Identifying why AIDSpatients had such a high baseline prevalence of Lam9, was a major issue in our study. Our regression models of patients with MDR-TB at the start of DOTS treatment, revealed an unexpected association between the risk of infection with the epidemic clone of Lam9 and diarrhea. Although the mechanisms underlying this association are purely speculative, an increased susceptibility for acquiring MDR-TB following infection with other diarrhea associated diseases might explain our results. The gastrointestinal tract has long been recognized as the most common site for opportunistic infections amongHIV- infected patients 45 110 , and humoral immune responses against diarrhea-associated parasites are thought to favor infection with M. tuberculosisandHIV 111 112 113 . We were unable to test this hypothesis in our study since we only evaluated patients for the presence of an underlying medical conditions (that included diarrhea), rather than detailed information specifically concerning diarrhea. However, future epidemiological studies on tuberculosisand diarrhea might be designed to examine the role that infection with different diarrhea- associated parasites has on the risk of infection and the development of active tuberculosis.
In a context of limited resources like Guinea, identifi- cation of a biomarker of MDR-TB treatment response that is easily measured and accessible in clinical practice would be beneficial for the management of patientsand for tuberculosiscontrol programs. Numerous studies have shown that malnutrition measured by body weight is associated with a poor MDR-TB treatment outcome, probably due to a complex relationship between lessened energy demands and decreased nutritional intake, and suggest that weight loss is a potential biomarker of treat- ment response [ 3 – 7 ]. Moreover, a longitudinal study showed that weight variation during the first 6 months differed according to the treatment outcome, a poor out- come being associated with decreasing weight over time [ 7 ]. The underlying hypothesis of the mixed linear model used to analyze weight change in this study is that all pa- tients have a unique mean profile of weight trajectory over time. But this assumption of homogeneous weight change seems untenable, because patients with MDR-TB often differed in the severity of the disease at baseline in terms of clinical presentation, number of episodes of TB, pres- ence of HIV co-infection or comorbidity (diabetes), sus- ceptibility to drug toxicity and resistance. Hence the need to identify homogeneous groups of patients with different weight changes, using an appropriate methodology as
infected individuals has progressively increased [ 6 – 8 ]. This increase of non-B viral infections has been reported in both newly diagnosed chronic HIV-1 infections [ 9 , 10 ] and individuals with primary or recent HIV-1 infection (PHI) [ 11 – 14 ]. AmongHIV-1 non-B subtypes, CRF02_ AG is one of the most prevalent recombinant forms in the world, responsible for at least 8% of total infections [ 15 ]. Though CRF02_AG is predominantly transmitted within heterosexuals in Sub-Saharan Africa, it has been increasingly reported among men who have sex with men (MSM) [ 16 ]. In a recent study conducted in newly diagnosed patients living in Europe, the proportion of circulating recombinant form CRF02_AG increased sig- nificantly between 2002 and 2010 [ 17 ]. A similar trend was also observed in Western and Central Europe, with an increased proportion of CRF02_AG from 5% in 2000–2003 to 8% in 2004–2007 [ 15 ]. In France, recent data showed a spread of non-B subtypes in individu- als of French origin and that the MSM group are par- ticularly involved in this dynamic [ 14 ]. Altogether, these reports emphasize the need for a better understanding of the spread of various HIV-1 subtypes through these transmission networks. The recent advances in molecu- lar epidemiology have greatly enhanced our ability to evaluate the dynamic of these transmission networks [ 2 ,
According to the World Health Organization
(WHO), the noteworthy drop in HIV incidence world- wide has been associated (in both genders) with sev- eral behavior indicators, including increased condom use, delayed sexual initiation, and reduction in mul- tiple partnerships. Hence, it is believed that the most important factors to control the spread of the infec- tion are the behavioral changes towards sexuality which can best be triggered by improving basic knowledge about HIV/AIDStransmission pathways and prevention measures. Estimating knowledge about HIV in the general population is a difficult task. It can be done on specific subgroups of individuals at risk but these groups may not be easily accessible. It can also be done locally or in restricted areas, but results can hardly be extrapolated to larger populations. By contrast, companies which employ large portions of the sexually ac- tive population are structured and recognized entities. Their workers have themselves a life outside the oc- cupational setting: family, friends, and social activities. Thus, assessing HIV/AIDS knowledge among workers of companies may have a far wider impact than in other settings.
