Toward a global health approach: lessons from the HIV and Ebola epidemics.

BACKGROUND: The imposing burden of non-communicable diseases, emerging infectious diseases, climate change, environmental consequences, migrations, urbanization, and other challenges, faced in a context that strives to make universal health coverage (UHC) a reality, compels global health professionals to ask: how do we construct a "global" roadmap that is both realistic and effective? To move forward and begin to answer this question, we draw on lessons and experiences gained during the "global" health crises triggered by the HIV and Ebola pandemics. MAIN TEXT: Improving the early response and committing to the long haul; developing inter-disciplinary and inter-sectoral responses; designing comprehensive and versatile interventions; and, most importantly, to work closely and effectively with civil society and communities are some of the critical elements that were identified. The health sector has changed dramatically in recent years; new tools and innovative technologies are transforming the culture and practice of public health. This calls for a new vision. Reprioritizing primary health care and community engagement, repositioning approaches to meet people's needs, applying integrated disease management to respond to problems caused by the silo approach, implementing UHC, and ensuring equity are some of the new strategies. CONCLUSION: These strategies must all undergo a mandatory revolution in health governance-locally and globally. It should be obvious that nothing can be improved on a global or sustainable scale without re-examining the architecture and governance of major funding and international organizations dedicated to health. Pressing economic, demographic, and climate issues related to health underscore the urgent need for these changes.

Prevalence of pulmonary tuberculosis among prison inmates: A cross-sectional survey at the Correctional and Detention Facility of Abidjan, Côte d'Ivoire.

BACKGROUND: In Côte d'Ivoire, a TB prison program has been developed since 1999. This program includes offering TB screening to prisoners who show up with TB symptoms at the infirmary. Our objective was to estimate the prevalence of pulmonary TB among inmates at the Correctional and Detention Facility of Abidjan, the largest prison of Côte d'Ivoire, 16 years after this TB program was implemented. METHODS: Between March and September 2015, inmates, were screened for pulmonary TB using systematic direct smear microscopy, culture and chest X-ray. All participants were also proposed HIV testing. TB was defined as either confirmed (positive culture), probable (positive microscopy and/or chest X-ray findings suggestive of TB) or possible (signs or symptoms suggestive of TB, no X-Ray or microbiological evidence). Factors associated with confirmed tuberculosis were analysed using multivariable logistic regression. RESULTS: Among the 943 inmates screened, 88 (9.3%) met the TB case definition, including 19 (2.0%) with confirmed TB, 40 (4.2%) with probable TB and 29 (3.1%) with possible TB. Of the 19 isolated TB strains, 10 (53%) were TB drug resistant, including 7 (37%) with multi-resistance. Of the 10 patients with TB resistant strain, only one had a past history of TB treatment. HIV prevalence was 3.1% overall, and 9.6%among TB cases. Factors associated with confirmed TB were age ≥30 years (Odds Ratio 3.8; 95% CI 1.1-13.3), prolonged cough (Odds Ratio 3.6; 95% CI 1.3-9.5) and fever (Odds Ratio 2.7; 95% CI 1.0-7.5). CONCLUSION: In the country largest prison, pulmonary TB is still 10 (confirmed) to 44 times (confirmed, probable or possible) as frequent as in the Côte d'Ivoire general population, despite a long-time running symptom-based program of TB detection. Decreasing TB prevalence and limiting the risk of MDR may require the implementation of annual in-cell TB screening campaigns that systematically target all prison inmates.

The ESTHER hospital partnership initiative: a powerful levy for building capacities to combat the HIV pandemic in low-resource countries.

Partnerships between hospitals in high income countries and low resource countries are uniquely capable of fulfilling the tripartite needs of care, training, and research required to address health care crises in low resource countries. Of particular interest, at a time when the EBOLA crisis highlights the weaknesses of health systems in resource-poor settings, the institutional resources and expertise of hospitals can also contribute to strengthening health systems with long-term sustainability.We describe a partnership network between French Hospitals and hospitals/health structures in 19 countries that demonstrates the power and efficacy of health partnership in the response to the HIV/AIDS pandemic in sub-Saharan Africa and south East Asia. Through the ESTHER initiative, the partnership network currently provides capacity development, care and treatment to over 165,000 HIV-positive patients at 87 urban and 92 peripheral sites in 17 countries and enrolls 19,000 new HIV positive patients, delivers psychosocial services to 120 000 people and tests more than 35,000 pregnant women for HIV annually. It also, engages communities and assists with the development of a robust electronic information system.Launched in 2002, the ESTHER (Ensemble pour une Solidarite Thérapeutique Hospitalière En Reseau) initiative has grown from small projects with a focus on access to antiretroviral treatment in a limited number of West African countries at its outset into a large and comprehensive HIV/AIDS-control system in Western and Central Africa. The partnership's rapid achievements in the fight against HIV/AIDS, combined with the comprehensive and long-term approach to countries' health care needs, suggest that this "twinning" and medical mentoring model can and should be duplicated and developed to address the ever more pressing demand for response to global health needs in low resource countries.

