The twelfth International Conference on AIDS and STDs in Africa in Ouagadougou, Burkina Faso has heard strong calls for wider access to antiretroviral drugs and a plenary presentation setting out a blueprint for delivering them.
In plenary presentations and in satellite meetings, there is a strong consensus in support of the principle embodied in the UNGASS Declaration of Commitment that the response to HIV and AIDS must include access to treatment and care, and that treatment must include access to antiretroviral drugs.
The World Health Organisation’s African Region sponsored an extremely well-attended satellite meeting on access to treatment, at which initiatives that are beginning to use antiretrovirals in Uganda, Senegal, Mali and Gabon were described. A series of recommendations were issued that place access to antiretrovirals as an integral part of what is needed in Africa in response to HIV and AIDS.
The recommendations include calls for international funding, for national commitments to strengthen health care systems and train health workers, support the use of generic antiretrovirals and other drugs, call for renegotiation of international trade agreements and publicising of the World Trade Organisation’s declaration from DOHA on trade and public health, for improved access to treatment
Dr Debrework Zewdie of the World Bank spoke on Tuesday morning on the mobilisation of resources, including strong statements supporting large-scale access to antiretroviral drugs. She opened her plenary presentation by expressing her delight that “we are finally discussing HIV treatment in terms of how and when, not if and perhaps.”
The need for African leadership
Dr Debrework Zewdie quoted a proverb, “If a household under attack does not shout, the neighbours would not be able to help” to emphasise that unless African governments and communities take the lead in identifying and addressing their needs, the international agencies and donors will not be in a position to help. More positively, she saw evidence that this is happening and that the response to the epidemic has entered a new phase.
AIDS in Africa was a “disaster foretold”. In the late 1980s, there had been reasonable planning and a sensible framework for responding to the epidemic. However, in the following decade there had been a failure of scale and of substance in the response. Initiatives were not scaled up even when there was clear evidence that they were effective. External support had been too little and too slow to mobilise. In substance, mobilisation too often did not go beyond the health sector into the rest of society.
The consequence of the failure was that African epidemics that stood at around 7 million in 1992 was now around four times as large. The reasons for the failure included demotivation of donors through political instability and armed conflict on the continent, lack of evidence for country-wide effectiveness of programmes, and poverty and growing inequality. African leaders had been reluctant to speak about AIDS and had, with a few very important exceptions, failed to mobilise societies in response.
Commitment Renewed?
Since 1998 there had been a renewal of efforts, initiated by UNAIDS with two reports that first highlighted the scale of the epidemic and then drew attention to the inadequacy of the response. This had led up to the UN General Assembly Special Session and the forthcoming launch of the Global Fund to fight AIDS, TB and Malaria. There were now agreed targets and consensus on what needed to be done to achieve those targets. There was new political commitment in the African Union and in key countries such as Nigeria and Ethiopia. The international response is now better coordinated than it was at the beginning of the 1990s. International assistance - she detailed that given in World Bank loans - is now growing fast after a period of stagnation and even decline during the 1990s.
Dr Zewdie finished with some comments on treatment. Despite the limitations of antiretrovirals, “Africans should never be denied from benefiting from these treatments.” Africa cannot wait for perfect infrastructure to deliver it, and she said the World Bank is committed to helping to get that infrastructure built.
Delivering Antiretrovirals in Africa
On Tuesday morning, Dr Remko van Leeuwen of the University of Amsterdam delivered a plenary presentation co-written by Dr Joep Lange, on the use of antiretrovirals in resource poor settings.
”The only appropriate way to do it is HAART!” he declared, showing a slide which compared death rates over time without treatment, with monotherapy, with dual therapy and with three or more antiretrovirals. Only in the case of HAART did the rates stabilise for any significant period of time.
Infrastructural challenges:
- lack of care and lab facilities
- drug distribution and storage (refrigeration)
- manpower
On the first point, he compared the Netherlands, where 5,000 people are currently on antiretrovirals, with what might be needed in Ouagadougou, a relatively small African city, with 35,000 likely to meet current criteria for treatment.
On the last point, he said “there is an enormous lack of medical personnel with sufficient knowledge of antiretroviral therapy.”
To expand access, it will be essential to keep regimens simple and restrict the number of options. Monitoring must also be kept simple and, in some circumstances, even dispensed with.
The choice of drugs, he said, must be driven by four equally important factors: efficacy, safety, simplicity (for the sake of adherence), and cost.
He cited work by Julio Montaner in Vancouver, Canada, which had shown that the only two factors which predicted success with antiretrovirals were adherence and the experience of the doctors who were prescribing them. In contrast, initial CD4 and viral load were unimportant.
Simpler Treatments
This led to a strong preference where drugs were concerned for a regimen of two NRTIs and one NNRTI or triple NRTIs. These needed to be in as few tablets as possible, and either once daily or at most twice daily.
He observed that the Indian generic company CIPLA’s three-in-one combinations of nevirapine with either 3TC and d4T or 3TC and AZT were “doing something new” and that “this should be addressed by the regular industry too”.
Glaxo SmithKline’s Trizivir - which combines abacavir, AZT and 3TC - was another potentially useful combined pill but far more expensive, at present, than CIPLA’s options and with added implications for training physicians because of abacavir’s side effects.
Once-daily options could include ddI, 3TC and efavirenz and also ddI, 3TC and ritonavir/saquinavir 100mg/1600mg. These could soon be extended by the new slow-release formulation of d4T and also by tenofovir.
TB and HIV as co-infections
Dr van Leeuwen addressed the specific issues where TB and HIV occur together, identifying the major problem as being the interaction of rifampicin - a mainstay of TB treatment in Africa - with protease inhibitors and NNRTIs. The option of substituting rifabutin, which is recommended in North America, combined with a ritonavir-boosted protease inhibitor, is seen as too costly in Africa. So what to do?
Obviously, the first need is to decide whether to treat both diseases. TB treatment is urgent when the disease is active, HIV can sometimes wait. If it could not wait, then triple NRTIs are an option. Efavirenz is the NNRTI least affected by rifampicin (a 26% decrease in efavirenz availability) and another option might be saquinavir boosted by ritonavir.
Simpler Monitoring
There is “no standard monitoring” was the main message Dr van Leeuwen gave to the conference. It must be adapted to the local setting, and not all settings are the same. Given the scale of the problem in Africa, cost will remain an issue even when there are well-equipped professional laboratories, so cheaper and simpler monitoring tools are essential.
CD4 counts may be more important than plasma HIV-1 RNA, but he cautioned that at least some viral load tests should be done initially to monitor the success of a new programme.
Experience in Haiti with using directly observed therapy in a rural setting, without monitoring, had recorded considerable success. He suggested that “Directly observed therapy without laboratory monitoring may be better than high tech monitoring without directly observed therapy” (a challenge that may well apply beyond Africa).
Even more provocatively, he asked whether it was “better to let two in 100 die of HAART toxicity than to have 100 out of 100 die because HAART is not available”?
The success of some efforts to scale up TB treatment with limited monitoring showed what could be done, and clearly HAART programmes should be linked to and learn from national TB treatment programmes.
In conclusion, lack of lab monitoring facilities should not keep us from bringing HAART to remote settings. But it was still essential to monitor the impact of treatment both on individuals and on populations, with a focus on the success or failure of treatment, what determines that success or failure, drug resistance, and the impact of treatment on transmission.