The two groups did not differ in median age, sex ratio andHIVtransmission groups or time of HIV follow-up. The distri- bution of KS cases that occurred in patients on ART according to HIV-pVL differed by the year of diagnosis. Indeed, 33% of KS cases in patients with detectable HIV-pVL occurred in 2010, while in patients with undetectable HIV-pVL, most KS cases occurred after 2010. Data concerning KS localization were avail- able for 48 patients (88.8%), and the distribution of KS localiza- tion did not differ between the two groups. Patients on ART with HIV-pVL ≤50 copies/mL presented significantly better immune parameters (median CD4 count and %, %CD4 >500/ mm 3 , nadir CD4, ratio CD4 : CD8) than those with detectable HIV-pVL. Moreover, the proportion of patients with nadir <200/mm 3 was significantly higher in patients with detectable
Including non-State actors in the political fight against HIV/AIDS is a dual meaning strategy for political and administrative authorities. They acquire some legitimacy amongpatients living with HIV/AIDSand increase their credibility vis-à-vis their international partners (Kojoué 2013). The constant centrality of State power is also explained by Cameroon tensed economic environment since the succession of structural adjustment plans that deeply undermined its ability to deliver public services (health, education, agriculture, etc.) since the early 1990’s. The scarcity of public resources and new governance requirements required from States with limited resources by the World Bank or the International Monetary Fund put them in competition with the leadership of new stakeholders who are increasingly numerous. In this context, civil society therefore has several reasons to be wary of financial sanctions (no more subsidies), civil sanctions (closure and seizure of premises) or criminal sanctions (fines, trials and convictions). Those who dare to publicly oppose State power run the risk of being severely punished. This is the case of the leader of Positive Generation a Non-governmental association who has been fighting against AIDS since the early 2000’s. This leader admits to have been taken to court so many times for disturbing public order and threatening the security of the State because his organization, has repeatedly organized public demonstrations to advocate for the rights of PLWHIV. The relatively confined management of public action for OVC, therefore, reflects a quest for strong State control, a quest that never dropped with the democratization of health policies.
Cuba's approach to the HIV epidemic is specific and has been debated. Today, with the availability of ART, the ways chosen by Cuba to control the HIV/AIDS epidemic may be seen differently . The intensive testing policy may be a useful approach to control an HIV epidemic, as a complement to other prevention approaches . In addition, it should be emphasised that the information given to the population about the epidemic since the death of the first person in 1986 on TV, radio and other media may also have played a role in reducing the spread of HIV by alerting the population. Today, special pro- grammes designed for teenagers have regular spots on HIV prevention and prevention of mother-to-child transmis- sion of HIV is efficient: Cuba has a low percentage of ver- tical transmission (12%) . The rising HIV prevalence is worrying. Despite current preventive and educational programmes carried out among MSM groups to advise them and to raise awareness about HIV acquisition andtransmission, the clear increase in HIVamong men shows that these programmes should be reinforced. Finally, more data, especially on sexual behaviour, are needed to analyse the Cuban HIV epidemic further and to gain insight into future trends in the epidemic.
80 viral load in infected patients. Yet, the treatment is unable to eliminate latent viral cellular reservoirs that become established during the early stages of infection, and these reservoirs can be reactivated upon treatment cessation. Even though these therapies enable patients to live a long and almost normal life cART is a life-long treatment that needs to be taken daily, carries a number of side effects and is costly. In addition, increased life expectancy revealed that HIV-1-infected patients have higher chances of developing other pathologies, including neuropathologies whose prevalence are increasing despite cART, and bone disorders, with up to a 6.4-fold increased risk of developing osteoporosis . Since its discovery in 1983, huge efforts have been made to controland eliminate HIV-1 infection, responsible for an important epidemic at the global scale. However, the capacity of HIV-1 to establish persistent reservoirs within its host makes treatment mandatory for a lifetime but prevents complete elimination of the pathogen. In addition to that, HIV-1 diagnosis, even if improved, remains an issue since a large proportion of infected people ignore their infection, and feed the invisible epidemic. As the infection continues to spread and cannot be cured, more efforts are still necessary to develop effective prevention measures, as well as to find a curative treatment. Within the last few years, several programs and world consortium have intensively focused their research on creating a vaccine against the virus, yet, designing an efficient vaccine against HIV-1 is more difficult than expected (for review, see  ). Most of the vaccine approaches are based on the utilization of soluble Env soluble trimers (HIV-1 receptors that allow the virus to infect a target cell), with the ultimate goal to create immune memory against the HIV-1 entry
Histoplasmosis andtuberculosis are probably among the most frequent AIDS- defining illnesses in the Amazon region and beyond . Whereas tuberculosis is a well-known disease present in clinical algorithms and in specific public health programs, disseminated histoplasmosis is relatively neglected in South and Central America [2,3]. Histoplasmosis and tuber- culosis are often presented as clinically and paraclinically similar . Recently, we showed that disseminated histoplasmosis, while having some similarities with tuber- culosis, had some marked differences with more pulmonary signs and inflammation in tuberculosis whereas histoplasmosis was more likely to be associated with cytope- nia, liver enzyme abnormalities, or symp- toms from the abdominal sphere .