Likely effect of the 2014 Ebola epidemic on HIV care in Liberia.

OBJECTIVE: Liberia's health system has been severely struck by the 2014 Ebola epidemic. We aimed to assess the potential effect of this epidemic on the care of HIV patient in two clinics [John F. Kennedy (JFK) and Redemption Hospitals] in Monrovia, which stayed open throughout the epidemic. DESIGN AND METHODS: A preexisting electronic database of HIV patient's follow-up visits was used to estimate three weekly parameters from January 2012 to October 2014: number of visits, number of new patient, and proportion of patients with follow-up delay. We used segmented negative binomial regressions to assess trends before and after the week of the Ebola outbreak defined in June 2014 by WHO. RESULTS: The cumulative number of patients in care comprised 5948 patients with a total of 56 287 visits between January 2012 and October 2014. From June 2014, the number of visit per week, stable since 2012, abruptly decreased (59%) in Redemption (P < 0.001) and progressively decreased by 3% per week in JFK (P < 0.001). In both the clinics, the weekly proportion of patient with follow-up delay sharply increased after the point break from June 2014 (P value < 0.001). From June 2014, a significant decrease in new patients per week occurred in both the clinics: by 57% (P value < 0.001) in Redemption and by 4.6% per week (P value < 0.001) in JFK. CONCLUSION: The Ebola epidemic had a significant effect on HIV care in Monrovia. Given the particular impact on the rate of patients with follow-up delay, a long-term impact is feared.

Prevalence and behavioural risks for HIV and HCV infections in a population of drug users of Dakar, Senegal: the ANRS 12243 UDSEN study.

OBJECTIVES: Data on the extent of drug use and associated HIV, hepatitis C and hepatitis B infection in West Africa are lacking. The objectives of ANRS12244 UDSEN study were to estimate the size of the heroin and/or cocaine drug user (DU) population living in the Dakar area (Senegal), and assess the prevalence and risk factors of HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV), including behavioural determinants in this population, in order to set up an integrated prevention and treatment programme for DUs. DESIGN AND METHODS: A capture-recapture method was applied for population size estimation, whereas the respondent-driven sampling (RDS) method was used to recruit a sample of DUs living in the Dakar area and determine HIV, HBV and HCV prevalence. Behavioural data were gathered during face-to-face interviews, and blood samples were collected on dried blood spots for analysis in a central laboratory. Data analysis was performed using the RDS analysis tool, and risk factors were determined by logistic regression. Access to laboratory results was organized for the participants. RESULTS: The size of the DU population in the Dakar area was estimated to reach 1324 (95% confidence interval (95% CI: 1281-1367)). Based on the 506 DUs included in the study, the HIV, HCV and HBV prevalence were 5.2% (95% CI: 3.8-6.3), 23.3% (95% CI: 21.2-25.2) and 7.9% (95% CI: 5.2-11.1), respectively. In people who inject drugs (PWID), prevalence levels increased to 9.4% for HIV and 38.9% for HCV (p=0.001 when compared to those who never injected). Women were more at risk of being HIV infected (prevalence: 13.04% versus 2.97% in males, p=0.001). Being PWID was a risk factor for HCV and HIV infection (odds ratio, OR: 2.7, 95% CI: 1.7-4.3, and OR: 4.3, 95% CI: 1.7-10.7, respectively), whereas older age and female sex were additional risk factors for HIV infection (10% increase per year of age, p=0.03 and OR: 4.9, 95% CI: 1.6-156, respectively). No specific determinant was associated with the risk of HBV infection. CONCLUSIONS: High HIV and HCV prevalence were estimated in this population of DUs (including non-injectors) living in the Dakar area, Senegal, whereas HBV prevalence was close to that of the global Senegalese population, reflecting a risk of infection independent of drug use. Women seem to be highly vulnerable and deserve targeted interventions for decreasing exposure to HIV, while behavioural risk factors for HIV and HCV include the use of unsafe injections, reflecting the urgent need for developing harm reduction interventions and access to opioid substitution therapy services.

