Should this be done? Can it be done? How can it be done? Is it a step towards, or a step away from effective treatment?
The widespread use of CTX to prevent PCP in North America and Western Europe was associated with a marked decline in mortality among people with HIV, which preceded the introduction of ARVs.
This experience, confirming what had been seen earlier in clinical trials, prompted a range of studies of different antibiotics, antifungals and antivirals to prevent diseases. As ever-lower CD4 thresholds were crossed, the diseases to be prevented would multiply, including candidiasis, atypical mycobacteria, and cytomegalovirus, requiring an increasingly complex and toxic cocktail of treatment.
The limitations to this approach are obvious and no physicians who are now able to prescribe ARVs are prepared to advocate it as a serious alternative to ARV treatment of HIV disease.
Using CTX alone, as an "affordable" public health measure in settings where ARVs are still not accessible to people or for people who cannot afford ARVs, is very difficult to sustain. Some people feel they are being "fobbed off" with something that is cheap and second-rate and can experience this as an insult, no matter how well it is intended. Worse, health-care providers can feel the same way. There is a world of difference, for providers as well as patients, between treatment that is just "delaying the inevitable" and something that is visibly "making people better".
Since CTX does NOT prevent fungal infections, especially candida, which are common and have an immediate impact on people's wellbeing, the perception can easily arise that it "doesn't work". Also the side effects - in particular, sulphonamide skin rash, may be all too familiar and may deter some people from taking them, even if they have never themselves experienced those side effects. The answer to this is (a) education and (b) specific treatment for conditions like oral thrush. Offering CTX to patients who (already) have oral thrush, following successful treatment with antifungals, could be one way to counter a reputation for CTX as a "failure" in that situation.
Since CTX is familiar as a treatment for infections associated with symptoms, often available cheaply without prescription, there can be an assumption that as soon as any symptoms have gone away, it can be discontinued. Clinics faced with large numbers of patients have limited time to explain that CTX prophylaxis is something different, and unless this message is communicated clearly and through multiple channels, including public education, it will not get across. Unfortunately, if the drug comes to be seen as "something that people with HIV take" this generates its own problems, where HIV status is still highly stigmatised. As with so many other diseases, effective treatment - which currently means ARVs - is likely to be the one truly effective and sustainable way to destigmatise HIV.
While there is not complete agreement on the value of primary prophylaxis, most are convinced that CTX can save lives, even before ARVs arrive. When ARVs do arrive, they too will need to be taken consistently, whether or not people feel unwell. People with HIV and their physicians in some communities are clearly making much more use of CTX than others, and some may be making more effective use of it. But whether it is useful may vary, depending not only on patterns of disease but also on the patterns and structures of clinical services provided for people with HIV.
TUMUSIIME: Patients taking co-trimoxazole as a prophylaxis here in Uganda have not expressed any fatigue in taking this drug so far, but the problem lies with us, the health care providers.
Due to the overwhelming numbers of patients to see, health care providers rarely have time to give information comprehensively on duration, when to replenish the home stock, action and possible side effects. This has some adverse effects, e.g patients relate co-trimoxazole to curative properties especially in the treatment of cough, so when the cough (or any other bacterial infection) resolves the patient stops taking the co-trimoxazole.
Under-staffing in health care settings gives no room for ongoing support counselling that is appropriate for someone with a chronic illness on taking medications for life, so patients on co-trimoxazole give themselves a break without knowing what they are doing!
Strategies to increase uptake and adherence to co-trimoxazole prophylaxis should include information-giving at all points of contact in a health facility. The doctors, nurses, pharmacy staff and counsellors should reinforce adherence messages at all those different levels.
Treatment advisory/counselling services will have a very important role to play especially in the administration of long term medications like ARVs and co-trimoxazole prophylaxis. They should be incorporated in the essential health care package for all PLWAs.
NDIR: In our Senegalese context, there is high uptake for co-trimoxazole. The reason is simple: before ARVs arrived, cotrimoxazole was widely used to treat bacterial infections. It is familiar to patients and it is not uncommon to see them take it without prescription when they feel sick. However, this has caused bacterial resistance in some cases.
So use of cotrimoxazole as prophylactic drug is not a big problem for our patients but correct use may be one. Indeed, we generally have to face two situations: patients who often need to take cotrimoxazole whether or not they feel unwell, patients who think that if they don't take cotrimoxazole, then they'll feel sick.
Now, [according to WHO guidelines] cotrimoxazole must be taken only when CD4 cell counts are less than 500/mm3.
So better monitoring of this prophylactic drug for a good compliance could be one of the best solutions. The fact remains that co-trimoxazole is not sufficiently available in care services.
I agree that if people can show that they can take co-trimoxazole correctly according to WHO or to their national AIDS control programme guidelines, then they (and their providers) will be able to make a stronger case that they are ready to make good use of ARVs.
WILSON: My impression is that people with symptomatic HIV infection are often eager to take therapy that is perceived as being helpful - ultimately patients will need to choose to "buy-into" the allopathic medical model - consistent messages from health-care workers, support groups and the media are important. The business sector (for example the insurance industry) have been involved in producing patient information booklets. Co-trimoxazole seems to have widespread acceptance in high HIV prevalence communities and is widely prescribed by the medical community in Cape Town.
PRABHU: My experience in Chennai, India, with co-trimoxazole prophylaxis is mixed. Certain patients feel that co-trimoxazole is an "HIV" drug because all HIV patients are taking them. Some patients regard their doctors as "gods", who can do no wrong ... others are very circumspect and if all they get is Septrin they would probably throw their medications away the moment they leave the clinic. Those that do take prophylaxis wonder why they still fall sick inspite of regularly taking medicines. When they develop oral thrush and episodes of itching, they are inclined to stop CTX. Another worrying prospect is the development of resistance, which would face us with some very serious decisions. Would it not be simpler to regularly follow up and treat episodes when they do develop, rather than offer prophylactic treatment which inevitably fails, and then be stuck wondering what to do next?
Today, we should be moving towards rational use of drugs. We must rethink this whole strategy of prophylaxis. We cannot afford to lose more drugs to resistance. We will be left with precious little to fight this disease should this happen!
The motivation for uptake of CTX prophylaxis is difficult. Since most often these medications are freely provided or are very cheap, affordability is not an issue. However, tolerability and side effects - rashes - are important issues, deterring uptake of these medicines. They do not drastically alter the quality of life, unlike ARV drugs where the patients feel the difference within a few months and so are motivated to continue ARV! Prophylaxis with CTX only seems to delay the inevitable and, if the broader issue of ARV therapy is neglected, the inexorable decline continues whether prophylaxis is given or not.
I firmly believe that regular clinical monitoring and periodical health visits and counselling are better options than thrusting pills down patients throats as a primary prophylaxis. Though if documented evidence exists for low CD4 counts or previous history of PCP pneumonia, secondary prophylaxis may be offered to selected patients who are motivated. Even here, I would prefer to treat episodes as they develop, rather than see patients irregularly who take prophylaxis since they are falling sick often, whether with vomitting or diarrhoea or skin rashes.
Do these prophylactic treatments really have a public heath benefit.? Do they really alter the course of infection and decrease the mortality of people living with HIV? I feel that people with HIV are dying at great speed, no matter what prophylaxis we would like to implement.... tons of Septrin, a lot of money and resources and many years down the line, we are still clutching at strategies which have clearly failed. I cannot but reiterate the difference ARV therapy has made to decrease morbidity, mortality and bring the HIV positives back into the mainstream of life. We need to look ahead at ways to ensure improved access to and proper prescribing of ARV drugs.