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.

Developing and delivering appropriate, affordable, well-adapted medicines for HIV/AIDS remains an urgent challenge: as first-line therapies fail, increasing numbers of people require costly second-line therapy; one-third of ARVs are not available in pediatric formulations; and certain key first- and second-line triple fixed-dose combinations do not exist or sufficient suppliers are lacking. UNITAID aims to help solve these problems through an innovative initiative for the collective management of intellectual property (IP) rights – a patent pool for HIV medicines. The idea behind a patent pool is that patent holders - companies, governments, researchers or universities - voluntarily offer, under certain conditions, the IP related to their inventions to the patent pool. Any company that wants to use the IP to produce or develop medicines can seek a license from the pool against the payment of royalties, and may then produce the medicines for use in developing countries (conditional upon meeting agreed quality standards). The patent pool will be a voluntary mechanism, meaning its success will largely depend on the willingness of pharmaceutical companies to participate and commit their IP to the pool. Generic producers must also be willing to cooperate. The pool has the potential to provide benefits to all.

This paper seeks to set the practical discipline of public interest intellectual property (IP) management in public health into its broader policy context. The most immediate and direct impact of IP systems on public welfare results not from international standards nor from national legislation – though these norms are fundamentally important - but rather from the accumulated impact of numerous practical choices whether or not to seek IP protection; where and where not; and how any exclusive rights are deployed, by whom, and to what end. IP management is the essentially practical exercise of limited exclusive rights over protected subject matter, the judicious use of those rights to leverage outcomes that advance an institution's or a firm's objectives. Exclusive rights are used to construct and define knowledge-based relationships, to leverage access to technology and other necessary resources, and to enhance market-based incentives. IP management choices range across a broad spectrum, spanning public domain strategies, open or exclusive licensing, and strong exclusivity. The idea of ‘exclusive rights’, as a specific legal mechanism, can run counter to expectations of greater openness and accessibility, but actual outcomes will depend very much on how these mechanisms are used in practice. For public interest or public sector institutions concerned with health research and development, particularly the development of new medicines, IP management choices can be just as critical as they are for private firms, although a predominant institutional concentration on advancing direct public interest objectives may lead to significantly different approaches in weighing and exercising practical choices for IP management: even so, a private sector approach should not be conflated with exclusivity as an end in itself, nor need public interest IP management eschew all leverage over IP. This paper offers a tentative framework for a richer typology of those choices, to give a sense of practical options available and the factors that might guide their application, but without advocating any particular approach.

Unaffordable prices still obstruct access to brand antiretroviral (ARV) treatments for HIV infection in the income-constrained countries, while being the challenges complicated by obstacles bound up with enforcement of World Trade Organization-WTO's Trade-Related Aspects of Intellectual Property Rights (TRIPS) [1].Definitely, patent protection, by eliminating generic competition, has skyrocketed the brand drug prices, while TRIPS-plus measures (such as exacerbated data exclusivity) do hamper the development of any new generic ARV formulation containing drugs with exclusive status.

Objectives:Individuals living in deprived neighbourhoods have poor health outcomes, including human immunodeficiency virus (HIV) infection mortality. We assessed the association between individual and neighbourhood characteristics, and HIV testing across Canada.Methods:We used logistic regression modelling to evaluate this association in 2219 men and 2815 women, aged 18-54 years, in Canada, using data from the National Population Health Survey (1996/7),. Socio-economic characteristics and presence of a sexually transmitted infection (STI) were the individual level characteristics. Small area of residence was classified according to categories of material and social deprivation; these were the ’neighbourhood’ variables in the model.Results:Ethnic minority women were less likely to report an HIV test than white women (OR 0.44, 95% CI: 0.23 to 0.86). Women without a regular doctor were significantly less likely to report ever having had an HIV test (OR 0.57, 95% CI: 0.35 to 0.93). Adjusting for individual level characteristics, we found that men and women living in the most materially deprived neighbourhoods were slightly less likely to report HIV testing than those living in the least deprived neighbourhoods (Men - OR 0.61, 95% CI: 0.34 to 1.08; Women - OR 0.62, 95% CI: 0.38 to 1.00).Discussion:Thus, living in poor neighbourhoods was associated with poor uptake of an HIV test. These economic disparities should be taken in account while designing future prevention strategies. Ethnic minority women were less likely to go for HIV testing and culturally appropriate messages may be required for prevention in ethnic minorities.