Sexually active HIV-infected women were more likely to consistently use condom than HIV-negative women. However the proportion of women who declared systematically using condoms during their sexual intercourses decreased over time and this tendency was even stronger amongHIV-infected women. By 24 months post-partum, condom use was as low as the one reported as a contraceptive method in the general population (INS & ORC Macro, 2001). In our study, the beneficial effect of counselling on the reduction of sexual transmission of HIV was important immediately after HIV testing. Similarly, a study conducted amongpatients of STIs clinics in the United States showed that the rate of condom use was high during the immediate period after HIV testing, and then decreased gradually for tending towards the rate of condom use observed in the general population
The demographic characteristics, clinic-radiological findings and management of the 8 HIV-negative pa- tients who died are presented in Table 3 . Three of four deceased patients started empirically on TB treatment were aged 65 years or more. All were started on TB treatment at the first consultation and this decision was based on the chest X-ray interpreted by the treating clinical officer. However, the radiologist who did a sec- ond reading for quality control only interpreted one X-ray as possible TB. Two patients had a high blood pressure on clinical examination, the radiologist de- scribed cardiomegaly on their chest X-ray and con- cluded that there were no radiological signs of TB. One of them also had oedema in the lower limbs. This clin- ical and radiological findings may indicate a cardiovas- cular disease in these two patients.
doing so, we diverge from the standard RDS procedures and consequently we did not apply RDS adjustments to our results. Indeed, they tended to be older and had recently started to inject, but their other characteristics were similar as those from the RDS participants. Enrolling older participants may underestimate the actual incidence values. The circulation of HCV within the PWID population is evaluated only among sero-negative participants, and cannot account for new infections among participants already seropositive. Reporting only seroconversion also underestimate the actual HCV incidence value. Risk factors analysis for HCV seroconversion was limited and further investigations are required to decipher other HCV risk factors (e.g. sharing of diluents, tattoos, pierc- ing, smoking pipes). Finally, HCV seroconversion could take place up to 6 months after infection, but this delay varies between individual and it is difficult to document without nucleic acid testing.
The HIV-1 structural Gag polyprotein is responsible for orchestrating the assembly process and alone is sufficient for the production of viral particles. Numerous recent studies have shown that HIV-1 Gag assembly could take place at the plasma membrane (PM) or/and in late endo- somal/multivesicular compartments (LE/MVB) depend- ing on the cell type, thus raising the possibility that LE/ MVB may represent early intermediates where HIV-1 assembly is initiated [36,37]. Delphine Muriaux (INSERM-École Normale Supérieure, Lyon, France) dis- cussed the intracellular trafficking and assembly of Gag and the role of Gag-RNA interactions in these processes. Using immunofluorescence/FISH coupled to confocal microscopy, sub-cellular fractionation and RT-PCR tech- niques, she showed that in the case of wild-type HIV-1 virus, Gag-mediated assembly and budding occur both at the PM and on intracellular endosomal membranes . In the case of NC mutants, in which NC-RNA interactions are impaired [39,40], she found that NC-mutated Gag dis- played decreased particle release and strongly accumu- lated at the PM. On the basis of these results, she favors the view that HIV-1 can assemble both at the PM and on LE/MVB membranes with the requirement of NC-RNA interactions for Gag assembly and trafficking.
