One-third of a group of 137 patients at Mulago Hospital in Kampala, Uganda had failed antiretroviral therapy after an average follow-up period of 38 weeks, and 22 per cent acquired resistance to NNRTIs, a Ugandan physician told the 7th International Congress on Drug Therapy in HIV Infection.
Dr. Moses Kamya told the congress that 36 patients were given a resistance test. Of the 27 on NNRTI-based regimens, 52 per cent had the K103N resistance mutation; and of the 27 taking 3TC (generally in the same fixed-dose combination), 74 per cent had the M184V mutation.
The main reason for treatment failure and the acquisition of resistance, said Dr. Kamya, was poor adherence. In a cross-sectional questionnaire, eleven per cent of patients had missed a dose in the previous four days and 18 per cent in the previous two weeks. The main reason cited by patients for poor adherence was the fact that some patients had to pay a contribution to the cost of therapy.
Nonetheless, said Dr. Kamya, the treatment programme resulted in overall health improvements. The mean CD4 count in the group rose from 55 cells/mm3 at baseline to 163 cells/mm3 at 38 weeks, and whereas 93 per cent of patients said they were unable to work before treatment, 85 per cent were able to work by this point.
The patient group had a mean age of 39, and 54% of them were women. Two-thirds had AIDS-defining illness at baseline, with 77% defined as symptomatic according to the WHO performance scale.
Of the 36 patients genotyped, 44% had subtype A and 42% subtype D of HIV, with the remaining 16% split evenly between A/D and A/E recombinant strains.
The regimens taken included 77% of patients on the d4T/3TC/nevirapine fixed dosed combination (Triomune); 14% on an efavirenz-based regimen; and 8% on protease inhibitors. Two patients took a triple-nucleoside regimen; both failed treatment without ever achieving viral undetectability and developed, according to Dr. Kamya, “extensive NRTI resistance”.
These two patients had been on AZT/3TC/abacavir for 37 and 57 weeks respectively before a viral load test was done. Dr. Kamya commented that at US$75 per test, “we just don’t do” viral load testing for patients in general, but that no cheaper surrogate marker for treatment failure had been found to be accurate.
Dr. Kamya commented that therapy needed to be optimised from the beginning by ensuring “stable drug supplies, durable and potent regimens, proper monitoring, and enabling adherence”. He said that the reliability of ARV programmes funded by the US PEPFAR initiative had proved better than ones funded by other agencies such as the Global Fund, where bureaucracy often delayed access.
His remarks were echoed by Dr. Joep Lange, former president of the Internaional AIDS Society, speaking immediately after Dr. Kamya.
“International NGOs like the World Bank and the WHO are inherently unable to deliver programmes unrealistically expected of them because they are obliged to go through an often non-functioning public sector,” he said.
He also forecast a ‘disaster for Africa’ in a few years time due to the widespread use of d4T and the likely development of lipodystrophy.
He urged better co-operation and an end to wasteful duplication of effort between agencies that had different remits and areas of expertise.
Kamya M.R. et al. Treatment outcomes for antiretroviral therapy in a routine clinical setting in Kampala, Uganda. 7th International Congress on Drug Therapy in HIV Infection, Glasgow. 2004. Abstract PL4.4.