Unusual primary HIV infection with colonic ulcer complicated by hemorrhagic shock: a case report

<p>Abstract</p> <p>Introduction</p> <p>Timely diagnosis of primary HIV infection is important to prevent further transmission of HIV. Primary HIV infection may take place without symptoms or may be associated with fever, pharyngitis or headache. Sometimes, the clinical presentation includes aseptic meningitis or cutaneous lesions. Intestinal ulceration due to opportunistic pathogens (cytomegalovirus, Epstein-Barr virus, <it>Toxoplasma gondii</it>) has been described in patients with AIDS. However, although invasion of intestinal lymphoid tissue is a prominent feature of human and simian lentivirus infections, colonic ulceration has not been reported in acute HIV infection.</p> <p>Case description</p> <p>A 42-year-old Caucasian man was treated with amoxicillin-clavulanate for pharyngitis. He did not improve, and a rash developed. History taking revealed a negative HIV antibody test five months previously and unprotected sex with a male partner the month before admission. Repeated tests revealed primary HIV infection with an exceptionally high HIV-1 RNA plasma concentration (3.6 × 10⁷copies/mL) and a low CD4 count (101 cells/mm³, seven percent of total lymphocytes). While being investigated, the patient had a life-threatening hematochezia. After angiographic occlusion of a branch of the ileocaecal artery and initiation of antiretroviral therapy, the patient became rapidly asymptomatic and could be discharged. Colonoscopy revealed a bleeding colonic ulcer. We were unable to identify an etiology other than HIV for this ulcer.</p> <p>Conclusion</p> <p>This case adds to the known protean manifestation of primary HIV infection. The lack of an alternative etiology, despite extensive investigations, suggests that this ulcer was directly caused by primary HIV infection. This conclusion is supported by the well-described extensive loss of intestinal mucosal CD4⁺T cells associated with primary HIV infection, the extremely high HIV viral load observed in our patient, and the rapid improvement of the ulcer after initiation of highly active antiretroviral therapy. This case also adds to the debate on treatment for primary HIV infection, especially in the context of severe symptoms and an extremely high viral load.</p

Long-term clinical, immunologic and virologic impact of glucocorticoids on the chronic phase of HIV infection

BACKGROUND: To test the hypothesis of down-regulating the increased immune system activation/destruction process associated with chronic HIV infection, we focused our interest on prednisolone (PDN), because we had showed that, in vitro, PDN had a strong anti-apoptotic activity on activated T cells of HIV-infected patients and no effect on viral replication. We thus designed in 1992 a pilot study to evaluate the clinical, immunologic and virologic effects of PDN. The drug was given to a group of 44 patients with CD4 T cells over 200/μl. After one year, no patient had developed clinical AIDS and the mean CD4 T cell count of the group had increased from 441 ± 21 cells/μl to 553 ± 43 cells/μl. Moreover, markers of immune activation had dropped back to normal levels while the mean viral load of the group had remained unchanged. Here we explore the long-term clinical, immunologic, and virologic impact of prednisolone on the chronic phase of HIV infection. METHODS: Retrospective study over 10 years starting between July 1992 and February 1993. A total of 44 patients with CD4 cells/μl ranging from 207 to 775 were treated with prednisolone, 0.5 mg/kg/d, over 6 months and 0.3 mg/kg/d thereafter. RESULTS: No clinical AIDS developed under prednisolone; side effects of the drug were mild. CD4 cells which increased from 421 cells/μl at entry to 625 cells/μl at day 15, slowly decreased to reach 426 cells/μl after two years; T cell apoptosis and activation markers dropped within 15 days to normal levels and reincreased slowly thereafter. Serum viral loads remained stable. The percentage of patients maintaining CD4 cells over entry was 43.2% at two years, 11.4% at five years and 4.6% at 10 years. Initial viral load was highly predictive of the rate of CD4 decrease under prednisolone. CONCLUSIONS: Prednisolone postponed CD4 cell decrease in a viral load dependent manner for a median of two years and for up to 10 years in a fraction of the patients with a low viral load. These findings might stimulate clinical trials as well as biological research on the role of antiapoptotic drugs in HIV infection

Epidemiology and interactions of Human Immunodeficiency Virus - 1 and Schistosoma mansoni in sub-Saharan Africa.