Results: 387 HIV‑1 infected adults (≥18 years) were consecutively enrolled when attending healthcare services for
their routine medical visit at 12 or 24 months on first‑line ART in five HIV care centers (four semi‑rural and one rural). Among them, 102 patients were on first‑line ART for 12 ± 2 months (M12) and 285 for 24 ± 2 months (M24). Virologi‑ cal failure was observed in 70 (18.1 %) patients ranging from 13.9 to 31.6 % at M12 and from 8.1 to 22.4 % at M24 across the different sites. For 67/70 patients, sequencing was successful and drug resistance mutations were observed in 65 (97 %). The global prevalence of drug resistance in the study population was thus at least 16.8 % (65/387). More‑ over, 32 (8.3 %) and 27 (6.9 %) patients were either on a completely ineffective ART regime or with only a single drug active. Several patients accumulated high numbers of mutations and developed also cross‑resistance to abacavir, didanosine or the new NNRTI drugs like etravirine and rilpivirine.
Hazan ( 2009 ) challenged this view by claiming that an increase in expected
lifetime labor supply is a necessary condition for an increase in longevity to induce more investment in schooling. Hazan ( 2009 ) then presents evidence of a sharp reduction in expected total working hours for US workers born in the period 1840-1970 that the author interprets as pointing to a violation of the necessary condition and concludes that the reduction in mortality rates in the U.S. over this period cannot account for any of the increase in education attainment. This conclusion has very important policy implications since it challenges the view that reducing mortality and improving health conditions may promote the acquisition of human capital, since it questions the empirical rationale of studying the relation between mortality and human capital.
27 Third, media coverage contributes to the portrayal of people living with HIV/AIDS as potential criminals and a threat to the general public. In the Canadian media, sero-positive people who have been charged (but not yet pronounced guilty) are often subject to the release of confidential data, including the person’s picture, name, age, city and work place, as well as detailed information regarding to their sexual practices. Such public disclosures highlight the distinction between people living with HIV/AIDSand those uninfected people for whom consensual sexual activities are private and not subject to public scrutiny. Moreover, the release of personal information clearly infringes upon their right to privacy- particularly if the person has not yet been convicted. 131 The police justify this infringement by explaining that their procedure is aimed at alerting the population that the person might be dangerous. 132 It is important to note here that the picture is often released even though the person has only engaged in consensual sex with one or two partners over a period of many years, and hence is not dangerous to the public at large. 133 This overly broad use of media coverage tends to send a misinformed message to the public reinforcing the false-impression that people living with HIV/AIDS are dangerous. As Carol L. Galletly has put it, HIV/AIDS criminal laws perpetuate the “us versus them” dichotomy that is central to prevailing theories of stigma. 134 . Furthermore, criminalizing HIV/AIDS sends a message that the responsibility to prevent the spread of HIV/AIDS falls on people living with HIV/AIDSand not on everyone.
Co-ordinating Centre: Kholoud Porter (Project Leader), Sara Lodi, Sarah Walker, Abdel
Babiker, Janet Darbyshire
Clinical Advisory Board: Heiner Bucher, Andrea de Luca, Martin Fisher, Roberto Muga
Collaborators: Australia Sydney AIDS Prospective Study and Sydney Primary HIV Infection cohort (John Kaldor, Tony Kelleher, Tim Ramacciotti, Linda Gelgor, David Cooper, Don Smith); Canada South Alberta clinic (John Gill); Denmark Copenhagen HIV Seroconverter Cohort (Louise Bruun Jørgensen, Claus Nielsen, Court Pedersen); Estonia Tartu Ülikool (Irja Lutsar); France Aquitaine cohort (Geneviève Chêne, Francois Dabis, Rodolphe Thiebaut, Bernard Masquelier), French Hospital Database (Dominique Costagliola, Marguerite Guiguet), Lyon Primary Infection cohort (Philippe Vanhems), SEROCO cohort (Laurence Meyer, Faroudy Boufassa); Germany German cohort (Osamah Hamouda, Claudia Kucherer); Greece Greek Haemophilia cohort (Giota Touloumi, Nikos Pantazis, Angelos Hatzakis, Dimitrios Paraskevis, Anastasia Karafoulidou); Italy Italian Seroconversion Study (Giovanni Rezza, Maria Dorrucci, Benedetta Longo, Claudia Balotta); Netherlands Amsterdam Cohort Studies among