T CD4+ cells count among patients co-infected with human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type 1 (HTLV-1): high prevalence of tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM)

Abstract

SUMMARYIntroduction: HIV positive patients co-infected with HTLV-1 may have an increase in their T CD4 + cell counts, thus rendering this parameter useless as an AIDS-defining event. Objective: To study the effects induced by the co-infection of HIV-1 and HTLV-1 upon CD4 + cells. Material and Methods: Since 1997, our group has been following a cohort of HTLV-1-infected patients, in order to study the interaction of HTLV-1 with HIV and/or with hepatitis C virus (HCV), as well as HTLV-1-only infected asymptomatic carriers and those with tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). One hundred and fifty HTLV-1-infected subjects have been referred to our clinic at the Institute of Infectious Diseases "Emílio Ribas", São Paulo. Twenty-seven of them were also infected with HIV-1 and HTLV-1-infection using two ELISAs and confirmed and typed by Western Blot (WB) or polymerase chain reaction (PCR). All subjects were evaluated by two neurologists, blinded to the patient's HTLV status, and the TSP/HAM diagnostic was based on the World Health Organization (WHO) classification. AIDS-defining events were in accordance with the Centers for Disease Control (CDC) classification of 1988. The first T CD4+ cells count available before starting antiretroviral therapy are shown compared to the HIV-1-infected subjects at the moment of AIDS defining event. Results: A total of 27 HIV-1/HTLV-1 co-infected subjects were identified in this cohort; 15 already had AIDS and 12 remained free of AIDS. The median of T CD4 + cell counts was 189 (98-688) cells/mm 3 and 89 (53-196) cells/mm 3 for co-infected subjects who had an AIDSdefining event, and HIV-only infected individuals, respectively (p = 0.036). Eight of 27 co-infected subjects (30%) were diagnosed as having a TSP/HAM simile diagnosis, and three of them had opportunistic infections but high T CD4 + cell counts at the time of their AIDS-defining event. Discussion: Our results indicate that higher T CD4 + cells count among HIV-1/HTLV-1-coinfected subjects was found in 12% of the patients who presented an AIDS-defining event. These subjects also showed a TSP/HAM simile picture when it was the first manifestation of disease; this incidence is 20 times higher than that for HTLV-1-only infected subjects in endemic areas.

Leukemia and Retroviral Disease

“…Importantly, the incidence of HAM/TSP in coinfected patients with AIDS was 20 times higher than those infected with only HTLV-1 infection. These results supported previous observations that HTLV-1/HIV-1 coinfection was associated with a higher probability of a more severe HTLV-1 infection along with an increase in the levels of CD4 + T cells [3]. These results have suggested the possibility that HTLV-1 may inhibit HIV-1 replication with a subsequent increase in CD4 + T-cell counts, thereby enhancing HTLV-1 disease progression.…”

“…One hundred and fifty HTLV-1-infected patients were enrolled in the study; 27 of them were coinfected with HIV-1, and 15 of the coinfected patients had already reported an AIDS-defining event. CD4 + T-cell counts were higher in coinfected individuals with AIDS than in HIV-1-monoinfected patients (median = 189 cells/mm 3 and 89 cells/mm 3 , respectively; p = 0.036). Moreover, five of the coinfected subjects who had AIDS and three of the coinfected patients without AIDS showed signs of HAM/TSP.…”

“…It is estimated that in endemic areas, 10% of HIV-1-infected patients are coinfected with HTLV-1 [3]. The frequency of HTLV-1 and HIV-1 coinfections is on the rise, especially in Africa and South America [4].…”

A comparative study of human T-cell lymphotropic virus-associated myelopathy in HIV-positive and HIV-negative patients in KwaZulu-Natal

“…It should be noted that although preserved, these CD4 cells are functionally impaired and ART should be considered regardless of the CD4 counts in these patients. 22,23 HIV leads to increased HTLV protein expression. 24,25 These effects may be a possible explanation as to how HTLV is more readily able to overcome the immune response.…”

Inhibition of HIV Type 1 Replication by Human T Lymphotropic Virus Types 1 and 2 Tax Proteinsin Vitro

“…In fact, in some geographic regions 5-10% of HIV-1-infected individuals may be coinfected with HTLV-1 or HTLV-2. 3,4 Several recent studies suggest three conclusions regarding HIV/HTLV coinfections: (1) HIV-1 and HTLV-1 coinfections are often seen in the context of patients with high CD4 + T cell counts and who manifest neurological complications 5,6 ; (2) HIV-1 and HTLV-2 coinfections have been linked in some cases to a ''long-term nonprogressor'' phenotype 3,7 ; and (3) differential function and/or overexpression of the HTLV-1 and HTLV-2 Tax proteins are likely to play a pivotal role in the clinical and immunological manifestations of HIV/HTLV coinfections. 8 Two retrospective case-controlled cohort studies investigating the clinical outcomes and survival probabilities among persons coinfected with HIV-1 and HTLV-1 or -2 showed that HTLV-2 coinfections resulted in improved survival and delayed progression to AIDS.…”