In the absence of chemoprophylaxis, HIV-1 transmission occurs in 13-42% of infants born to HIV-1 positive mothers. All exposed infants acquire maternal HIV-1 antibodies that persist for up to 15 months, thereby hampering diagnosis. In resource limited settings, clinical symptoms are the indices of established infection against validated laboratorybased markers. Here we enrolled 1200 children hospitalized for diarrheal and other illnesses. 20-25% of those tested, aged 15 months or younger, were found to be HIV-1-seropositive. Where sufficient plasma was available, HIV-1 RNA detection was performed using a subtype-insensitive assay, with 71.1% of seropositive infants presenting with diarrhea showing positive. From sub-typing analysis, we identified that viruses of the C’ sub-cluster were predominated amongst infants. Although this study may overestimate the HIV-1 frequency through testing symptomatic infants, diarrhea can be seen as a useful marker indicating HIV-1 infection in infants less than 15 months old.

CD8+ T-cells are involved in controlling HIV-1 infection by eliminating infected cells and secreting soluble factors that inhibit viral replication. To investigate the mechanism and significance of infection of CD8+ T-cells by HIV-1 in vitro, we examined the susceptibility of these cells and their subsets to infection. CD8+ T-cells supported greater levels of replication with T-cell tropic strains of HIV-1, though viral production was lower than that observed in CD4+ T-cells. CD8+ T-cell infection was found to be productive through ELISA, RT-PCR and flow cytometric analyses. In addition, the CD8+CD45RO+ memory T-cell population supported higher levels of HIV-1 replication than CD8+CD45RA+ naïve T-cells. However, infection of CD8+CD45RO+ T-cells did not affect their proliferative response to the majority of mitogens tested. We conclude, with numerous lines of evidence detecting and measuring infection of CD8+ T-cells and their subsets, that this cellular target and potential reservoir may be central to HIV-1 pathogenesis.

The use of nucleoside reverse transcriptase inhibitors in the treatment of HIV infection is associated with antiretroviral toxic polyneuropathy (ATN). Previous studies suggest that long term treatment with Acetyl-L-carnitine (ALCAR) 1.5 gram twice daily improves symptoms and promotes nerve regeneration. It is unknown whether the drug’s pharmacokinetic profile would allow for a once daily administration. Twenty three HIV-1 infected subjects taking ALCAR for ATN were enrolled in a cross over trial and switched from twice to once daily dosing. Their regimen was changed from 1.5g twice daily to 1g (4 patients), 2g (7), and 3g (12) once daily, respectively. Twelve healthy volunteers served as control. Plasma levels of ALCAR and its metabolite L-carnitine were measured. Patients receiving ALCAR had higher pre-dose levels than control subjects. Post dose levels were not significantly higher than pre dose levels in any treatment group. The pre / post dose ALCAR concentrations were 7.6 / 7.7, 7.1 / 6.8, 7.7 / 6.8, and 7.1 / 7.5 µmol/l for 1.5g twice daily, 1g once daily, 2g once daily, and 3g once daily, respectively. All values were significantly higher than the mean concentration in the control group (4.3 µmol/l). For ALCAR and L-carnitine, measurements for once daily regimens did not differ from the twice daily regimen. Once daily dosing of ALCAR can achieve similar plasma levels as twice daily dosing but intra-mitochondrial levels remain unknown. The pharmacokinetic profile of orally administered ALCAR is complex and likely to be highly affected by endogenous concentrations.

Background:There is increasing evidence that metabolic adverse effects associated with antiretroviral therapy may translate into an increased cardiovascular risk in HIV-1-infected patients.Objectives:To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-1-infected persons, and to investigate any association between them, stage of HIV-1 disease, and use of antiretroviral therapies.Methods:Multicentric, cross-sectional analysis of CVD risk factors of treated patients in the VACH cohort. The data collected includes: demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidemia, body mass index, stage of HIV-1 infection, and antiretroviral therapy.Results:The analysis included 2358 patients. More than 18% of the study population was at an age of appreciable risk of CVD. 1.7% had previous CVD and 59.2% were smokers. Increased prevalence of elevated total cholesterol was observed among subjects receiving an NNRTI but no PI [odds ratio (OR), 3.34; 95% confidence interval (CI), 1.77–6.31], PI but no NNRTI (OR, 4.04; 95% CI, 2.12–7.71), or NNRTI + PI (OR, 17.77; 95% CI, 7.24–43.59) compared to patients treated only with nucleoside reverse transcriptase inhibitors (NRTI). Higher CD4 cell count, lower plasma HIV-1 RNA levels, clinical signs of lipodystrophy, longer exposure times to NNRTI and PI, and older age were all also associated with elevated cholesterol levels. The use of lipid lowering agents was very low among our patients.Conclusion:Patients in the VACH cohort present multiple known risk factors for CVD, and a very low rate of lipid lowering therapy use. NNRTI and/or PI-based antiretroviral therapies are associated with the worst lipid profile. This is more frequent in older subjects with greater CD4 counts and controlled HIV-1 replication.