Making patients in impoverished countries contribute towards the cost of their antiretroviral treatment is one of the major causes of non-adherence to treatment according to presentations earlier this month at the Fifteenth International AIDS Conference in Bangkok.
Charges for treatment are widespread in resource-limited settings and some degree of user fee funding of health care has been promoted as an orthodoxy in public finance over the past fifteen years by the World Bank and donor governments.
However researchers from Senegal, which has one of Africa’s most longest standing public sector treatment programmes, reported to the conference that charging does affect adherence. They also found that the longer patients stay on treatment, the more difficulties they have with adherence.
Senegal
The Senegalese study, conducted in collaboration with the French AIDS research body ANRS, followed 159 patients for a maximum of 54 months to monitor their adherence to treatment. Half were taking a triple combination including efavirenz, 38% were taking a triple combination containing indinavir, and the remainder were taking either dual nucleoside analogue combinations or combinations containing either nevirapine or nelfinavir. Eighty were taking part in clinical trials and thus might be expected to have a higher level of adherence due to more frequent monitoring.
Until 2000 all patients apart from those in trials were required to pay around $35 a month for treatment. In 2001 patients without finance were given antiretrovirals free of charge, and in 2003 the government was able to introduce free antiretroviral treatment for all.
The study found a mean monthly adherence rate of 90.2% over 54 months of follow-up.
In 1999-2000 over 50% of patients who interrupted treatment for more than five days reported that the treatment break was due to financial problems. By 2003 this proportion had fallen to 15%, with travel and voluntary treatment interruptions the chief reasons for treatment breaks.
Cost of treatment and duration of treatment, as well as commencing treatment with symptomatic HIV disease, were associated with poorer adherence.
The authors recommended that measures to support long-term adherence need to be planned at the outset of therapy (Laniece).
A small study in Nigeria which followed adherence in 53 patients (40 who received free medication and 13 who paid for treatment) found a trend towards better adherence in those who received free treatment, although this was not statistically significant (85% vs 61% reported adherence of at least 95% during the past seven days, p = 0.069). The most frequently reported reason for non-adherence was inability to afford medication (Daniel).
However, even where patients must pay for treatment very good levels of adherence have been reported during the first 12-24 weeks of therapy.
Uganda
Ugandan researchers working in collaboration with a team from the University of California San Francisco assessed adherence during the first 24 weeks of treatment in 97 patients who began treatment with either Triomune or Maxivir. The findings, published in a preliminary form in the August 15th edition of the Journal of Acquired Immune Deficiency Syndromes , were updated at the XV International AIDS Conference.
The study compared four measures of adherence: three-day patient self-report of the number of number of doses missed, 30-day visual analogue scale of percentage of pills missed, electronic medication monitoring and unannounced home pill count. Patient adherence assessments were carried out monthly during the first twelve weeks of treatment during home visits.
Ninety seven patients began treatment, but 10% had to discontinue treatment due to the diagnosis of active TB (tuberculosis treatment with rifampicin reduces nevirapine levels).
One third had primary education only, 63% were female and one quarter were unemployed. During the first phase of the study, reported in JAIDS, 53% of patients had a monthly income of less than US$50 a month, a modest income by Ugandan standards. Triomune cost $US20-25 a month during the period reported (Sept 2002-July 2003), implying a substantial monthly expenditure on medication.
During this phase of the study, mean adherence was measured at 94.4% by three day report, 93.5% by thirty day report, 90.9% by electronic medication monitoring and 93.7% by pill count. There was no significant difference between any of these measures, suggesting that three day or thirty day report are equally valid measures of adherence in the Ugandan setting. The investigators note that the thirty day scale, which asks patients to draw a line on a scale indicating what proportion of pills they have taken, proved considerably easier to administer. Surprisingly its results were concordant with those of the three day pill taking report, despite using a more abstract measure of pill taking.
Viral load at week 12 was significantly associated with all measures of adherence. A non-significant decline in adherence between weeks 12 and 24 was reported to the International AIDS Conference, suggesting that longer term studies of adherence are needed in the African context.
The chief limitation of the study, say its authors, is the possibility that the monitoring method (home visits) may have reinforced adherence. However, given that most programmes now introducing antiretrovirals in Africa include some form of adherence support, this limitation is unlikely to affect the generalisability of these data.
A more important caveat is the authors’ reminder that their study looked at adherence to one pill twice a day (Triomune is a coformulation of three drugs). They comment: “Adherence to more complicated regimens might be lower.” Evidence from Spain also presented at the conference showed that when patients switched to a regimen with a lower pill burden, their adherence improved (see Fewer pills mean better adherence, says Spanish study). Typically patients switched from a protease inhibitor containing regimen with higher pill burden to a compact regimen of one efavirenz tablet and one or two nucleoside analogue tablets twice a day. More detailed comparison of how smaller differences in pill burden has not been carried out.
References
Laniece I et al. Determinants of long-term adherence to antiretroviral drugs among adults followed for over four years in Dakar, Senegal. XV International AIDS Conference, Bangkok, abstract WeOrC1320, 2004.
Daniel OJ et al. Adherence pattern to ARV drugs among AIDS patients on self-purchased drugs and those on free medications in Sagamu, Nigeria. XV International AIDS Conference, Bangkok, abstract WePeB5768, 2004.
Oyugi JH et al. Treatment outcomes and adherence to Triomune and Maxivir in Kampala, Uganda. XV International AIDS Conference, Bangkok, abstract WeOrC1323, 2004.
Oyugi JH et al. Multiple validated measures of adherence indicate high levels of adherence to generic HIV antiretroviral therapy in a resource-limited setting. JAIDS 36(5): 1100-02, 2004.