homosexual men and drug users (Maria Prins, Liselotte van Asten, Akke van der Bij, Ronald Geskus, Roel Coutinho); Norway Oslo and Ulleval Hospital cohorts (Mette Sannes, Oddbjorn Brubakk, Anne Eskild, Johan N Bruun); Poland National Institute of Hygiene (Magdalena Rosinska); Portugal Universidade Nova de Lisboa (Ricardo Camacho); Russia Pasteur Institute (Tatyana Smolskaya); Spain Badalona IDU hospital cohort (Roberto Muga, Jordi Tor), Barcelona IDU Cohort (Patricia Garcia de Olalla, Joan Cayla), Madrid cohort (Julia Del Amo, Jorge del Romero), Valencia IDU cohort (Santiago Pérez-Hoyos, Ildefonso Hernandez Aguado); Switzerland Swiss HIV Cohort Study (Heiner C. Bucher, Martin Rickenbach, Patrick Francioli); Ukraine Perinatal Prevention of AIDS Initiative (Ruslan Malyuta); United Kingdom Edinburgh Hospital cohort (Ray Brettle), Health Protection Agency (Valerie Delpech, Sam Lattimore, Gary Murphy, John Parry, Noel Gill), Royal Free haemophilia cohort (Caroline Sabin, Christine Lee), UK Register of HIV Seroconverters (Kholoud Porter, Anne Johnson, Andrew Phillips, Abdel Babiker, Janet
study. Typical outcomes evaluated included cost per neonatal HIV infection prevented for CEA and cost per QALY or DALY for CUA.
3.2. Research Domain.
The research design that was applied to this study was a systematic review of the available evidence on the economic evaluations of PMTCT of HIV in developing countries. A systematic review includes a comprehensive, exhaustive search for primary studies on a focused question, selection of studies using clear and reproducible eligibility criteria, critical appraisal of studies for quality, and synthesis of results according to a pre- determined and explicit method(Pai, McCulloch et al. 2004). According to Egger et al (2001), the goal of a systematic review is to primarily summarize available evidence on a specific research question, assessing the quality of the primary studies, as well as assisting in the formulation of new research questions. Glasziou et al (Glasziou P 2001) identify two major advantages of systematic reviews; firstly, combining data of all studies that have attempted to answer the same question considerably improves the ability to study the consistency of available results. Secondly, studying similar outcomes across a wide variety of settings and designs makes it possible to assess the rigor of available evidence, and the transferability of the results.
be classified into early, intermediate, and late, depending on the expression timing during poxvirus infection [ 55 , 56 ]. The modification of the promoter sequence is an excellent approach to control transgene expression; for example, some have both early and late elements, allowing their open reading frames or recombinant antigens to be expressed early in the virus infection and late after the viral genome replication. In the last few years, a number of poxviral promoters have been tested in recombinant MVA vectors, to increase recombinant antigen expression and, potentially, enhance antigen-specific immune responses [ 19 , 20 , 29 , 30 , 57 , 58 ]. Among them, one of the most promising is the novel synthetic VACV LEO promoter, which was previously designed in our laboratory using bioinformatic approaches and contains a late motif followed by an optimized immediate-early motif that allowed the transcriptional control of a heterologous antigen. The LEO promoter enhanced GFP expression and the magnitude of GFP-specific CD8 + T cells in immunized mice [ 30 ]. Further improvement of the LEO promoter was achieved by elongating from 38 to 160 nucleotides the spacer sequence between the promoter elements and the transgene transcriptional start site (termed LEO160 promoter), thus improving antigen-specific memory CD4 + and CD8 + T cell responses in immunized mice, as tested with GFP or the Leishmania antigen LACK [ 29 ]. Thus, considering the strength of the LEO160 promoter in inducing better early expression of the intracellular GFP and LACK antigens, and improving antigen-specific cellular immune responses in immunized mice, this promoter modification was introduced in the context of an MVA-based HIV/AIDS vaccine candidate. Therefore, insertion of the novel VACV optimized LEO160 promoter was introduced in MVA to try to enhance the expression and immunogenicity of the HIV-1 gp120 antigen from clade B. The recombinant virus MVA-LEO160-gp120 was generated with the aim to define the role of the LEO160 promoter strength in the early expression and secretion of the soluble HIV-1 gp120 antigen, and to test whether gp120-specific cellular and humoral immune responses could be enhanced.