Racing to Keep Resistant HIV At Bay
Racing to Keep Resistant HIV At Bay
UN Integrated Regional Information Networks
June 13, 2006
Posted to the web June 13, 2006
The sustainability of the national HIV treatment programme in Botswana, and
elsewhere in Africa, depends on avoiding widespread drug resistance that could
threaten long-term affordability. Patients who miss even five percent of their
drug doses can develop resistant strains of the virus, and will need to switch
to second-line medication at more than double the cost.
Botswana was the first country in Africa to implement a nationwide
antiretroviral (ARV) programme. Four years later, 85 percent of patients,
including those using the private sector, are receiving treatment, and the
programme has often been held up as a test case for the rest of the continent.
Other countries in the region lag far behind - while they are focusing on a
wider distribution of ARVs, Botswana's major challenge is to ensure that
patients stick to their daily regimen.
When Botswana began enrolling patients for treatment in 2002, the question of
whether such a programme could succeed outside the developed world was still
unanswered. Some of the concerns were whether people living in resource-poor
settings would have the necessary education levels to grasp the importance of
taking a complex combination of drugs every day for the rest of their lives, or
the economic means to access proper nutrition and transport to and from clinics.
These concerns have turned out to be largely unfounded. In a study on treatment
adherence and drug resistance, researchers at the Botswana-Harvard AIDS
Institute found little evidence of treatment fatigue - becoming less vigilant
about taking the pills over time - and patients have so far demonstrated better
or at least the equivalent adherence of their western counterparts.
"People here are very committed to getting well," said Hermann Bussmann, one of
the researchers. "They know the importance of not missing doses."
The study compares the effectiveness of two drug adherence strategies: the
standard approach of Botswana's National AIDS Coordinating Agency, which
matches patients with a 'buddy' who supports and encourages them to take their
medication on time; and directly observed treatment (DOT), already used with TB
patients, in which community health workers supervise patients while they take
The results will not be available for at least another year, but according to
Dr Ava Avalos, part of a team at the Infectious Diseases Care Clinic (IDCC) at
Princess Marina Hospital in Gaborone that monitors and manages patients with
treatment failure, only four percent of the clinic's 14,000 patients have had
to be switched to second or third-line regimens.
"We're doing much better than anyone had anticipated," Avalos said. "At this
clinic we really bombard patients with information and adherence counselling
services. Because we're a specialised HIV clinic we can do that, but not every
rollout clinic can."
Data on whether other clinics in the country or the continent have similarly
low levels of first-line treatment failure are not yet available. According to
Dr. Jos Perriens, of the AIDS Medicines and Diagnostics Service at the World
Health Organisation (WHO), second-line drugs comprised only 1.5 percent of
total ARV procurement by low- and middle-income countries last year.
This did not necessarily reflect the real incidence of treatment failure, he
added, and could also be the result of difficulty in procuring or affording
Medecins Sans Frontieres (MSF), the international humanitarian medical aid
agency, has warned that unless drug manufacturers and regulatory authorities
start fast-tracking the availability of second-line drugs in Africa, and
significantly lowering the cost, a crisis could occur when large numbers of
patients start developing resistance to first-line treatment in a few years'
Avalos conceded that accessing second-line and even third-line drugs was not a
problem for patients at Princess Marina's IDCC - Botswana's government has more
money to spend on its national treatment programme than most others on the
continent and has also received considerable expertise and support from foreign
partners, such as the Bill and Melinda Gates Foundation and the Merck
pharmaceuticals company, which donates two of the ARV drugs used in the
Part of the key to the IDCC's success has been in monitoring the viral load,
which measures the amount of virus in the system and is the only reliable
indication that a patient is harbouring resistant mutations of the virus. A
drug-resistant patient can look and feel healthy, and even have a normal CD4
count, which measures the strength of the immune system, Avalos explained.
A national protocol to manage first-line drug failure is being rolled out in
Botswana and will include training in how to track viral loads, but Avalos
predicted that monitoring drug resistance would be "our biggest challenge" in
African countries that cannot afford to do frequent viral load tests.
A new multi-country study funded by GlaxoSmithKline, the British Department for
International Development (DFID) and Antiretroviral Therapy in Lower Income
Countries (ART-LINC), aims at a better understanding of the factors that affect
adherence in poor countries.
Based on a small pilot study at Princess Marina last year, researcher Sara Nam
of the London School of Hygiene & Tropical Medicine found the biggest factors
were not socioeconomic, but psychological and emotional issues similar to those
of patients in developed countries: the degree to which patients accepted their
HIV status, the amount of support they received from people close to them, and
the level of faith in their doctors and the drugs.
The multi-country research, now recruiting participants, will include questions
about patients' religious beliefs, use of traditional medicines, how concerned
they are about stigma, whether they are breadwinners and their alcohol use.
Poor adherence is the biggest but not the only cause of drug resistance. Some
of the patients Avalos treats, particularly women who have difficulty
negotiating condom use, contract resistant strains of the virus by having
unprotected sex with HIV-positive partners.
Drug resistance is rising in countries where ARVs are not widely available in
government programmes and people buy the medicines from the private sector and
then interrupt treatment during periods when they cannot afford them. Patients
often switch to free drugs when they become available without informing their
doctors of which ARVs they were taking previously.
According to Bussmann, prescribing a single dose of the ARV drug, nevirapine,
to pregnant women - the most common method of preventing
mother-to-child-transmission in Africa - can also cause resistance problems
when they begin ARV treatment, but "It's too early to say what will happen in
the longer term," he said.
Previous assumptions about high numbers of patients defaulting on their
medication have proved false in Botswana, but no one knows if other countries
with less infrastructure and fewer resources will have similarly good outcomes
or access to second-line drugs.
Perriens of the WHO believes such concerns may be premature, considering that
only 20 percent of people in need of treatment in developing countries are
currently receiving it: "Our worry about the possible unavailability of
second-line drugs should not absorb the energy we need to ensure people get
their first chance of survival, which is first-line treatment."
[This report does not necessarily reflect the views of the United Nations]
Leela McCullough, Ed.D.
Director of Information Services
30 California Street, Watertown, MA 02472, USA
Tel: +1-617-926-9400 Fax: +1-617-926-1212