Affordable antiretroviral drugs for the under-served markets: how to expand equitable access against the backdrop of challenging scenarios?

BACKGROUND: Threats by enforced Intellectual Property (IP) rights to equitable HIV treatment access by poor populations are impending. India and China's policy directions in the field will be crucial in ultimately affecting the affordability and accessibility of antiretroviral (ARV) therapy in the under-served markets. These directions, together with the exploitation level of IP-bound flexibilities and the evolutionary modelling in partnerships and trade agreements between research-based and generic pharmaceutical industry, will also affect the outcomes of self-sufficiency efforts now at their beginning in the developing world as far as domestic manufacturing of generic ARV drugs is concerned. AIMS: This paper explores key issues, implications and interaction dynamics across these challenging scenarios while attempting to provide equitable solution glimpses into the near future. RESULTS: Access-oriented long-term drug policy strategies entitled to pass muster of governments, research-based as well as generic industries in both developed and developing countries are needed if equitable access to affordable ARV treatments by poor people has to be achieved despite enforced IP rights. Predictable dynamics between western multinationals and transitional country generic corporations let regard IP-bound Voluntary License flexibilities as a fitting measure into just mentioned needs especially if substantial incentives to generic corporations are concurrently secured. Efforts to equitably expand ARV drug access through exploiting IP opportunities should encompass attainment of self-sufficiency in domestic drug manufacturing whenever basic requirements are in place in the developing world as a whole. A credible industrial potential would act, indeed, as a boosting factor for drawing branded drug producers into technology transfer agreements, the terms of which would let all contractors enjoy substantial advantages. These perspectives consistently bind up with the foreseeable long-term trade and drug policy directions of India and China according to frontier crossing implications of their key IP management trends as well as their multifaceted penetration strategies of both the wealthy and under-served markets worldwide. As coherent with these perspectives, more disbursement by wealthy country governments and donors to basic infrastructure development in sub-Saharan African nations with stable governments in place is urged both as a priority for improving Africa's economy and a prerequisite for allowing domestic industrial plants to take off. Aiming at the targets just underscored, WHO's brokering role in negotiated agreements between wealthy and developing country-based firms as well as its technical guidance in setting international standards have always to be sought if equitable and appropriate end results are to be attained. CONCLUSION: Overall insights in this paper would mean that, while research-based corporations are to be praised whenever waiving, on humanitarian purposes, part of their profits, the trade and profit rules cannot basically be given up if long-term sustainable results are the goal to look for. Only negotiated agreements securing all contracting parties lasting advantages may ensure shifting of such a goal from mere vision to a really sustainable attainment.

Experimentally-induced acute lung injury: the protective effect of hydroxyethyl starch.

The objective of this study was to evaluate the effects of hydroxyethyl starch, (130/0.4) 6%, compared to Ringer's acetate and modified gelatin on hypoxemia, inflammatory response, and oxidative stress in an experimental model of acute lung injury (ALI). The ALI/Adult Respiratory Distress Syndrome (ARDS) experimental model was produced by a bronchoalveolar saline lavage. Mature New Zealand white rabbits were anesthetized, provided with a tracheostomy and vascular catheters, and randomized to receive 25 ml/kg/hr of Ringer's acetate (group R, n = 7), 25 ml/kg/hr of modified gelatin (group G, n = 7), or 25 ml/kg/hr of hydroxyethyl starch (group S, n = 7). All of the rabbits received mechanical ventilation to maintain the PaCO2 between 35 and 45 mm Hg. Blood gas levels and hemodynamic values were recorded before induction of lung injury (T0) and 10 (T10), 120 (T120) and 240 (T240) min following induction of lung injury. At the same time-points, blood samples were collected to measure the plasma levels of TNFalpha (tumor necrosis factor-alpha) and TBARS (thiobarbituric acid-reactive substances). The experiment yielded the following results: The blood PaO2/FiO2 ratio was higher in group S than in groups R and G at T10, T120, and T240 (p <0.05). In group S, the plasma TNFalpha and TBARS concentrations were lower than in groups R and G at T120 and T240 (p <0.05). In conclusion, rabbits treated with hydroxyethyl starch, (130/0.4) 6%, demonstrated reductions of hypoxemia, inflammatory response, and oxidative lung damage, compared to raabbits treated with Ringer's acetate or modified gelatin.

Streptococcus agalactiae: prevalence of antimicrobial resistance in vaginal and rectal swabs in Italian pregnant women.

Intrapartum antibiotic prophylaxis (IAP) reduces both the vertical transmission of Streptococcus agalactiae or Group B Streptococcus (GBS) and the early onset of neonatal sepsis. However, existing guidelines do not recommend that antimicrobial susceptibility testing (AST) be routinely performed. Penicillin or ampicillin are indicated as first-choice antibiotics, cefazolin being an alternative in the case of history of mild allergic reactions, and vancomycin or clindamycin an alternative in the event of severe reactions. We performed a cross-sectional analysis to identify the presence of any bacterial resistance towards the antibiotics most frequently used for IAP in pregnant women with GBS positive vaginal-rectal swabs, in the Pistoia area of central Italy. Of the 255 tested samples, 65 (25.5%) were positive for GBS. Sensitivity to glycopeptides was over 90%, but lower to ampicillin and penicillin (87.10% and 87.93% respectively). Resistance towards clindamycin and erythromycin was as high as 43.75% and 32.20%. All tested GBS proved susceptible to moxifloxacin, linezolid and tigecycline. Our observed prevalence is aligned or slightly higher than data reported in other series. The less than full effectiveness and low percentages of ampicillin and penicillin sensitivity observed give cause for concern. We confirmed the increase in clindamycin and erythromycin resistance. Glycopeptides can be used as second-line antibiotics, but the complete AST of GBS should always be performed before IAP. Given that gentamicin is used synergically with penicillin when treating chorioamnionitis, it needs to be always included in the AST. This is the first study on the GBS sensitivity profile in Tuscany. Further investigation on a larger scale is required prior to implementing any changes in the current guidelines.

