Association between different anti-Tat antibody isotypes and HIV disease progression: data from an African cohort.

BACKGROUND: The presence of IgG and IgM against Tat, an HIV protein important for viral replication and immune dysfunction, is associated with slow disease progression in clade B HIV-infected individuals. However, although Tat activities strictly depend on the viral clade, our knowledge about the importance of anti-Tat antibodies in non-clade B HIV infection is poor. The objective of this study was to investigate the association of different anti-Tat antibody isotypes with disease progression in non-clade B HIV-infected subjects and to study the relationship between anti-Tat humoral responses and immunological abnormalities. METHODS: Anti-clade B and -clade C Tat IgG, IgM and IgA titers were assessed in serum samples from 96 cART-naïve subjects with chronic HIV infection from Mbeya, Tanzania, and associated with CD4(+) T cell count, plasma viremia and CD4(+) and CD8(+) T cell phenotypes. RESULTS: Anti-Tat IgM were preferentially detected in chronic HIV-infected subjects with low T cell activation (p-value = 0.03) and correlated with higher CD4(+) T cell counts and lower viral loads irrespective of the duration of infection (p-value = 0.019 and p-value = 0.037 respectively). Conversely, anti-Tat IgA were preferentially detected in individuals with low CD4(+) T cell counts and high viral load (p-value = 0.02 and p-value < 0.001 respectively). The simultaneous presence of anti-Tat IgG and IgM protected from fast CD4(+) T cell decline (p-value < 0.01) and accumulation of CD38(+)HLADR(+)CD8(+) T cells (p- value = 0.029). CONCLUSIONS: Anti-Tat IgG alone are not protective in non-clade B infected subjects, unless concomitant with IgM, suggesting a protective role of persistent anti-Tat IgM irrespective of the infecting clade.

Increased and expedited case detection by Xpert MTB/RIF assay in childhood tuberculosis: a prospective cohort study.

BACKGROUND: Diagnosis and timely treatment of tuberculosis in children is hampered by the absence of fast and reliable tests, especially in the era of human immunodeficiency virus (HIV). The aim of this study was to evaluate the diagnostic performance of the Xpert MTB/RIF assay (Xpert) in children with suspected tuberculosis in a high tuberculosis/HIV-burden setting. METHODS: In a prospective study with a minimum follow-up of 12 months, 164 children with suspected tuberculosis were assigned to predefined diagnostic subgroups, based on microbiological and clinical findings. Results of smear microscopy and culture were compared against diagnostic performance of Xpert. RESULTS: Twenty-eight of 164 children (17.1%) had confirmed tuberculosis. Xpert detected 100% (95% confidence interval [CI], 59.0%-100%) of smear-positive cases and 66.6% (95% CI, 43.0%-85.4%) of culture-positive but smear-negative cases. In the per-sample analysis, Xpert displayed a similar sensitivity (54.7% [95% CI, 42.7%-66.2%]) compared with culture methods. Xpert detected 3-fold more confirmed tuberculosis cases than smear microscopy but with equal rapidity. Four additional cases (8.5%) with clinical tuberculosis but negative culture were diagnosed by Xpert. Testing second and third samples increased sensitivity by 20% and an additional 16%, respectively. When tuberculosis was reliably excluded, Xpert's specificity was 100%. HIV infection did not affect diagnostic accuracy of Xpert. CONCLUSIONS: Xpert was easy to perform and displayed similar diagnostic accuracy as culture methods in children with suspected tuberculosis. Rapid turnaround times should reduce treatment delay and improve patient outcome, although sensitivity remains suboptimal and access is dependent on local laboratory infrastructure.

Helminth-associated systemic immune activation and HIV co-receptor expression: response to albendazole/praziquantel treatment.

BACKGROUND: It has been hypothesized that helminth infections increase HIV susceptibility by enhancing systemic immune activation and hence contribute to elevated HIV-1 transmission in sub-Saharan Africa. OBJECTIVE: To study systemic immune activation and HIV-1 co-receptor expression in relation to different helminth infections and in response to helminth treatment. METHODS: HIV-negative adults with (n = 189) or without (n = 57) different helminth infections, as diagnosed by Kato-Katz, were enrolled in Mbeya, Tanzania. Blinded to helminth infection status, T cell differentiation (CD45RO, CD27), activation (HLA-DR, CD38) and CCR5 expression was determined at baseline and 3 months after Albendazole/Praziquantel treatment. Plasma cytokine levels were compared using a cytometric bead array. RESULTS: Trichuris and Ascaris infections were linked to increased frequencies of "activated" CD4 and/or CD8 T cells (p<0.05), whereas Hookworm infection was associated with a trend towards decreased HLA-DR+ CD8 T cell frequencies (p = 0.222). In Trichuris infected subjects, there was a linear correlation between HLA-DR+ CD4 T cell frequencies and the cytokines IL-1ß and IL-10 (p<0.05). Helminth treatment with Albendazole and Praziquantel significantly decreased eosinophilia for S. mansoni and Hookworm infections (p<0.005) but not for Trichuris infection and only moderately modulated T cell activation. CCR5 surface density on memory CD4 T cells was increased by 1.2-fold during Trichuris infection (p-value: 0.053) and reduced after treatment (p = 0.003). CONCLUSIONS: Increased expression of T cell activation markers was associated with Trichuris and Ascaris infections with relatively little effect of helminth treatment.