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Molecular epidemiological studies revealed that the epicenter of the HIV pandemic was Kinshasa, the capital city of the Democratic Republic of the Congo (DRC) in Central Africa. All known subtypes and numerous complex recombinant strains co-circulate in the DRC. Moreover, high intra-subtype diversity has been also documented. During two previous surveys on HIV-1 antiretroviral drug resistance in the DRC, we identified two divergent subtype C lineages in the protease and partial reverse transcriptase gene regions. We sequenced eight near full-length genomes and classified them using bootscanning and likelihood-based phylogenetic analyses. Four strains are more closely related to subtype C although within the range of inter sub-subtype distances. However, these strains also have small unclassified fragments and thus were named CRF92_C2U. Another strain is a unique recombinant of CRF92_C2U with an additional small unclassified fragment and a small divergent subtype A fragment. The three remaining strains represent a complex mosaic named CRF93_cpx. CRF93_cpx have two fragments of divergent subtype C sequences, which are not conventional subtype C nor the above described C2, and multiple divergent subtype A-like fragments. We then inferred the time-scaled evolutionary history of subtype C following a Bayesian approach and a partitioned analysis using major genomic regions. CRF92_C2U and CRF93_cpx had the most recent common ancestor with conventional subtype C around 1932 and 1928, respectively. A Bayesian demographic reconstruction corroborated that the subtype C transition to a faster phase of exponential growth occurred during the 1950s. Our analysis showed considerable differences between the newly discovered early-divergent strains and the conventional subtype C and therefore suggested that this virus has been diverging in humans for several decades before the HIV/M diversity boom in the 1950s.

Isoniazid preventive therapy (IPT) is recognised as an important component of collaborative tuberculosis (TB) and human immunodeficiency virus (HIV) activities to reduce the burden of TB in people living with HIV (PLHIV). However, there has been little in the way of IPT implementation at country level. This failure has resulted in a recent call to arms under the banner title of the 'Three I's' (infection control to prevent nosocomial transmission of TB in health care settings, intensified TB case finding and IPT). In this paper, we review the background of IPT. We then discuss the important challenges of IPT in PLHIV, namely responsibility and accountability for the implementation, identification of latent TB infection, exclusion of active TB and prevention of isoniazid resistance, length of treatment and duration of protective efficacy. We also highlight several research questions that currently remain unanswered. We finally offer practical suggestions about how to scale up IPT in the field, including the need to integrate IPT into a package of care for PLHIV, the setting up of operational projects with the philosophy of 'learning while doing', the development of flow charts for eligibility for IPT, the development and implementation of care prior to antiretroviral treatment, and finally issues around procurement, distribution, monitoring and evaluation. We support the implementation of IPT, but only if it is done in a safe and structured way. There is a definite risk that 'sloppy' IPT will be inefficient and, worse, could lead to the development of multidrug-resistant TB, and this must be avoided at all costs.

Since 2000, the emergence of several large disease-specific global health initiatives (GHIs) has changed the way in which international donors provide assistance for public health. Some critics have claimed that these initiatives burden health systems that are already fragile in countries with few resources, whereas others have asserted that weak health systems prevent progress in meeting disease-specific targets. So far, most of the evidence for this debate has been provided by speculation and anecdotes. We use a review and analysis of existing data, and 15 new studies that were submitted to WHO for the purpose of writing this Report to describe the complex nature of the interplay between country health systems and GHIs. We suggest that this Report provides the most detailed compilation of published and emerging evidence so far, and provides a basis for identification of the ways in which GHIs and health systems can interact to mutually reinforce their effects. On the basis of the findings, we make some general recommendations and identify a series of action points for international partners, governments, and other stakeholders that will help ensure that investments in GHIs and country health systems can fulfil their potential to produce comprehensive and lasting results in disease-specific work, and advance the general public health agenda. The target date for achievement of the health-related Millennium Development Goals is drawing close, and the economic downturn threatens to undermine the improvements in health outcomes that have been achieved in the past few years. If adjustments to the interactions between GHIs and country health systems will improve efficiency, equity value for money, and outcomes in global public health, then these opportunities should not be missed.

Marseille; International audience

International audience

International audience

Evaluation de l'utilisation sur le terrain de la technique des taches de sang séchées sur papier filtre pour la surveillance de la tuberculose associée au virus de l'immunodéficience humaine (VIH). La technique a été évaluée par comparaison avec le sérum chez 359 patients consentants enregistrés dans le registre de district de la tuberculose dans la capitale. Des tests répétés par ELISA utilisant des antigènes différents ont été effectués sur les éluats des papiers-filtres. Les sérums ont été testés par ELISA avec confirmation par LIA (étalon). Les coûts ont été comparés à ceux de tests rapides/simples sur du sang complet. Au cours d'une deuxième phase, la technique a été utilisée dans une enquête de séro-surveillance nationale anonyme chez 582 patients enregistrés dans les registres de la tuberculose des districts. La spécificité pour VIH-1 et VIH-2 de la méthode des taches de sang séchées est de 100%, et la sensibilité est respectivement de 100% et de 87,5%. Cette stratégie ne coûte que la moitié de celle utilisant les tests rapides/simples sur sang complet. En 1995, la séroprévalence de VIH-1 associé à la tuberculose était de 2,41%. La méthode proposée pour la surveillance en Afrique de l'infection à VIH-1 associée à la tuberculose est simple, peu coûteuse et précise. Des investigations complémentaires s'imposent pour évaluer sa sensibilité en matière de VIH-2, ainsi que l'épidémiologie de l'infection à VIH-2 en Sierra Leone. (Résumé d'auteur)