Priority strategies for sustainable fight against HIV/AIDS in low-income countries.

Response to HIV/AIDS epidemic in resource-constrained countries is still woefully disappointing. This paper highlights some priorities shared at recent Florence World Conference (Florence, Italy: January 21st-24th, 2004) on how to overcome the obstacles still delaying sustainable fight against HIV/AIDS in developing world areas. Messages reported here result from selection made by the authors among challenging topics by more than one hundred speakers and have been chosen because of their value as most practical ways to secure prevention, treatment and care and achieve self-managing in fighting epidemic in income-limited settings. Building for success means to set up combined strategies--actively involving people living with HIV/AIDS (PLWHA) and grounded on coordination, coalition and partnership among all players--to prevent HIV transmission at mother-to-child, young and adult levels and to improve availability and access to laboratory testing and monitoring as well as to essential drugs for HIV/AIDS and related diseases. Building for success also means to provide women with reliable and affordable vaginal microbicides and to look for control of co-infections such as viral hepatitis, intestinal and sexually transmitted diseases as well as tuberculosis and malaria. Among the measures taken into account, the need for education and training is emphasised because its value may be even more important than funding in some countries. Priorities suggested in this paper reinforce each other underscoring the bidirectional value and synergy of the treatment and prevention strategies together with the need for keeping prevention in people giving successful antiretroviral treatment. In the Author's opinion, the current HIV/AIDS scenario may be reversed if the priorities taken into account will entirely be applied through adaptation to the different cultural backgrounds and social settings, and based on achievement of government's political will and accountability as well as on properly coordinated technical, financial and human support from international health cooperation.

Designing ARVs Patent Pool Up to Trade & Policy Evolutionary Dynamics.

Patent pools for second and third-line Fixed Dose Combination (FDC) antiretroviral drugs (ARVs) should not be delayed as they are instrumental to urgent public health needs in the under-served markets.Nonetheless, multinational originator companies still seem to perceive patent pooling for ARVs as a minefield that would offer the generic competitors lots of deeply exploitable opportunities, to the detriment of patent owner's rights.This paper analyses the brand industry concerns, while looking for a strategy up to a really equitable and free world market, without any discrimination between end-users in wealthy and resource-limited countries.This strategy would urge partnerships between originator companies first to make newer FDC ARVs quickly available and allow patent pool agreements with generic counterparts to be negotiated straight afterwards.The patent pool strategy highlighted in this paper would assert the primacy of health over for-profit policies, while aligning with the 61(st) WHO's Assembly recommendations and G7, G8 and World Trade Organisation's warnings and pledges against trade protectionism.

What strategies to boost production of affordable fixed-dose anti-retroviral drug combinations for children in the developing world?

BACKGROUND: No more than 8% of HIV positive children needing treatment in low- and middle-income countries have access to antiretroviral drugs (ARVs). Children presently account for about 4% of all treated patients, while for equitable access they should make up at least 13%. AIMS: This study explores key issues, implications and interaction dynamics to boost production of easy-to-use and affordable fixed-dose combination (FDC) ARVs for children in the developing world. Potentials for equitable solutions are examined including priority steps and actions, appropriate treatment options and reliable forecasting methods for paediatric ARVs, as well as combination incentives to generic companies against market unattractiveness and enforced intellectual property (IP) rights. Moreover, implementation strategies to enhance the development and production of affordable ARV paediatric formulations and appropriate supply systems to ensure availability are investigated. RESULTS: The current market for FDC paediatric ARVs is already substantial and will only grow with improved and scaled up diagnosis and monitoring of children. This provides an argument for immediate increase of production and development of FDC ARVs for children. These formulations must be low cost and included in the list of Essential Medicines to avoid children continuing to lag behind in access to treatment. Access-oriented, long-term drug policy strategies with the ability to pass muster of governments, the UN system, as well as generic and research-based enterprises are needed to let children gain expanded and sustained access to FDC ARVs. Under the requirements listed above, IP-bound Voluntary License (VL) flexibilities do appear, if coupled with substantial combination incentives to generic firms, as a fitting tool into the needs. Policies must consider enhancing human resource capacity in the area of caregivers and social and health workers aiming to spread correct information and awareness on effectiveness and rationale of FDC ARVs for children. Policies should urge that paediatric ARV treatment programmes entwine with extant interventions on prevention of mother-to-child transmission, as well as with HIV treatment initiatives focused on mothers and household members. Policies, again, should consider centralising functions and pooling resources to help overcome drug supply barriers. WHO's brokering role in VL-based agreements between wealthy and developing country industries, as well as its technical guidance in setting international standards should not be waived while looking for sustained access to optimised ARV treatments for children. Strategies discussed in this paper, while taking unavoidability of marketing and profit rules into account, look closely into the trade and drug policy directions of China and India according to frontier crossing implications of their IP management trends as well as their multi-faceted penetration strategies of both the wealthy and under-served markets the world over.