The announcement last month by the Medicines Control Council (MCC) that nevirapine should not be used as monotherapy to prevent mother-to-child transmission (PMTCT) of HIV has caused much consternation, both in South Africa and abroad.
Many countries in Africa take their cue from the MCC, an independent institution that protects the public against dangerous and sub-standard drugs. So the MCC statement has the potential to damage the PMTCT programme throughout the continent.
Where I work, pregnant women, their spouses, the nurses, doctors and counsellors are asking what is wrong with nevirapine. Some women are reluctant to take the drug. Health-care workers and counsellors are faced with difficulties when trying to explain apparent contradictions between their government protocols and recent press statements by the MCC and the Minister of Health Manto Tshabalala- Msimang. We are seeing mistrust of the health-care workers by women, with many believing that nevirapine alone is “bad” for one’s health.
The MCC statement, which cited the dangers of drug resistance, implies that monotherapy is the reason for that resistance. However, the published data shows that any nevirapine- containing regime (whether single, dual or triple) given as a single dose can cause drug resistance in some women.
We have known for several years that resistant mutations occur after a single dose of nevirapine. But what that means is still unknown.
The key issue is that there is no research, nor are there studies completed, on the clinical significance of drug resistance in HIV-infected women who have taken a single dose of nevirapine. We do not know whether it is very harmful to a significant proportion of women or their babies, or whether the harm outweighs the benefits in terms of the health of an individual or a group.
However new, good-quality evidence has arisen showing that drug regimes containing more than one drug are more effective than nevirapine alone. This has led some authorities (including the Western Cape health authority and the Thai Ministry for Health) to recommend these more effective drug regimes for PMTCT — not because of the dangers of drug resistance, but because they work better. Resistance has not been deemed by them to be an area where new data requires urgent and dramatic responses.
In short, nevirapine works as a single dose and has saved the lives of many thousands of babies in South Africa. It works even better in combination with other drugs. And we do not yet know the clinical significance of the resistance a single dose causes in women.
Since there seem to be no science and no logical reasoning behind the MCC statement, one is left to wonder what are the intentions behind making it.
Improving a protocol recommendation is to be welcomed. This is very different from the irresponsible act of not recommending the current protocol while omitting to recommend another, more appropriate protocol. Tshabalala-Msimang issued a statement on July 15 saying the government’s recommendations for management of MTCT remain unchanged, and that a consultative workshop would be held to revisit treatment recommendations. We are still waiting for the press release on this proposed workshop.
Meanwhile, the confusion at the clinics continues. This could have been avoided if the MCC and the government had simply announced that more effective regimes were going to be looked at.
Here is what we know about nevirapine and resistance: we know that rates of nevirapine resistance reduce over time in a person who has taken the drug. After a single dose of nevirapine given for PMTCT, published studies have shown that resistance levels decrease from higher levels after 10 days to virtual disappearance after 18 to 24 months, although some drug-resistant virus is stored in the lymph tissue. We do not yet know if this is a problem.
There is, however, the option of providing combinations of drugs that do not include nevirapine for people with drug resistance. We also know that the women most likely to become drug resistant after one dose of nevirapine are women with high viral loads and low CD4 counts, who should in any case be on life-long triple anti-retroviral (ARV) therapy.
To mitigate the damaging effects the MCC announcement has had on the PMTCT programme, I would like to see a clear and unequivocal statement by our government that:
Where possible, to decrease rates of transmission, azidothymidine (AZT) should be administered from 28 weeks as well as the single dose of nevirapine at delivery;
Nevirapine, as currently recommended, should be available in all clinics and hospitals in South Africa that are waiting to receive supplies of AZT. It should be offered to all women who are HIV-infected and book into clinics for antenatal care later than the 28th week of pregnancy;
The roll-out of highly active antiretroviral therapy (Haart) should be accelerated and expanded to all areas of South Africa;
Research should be funded to examine Haart in pregnancy and the clinical implications of drug resistance;
Once higher-grade, published scientific work is available, review of the treatment protocols should occur. Until then, we should follow World Health Organisation (WHO) recommendations;
Either free formula feeds or exclusive breastfeeding should be offered as a choice to women. The problems of increased transmission with mixed feeding should be emphasised; and
Pressure should be increased to lower drug prices (especially of the drug class of protease inhibitors) and to make WHO pre-qualified generics available.
Dr Natalya Dinat MD, FCOG (SA), is a specialist obstetrician-gynaecologist. She writes in her personal capacity
The science behind the drug
Nevirapine is provided for two reasons:
For treatment, as part of an anti-retroviral (ARV) package of three drugs; or
For prevention of HIV, especially prevention of mother-to-child infection.
When given as part of a treatment package, it is only given to people with a CD4 count of less than 200 cells a mm3. When given as prevention, it is given to all HIV- infected women — regardless of their CD4 count — and their babies, to prevent infection in their babies.
Women who are pregnant and need triple ARV therapy (a CD4 count of less than 200) should be offered an ARV package of three drugs, which both treat the mother and prevent infection in the baby.
For women who are pregnant and HIV-infected with a CD4 count of more than 200, the current thinking is to prevent infection with ARV drugs, caesarean sections, formula feeding and other interventions.
When a woman’s CD4 count has fallen, she should be offered triple ARV therapy. This can be any time from six weeks after delivery to 10 years or more.
ARV therapy is given — as opposed to mono or dual therapy — for treatment to prevent drug resistance. It works well, and has reduced tuberculosis rates and deaths from TB, other opportunistic infections, and prevented death by Aids in many people.