HIV-2 Integrase Variation in Integrase Inhibitor-Na?ve Adults in Senegal,West Africa

Background

Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs) raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance.

Methods

We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2–infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1.

Results

No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155). Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein.

Conclusion

Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at “secondary” HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2–infected patients.     

Bone marrow suppression and severe anaemia associated with persistent Plasmodium falciparum infection in African children with microscopically undetectable parasitaemia

In sub-Saharan Africa the highest overlap between malaria and HIV infections occurs in female adolescents. Yet control activities for these infections are directed to different target groups, using disparate channels. This reflects the lack of priority given to adolescents and the absence of an accepted framework for delivering health and health-related interventions to this high-risk group. In this paper it is argued that female adolescents require a continuum of care for malaria and HIV – prior to conception, during and after pregnancy and that this should be provided through adolescent services. The evidence for this conclusion is presented. A number of African countries are commencing to formulate and implement adolescent-friendly policies and services and disease control programs for malaria and HIV will need to locate their interventions within such programs to ensure widespread coverage of this important target group. Failure to prioritize adolescent health in this way will seriously limit the success of disease control programs for malaria and HIV prevention.     

Retinoic Acid and Vitamin E Modulate Expression and Release of CD178 in Carcinoma Cells: Consequences for Induction of Apoptosis in CD95-Sensitive Cells

CD178 (CD95-ligand) is expressed on several tumor cells and likely influences the interaction of the tumor with the host immune system. However, little is known about the mechanisms that regulate its expression on the cell surface. We have evaluated the ability of various compounds and cytokines to regulate cell surface expression and release of soluble CD178 in various carcinoma cell lines. Vitamin E succinate (VES) and retinoic acid (RA) were found to reduce CD178 surface expression, whereas interferon-gamma stimulated a slight upregulation. At 48 h, the regulation of surface CD178 by VES and RA arose from a small decrease in CD178 mRNA and to a greater extent due to an increase in the release of soluble CD178; the latter was blocked by addition of a metalloproteinase inhibitor. Accordingly, VES and RA treatment diminished the ability of tumor cells to kill CD95-sensitive cells and this effect was markedly reduced by the presence of a metalloproteinase inhibitor. Our results indicate that, in vitro, CD178 expression on the cell surface of tumor cells can be regulated by agents that alter both expression and release of the ligand. In vivo, such treatments may play an important role in the outcome of tumor sensitivity or resistance to host immune mechanisms.     

A microquantitative method to characterize lectin-induced cytoagglutination

A microquantitative method to characterize lectin-induced cytoagglutination reactions is described. The assay, which utilizes an electronic particle counter, measures the disappearance of single cells from cell suspensions containing various concentrations of lectin. The method is sensitive, requiring only μg quantities of lectin, reproducible, and amenable to thorough statistical analysis. It was also utilized to quantitate the inhibition of lectin-induced cytoagglutination by various saccharides. The method was employed to characterize ConA-induced agglutination of guinea pig erythrocytes and Novikoff ascites hepatoma cells, and to investigate several parameters which influence lectin-induced cytoagglutination reactions.     

Strategies for farmers and policy makers to control nitro-gen losses whilst maintaining crop production

The nitrogen (N) cycle is essentially 'leaky'. The losses of small amounts of nitrate to waters and of ammonia and nitrous oxide to the atmosphere are a part of the global biogeo-chemical N cycle. However, intensive agricultural production, industry and vehicle use have more than doubled the amount of 'reactive' N in the environment, resulting in eutrophication, ecosystem change and health concerns. Research has identified agricultural practices that cause large losses of N and, in some cases, developed solutions. This paper discusses the problems of maintaining productivity while reducing N losses, compares conventional with low input (integrated) and organic farming systems, and discusses wider options. It also looks at the need to integrate studies on N with other environmental impacts, set in the context of the whole farm system, to provide truly sustainable agricultural systems.     

Proximate and ultimate causes of reproductive suppression among female yellow baboons at Mikumi National Park,Tanzania

Attack coalitions, whereby two or more individuals attack another animal simultaneously, were studied in 53 sexually mature female baboons from one small and two large troops at Mikumi National Park, Tanzania. For 14 months, three observers recorded coalition behavior throughout the day, using focal group sampling on a behavior-dependent basis. Coalition rates were considerably greater in the two large troops than in the small troop, and primarily involved natal females rather than males. Coalition frequencies corresponded closely to measures of reproductive synchrony, both within and between troops. Involvement in attack coalition behavior depended on the reproductive states and ranks of both attackers and recipients. The first few females to give birth in the cohort received particularly high amounts of coalition aggression just before and immediately after giving birth. Receipt of attack coalitions was significantly associated with an increased number of cycles to conception and longer interbirth intervals, as well spontaneous abortion, premature birth, and prolonged gestation. A parallel study on survivorship patterns of immature baboons at Mikumi provided evidence for ultimate cause of the observed coalition patterns. These combined results suggest that attack coalition behavior is a form of reproductive competition whereby females attempt to suppress the reproduction of others at predictably competitive times and thereby reduce the competition their own infants face from the time they are weaned.