How to combat the threat of HIV drug resistance

A mother holds her antiretroviral drugs, Triomune, at a HIV testing and treatment clinic in Lagos, Nigeria. Photograph: David Levene for the Guardian

As we strive for an Aids-free generation, we must help people adhere to antiretroviral treatment to stop them developing resistance.

For people living with HIV, antiretroviral treatment (ART) has been a life-saver. ART stops HIV from making copies of itself and prevents HIV from attacking the body’s immune system.

At the end of 2015, 17 million people were taking ART around the world and Aids-related deaths had fallen by 45% since the peak in 2005.

Story via The Guardian

But those who don’t stick to the ART regimen set out by their doctor or health worker might become resistant to the drugs. Resistance occurs when ART regimens are not taken as prescribed, which allows HIV to make copies of itself and increases the risk that the virus will mutate and produce drug-resistant HIV. A person who is on a drug such as Efavirenz can develop resistance after as little as a two-day interruption of treatment.

Globally, HIV drug resistance is on the rise. The World Health Organisation (WHO) reported that up to 2010, HIV drug resistance levels remained at 7% in developing countries. However, recently, some countries have reported levels at or above 10% among those starting ART, and up to 40% among people restarting ART.

At the beginning of the epidemic in sub-Saharan Africa, there was fear among the international community that people living with HIV in resource-limited settings would not be able to adhere to their treatment due to a lack of education and resources. Would they be able to keep time well enough to take their ART at the same time every day?

However, studies have demonstrated that people in sub-Saharan Africa may be better than people in the west at taking their ART as prescribed. The issue in developing countries is that people lack the resources to get to a clinic and pick up their pills. I’ve worked in Namibia since 2009, and whenever I visit ART clinics, there are long queues stretching out the door. People often have to wait all day and many can’t afford to take this time off work every month.

The stigma associated with being seen waiting in a queue to pick up medication is also a factor in people not adhering to their treatment plans. To avoid this, some people on ARTs travel to a clinic many kilometres away from their town, so they can receive treatment without anyone recognising them. And if you took a whole day off work, borrowed money for the transport and stood in a queue all day, only to learn that the clinic had run out of your pills, what would you do?

ARTs & HIV drug resistance

As the use of ART increases, so does the risk of HIV drug resistance. It’s no surprise, then, that global HIV drug resistance is on the rise, both among those already on ART and those just starting on it.

What could happen if levels of drug resistance reached critical levels? Their ART regimens would no longer be able to stop the HIV in their bodies from making copies of itself and they would then have to be switched to second-line regimens, if available.

But second-line regimens are more expensive. For countries already struggling to provide ART to those who need it, this would is likely to mean that fewer people could be started on ART.

Second-line regimens may also have more negative side effects, such as nausea, vomiting, headache, weakness or changes in the shape or location of body fat. These plans can also be more challenging because of the large number of pills that need to be taken. As a clinician, I’ve seen patients who’ve reached the point where they have to take more than 10 pills a day.

Drug resistance has been a problem since the beginning of the HIV epidemic. In the west the problem was usually limited to individual patients. But in resource-limited settings, if a high percentage of the population develops drug resistance we could see large increases in Aids-related deaths and higher healthcare costs.

We must act now to help people adhere to their treatment plans, before it’s too late. Globally, there has been a huge focus on getting more people on treatment, but the quality of how it’s delivered has fallen by the wayside.

Drug resistance will rise when ART is not delivered in a well thought-out way. That requires strong drug supply systems with zero tolerance for an interruption of ART drug supply, strong and locally appropriate counselling to promote adherence, support for patients who don’t have the resources to access care, re-engagement of patients who have stopped going to the clinics, alternative ways to deliver care such as community-based ART groups, and strong medical record systems.

As we strive to end Aids as a public health threat by 2030, greater attention must be focused on identifying and correcting gaps in the quality of ART service delivery. Many lives depend on it and the time to act is now. If we don’t, we may find ourselves with a new global pandemic of drug-resistant HIV and be faced with a deadlier enemy than we started with.

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HIV treatment breaks lead to drug resistance in the female genital tract

Antiretroviral treatment interruptions of 48 hours or more are associated with the emergence of resistant strains of HIV in the female genital tract, investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

The study included 102 women in Kenya who started first-line antiretroviral therapy based on a non-nucleoside reverse transcriptase inhibitor (NNRTI). Drug-resistant virus was detected in the genital tract of five women in the twelve months after treatment was started. Treatment interruptions were the most important risk factor for this outcome.

“We found that ART [antiretroviral therapy] adherence was a key determinant of genital tract resistance and that treatment interruptions of whatever cause lead to a substantial increase in the hazard of detecting genotypic resistance to antiretrovirals in female genital tract secretions,” write the authors. “Efforts to prevent treatment interruptions by improving program effectiveness, promoting adherence and timely refills, and avoiding the use of more toxic antiretroviral agents could therefore play an important role in reducing transmitted drug resistance.”

First-line HIV therapy often comprises two nucleoside reverse transcriptase inhibitors (NRTIs) combined with an NNRTI. This treatment can have a powerful and durable anti-HIV effect. However, it requires high levels of adherence. Drug-resistant strains of HIV can emerge with poorer adherence. Older drugs in the NNRTI class, nevirapine (Viramune) and efavirenz (Sustiva or Stocrin), have a low barrier to resistance.

Little is currently known about the emergence of drug-resistant virus in the genital tract of women treated with NNRTI-based therapy. This is an important gap in knowledge as drug-resistant virus is potentially transmissible.

Investigators therefore designed a prospective study involving women who started first-line HIV treatment in Mombasa between 2005 and 2008. During the first twelve months after starting therapy viral load was monitored at three-monthly intervals in both plasma and the genital tract. Samples with viral load above 1000 copies/ml were sent for resistance testing. The investigators conducted analysis to see which factors were associated with the emergence of drug-resistant virus in the genital tract.

Overall, the women had high levels of adherence to their antiretroviral therapy. Assessed by pill count, median adherence was 97%. However, there were 40 treatment interruptions. Their median duration was four days. Median pill-count adherence following treatment interruptions was just 83%.

Drug-resistant virus was detected in the blood of nine women (incidence, 10 per 100 person-years) and in the genital secretions of five individuals (incidence, 5.5 per 100 person-years). All five women with resistant HIV in their genital secretions also had resistant virus in their blood.

The investigators’ first set of analysis showed that a number of factors were associated with genital tract resistance. These included treatment interruptions (p = 0.006), pill-count adherence (p = 0.001) and a higher baseline viral load (p = 0.04).

But only treatment interruptions remained significant after controlling for potentially confounding factors. Interruptions were associated with a more than 14-fold increase in the risk of genital tract resistance (aHR = 14.2; 95% CI, 1.3-158.4; p = 0.03).

“The reasons for treatment interruption in this study included both unavoidable discontinuations due to drug toxicity or systemic illness and avoidable interruptions due to late refills, when it is likely that consecutive doses were missed,” note the investigators. “Despite a comprehensive program of adherence support including pre-ART counseling, directly administered therapy during the first month of treatment, a support group, pill boxes and transportation reimbursements, we were unable to prevent these events.”

Transport problems and pharmacy stock-outs have emerged as major barriers to adherence in resource-limited settings. The investigators are concerned that “such barriers may lead to the development of genital tract resistance due to treatment interruptions, suggesting an increased risk for transmission of drug-resistant virus”.

The Aids Library of Philadelphia FIGHT has a video on YouTube which explore the subject of HIV which is resistant to anti-HIV medications. Further information can be found on their website.

Original Article via NAM and Philadelphia Fight’s YouTube Channel

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