Human Immunodeficiency Virus-1/AIDS and Schistosoma mansoni are widespread in sub-Saharan Africa and co-infection occurs commonly. Since the early 1990s, it has been suggested that the two infections may interact and potentiate the effects of each other within co-infected human hosts. Indeed, S. mansoni infection has been suggested to be a risk factor for HIV transmission and progression in Africa. If so, it would follow that mass deworming could have beneficial effects on HIV-1 transmission dynamics. The epidemiology of HIV in African countries is changing, shifting from urban to rural areas where the prevalence of Schistosoma mansoni is high and public health services are deficient. On the other side, the consequent pathogenesis of HIV-1/S. mansoni co-infection remains unknown. Here we give an account of the epidemiology of HIV-1 and S. mansoni, discuss co-infection and possible biological causal relationships between the two infections, and the potential impact of praziquantel treatment on HIV-1 viral loads, CD4+ counts and CD4+/CD8+ ratio. Our review of the available literature indicates that there is evidence to support the hypothesis that S. mansoni infections can influence the replication of the HIV-1, cell-to-cell transmission, as well as increase HIV progression as measured by reduced CD4+ T lymphocytes counts. If so, then deworming of HIV positive individuals living in endemic areas may impact on HIV-1 viral loads and CD4+ T lymphocyte counts.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Increased HIV-1 transcriptional activity and infectious burden in peripheral blood and gut-associated CD4+ T cells expressing CD30

HIV-1-infected cells persist indefinitely despite the use of combination antiretroviral therapy (ART), and novel therapeutic strategies to target and purge residual infected cells in individuals on ART are urgently needed. Here, we demonstrate that CD4+ T cell-associated HIV-1 RNA is often highly enriched in cells expressing CD30, and that cells expressing this marker considerably contribute to the total pool of transcriptionally active CD4+ lymphocytes in individuals on suppressive ART. Using in situ RNA hybridization studies, we show co-localization of CD30 with HIV-1 transcriptional activity in gut-associated lymphoid tissues. We also demonstrate that ex vivo treatment with brentuximab vedotin, an antibody-drug conjugate (ADC) that targets CD30, significantly reduces the total amount of HIV-1 DNA in peripheral blood mononuclear cells obtained from infected, ART-suppressed individuals. Finally, we observed that an HIV-1-infected individual, who received repeated brentuximab vedotin infusions for lymphoma, had no detectable virus in peripheral blood mononuclear cells. Overall, CD30 may be a marker of residual, transcriptionally active HIV-1 infected cells in the setting of suppressive ART. Given that CD30 is only expressed on a small number of total mononuclear cells, it is a potential therapeutic target of persistent HIV-1 infection

Tyrosine kinase inhibitors: potential use and safety considerations in HIV-1 infection

INTRODUCTION: Infection caused by HIV-1 is nowadays a chronic disease due to a highly efficient antiretroviral treatment that is nevertheless, unable to eliminate the virus from the organism. New strategies are necessary in order to impede the formation of the viral reservoirs, responsible for the failure of the antiretroviral treatment to cure the infection. Areas covered: The purpose of this review is to discuss the possibility of using tyrosine kinase inhibitors (TKIs) for the treatment of HIV-1 infection. These inhibitors are successfully used in patients with distinct cancers such as chronic myeloid leukemia. The most relevant papers have been selected and commented. Expert opinion: The family of TKIs are directed against the activation of tyrosine kinases from the Src family. Some of these kinases are essential for the activation of CD4 + T cells, the major target of HIV-1. During acute or primary infection the CD4 + T cells are massively activated, which is mostly responsible for the generation of the reservoirs, the spread of the infection and the destruction of activated CD4 + T cells, infected or not. Consequently, we discuss the possibility of using TKIs as adjuvant of the antiretroviral treatment against HIV-1 infection mostly, but not exclusively, during the acute/recent phase.This work was supported by the Spanish Ministry of Economy and Competitiveness (SAF2013-44677-R, SAF2016-78480-R); the Instituto de Salud Carlos III (INT15/00168, ISCIII-FIS PI16CIII/00034); the Spanish AIDS Research Network RD12/0036/0004, RD16CIII/0002/0001-ISCIII-FEDER and the grant RD12/0036/0004; Bristol-Myers Squibb partially financed our study (grant BMS AI471-041). J Ambrosioni developed this work in the frame of a ‘Juan de la Cierva 2012ʹ postdoctoral program, Spanish Ministry of Economy and Competitiveness, Spain. JMM received a personal intensification research grant INT15/00168 in 2016 from Instituto de Salud Carlos III, Madrid, Spain. The European Regional Development Fund (ERDF) ‘A way to build Europe’ also provided funding.S