts were studied for evidence of heterosexual, perinatal, and household spread of human T-cell lymphotropic virus type III (HTLV-III) infection. Of the 45 spouses enrolled, 26 (58%) had antibody to HTLV-III, including 12 (71%) of 17 male spouses and 14 (50%) of 28 female spouses. Of the 12 seropositive male spouses, nine were seropositive at enrollment and three had seroconversion. Of the 14 seropositive female spouses, four were seropositive at enrollment and ten seroconverted. Lack of barrier contraceptive use and oral sex were associated with seroconversion. Of the 109 children enrolled, 15 had AIDS or an AIDS-related illness, two had evidence of passive transfer of maternal antibodies, and two had HTLV-III infection acquired outside the household. None of the 90 seronegative children seroconverted. Of 29 household contacts studied, none developed antibody to HTLV-III.

HTLV-III Antibodies After Immune Globulin

To the Editor.— In their recent letter, Wolfe et al 1 presented an analysis of the potential of a transient false-positive reaction on an enzyme-linked immunosorbent assay for antibody to human T-cell lymphotropic virus type III (HTLV-III) in recipients of immune globulin (IG) made from unscreened source material. Their analysis was limited to the case of intramuscular administration of a 5-mL dose of IG to US military personnel. Two factors not included in the case analyzed by Wolfe et al can greatly increase the chance of observing a transient false-positive in the HTLV-III antibody test. The standard dose in the case presented by these authors, calculated on the basis of their assumptions, is 10 mg/kg. Intravenous (IV) IG therapy is often given at a dosage of 400 mg/kg. Consequently, a recipient of IV IG may have a serum titer of passively received antibodies that is 40 times greater than that

Antibody to Human Lymphotropic Virus Type III

Twenty homosexual men who reported having sexual contact with homosexual men who had the acquired immunodeficiency syndrome (AIDS) or the AIDS-related complex were examined to determine their clinical status, immunologic profiles, and the presence of antibody to the human T-cell lymphotropic virus type III (HTLV-III). Of the 20, eight men had one or more signs or symptoms of the AIDS-related complex and 12 were asymptomatic. Antibodies to HTLV-III were present in 14 (70%) of 20 of the sexual contacts as compared with four (10%) of 40 healthy homosexuals without known contact with a patient who had AIDS (P less than .0001). Seropositive contacts had significantly higher mean counts of suppressor lymphocytes and lower helper: suppressor ratios (P less than .05 and .005, respectively) and higher serum levels of IgG than seronegative contacts (P less than .05). It was not possible to determine significant differences in sexual practices, drug use, length of relationship, or numbers of different sexual partners between symptomatic and asymptomatic contacts or between seropositive and seronegative contacts in this study.

Inhibition of replication and cytopathic effect of human T cell lymphotropic virus type III/lymphadenopathy-associated virus by 3'-azido-3'-deoxythymidine in vitro

Human T cell lymphotropic virus type III (HTLV-III)/lymphadenopathy-associated virus is the etiologic agent of the acquired immune deficiency syndrome (AIDS) and AIDS-related complex. The effect of 3'-azido-3'-deoxythymidine (AZT) on the HTLV-III/lymphadenopathy-associated virus infection was quantitatively studied with HTLV type I-carrying MT-4 cells. The AZT compound inhibited HTLV-III-induced cytopathic effect and virus-specific antigen expression in MT-4 cells at concentrations of 5 and 10 microM. In addition, a plaque-forming assay was performed to assess the effect of AZT on virus replication in MT-4 cells freshly infected with HTLV-III and in continuous HTLV-III-producing Molt-4/HTLV-III cells. Results showed that AZT efficiently and effectively inhibited the replication of HTLV-III in infected MT-4 cells. AZT is a strong inhibitor of reverse transcriptase activity of HTLV-III as a triphosphate, to such a degree that even 1.0 pM azido-TTP inhibits 50% of reverse transcriptase activity. However, it did not show any effect in the HTLV-III-producing cell line Molt-4/HTLV-III. Thus, AZT has no effect on virus replication of an already integrated virus. When 5 microM AZT was added to HTLV-III-infected MT-4 within 20 h after infection, a striking suppressive effect was noticed. This concentration was much lower than that which inhibits the growth of MT-4 cells. These results confirm those found in a previous report (H. Mitsuya, K. J. Weinhold, P. S. Furman, H. S. Clair, S. N. Lehrman, R. C. Gallo, D. Bolognesi, D. W. Barry, and S. Broder, Proc. Natl. Acad. Sci. USA 82:7096-7100, 1985) and suggest that AZT might be used as an experimental antiviral agent for AIDS and AIDS-related complex.

