NAPWA

The Nuke backbone

The backbone of HIV treatment has long been the use of two nucleoside reverse transcriptase inhibitors (NRTIs) which are combined with either a protease inhibitor (boosted with ritonavir) or a non-NRTI. More recently other drugs classes have been added, e.g. maraviroc (a CCR5 inhibitor) and raltegravir (an integrase inhibitor).

Currently tenofovir and abacavir are the preferred NRTIs; however, there has been considerable debate over the long-term side effects of both. Tenofovir has been associated with reduced kidney function and bone changes, while abacavir has been associated with an increased risk of cardiovascular disease. These concerns will be well known to many readers of this magazine.

Monotherapy

A number of papers reported results on studies in which use of NRTIs has been discontinued (so-called NRTI-sparing regimes). Of particular interest has been the use of ritonavir-boosted PIs as ‘monotherapy’.

One paper by Dutch researchers analysed the combined results of 10 randomisedA method based on chance by which study participants are assigned to a treatment group. Randomization minimizes the differences among groups by equally distributing people with particular characteristics among all the trial arms. The researchers do not know which treatment is better. From what is known at the time, any one of the treatments chosen could be of benefit to the participant clinical trials of boosted PIs comparing them to treatments which contained NRTIs. It concluded that boosted PI treatments were slightly (but statistically significantly) less effective than traditional combination treatments which included NRTIs.

Another European study looked at over 200 people who had effective control of HIV (ie VL <50 copies/mL). Half of them switched to a once-daily dose of boosted darunavir (DRV/r) alone (monotherapy), the other half switched to the same dose of boosted darunavir plus 2 NRTIs. The authors concluded that ‘switching to DRV/r monotherapy showed similar levels of HIV RNA suppression to DRV/r + 2NRTIs, using more sensitive PCR assay techniques.’

The use of PI monotherapy is not yet recommended. However, for some people who have been on long-term treatment with good virological control (extended periods where VL has been undetectable) and with known problems with the use of NRTIs, it may be an option.

Polypharmacy

One of the issues for ageing PLHIVPerson (or people) Living with HIV. This term is now preferred over the older PLWHA. is polypharmacy (or the taking of a range of drugs: for HIV and a range of other conditions, for example hypertensionPersistently high blood pressure, an outwardly symptomless condition which carries an increased risk of serious illnesses such as stroke, heart disease and heart attack., depression, cardiovascular conditions and diabetes[Diabetes mellitus] A disorder in which sugars in the diet cannot be metabolised into energy due to a lack of the enzyme insulin. Late-onset diabetes mellitus may be a long-term side effect of some anti-HIV drugs.). Many drugs have the potential to interact, with negative consequences, with HIV drugs. As part of the ageing process drug absorption and clearance can alter and this may affect drug-drug interactions. Many HIV drugs are metabolized in the liverA large organ, located in the upper right abdomen, which assists in digestion by metabolising carbohydrates, fats and proteins, stores vitamins and minerals, produces amino acids, bile and cholesterol, and removes toxins from the blood. and may affect and be affected by the processing of other drugs using the same metabolic pathways.

Many of these interactions are now well understood; however, unexpected drug-drug interactions will continue to emerge and will need to be managed. The papers presented highlight the need for people on multiple drugs to have good clinicalPertaining to or founded on observation and treatment of participants, as distinguished from theoretical or basic science. management by their doctors and open communication between their doctors about drugs being prescribed for them.

Bone health

In an overview on bone health a Swiss reviewer noted that PLHIV may exhibit increased bone turnover and are at risk of osteoporosis earlier than might be expected. There is a suggestion that drug-related changes in kidney metabolism may contribute to this bone loss. He suggested that correction of vitamin D deficiency should be part of the clinical care of ageing PLHIV.

Data from the UK-based PROBONO-1 study which investigated bone health and fracture risk in 223 UK PLHIV concluded that reduced bone mineral density (BMD) and subsequent fracture risk is much commoner in PLHIV compared to controls, especially for those on HAARTHighly Active AntiRetroviral Therapy ??? aggressive treatment of HIV infection using several different drugs together. and occurs across the age ranges. Study results suggest screening for these risks is indicated in PLHIV at a younger age than in the general population, especially for those on treatment.

Maraviroc

Maraviroc was the subject of a number of presentations. One study was on people who had only a small restoration of their immune responses despite having received HIV treatment for extended periods. Those who included maraviroc into their drug combination showed a better immune response and better control of the inflammation associated with HIV.

In an analysis of data from the MOTIVATE and MERIT studies, greater increases in CD4 and CD8 counts were consistently achieved with maraviroc-containing regimens, compared to those without. These increases persisted through at least two years of therapy in people just starting treatment or those on longer term treatment.

New integrase inhibitor

Several presentations reported on results of the new integrase inhibitor under development S/GSK1349572 (known sometimes as 572).

In the SPRING-1 trial, comparing 572-containing regimes with efavirenz-containing regimes, LDL-cholesterolAn essential component of cell membranes and nerve fibre insulation, cholesterol is important for the metabolism and transport of fatty acids and the production of hormones and Vitamin D. Cholesterol is manufactured by the liver, and is also present in certain foods. High blood cholesterol levels have been linked to heart disease and may be a side effect of some anti-HIV medications. was not increased as much in people receiving 572. A greater proportion of people achieved an undetectable viral loadA measurement of the quantity of HIV RNA in the blood. Viral load blood test results are expressed as the number of copies (of HIV) per milliliter of blood plasma. and there fewer side effects for those who received 572.

In results from the VIKING study of people who had been on many combinations (an average of 18 different drugs in the past), who were failing treatment and had significant resistance to raltegravir, almost half by week 24 had achieved undetectable VL.

572 is also well tolerated and the data suggests that 572 may have a role in controlling HIV in those whose treatment options are very limited and who are highly treatment-experienced and have multiple drug resistance.

New NNRTI

Favourable laboratory results were presented for lersivirine, the NNRTI under development. It demonstrated anti-HIV activity over a whole range of HIV-types which were resistantHIV which has mutated and is less susceptible to the effects of one or more anti-HIV drugs is said to be resistant. to etravirine, another NNRTI. Development of this new investigational(Of a drug) Not licensed for use in humans, or as a treatment for a particular condition. Experimental drugs are studied in clinical trials to determine their safety and efficacy, and are sometimes made available via Special Access Schemes prior to their approval. drug will continue.

Protease inhibitors

Results were presented from the ARTEMIS trial comparing boosted darunavir with Kaletra (boosted lopinavir). DRV/r demonstrated sustained efficacy(Of a drug or treatment). The maximum ability of a drug or treatment to produce a result regardless of dosage. A drug passes efficacy trials if it is effective at the dose tested and against the illness for which it is prescribed. In the standard procedure, Phase II clinical trials gauge efficacy, and Phase III trials confirm it. with noninferiority and superiority to LPV/r over 192 weeks. Development of resistance was low for both drugs. DRV/r was associated with smaller increases in total cholesterol and triglycerides than LPV/r, and a lower incidence of moderate diarrhoea.

Presentations at the International Congress were made in 13 differing categories, including Treatment Strategies, Adverse Effects of Treatments, Adherence and Resistance, HIV Co-infections and non-AIDS related disease.

The abstracts and full-text of most presentations are available at: http://www.jiasociety.org/supplements/13/S4