SUMMARY The tuberculosis (TB) bacillus, Mycobacterium tuberculosis (Mtb), and HIV-1 act synergistically; however, the mechanisms by which Mtb exacerbates HIV-1 pathogenesis are not well known. Using in vitro and ex vivo cell culture systems, we show that human M(IL-10) anti-inflammatory macrophages, present in TB-associated microenvironments, produce high levels of HIV-1. In vivo, M(IL-10) macrophages are expanded in lungs of co-infected non-human primates, which correlates with disease severity. Further, HIV-1/Mtb co-infected patients display an accumulation of M(IL-10) macrophage markers (soluble CD163 and MerTK). These M(IL-10) macrophages form direct cell-to-cell bridges, which we identified as tunneling nanotubes (TNTs) involved in viral transfer. TNT formation requires the IL-10/STAT3 signaling pathway, and targeted inhibition of TNTs substantially reduces the enhancement of HIV-1 cell-to-cell transfer and overproduction in M(IL-10) macrophages. Our study reveals that TNTs facilitate viral transfer and amplification, thereby promoting TNT formation as a mechanism to be explored in TB/AIDS potential therapeutics.

Many practical clinical questions regarding the management of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remain unanswered. We sought to identify and develop practical answers to key clinical questions in HAND management. Sixty-six specialists from 30 countries provided input into the program, which was overseen by a steering committee. Fourteen questions were rated as being of greatest clinical importance. Answers were drafted by an expert group based on a comprehensive literature review. Sixty-three experts convened to determine consensus and level of evidence for the answers. Consensus was reached on all answers. For instance, good practice suggests that all HIV patients should be screened for HAND early in disease using standardized tools. Follow-up frequency depends on whether HAND is already present or whether clinical data suggest risk for developing HAND. Worsening neurocognitive impairment may trigger consideration of antiretroviral modification when other causes have been excluded. The Mind Exchange program provides practical guidance in the diagnosis, monitoring, and treatment of HAND.

Although neurological involvement is infrequent, it has a high mortality and morbidity rate when is not well diagnosed and treated on time.

Disseminated Mycobacterium avium complex (MAC) infection is a severe complication of advanced HIV/AIDS disease. Disseminated infection due to MAC appeared later in the natural history of HIV disease and was an independent predictor of mortality in patients before the extended use of highly active antiretroviral therapy (HAART). The use of combination schemes, including three or four antimicrobial agents followed by secondary prophylaxis and HAARTs, improved the survival and reduced mortality rates. However, subjects who ignore their serological status for HIV, or who are not receiving or do not tolerate HAART, are at high risk of developing disseminated MAC disease. In addition, patients who show a good immunological and virological response to HAART can develop episodes of immune reconstitution inflammatory syndrome associated with MAC, including supurative lymphadenitis and subcutaneous or soft-tissue abscesses. In this article, we describe the epidemiological, clinical, immunological, therapeutic and preventive aspects of MAC infection in HIV-seropositive patients in the pre- and post-HAART era.

The objective of this study was to identify prognostic factors of death in patients with tuberculous meningitis (TM) and show the impact of infection by multidrug-resistant strains on the outcome of this disease. We retrospectively analysed clinical charts of HIV-infected patients with culture-confirmed TM attending our institution during 1996-2004. The following variables were associated with death during hospitalization: neurological signs at admission, a CD4 T-cell count less than 50 cells/microl and infection by multidrug-resistant strains.