How mass use of ARTs, genetic changes fuel HIV drug resistance

Chijioke Iremeka

Changes in genetic structures, wrong patients’ compliance to medications and use of donors’ antiretroviral therapy for all patients have been identified by Infectious diseases specialists as key factors fuelling Human Immunodeficiency Virus drug resistance.

They insist that tests should be carried out on patients before being placed on ART, warning that scheduling all HIV patients on a particular ART without evaluation to determine which medication would work for them is another reason why there is growing HIV drug resistance.

According to the Pan-American Health Organisation, HIV drug resistance is the ability of HIV to mutate and reproduce in the presence of antiretroviral drugs.

“The consequences of this include treatment failure; transmission of drug-resistant HIV; increased direct and indirect costs for patients as well as the health systems due to more expensive, complex and toxic second-and third-line antiretroviral regimens,” PAHO stated.

Meanwhile, physicians who spoke with PUNCH Healthwise, said HIV drug resistance has never been so serious, noting that this is because Nigeria has not been able to give HIV patients the medication they need as it relies solely on donors.

A Professor of Community Medicine and Public Health at the Ebonyi State University Abakaliki, Ebonyi State, Ulu Ogbonnanya said though HIVDR is not new, it has never been a problem the way it is currently.

Professor Ulu Ogbonnanya

He said that wrong compliance to treatment, multiplication of the virus and placing all patients on a frontline ART regardless of their HIV variants, are contributors to the increasing HIVDR in Nigeria.

The don also noted that errors in HIV genetic materials and receptors are common factors too.

Ogbonnanya, who was the former Dean, Faculty of Clinical Medicine, College of Health Sciences, Ebonyi State University, Abakaliki, explains, “You can imagine a bread factory that produces at 1000 loaves capacity per hour and another producing at 100 loaves capacity per hour.

“Of course, there will be more mistakes in the one producing 1000 loaves per hour than the other producing 100. Now, because the viral particles multiply at a rapid rate, there are tendencies to make mistakes. This production is just a multiplication of genetic materials of the viral particles.

“So such a mistake expresses itself in resistance. There are what is called antigens and receptors. The structure of the antigen and receptor can change in this process. The antigen that normally fits into a receptor will no longer fit into it.

“When the drugs get to the receptor, it will not fit into it to kill the virus and the virus becomes resistant to it. Remember that drugs naturally create a toxic environment for the microorganism in such a way that the organisms won’t survive.”

He noted that many of these particles will be killed but a few that remain will develop a means of evading the toxic environment and become resistant to that particular drug.

According to him, if somebody gets infected by a virus that is primarily resistant to a particular drug, that person has acquired a virus particle that is already resistant.

Ogbonnanya further noted that mismanagement in Nigeria has worsened the situation as Nigeria’s health system has not grown to test patients to know the virus that infected them before placing them on ART.

“This is further worsened by Nigeria’s dependence on donor drugs. Of course, there are first-line, second-line and third-line drugs; they are generic. Donors will choose the first-line drugs and place everybody on them.

“Whether the person is already resistant to that drug or not is immaterial. It is only when the person does not do well with the treatment that they will suspect resistant HIV. These are factors fuelling HIVDR,” Ogbonnanya added.

Speaking on the way forward, a Consultant Public Health Physician at the Federal Medical Centre, Asaba, Delta State Ovie Efekodo, said to end HIV drug resistance, stakeholders across the world must promote the availability of optimal medicines to treat HIV infections.

He noted that Nigeria will do well by sponsoring its own ART and increasing access to and use of viral load testing to determine if HIV treatment is effective.

Efekodo said, “HIV patients should take their drugs as prescribed. Comply with treatment so that the drugs can clear the organisms in the blood even though the pill burden makes HIV treatment difficult.

“Pill burden is the number of tablets, capsules, or other dosage forms that a person takes on a regular basis. Many people find it difficult to take medication everyday and they grow tired and wish they could stop. And because they have suppressed the virus, and there are no symptoms, they stop medications, yet the virus has not been cleared.

“So, we need to properly counsel patients on the importance and consequences of taking their drugs as prescribed.”

Meanwhile, a study published in the National Library of Medicine by Dr Martin Zdanowicz, titled, ‘The Pharmacology of HIV Drug Resistance’, said several factors related to the life cycle and replications of HIV are key contributors toward the rapid spread of the organism resistance.

The study stated that the HIV reverse transcriptase enzyme is notoriously ‘low fidelity’ and prone to errors when copying viral Ribonucleic acid into Deoxyribonucleic acid.

“By some estimates, HIV RT makes one error in each HIV genome per round of replication. This translates into one mutation for every 2000 nucleosides. This high rate of replication coupled with the high rate of error for RT means that numerous HIV ‘variants’ are rapidly formed and propagated.

“Patients, who are infected with HIV, can have multiple variants of the virus present in their system. These variants can have greatly different sensitivities to antiretroviral agents, a factor that can significantly complicate the selection of drugs and the course of therapy.

“Additional factors that may contribute to the development of HIV drug resistance include poor patient compliance, sub-therapeutic blood levels of antiretroviral agents, and inappropriate choice of antiretroviral agent(s).”

 

 

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