[Community health workers in HIV/AIDS care]. / Les agents de santé communautaire dans la prise en charge thérapeutique du VIH/sida.

INTRODUCTION: Faced with the lack of human resources manage people living with HIV/AIDS (PLWHA) in developing countries, community health workers (CHWs) provide support to health professionals. The objective of this study was to describe the characteristics of CHWs and study the impact of their intervention on HIV care. A literature search was performed on Pubmed and the websites of international organizations. METHODS: A literature review was conducted, including studies describing the impact of the CHWs' intervention on the care of PLWHA. RESULTS: Thirteen articles were selected concerning twelve studies. The names and functions of CHWs are multiple; training and remuneration are very heterogeneous. Nevertheless, the impact of their intervention appears to be positive. Trials comparing community-based care versus hospital care show no difference between the two in terms of survival, retention, viral load or CD4 counts. The support provided by CHWs improves quality of life, compliance and self-confidence and decreases stigma (qualitative studies). It also allows coverage of previously remote areas. CONCLUSION: CHWs have various names, functions, formations and salaries. Their actions appear to have a positive impact both on the therapeutic management of PLHIV and on strengthening health systems. Recognition of CHWs by health systems remains marginal and remains a public health priority.

Preferred antiretroviral drugs for the next decade of scale up.

Global commitments aim to provide antiretroviral therapy (ART) to 15 million people living with HIV by 2015, and recent studies have demonstrated the potential for widespread ART to prevent HIV transmission. Increasingly, countries are adapting their national guidelines to start ART earlier, for both clinical and preventive benefits. To maximize the benefits of ART in resource-limited settings, six key principles need to guide ART choice: simplicity, tolerability and safety, durability, universal applicability, affordability and heat stability. Currently available drugs, combined with those in late-stage clinical development, hold great promise to simplify treatment in the short term. Over the longer-term, newer technologies, such as long-acting formulations and nanotechnology, could radically alter the treatment paradigm. This commentary reviews recommendations made in an expert consultation on treatment scale up in resource-limited settings.

In the shadow of HIV/AIDS: forgotten diseases in sub-Saharan Africa: global health issues and funding agency responsibilities.

The HIV/AIDS pandemic has generated international solidarity, particularly with sub-Saharan Africa. The mainly vertical approach to this challenge has, however, mobilized so much attention and so many resources that other crucial public health problems, such as chronic viral hepatitis and non-communicable diseases (NCDs), have been left in the shadows. One year after the first official World Hepatitis Day launched by WHO and the first UN meeting on NCDs, the world needs a vigorous debate on a more comprehensive approach to public health challenges in developing countries.

Drug use and HIV in West Africa: a neglected epidemic.

Injecting drug use is poorly documented in West Africa. HIV prevalence studies are still rare. Recent studies show that drug injection is on the rise. There is an urgent need to take this component of the HIV epidemic into account and to establish adapted intervention strategies.

Effect of highly active antiretroviral therapy on survival of HIV infected patients with non-small-cell lung cancer.

OBJECTIVE: To evaluate the impact of highly active antiretroviral therapy (HAART) on survival in HIV infected patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: All consecutive HIV infected patients with NSCLC diagnosed between 06/1996 and 03/2007 at two University hospitals in Paris (France) were prospectively followed until death. The association between survival and clinical and biological factors was analyzed by univariate and multivariate models. Survival analysis was performed by Kaplan-Meier estimates and the Cox proportional hazards regression model. RESULTS: During the study period, NSCLC was diagnosed in 49 consecutive HIV infected patients (median age 46 years); 84% had advanced disease. Median survival was 8.1 months (range 5-10 months). In multivariate analysis, baseline parameters with significant positive impact on survival included performance status (PS) < or =1 (HR=0.2, 95%CI [0.09, 0.46], p=0.0001), stage I-II disease (HR=0.15, 95%CI [0.04, 0.53], p=0.003), and use of HAART (HR=0.4, 95%CI [0.2, 0.9], p=0.027). CONCLUSION: HAART is a good prognostic factor for survival in HIV infected patients with NSCLC. Stage of disease and PS are two other valid survival prognostic factors.

