Impact of highly active antiretroviral therapy on anemia and relationship between anemia and survival in a large cohort of HIV-infected women: Women's Interagency HIV Study

BACKGROUND: Anemia is common in HIV-infected individuals and may be associated with decreased survival. OBJECTIVE: To ascertain the impact of highly active antiretroviral therapy (HAART) on anemia and the relationship between anemia and overall survival in HIV-infected women. METHODS: A prospective multicenter study of HIV-1 infection in women. Visits occurred every 6 months, including a standardized history, physical examination, and comprehensive laboratory evaluation. The setting was a university-affiliated clinic at 6 sites in the United States. Participants were 2056 HIV-infected women from the Women's Interagency HIV Study (WIHS). The outcome measure was anemia, defined as hemoglobin (Hb) <12 g/dL. Survival analysis was based on overall mortality during the follow-up period. RESULTS: Among HIV-infected women who were not anemic at baseline, 47% became anemic by 3.5 years of follow-up. On multivariate analysis, the use of HAART was associated with resolution of anemia even when used for only 6 months (odds ratio [OR] = 1.45; P < 0.05). In the multivariate model, a CD4 cell count <200 cells/microL (OR = 0.56; P < 0.001); HIV-1 RNA level > or =50,000 copies/mL (OR = 0.65; P < 0.001), and mean corpuscular volume (MCV) value <80 fL (OR = 0.40; P < 0.001) were also associated with an inability to correct anemia. Similarly, use of HAART for 12 months or more was associated with a protective effect against development of anemia (OR = 0.71; P < 0.001). Among HIV-infected women, anemia was independently associated with decreased survival (hazard ratio [HR] = 2.58; P < 0.001). Other factors associated with decreased survival included a CD4 cell count <200 cells/microL (HR = 5.83; P < 0.001), HIV-1 RNA level > or = 50,000 copies/mL (HR = 2.12; P < 0.001), and clinical diagnosis of AIDS (HR = 2.83; P < 0.001). CONCLUSIONS: Anemia is an independent risk factor for decreased survival among HIV-infected women. HAART therapy for as little as 6 months is associated with resolution of anemia.     

cC1q-R (calreticulin) and gC1q-R/p33: ubiquitously expressed multi-ligand binding cellular proteins involved in inflammation and infection

The first component of complement, C1, is a multi-molecular complex comprising of C1q and the Ca(2+)-dependent tetramer C1r(2)-C1s(2). The traditional role of C1q within the complex is that of recognition signal-a signal, which is instantly converted into a highly specific intramolecular proteolytic activation of the C1r(2)-C1s(2) tetramer thereby triggering activation of the classical pathway. Another important function of C1q is its ability to bind to a wide range of cell types resulting in the induction of cell-specific biological responses. These cells include polymorphonuclear leukocytes, monocytes, lymphocytes, dendritic cells, endothelial cells and platelets. Interaction of C1q with endothelial cells and platelets, for example, leads to cellular activation followed by release of biological mediators and/or expression of adhesion molecules, all of which contribute, directly or indirectly to the inflammatory process. These specific responses are mediated by the interaction of C1q with C1q binding proteins or receptors on the cell surface. To date, four types of putative C1q binding cell surface expressed proteins/receptors have been described. These include cC1q-R/CR, or calreticulin (CR), a 60 kDa protein, which is also known as collectin receptor; gC1q-R/p33, a 33 kDa homotrimeric protein; C1q-Rp (CD93), a 120 kDa, O-sialoglycoprotein; and CR1 (CD35), the receptor for C3b. Although the specific role of each of these molecules in a given C1q-mediated cellular response is yet to be worked out, all of them may, in one form or another, participate in the inflammatory processes associated with vascular or atherosclerotic lesions, autoimmune diseases, or infections. The main focus of our laboratory for the past 20 years has been to elucidate the structure and function of cC1q-R/CR and gC1q-R/p33, both of which have been isolated and characterized on the basis of their ability to bind C1q. The purpose of this article is therefore to provide an up to date overview of these two proteins with particular emphasis on their unique structural and functional features, their multi-faceted nature and most importantly their role in infection and inflammation.     

Outbreak of Rabbit Hemorrhagic Disease Virus 2 Infections,Ghana

In September 2019, high mortality in commercial rabbits was reported in the Greater Accra Region of Ghana. Rabbit hemorrhagic disease virus 2 phylogenetically related to isolates from 2015–2017 outbreaks in the Netherlands was confirmed as the causative agent. The virus has not yet been detected in native rabbits in Ghana.     

Development of pre and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection

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DC-SIGN, C1q, and gC1qR form a trimolecular receptor complex on the surface of monocyte-derived immature dendritic cells

C1q modulates the differentiation and function of cells committed to the monocyte-derived dendritic cell (DC) lineage. Because the 2 C1q receptors found on the DC surface-gC1qR and cC1qR-lack a direct conduit into intracellular elements, we postulated that the receptors must form complexes with transmembrane partners. In the present study, we show that DC-SIGN, a C-type lectin expressed on DCs, binds directly to C1q, as assessed by ELISA, flow cytometry, and immunoprecipitation experiments. Surface plasmon resonance analysis revealed that the interaction was specific, and both intact C1q and the globular portion of C1q bound to DC-SIGN. Whereas IgG reduced this binding significantly, the Arg residues (162-163) of the C1q-A chain, which are thought to contribute to the C1q-IgG interaction, were not required for C1q binding to DC-SIGN. Binding was reduced significantly in the absence of Ca(2+) and by preincubation of DC-SIGN with mannan, suggesting that C1q binds to DC-SIGN at its principal Ca(2+)-binding pocket, which has increased affinity for mannose residues. Antigen-capture ELISA and immunofluorescence microscopy revealed that C1q and gC1qR associate with DC-SIGN on blood DC precursors and immature DCs. The results of the present study suggest that C1q/gC1qR may regulate DC differentiation and function through the DC-SIGN-mediated induction of cell-signaling pathways.     

Patient referral alone is not an effective strategy to capture partners of patients with sexually transmitted infections in low-resource settings: a case-control study

Aim

Partner notification (PN) is a key public health intervention aimed at preventing re-infection and controlling the spread of STIs. However, only limited research has been conducted to investigate factors associated with PN in Ethiopia.

Subject and methods

A nested case-control study was undertaken within a cohort of individuals being treated for STIs in public health facilities in Ethiopia. Hierarchical binary logistic regression was used to identify socio-demographic, behavioral and psychosocial factors associated with PN.

Results

A total of 250 patients on STI treatment who notified their partners (cases) were compared with 185 patients who did not notify their partners (controls). STI patients were less likely to notify their partner if they were single [AOR = 0.33, 95% CI: (0.15–0.73)], in a casual partnership [adjusted odds ratio (AOR) = 0.33, 95% CI: (0.15–73)], not knowledgeable about a partner’s sexual behavior [AOR = 0.43, 95% CI: (0.24–0.77)], had poor knowledge of risky sexual behavior [AOR = 0.23, 95% CI: (0.12–0.43)] and had no intention of notifying partners [AOR = 0.19, 95% CI: (0.10–0.36)]. The odds of PN were higher among highly educated respondents [AOR = 5.16; 95% CI: (1.83–14.54)].

Conclusion

Capturing STI cases through patient referral partner notification is less likely to be successful among patients who are single and in a casual relationship.