Myelodysplasia Progressing to Acute Myeloblastic Leukemia in an HTLV-III Virus-Positive Homosexual Man with AIDS-Related Complex

Myelodysplastic changes have recently been described in patients with the acquired immunodeficiency syndrome (AIDS). The authors report a patient with AIDS-related complex and myelodysplasia who rapidly progressed to acute myeloblastic leukemia. Infection with human T-cell lymphotropic virus type III (HTLV-III) was documented by culture and by serology. Chromosome studies showed monosomy of chromosome 7 and structural abnormality of the long arm of chromosome 3. The association of HTLV-III infection with myelodysplasia and acute myeloblastic leukemia may have been coincidental in this reported case, but it is also possible that the leukemia was secondary to the HTLV-III infection. Further investigation appears justified.

Human T-Cell Lymphotropic Virus Type III (HTLV-III) Embryopathy

• Twenty infants and children with positive serologic tests for the human T-cell lymphotropic virus type III (HTLV-III) were noted to have similar features including growth failure (75%), microcephaly (70%), and craniofacial abnormalities consisting of ocular hypertelorism (50%); prominent box-like appearance of the forehead (75%); flat nasal bridge (70%); mild upward or downward obliquity of the eyes (65%); long palpebral fissures with blue sclerae (60%); short nose with flattened columella and well-formed, triangular philtrum (65%); and patulous lips (60%). These features constitute a new and distinct dysmorphic syndrome, the HTLV-III embryopathy. ( AJDC 1986;140:638-640)

Health education and knowledge assessment of HTLV-III diseases among intravenous drug users.

The human T-cell lymphotropic virus, type III (HTLV-III) is the causative agent of acquired immunodeficiency syndrome (AIDS). Since AIDS is not curable, public health efforts must be focused on decreasing AIDS transmission. 72% of all AIDS cases are male homosexuals; 17% are intravenous (IV) drug users; and 3% are hemophiliacs, blood recipients, and infants of these groups. The gay community is sufficiently organized to provide the necessary infrastructure for AIDS education and treatment; the drug users are not, and at least 1/3 of IV drug users share needles and syringes. In 1984 a cooperative study was undertaken in New Jersey by the New Jersey State Department of Health, the National Cancer Institute (NCI), and the National Institute on Drug Abuse (NIDA) to determine the seroprevalence of HTLV-III among IV drug users and to assess their knowledge about AIDS. Over 95% knew the severer symptoms of AIDS; 76% knew that most AIDS patients die within 2 years of diagnosis; but 9% thought AIDS could be treated. A year later in 1985 a similar knowledge assessment survey was done among 577 clients entering drug treatment programs in New Jersey. 90% of these respondents knew that homosexuals and IV drug users were the primary risk groups, but 11% thought alcoholics were also at risk, and 43% did not know that the infants of drug users were at risk. 84% knew that sex and shared needles were the major modes of transmission, but 1/3 thought that an infected person would immediately show visible signs of illness, and many did not know how rapidly AIDS killed. Also, many did not know how to adequately clean syringes. They thought boiling would damage the syringes, and only 1/3 knew that a dilute solution of household bleach kills the virus. New Jersey decided to use indigenous health workers, recruited from rehabilitated drug users, to educate the drug community. The core message was: get treatment; don't share needles; and if you must share needles, clean them. The same message reaches drug users on late-night television and radio and English language newspapers. Drug users are educable; whether education and peer pressure will effect behavior modification remains to be seen.

Detection of HTLV-III RNA in Lungs of Patients With AIDS and Pulmonary Involvement

A majority of pediatric patients and rare adult patients with the acquired immunodeficiency syndrome (AIDS) develop a chronic respiratory disorder referred to as "lymphocytic interstitial pneumonitis" (LIP). Efforts to identify an infectious agent responsible for this process so far have failed. In this study, frozen sections of lungs from patients with AIDS and pulmonary disease were tested by in situ molecular hybridization for the presence of cells infected with human T-cell lymphotropic virus type III (HTLV-III) and expressing viral RNA. In the case of an infant with LIP, a relatively high frequency (0.1%) of cells in the lung were found to be positive for HTLV-III RNA. This number is the lower limit of total cells infected since the in situ hybridization technique as applied in this study depends on expression of HTLV-III genes, and previous evidence indicates that a proportion of cells infected with HTLV-III may not express viral RNA. Moreover, this degree of infection of the lung is likely limited to LIP, since in ten patients with AIDS and pulmonary diseases other than LIP, only 0% to 0.002% of cells in lung were positive for viral RNA expression. Thus, HTLV-III may play a direct causal role in the development of LIP in infected patients, implicating its involvement in yet another of the diverse clinical diseases associated with this virus.