Complete cure of HBV-HDV co-infection after 24weeks of combination therapy with pegylated interferon and ribavirin in a patient co-infected with HBV/HCV/HDV/HIV.

Multiple hepatitis co-infections are frequent in HIV-infected patients, often resulting in severe liver diseases that are difficult to treat. We report here the complete resolution of a chronic hepatitis B and D co-infection in a patient who was also infected with HCV and HIV. This cure was observed after 24weeks of combination therapy associating pegylated-IFN and ribavirin, which was initially given to treat HCV. An unexpected and extensive HDV replication was observed in this patient after HBs Ag had cleared from the serum, which was followed by a stable halt in HDV replication. Implications of this unusual observation will be discussed.

Predictive values of the human immunodeficiency virus phenotype and genotype and of amprenavir and lopinavir inhibitory quotients in heavily pretreated patients on a ritonavir-boosted dual-protease-inhibitor regimen.

The inhibitory quotient (IQ) of human immunodeficiency virus (HIV) protease inhibitors (PIs), which is the ratio of drug concentration to viral susceptibility, is considered to be predictive of the virological response. We used several approaches to calculate the IQs of amprenavir and lopinavir in a subset of heavily pretreated patients participating in the French National Agency for AIDS Research (ANRS) 104 trial and then compared their potentials for predicting changes in the plasma HIV RNA level. Thirty-seven patients were randomly assigned to receive either amprenavir (600 mg twice a day [BID]) or lopinavir (400 mg BID) plus ritonavir (100 or 200 mg BID) for 2 weeks before combining the two PIs. The 90% inhibitory concentration (IC(90)) was measured using a recombinant assay without or with additional human serum (IC(90+serum)). Total and unbound PI concentrations in plasma were measured. Univariate linear regression was used to estimate the relation between the change in viral load and the IC(90) or IQ values. The amprenavir phenotypic IQ values were very similar when measured with the standard and protein binding-adjusted IC(90)s. No relationship was found between the viral load decline and the lopinavir IQ. During combination therapy, the amprenavir and lopinavir genotypic IQ values were predictive of the viral response at week 6 (P = 0.03). The number of protease mutations (< 5 or > or = 5) was related to the virological response throughout the study. These findings suggest that the combined genotypic IQ and the number of protease mutations are the best predictors of virological response. High amprenavir and lopinavir concentrations in these patients might explain why plasma concentrations and the phenotypic IQ have poor predictive value.

Salvage therapy with amprenavir, lopinavir and ritonavir is durably potent in HIV-infected patients in virological failure: 1-year results.

We report the results of the extended follow-up at one year of a randomized trial evaluating the virological efficacy of a salvage therapy combining lopinavir and amprenavir with either 200 or 400 mg/day ritonavir, along with optimized nucleoside reverse transcriptase inhibitors, in patients carrying multidrug-resistant isolates. The combination of amprenavir, lopinavir and ritonavir (400 mg/day) is durably potent, yielding a sustained virological response (HIV RNA < 50 copies) in 39% of cases.

Low genetic barrier to large increases in HIV-1 cross-resistance to protease inhibitors during salvage therapy.

HIV-1 resistance to protease inhibitors (PIs) is characterized by extensive cross-resistance within this drug class. Some PIs, however, appear less affected by cross-resistance and are often prescribed in salvage therapy regimens for patients who have failed previous PI treatment. To examine the capacity of HIV-1 to adapt to these treatment changes, we have followed the evolution of HIV-1 protease genotypes and phenotypes in 21 protease-inhibitor-experienced patients in whom 26 weeks of an aggressive salvage regimen associating lopinavir, amprenavir and ritonavir failed to suppress viral replication. Baseline genotypes exhibited a median of seven resistance mutations in the protease. After 26 weeks of treatment, changes in protease genotypes were seen in 13/21 patients. The evolution of these protease genotypes was rapid, with more than one-third of the changes occurring during the first 6 weeks. Although the mean number of additional mutations was small (2.15 new mutations at week 26) these mutations were sufficient to promote remarkable changes in resistance phenotype. In several patients, some of the new mutations were found to exist before salvage treatment as part of minority quasi-species. Thus, in the face of the strong pharmacological pressure exerted by combinations of PIs to which it has never been exposed, and in spite of limited cross-resistance to these drugs before salvage therapy, HIV-1 can rapidly adapt its resistance genotype and phenotype at a minimal evolutionary cost.

