Contraception and Increased Risk of HIV-1 Acquisition Debated

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UKZN’s College of Health Sciences and the K-RITH Research Lecture Series hosted a talk by Dr Zdenek Hel, Associate Professor in the Department of Pathology and the Department of Microbiology at the University of Alabama in the United States.

Hel spoke about his work on the role of Neutrophils in the immune response to HIV1 and also on how certain types of injectable contraceptives may influence HIV1 transmission.

Titled: “The Role of Neutrophils in HIV-1/AIDS Effect of Hormonal Contraception on Mucosal HIV-1 Transmission”, the talk was attended by students from K-RITH, CAPRISA, HPP and UKZN.

According to Hel, contraception represents a critical component of preventive health care.  It provides women with a control over their reproductive health, reduces the number of unintended pregnancies, decreases maternal and infant mortality and morbidity, reduces recourse to abortion, lowers the risk of mother-to-child transmission of HIV-1, and provides additional benefits including reduction of poverty and improved access to education.

He said hormonal contraception is highly popular as it provided multiple advantages over other forms of contraception, including high effectiveness and a long-term effect.

Depot medroxyprogesterone acetate (DMPA; Depo-Provera), a progestin-only contraceptive typically administered in the form of three-monthly intramuscular injections, is one of the most commonly used contraceptives in sub-Saharan Africa and other areas with high HIV-1 prevalence.

Hel said: ‘It is estimated that 20-50 million women worldwide use DMPA and the number is steadily increasing. In some countries, DMPA is the method of choice for over 50 percent of women using modern methods of contraception. Unfortunately, multiple observational studies suggest an association between the use of hormonal contraception and increased risk of HIV-1 acquisition and transmission. We have recently demonstrated that DMPA suppresses the production of key regulators of cellular and antibody-mediated immunity.’

He said the effect of hormonal contraception on HIV-1 acquisition and transmission represented a critical global public health issue.

‘A recent WHO meeting on programmatic and research priorities for contraception for women at risk of HIV, identified the research addressing the association between various methods of hormonal contraception and HIV acquisition and transmission as a top priority, with an emphasis on injectables and other long-term methods,’ he said.

Accumulated studies indicating the immunosuppressive properties of DMPA, and the epidemiological evidence demonstrating an association between DMPA use and increased risk of HIV-1 and other infections, strongly suggest that the use of DMPA should be discontinued, especially in areas with high HIV-1 prevalence.

‘It must be stressed that DMPA use should not be discontinued unless it is replaced with equally effective pregnancy control. Thus, it is critical to identify a contraceptive regimen that could effectively replace DMPA without exerting undesired side effects,’ Hel said.

He said identification of contraceptives that did not suppress the protective properties of the immune system was critical for the selection of safe hormonal contraception in areas with high HIV-1 prevalence.

‘In order to find safe alternatives to DMPA, we analysed the effect of commonly used progestins on the adaptive and innate immune systems. The presented data identify several progestins that can be considered as alternatives to DMPA.

‘Importantly, women using any form of hormonal contraception should be strongly advised to use condoms, male or female, as recommended by recent WHO guidelines,’ he said.  Hel also discussed the role of neutrophils in HIV-1 infection and HIV-1/tuberculosis co-infection.

Neutrophils, the most abundant leukocyte type representing 50-70 percent of white blood cells, are traditionally recognised as essential effector cells of the innate immune system in the host defense against invading pathogens.

In recent years, a new appreciation of the role of neutrophils in interacting with and regulating the adaptive arm of the immune system has emerged.

Neutrophils co-localise and actively communicate with T cells at sites of persistent infection and chronic inflammation and migrate to the draining lymph nodes where they are involved in the induction and regulation of cellular and humoral immune responses.

Accumulating evidence supports the role played by neutrophils in the negative regulation of T cell function.

Hel said: ‘We have demonstrated that neutrophils in HIV-1-infected individuals are highly suppressive and contribute to ongoing T cell exhaustion and immune suppression in HIV-1 infection. Blocking the activation and suppressor function of neutrophils could improve immune competence in patients with AIDS.’

Neutrophils have been recently shown to be the major population of cells infected in patients with active TB, he added. ‘Importantly, we believe that the HIV-induced changes in the properties of human neutrophils may lead to reactivation of TB in HIV-1/TB co-infected individuals.’

Last month, Hel obtained a pilot grant aimed at establishing a collaboration between the scientists at K-RITH and the University of Alabama.

K-RITH is a unique institution performing the highest quality of research at a place where it matters most in the centre of an HIV and TB epidemic.

Professor Alasdair Leslie, Assistant Investigator, K-RITH: KwaZulu-Natal Research Institute for Tuberculosis and HIV said Hel was invited so a wide audience could learn about the kind of research he is undertaking and to stimulate discussions about the possibility of establishing collaborations between his group and research groups based at the College of Health Sciences.

During his three-day visit, Hel met staff to discuss their research, talk about areas of shared interest and discussed potential future collaboration.

Leslie said: ‘One direct benefit is that Dr Hel and my group have recently been awarded a small pilot grant (50,000 USD) from the University of Alabama to look at the Neutrophil response in patients infected with HIV/TB co-infection.’

Hel said: ‘We are excited about our collaboration with the excellent scientists at K-RITH, namely Al Leslie and Andries Steyn, and have big plans for the future.’

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