Kenya's HIV drug combo is safe from resistance - report

HIV treatment drugs

A new study has found that resistance to dolutegravir (DTG), the backbone of Kenya’s first-line HIV treatment, appears far less likely when combined with tenofovir than with older drugs such as zidovudine or abacavir.

DTG has a high barrier to resistance, but if given on its own, the virus can still adapt. That is why the World Health Organization recommends that DTG always be combined with two other drugs of a different class.

The study looked at 660 patients in Kenya, South Africa and other regions. Among 183 patients with ongoing detectable virus, 11.5 per cent showed dolutegravir resistance.

Patients taking zidovudine were almost 20 times more likely to develop resistance compared to those on tenofovir. Those on abacavir were more than five times more likely.

The study was published last week in the Clinical Infectious Diseases journal, under the title "HIV resistance to dolutegravir varies with co-administered agents."

“Our multi-cohort analysis suggests that HIV genotypic dolutegravir-resistance is more common when dolutegravir+lamivudine is co-administered with either zidovudine or abacavir compared to tenofovir," teh authors said.

The science comes down to a drug's “half-life”, or how long an active drug stays in the body. Dolutegravir binds tightly to HIV for more than 70 hours. Tenofovir’s active form also stays in cells for several days. But abacavir and zidovudine fade much faster.

When patients miss doses, dolutegravir can end up working alone, a situation that gives HIV a chance to adapt and develop resistance. That is why the study found far more resistance in regimens built on abacavir or zidovudine.

“We hypothesize that an NRTI (drugs such as zidovudine and abacavir) increases the risk of dolutegravir-resistance when its active metabolite’s intracellular half-life is relatively short," the authors said.

Kenya shifted to dolutegravir in 2019, introducing the TLD combination (tenofovir + lamivudine+dolutegravir) as the national standard for adults and adolescents. According to the Ministry of Health’s 2022 HIV guidelines, TLD is the preferred first-line treatment for most patients.

But children are a different case. For those weighing under 30kg, the guidelines recommend abacavir + lamivudine + dolutegravir (ABC/3TC/DTG) as the preferred option.

Tenofovir is not recommended in children because it can damage bones and kidneys in young children. If a child reacts badly to abacavir, zidovudine (another weak link) may be used as a substitute. This leaves them more vulnerable to resistance.

This means that while most Kenyan adults are on the safer tenofovir-based combination, thousands of children are still routinely given abacavir or zidovudine with dolutegravir.

Globally, HIV drug resistance has undermined several treatment strategies in the past. In the early 2000s, widespread resistance to nevirapine and efavirenz forced African countries, including Kenya, to replace entire treatment lines.

 Dolutegravir was praised as a game changer because resistance was expected to be rare. The new evidence challenges that assumption, at least in some settings.

Drug resistance has serious consequences for patients because once the virus adapts, the standard regimen stops working. Patients must be switched to second-line or third-line drugs that are more expensive, harder to tolerate and less widely available.

Children are especially vulnerable because if resistance develops early, they may burn through the limited number of treatment options available before reaching adulthood. That could put them on lifelong cycles of drug changes and hospital visits.

A few nurses working in HIV clinics in Kenya told the Star that resistance is rare. However, there are a few cases of patients with high viral load despite consistent treatment.

“The problem is we still do not do Drug Susceptibility Testing (DST)  to check if the virus is resistant to certain drugs. When we do a case summary for referral to Kemri, we are given a ‘Nat’ number but told there are no reagents for testing,” one said.