Dr Bernadett Gosnel.TB Patients at Risk of Failing HAART
A study to assess the role of anti-TB treatment in patients failing second line highly active antiretroviral therapy (HAART) has been completed by UKZN’s Principal Medical Officer in the Department of Infectious Diseases, Dr Bernadett Gosnell.
The study titled: “Tuberculosis Treatment and 2nd Line Antiretroviral Therapy Failure in Adults”, examined changes that might occur in the HIV virus when a person failed second line anti-retroviral treatment that is used to kill the virus.
The study found that patients receiving rifampicin based anti-TB treatment without LPV/r dose adjustment were at high risk of failing HAART with resistance mutations.
Gosnell said when a treatment directed against the virus did not work it could be because the patient was not taking their treatment or the virus has found a way to prevent itself from being killed by the drug.
‘With our study we tried to find the reasons why the patients experienced treatment failure. We offered an expensive genotype test to check if the HIV virus had changed in the blood of the patients and if that was the reason for their high viral load.’
According to Gosnell, South Africa has the highest percentage of TB and HIV co- infected adults in the world. She said complex drug-drug interactions between rifampicin and HAART increase the risk for suboptimal drug levels of Lopinavir/ritonavir (LPV/r) based 2nd line HAART.
The study analysed patients presenting to the Specialist Infectious Diseases Clinic for failure of 2nd line HAART. All patients were genotyped to examine for drug resistance.
In a cohort of 105 patients who failed LPV/r based therapy, 24 (22%) had anti-TB treatment while on LPV/r, nine had appropriate dose adjustment of the LPV/r dose while 15 had no adjustment. Twelve of 15 (80%) without adjustment demonstrated LPV/r resistance mutations compared to two of nine (22%) with adjustment (p=<0.001). Of the 81 patients with no TB treatment exposure 12 (15%) had LPV/r resistance mutations.
Gosnell said the study was important in their setting where many people required antiretroviral therapy. ‘It will give clinicians an understanding of why the medication is not working and how taking TB treatment while on HIV treatment can make HIV more difficult to treat. It emphasises the need to adjust HIV treatment when treating a patient for TB.’
She said when a person was first diagnosed with HIV, he or she were offered a CD4 count to determine the state of the immune system. If the CD4 count was below 350 cells per microlitre, antiretrovirals were recommended and the person would be offered anti-retroviral medication.
‘At the present moment the first antiretrovirals that would be offered to the patients are three different antiretrovirals all combined in one tablet. When a person takes this one tablet at night time every day, the HIV viral load should become undetectable in the blood and the CD4 count should rise again. If a patient fails to supress their viral load on this first combination tablet, even though he or she is taking the tablet well, the doctor or HAART providing nurse will change their antiretroviral to the second combination of tablets, which we call 2nd line therapy.’
According to Gosnell the new tablets have to be taken morning and evening, they are a lot more expensive and have more side effects, but are chosen to work on clearing the HIV virus from the blood and strengthening the immune system.
‘Now, if these 2nd line tablets fail to suppress the virus in the blood, a genotype test needs to be done. A blood sample is taken and the HIV virus is extracted and analysed to see if it has changed in a way that allows it to continue infecting new cells and multiplying despite anti-retrovirals being present in the bloodstream. If the virus is found to have mutations, ie to have changed, then again a new combination of even more expensive anti-retroviral medication needs to be given to try to suppress the virus. This is then called the 3rd line,’ she explained.
The study, done in collaboration with Dr Michelle Gordon as Principal Investigator and Professor MYS Moosa and Dr H Sunpath as co-investigators, took four years to complete. It was started at a time when there were very few 2nd line anti-retroviral failure patients.
‘Unfortunately this is no longer the case and it is now quite alarming how many patients have resistant HIV viruses. This is very dangerous because, if someone with resistant virus has unprotected sex, they can transmit their resistant virus to their partner making it more difficult to treat the infection in their partner,’ explained Gosnell.
She is also interested in doing research on sexually transmitted diseases (STIs), especially non-healing genital ulcers. ‘I found that a lot of patients are very shy when it comes to talking about “a problem down there”. Due to HIV and other factors, the treatment offered at the clinics for STIs and genital ulcers doesn’t always work. Patients then go to another health care provider and maybe a third and a fourth until they end up at our infectious diseases specialist clinic.
‘I would love to specialise in Oncology as I see with longevity and HIV, every person has a considerable life-time risk of being diagnosed with cancer. I consider myself as a caring, empathetic person, who will walk the distance with a patient providing quality medical care and holistic support.’
Originally from Germany, Gosnell completed her schooling at Waterford KaMhlamba in Swaziland. ‘I followed in my parents’ footsteps with my subject choices and completed a Masters in Chemistry and a medical bachelor degree at my home town, the Philipps-University of Marburg, Germany followed by a medical doctorate.’
Gosnell lives in Durban with her husband and five children, ‘I have been working at different government hospitals in Durban since 2001 and done my bit running a PEPFAR- funded antiretroviral-rollout for the Catholic archdiocese in Groutville as the Medical Doctor and Project Manager.’
She says her religion is part of her life. Her family loves nature, especially the ocean, ‘As a family we try to have as little impact on the environment as possible by recycling and keeping our own chicken for eggs.’
Nombuso Dlamini