Salvage therapy with amprenavir, lopinavir and ritonavir 200 mg/d or 400 mg/d in HIV-infected patients in virological failure.

OBJECTIVES: To compare the antiviral efficacy of a salvage therapy combining lopinavir and amprenavir with 200 mg/d or 400 mg/d ritonavir, together with nucleoside reverse transcriptase inhibitors, over a 26-week period in HIV-infected patients in whom multiple antiretroviral regimens had failed. DESIGN: Phase IIb, randomized, open-label, multicentre trial. Patients were eligible if they had <500 CD4+ cells/mm3 and >4 log10 copies/ml HIV-RNA after treatment with at least two protease inhibitors (PIs) and one non-nucleoside reverse transcriptase inhibitor. RESULTS: At baseline (n=37), the median CD4+ cell count was 207/mm3 and the median plasma HIV-1 RNA level was 4.7 log10 copies/ml; the median number of PI mutations was seven and the median decrease in phenotypic susceptibility to lopinavir and amprenavir was 9.7 and 2.6, respectively. The mean number of antiretrovirals received prior to randomization was 7.7. The fall in the median HIV-1 RNA level at week 26 was -1.4 log10 copies/ml in the 200 mg/d ritonavir group and -2.5 log10 copies/ml in the 400 mg/d group (P=0.02). Viral load fell below 50 copies/ml in 32% and 61% of patients, respectively (P=0.07). After adjustment for the ritonavir dose, a smaller number of PI mutations was the only baseline characteristic associated with a better virological response at week 26. Amprenavir concentrations were significantly lower in presence of lopinavir. The lopinavir inhibitory quotient at week 6 correlated weakly with the change in the HIV-RNA level at week 26. CONCLUSION: Combination of amprenavir, lopinavir and 400 mg/d ritonavir shows significant virological efficacy without increased toxicity in HIV-infected patients in whom multiple antiretroviral regimens have failed.

Interactions between amprenavir and the lopinavir-ritonavir combination in heavily pretreated patients infected with human immunodeficiency virus.

OBJECTIVE: This pharmacokinetic study was designed to characterize interactions between amprenavir and the lopinavir-ritonavir combination in patients infected with human immunodeficiency virus in whom previous antiretroviral therapy had failed. METHODS: Twenty-seven patients included in a randomized clinical trial (ANRS [National Agency for AIDS Research] Protocol 104) participated in this study. They were randomized to receive ritonavir at a dose of either 100 mg twice daily or 200 mg twice daily. For the first 2 weeks of therapy, they were randomly assigned to receive lopinavir (400 mg twice daily) and ritonavir (100 mg twice daily), amprenavir (600 mg twice daily) plus ritonavir (100 mg twice daily), lopinavir (400 mg twice daily) and ritonavir (100 mg twice daily) plus additional ritonavir (100 mg twice daily), or amprenavir (600 mg twice daily) plus ritonavir (200 mg twice daily). From week 3 onward, all patients received amprenavir plus lopinavir-ritonavir with or without an additional ritonavir dose (100 mg twice daily). The pharmacokinetics of the 3 drugs was studied in weeks 2 and 6 of therapy. RESULTS: Median amprenavir concentrations decreased by 54% (P =.004) when lopinavir was added to the amprenavir-ritonavir regimen. Lopinavir weakly displaced amprenavir from plasma proteins: The average unbound fraction of amprenavir was 0.089 in week 2 and 0.114 in week 6 (P =.03), but this did not fully account for the observed interaction. Increasing the ritonavir dose did not affect the amprenavir concentration. The relationship between lopinavir and ritonavir concentrations fitted a maximum effect (E(max)) model;the average concentration of ritonavir that yielded a lopinavir concentration of 8119 ng/mL (50% of E(max)) was 602 ng/mL (coefficient of variation, 22%). There was a significant relationship between the lopinavir inhibitory quotient and the virologic response in week 2 (P =.005). CONCLUSION: Lopinavir markedly decreases the amprenavir concentration during amprenavir and lopinavir-ritonavir combination therapy. The inhibitory quotients were more predictive of the short-term virologic response than was the level of drug exposure.