From Now On

It is not easy today to depict which will be the real long-term perspective of HIV infection. There are several major points which deserve careful consideration. One is certainly epidemiology and the future trends of HIV diffusion in the different regions of the world.

The major focus here is on developing countries, on the access to appropriate care in these regions and on the global impact that the ongoing preventive and therapeutic efforts will have on HIV epidemiology in the short-, mid- and long-term. Since a few years ago, a considerable amount of resources has been delivered to developing countries for the prevention and treatment of HIV infection, and an additional question relates to how long this will be affordable.

The epidemiologic tendency is also of great concern for western countries, where the extent to which preventive efforts are made is quite variable and there is much uncertainty about the future directions to be undertaken in this setting. The life expectancy of HIV-infected patients increased considerably following the introduction of HAART, a rather constant number of new infections are being diagnosed each year and, as a simple numerical consequence, the perspective is that of a growing proportion of our societies consisting of subjects with HIV infection, which corresponds to a growing number of subjects requiring antiretroviral treatment.

From a more technical viewpoint, that of chemotherapy, the question is whether the newly released antiretroviral drugs and those in the last portion of the pipeline will modify or not the current global treatment perspective. While viral eradication is still far beyond our current possibilities and continuous anti-HIV treatment remains substantially unavoidable, some recent results achieved in the use of new drug classes seem to indicate that our weapons against HIV infection are about to grow remarkably.

It is noteworthy that the virological threshold defining treatment success has now been established at 50 HIV-RNA copies/ml instead of the more permissive value of 400/ml, both in the case of fully susceptible treatment-naive infections and of multiexperienced patients. Although the threshold of 400 copies/ml is still considered in the case of registration trials, the development of a new series of antiretrovirals in the last 3 years has also improved our current efficacy expectations in the case of prior multidrug failure, thus making it possible to consider the value of 50 copies/ml as the target achievable in the vast majority of cases. New PIs (e.g. darunavir, DRV), new NNRTIs (etravirine, rilpivirine), new classes like integrase inhibitors and co-receptor (CCR5) inhibitors gave convincing evidence of their capacity to overcome existing viral resistance [58]. The rather abundant offer in terms of new drugs and new classes makes it now possible to use appropriate combinations to treat multiple-drug resistant infections by relying upon at least two new fully active compounds, which meets the basic principle of multi-drug therapy. The other side of the coin concerning these newly available antiretrovirals is their possible use in treatment-naive patients. We have been successfully using N/NtRTIs in combination with PIs or NNRTIs as first-line treatment for years, but now additional options are about to be defined. This will make it easier to tailor antiretroviral treatment on the basis of individual characteristics. Individual issues like allergies, other forms of drug intolerance, family history of glucose intolerance or diabetes, pre-existing cardiovascular risk factors, concurrent use of other medications, or behavioural variables, will be more likely to find drug combinations adequate for long-term use. These new therapeutic resources are particularly welcome in the light of the changing perspectives of subjects living with HIV infection. Furthermore, regarding the risk of developing HIV-unrelated diseases requiring other forms of medical and/or surgical treatment (to be compatible with the ongoing antiretroviral treatment), persons living with HIV infection are also increasingly being considered eligible for extreme treatment modalities like organ transplantation.

This clearly implies that the larger the choice of antiretrovirals, the wider the perspectives of successfully combining the continuous intake of antiretrovirals with the emerging therapeutic requirements of people whose life expectancy is well over the dramatic boundaries of the natural course of HIV infection.

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Source: Barbaro Giuseppe, Boccara Franc (eds.). Cardiovascular Disease in AIDS. 2nd edition. — Springer,2009. — 169 p.. 2009

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