On the research front

On the research front

Transmission risk

In March 2014, researchers reported at the 21st Conference on Retroviruses and Opportunistic Infections (CROI) that no HIV-positive study participants with undetectable viral load counts had transmitted HIV during the first two years of the Partner Study (a study of the HIV transmission rates in partners, one of whom is HIV positive and the other not). The interim analysis tracked 767 couples, of which just less than 40% were homosexual. (An undetectable viral load count does not mean that there is no HIV in a person’s body, but that that virus levels are so low that standard tests can’t detect it.)

These interim results from the Partner Study provide further evidence that people who are stable on antiretroviral treatment and who have undetectable viral load counts are extremely unlikely to transmit HIV to their sexual partners. Findings from the pivotal HPTN052 study had earlier found that the risk of HIV transmission was reduced by 96 percent if the HIV-positive partner in a heterosexual relationship started antiretroviral treatment immediately rather than waiting for his or her CD4 count to drop below 250 cells/mm2. While the HPTN052 study reported exclusively on heterosexual couples, the Partner trial includes homosexual couples and examines risk from both anal and vaginal sex.

The Partner Study is ongoing. Final results will be available in 2017.


Sugar daddy theory not supported

For some time the theory has prevailed that high HIV rates in young women are driven by relationships with older men – so-called age-disparate relationships. This theory was mainly based on the fact that HIV prevalence peaks in a much younger age in women than in men, and concluding that older men are transmitting HIV to young women. Extensive communication campaigns in Kwazulu-Natal and the Western Cape have sought to stigmatise such age-disparate relationships.

New research presented at CROI sought to establish whether age-disparate sexual relationships actually do put women at higher risk of contracting HIV than sexual relationships with men their own age. The researchers tracked new infections in more than 4,000 women over seven years and linked those new infections to self-reports of the age of the men with whom the women last had sex.

Contrary to the widely held ‘sugar-daddy’ theory, the researchers found that, for women aged from 15 to 29, the risk of contracting HIV was not correlated to the ages of the men they had sex with. For women over 30, the researchers found the opposite of the ‘sugar-daddy’ theory – women over 30 had a higher risk of contracting HIV when sleeping with men their own age than with men who were older.

While this study has caveats, it is large and well-conducted research that provides the first direct evidence on the impact of age-disparate relationships on HIV risk. While additional studies will further elucidate the reasons for the higher HIV prevalence in young women, the ‘sugar-daddy’ theory must be considered wrong, pending further research.


Price inhibits use of Raltegravir

The integrase inhibitor Raltegravir is one of a number of medicines currently used as third-line treatment in the South African public sector. The pharmaceutical company Merck, Sharp and Dohm (MSD) holds the patent on Raltegravir and it is currently being procured for the public sector at RX per patient per month (The private sector price is R770, excluding VAT, per patient per month). The most common first-line treatment combination in the public sector costs R90 per patient per month.

A three-way comparison presented at CROI compared Raltegravir to Atazanavir boosted with Ritonavir and Darunavir boosted with Ritonavir in a total of 1,809 HIV-positive people who had not taken ARVs before. In all three arms, study participants were also given tenofovir and FTC. All three of these study treatments are considered options for first-line treatment under current HIV treatment guidelines in the United States.

After 96 weeks of follow-up, patients in the Raltegravir arm did best on a range of measures, with the Darunavir/Ritonavir arm second and the Atazanavir/Ritonavir arm third. Gastrointestinal problems were of particular concern in the latter two arms, while jaundice was a problem in the Atazanavir arm and led to a number of treatment discontinuations.

Promising as these results are, the high price of Raltegravir makes it extremely unlikely that this drug will be considered as part of first-line treatment in the South African public sector.


Efavirenz: How much is enough?

The non-nucleoside reverse transcriptase inhibitor (NNRTI) Efavirenz forms part of the three-drug combination given to most first-line HIV patients in the public healthcare system in South Africa. Currently, patients are given 600 mg of Efavirenz per day, combined into one pill with tenofovir and FTC.

However, recent research published in the Lancet medical journal suggests that a lower dose of Efavirenz may be as effective as the current standard. After 48 weeks of the Encore1 Study of 630 participants, patients receiving 400 mg of Efavirenz per day had similar rates of viralogical failure to patients taking 600 mg per day.

An Encore1 sub study presented at CROI compared the pharmacokinetics (how the body takes up the drug) of 28 patients in the 400 mg arm with 18 patients in the 600 mg arm. The researchers found that even though the drug exposure in the body was lower than previously thought necessary, the patients in the 400 mg group nevertheless managed to suppress the virus.

These findings suggest that current Efavirenz dosing is unnecessarily high and a 400 mg dose should be considered. However, some uncertainty remains as to whether the 400 mg dose will be high enough during pregnancy or for patients who are also being treated for tuberculosis. Additional studies should be conducted to answer these questions.

Reducing the daily dose of Efavirenz from 600 mg to 400 mg will lead to a reduction in price over the medium to long term – although switching may incur some higher costs in the short term, given the cost of creating new fixed-dose combination pills.


HIV infections on the increase?

In April, the Human Science Research Council published its long-awaited fourth National HIV Prevalence, Incidence and Behaviour Survey. It reported an estimated 469,000 new HIV infections (incidence) in 2012. This incidence figure was much higher than expected and some doubts remain over its accuracy. In January this year, the UNAIDS South Africa 2012 HIV Estimates and Projections at-a-glance report estimated an incidence rate of 370,000 for the same year (2012).

HIV prevalence (percentage of population living with HIV) in South Africa was estimated to have increased from 10.6 percent in 2008 to 12.2 percent in 2012. This increase is however not all bad news since it reflects the fact that people living with HIV are living longer due to antiretroviral treatment. In this regard, the survey prevalence estimates fit well with increases in general life expectancy reported in other recent reports from the South African Medical Research Council and Statistics South Africa. Had it not been for the antiretroviral treatment programme many of the 6.4 million people living with HIV in South Africa would not be alive and the prevalence rate would therefore be lower.