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NAM aidsmap

18th Conference on Retroviruses and Opportunistic Infections, Boston, 27 February-2 March 2011


HIV treatment: experimental gene therapy first step to 'cure'

Gene therapy can prevent cells from becoming infected with HIV, pointing the way to a possible cure.

Investigators from Quest Clinical Research in San Francisco used gene therapy to produce cells that lacked the CCR5 co-receptor that HIV uses to infect cells.

Their research was inspired by study of ‘elite controllers’ – HIV-positive individuals who maintain a healthy immune system and an undetectable viral load without HIV therapy. These individuals do not have CCR5 on their cells.

The small phase 1 study involved six HIV-positive patients. All were taking HIV treatment and had an undetectable viral load. However, they had had a poor immune response to treatment and their CD4 cell counts were in the 200 to 500 cells/mm3 range.

Blood was drawn from the patients, the T-cells were filtered out, and the blood was then returned. These cells were treated in the laboratory with a type of gene therapy called zinc finger technology that disables the CCR5 co-receptor.

Modification of cells was successful in about a quarter of cases. These cells were then re-introduced into the patients.

Five of the six patients experienced good increases in their CD4 cell count, and their immune profiles improved.

Three months later, 7% of CD4 cells lacked the CCR5 co-receptor.

The researchers emphasise that it’s too early to talk about a cure. But they believe their results are a proof of concept, and further research is planned.

Separate research showed that gene therapy also successfully altered some cells that used the CXCR4 co-receptor. This is normally found in patients who have extensive experience of antiretroviral therapy, or who are ill because of HIV. A protective effect was evident by 14 days after re-infusion, although the effect waned over time.

HIV treatment and TB: start early when CD4 cell count is low

Starting HIV treatment soon after therapy for tuberculosis (TB) reduces the risk of death for patients with very low CD4 cell counts.

There has been a lot of debate about the best time to start antiretroviral therapy in patients with TB.

The risk of drug interactions and of immune reconstitution inflammatory syndrome (IRIS) means that HIV therapy is normally deferred until TB is brought under control.

However, there is concern that this means patients with very weak immune systems have a high risk of death.

Now two randomised trials have shown that starting HIV therapy within four weeks of beginning TB treatment cuts mortality rates – but only for patients with a CD4 cell count below 50 cells/mm3.

The SAPIT study, conducted in South Africa, showed that patients with HIV and TB, who had very low CD4 cell counts and who received early HIV therapy, were 68% less likely to die than individuals with a similar immune profile who deferred antiretroviral treatment.

The international ACTG 5221 STRIDE study had similar results. Mortality rates were cut substantially among patients with a CD4 cell count below 50 cells/mm3 who started HIV treatment within four weeks of TB therapy.

However, in neither study did starting HIV treatment sooner have a survival benefit for patients with higher CD4 cell counts. In addition, early treatment increased the risk of IRIS.

The researchers believe their studies show the importance of the integration of HIV and TB services.

HIV testing: self-testing acceptable in Malawi

Self-testing for HIV is acceptable and perceived to have a number of advantages, a study conducted in Malawi shows.

People used oral HIV tests, and confirmatory screens were conducted.

Increasing testing rates is seen as key to controlling HIV. But only a fifth of people in Malawi had an HIV test in 2009.

Self-testing is being explored as a way of improving the uptake of testing.

Now research conducted in Blantyre shows that many people find self-testing acceptable. Individuals were offered the option of a clinic-based test or to self-test – 93% opted for the latter.

Nearly all the patients said self-testing was easy, but about 10% made mistakes in the testing process.

Individuals had confidence in the accuracy of self-testing, and said they would recommend it to family and friends.

Participants believed that self-testing had a number of advantages. These included privacy, and the ease of encouraging other family members to test.

But there were some reservations about self-testing, especially concerning support for people who test positive.

Preventing HIV: PrEP

Pre-exposure prophylaxis (PrEP) using Truvada (FTC and tenofovir) is still effective if exposure involves virus that is resistant to FTC.

An animal study showed that the drug was effective when virus with the M184V resistance mutation was present. Monkeys given Truvada and exposed to resistant virus remained uninfected.

“Exposure to drug-resistant viruses does not necessarily associate with failure of PrEP,” said the researchers.

Preventing HIV: microbicides

Vaginal microbicides may need reformulating for rectal use.

Researchers have been testing a tenofovir-containing gel as a rectal microbicide in 18 HIV-negative volunteers. The gel is identical to the one which has shown effectiveness when used vaginally.

Rectal use of the gel was effective – it prevented HIV from infecting cells in 80% of cases.

However, it caused unpleasant side-effects, most notably stomach cramps. Only a quarter of study participants said they were happy using it. Nevertheless, 75% said they would be willing to use it again if it protected them against HIV.

Preventing HIV: circumcision

The protective effect of male circumcision against infection with HIV may be even stronger than previously thought.

Updated results from the Rakai study were presented to CROI. The study was stopped early in 2006 after interim analysis showed that circumcision reduced the risk of infection with HIV by 50%.

Post-trial analysis has shown that 80% of men in the control arm have since opted for circumcision.

Overall, circumcision reduced the risk of infection with HIV by up to 73%.

There was an increase in the proportion of men who said that they never or inconsistently used condoms. But the researchers think that this is because of reduced condom availability rather than because circumcision reduced inhibitions.