How HIV shaped us
By Professor Glenda Gray & Professor James A. McIntyre
HIV changed the nature of health in South Africa as our new democracy emerged. Seemingly overnight, in front of our eyes, young people and children died in unprecedented numbers. HIV slashed life expectancy, wiped out a generation of economically active adults in their prime across sub-Saharan Africa, reversed gains in under-five mortality and created a cohort of AIDS orphans. It also revealed the inter-relatedness between social behaviour, stigmatisation, cultural mores, religious beliefs and human health. HIV changed our society at a time when South Africa needed no distraction as it battled to rebuild a nation post-apartheid.
From 1998 to 2003, civil society together with AIDS activists, doctors and scientists used scientific evidence, in the face of government AIDS denialism, to force the use of antiretrovirals for the prevention of mother to child transmission of HIV-1, and subsequently the roll out of antiretrovirals as life-saving treatment. Our work at the Perinatal HIV Research Unit (PHRU) in Soweto was at the centre of these controversies. We had established the PHRU when we commenced research into the prevention of mother to child transmission of HIV-1 (PMTCT). Initially, we evaluated interventions to minimise breast milk transmission of HIV-1, before embarking upon the PETRA study, one of the first antiretroviral perinatal transmission studies to be conducted after the famous USA ACTG 076 study, which demonstrated that AZT could reduce perinatal transmission significantly. Because of our involvement in the management and follow-up of HIV-1 infected pregnant women and their infants, we became one of the first public sector sites to conduct antiretroviral treatment trials in adults and children. This gave us the necessary comfort to propagate the use of antiretrovirals in Soweto. Soweto, thus became one of the first demonstration projects for both PMTCT and ARV treatment roll-out, funded by the French government’s Fonds de Solidarité Thérapeutique International (FSTI) in a direct grant to the PHRU.
This Demonstration of Antiretroviral Treatment (DART) was approved under strict conditions by the then Minister of Health, Dr Manto Tshabalala-Msimang. However, as the governmental denialism intensified, our efforts to secure additional funding from the Pangaea Global AIDS Foundation and Clinton Foundation were closed down. We received a phone call from the then AIDS Director at the National Department of Health (NDOH), instructing us to stop developing the proposal, and communication with the donors then stopped without explanation. A decade later, Pangaea acknowledged the South African government pressure to stop working with us.
Political interference at this time was rife and the use of antiretrovirals for PMTCT was seen as a subversive activity. The Castro Hlongwane, Caravans, Cats, Geese, Foot & Mouth and Statistics: HIV/AIDS and the Struggle for the Humanisation of the African document – partly penned by Thabo Mbeki and distributed to ANC branches throughout South Africa – attacked South Africa’s earliest and most prominent AIDS scientists, including Salim Abdool Karim and ourselves. Abdool Karim’s research was characterised as “anti-human” promoted by “corporate forces” and we were singled out, because of our work using antiretrovirals for preventing mother-to-child transmission of HIV, as “killers of Black Women”.
In 1999, results from a study in Uganda, showed that a single dose of nevirapine given to HIV-1 infected pregnant women in labour and a dose administered to their infants within 72 hours could reduce PMTCT. These results galvanised us to try and secure this nevirapine-based intervention for HIV-1 infected women in our clinic, and we relied on donations to keep a steady supply before nevirapine was officially available for PMTCT. We supplied nevirapine under tense conditions at the Chris Hani Baragwanath Hospital. One day, a doctor from a peripheral hospital phoned, asking us to supply nevirapine to a HIV-infected woman in labour. He sent an ambulance to the PHRU. We gave the driver the nevirapine tablet and syrup, only to be phoned by the hospital superintendent admonishing us, as he barred this pregnant woman from access to a drug proven to be efficacious, effectively allowing HIV exposure during birth without prophylaxis.
In 2003/2004, government policy changed under pressure mounting from civil society as well as political pressure within the political-government structures. In an era where the cost of drugs was declining, we were fortunate beneficiaries of USAID and Elizabeth Glaser Pediatric AIDS Foundation funding that enabled scaling up treatment in Soweto. In a space of six months, our team, lead by Dr Lerato Mohapi, put just under 1 000 people in treatment; and our PMTCT programme directed by Dr Avy Violari, expanded in Soweto, accelerating access by opening PMTCT programmes in every antenatal clinic.
Even though we were involved with rolling out care, and scaling up interventions for maximum impact, we knew we also had to focus on the clinical science, and designed a number of programmes, which were funded under the CIPRA-SA banner. Studies executed under this programme impacted on international guidelines that revolutionised treatment management for infants, as well as defining that antiretroviral treatment could be executed by nurses instead of doctors. The Children with HIV Early Antiretroviral (CHER) study, undertaken at the Chris Hani Baragwanath and Tygerberg Hospitals showed that early treatment in HIV-infected infants could significantly reduce deaths3. The CIPRA-SA study demonstrating that ARV care could be task-shifted to nurses allowed for the mass roll out of treatment in South Africa and beyond3. We continued with PMTCT research which continued to help elucidate and refine regimens to make them more potent, the requirement to eliminate paediatric HIV.
Knowing that the only effective way to control the HIV epidemic was through prevention, the PHRU expanded its focus beyond PMTCT and ARV treatment for adults and children.
At this time the South African AIDS Vaccine Initiative, was established, and Glenda Gray transitioned from treatment into prevention. Tasked with taking the South African developed HIV vaccine candidates into first-in-man studies10, both in South Africa and the US, Gray would embark on leading these studies as well as lead the first HIV vaccine efficacy study in South Africa. For the past decade, finding an effective vaccine has been the fixation of most of Gray’s clinical research.
James McIntyre, driven by the need to continue to fine-tune innovation to take interventions to scale, turned to implementation science which saw the wide-spread roll out of treatment and PMTCT programmes. Concerned by the huge burden of HIV amongst men who have sex with men (MSM) and the lack of appropriate treatment for MSM in the public sector, McIntyre pioneered the development of MSM services in South Africa, that have become a model for both prevention and treatment.
Now, just over a decade and a half after the International AIDS Conference in 2000, South Africa’s burden of disease estimates indicate a nine-year increase in the average life expectancy from an all-time low in 2005, where total life expectancy was under 55 years. Our under-five mortality has been slashed by half from 80/1 000 to 40/1 000. Similarly spectacular gains have been made in infant mortality rates: from 54/1 000 to just under 30/1 000. Maternal deaths have also declined from 190 to 155/100 000. Most of this is attributed to the scale up of antiretovirals in the public sector.
These spectacular gains made by South Africa are a tribute to the activists, health care workers and scientists, who, faced with a horrific epidemic, did the right thing, and “en masse” spoke truth to power, and were relentless in their pursuit of scientific evidence and ruthless in their implementation of that. To have been part of this crusade, and look back, and see how much progress has been made is gratifying. Now we have to ensure that the lessons garnered in our experience with the HIV epidemic, are recapitulated in the quadruple burden of disease and the interconnecting epidemics of: communicable and non-communicable diseases; maternal and child mortality; and injury and violence.
Professor Glenda Gray is the President of the South African Medical Research Council, Research Professor of Paediatrics at the University of the Witwatersrand.
Professor James A. McIntyre is the Executive Director of the Anova Health Institute, International vice-chair of the International Maternal Paediatric and Adolescent AIDS Clinical Trials Network.