(ARV-) Free State? The moratorium's threat to patients’ adherence and the development of drug-resistant HIV

Article (PDF Available)inSouth African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 99(6):412, 414 · July 2009with27 Reads
Source: PubMed
June 2009, Vol. 99, No. 6 SAMJ
Treat the patient, not the result
To the Editor: Several episodes of nursing and laboratory
staff at a specialist tuberculosis (TB) hospital presenting
with flu-like symptoms, who on further investigation were
found to have acid-fast bacilli in their sputum yet normal
chest radiographs, have occurred. In many instances, in the
absence of other evidence of TB, these staff were not initiated
on anti-TB treatment. Serial sputum investigations remained
negative and the symptoms disappeared. Similarly, in the same
institution there have been several reports of patients referred
with a microbiological diagnosis of multi- or extensively
drug-resistant tuberculosis. Owing to the protracted period
of time needed to grow these organisms, the individuals
concerned are commenced on first-line TB treatment. By the
time the susceptibility results are received (usually several
months later) and the patients referred to the specialist TB
hospital for further management, both clinical and radiological
improvement in response to first-line TB treatment has taken
place, which suggests that there might have been some contact
with TB (drug-susceptible or resistant), and the bacillus could
have infected and behaved as a commensal for a short period
and not caused disease in the ‘carrier’. This scenario is more
relevant today, with the prevalence of MDR and XDR TB.
If a chest radiograph is reported as clear by an experienced
reader, and the individual is asymptomatic, then the sputum
test should be repeated, including culture and susceptibility
testing, before embarking on therapy with potentially toxic
second-line TB drugs. Health workers should be cognisant of
these confounders and remember to treat the patient – and not
laboratory reports or radiographs.
Nesri Padayatchi
Department of Community Health
University of KwaZulu-Natal
John Quantrill
King George V Hospital
1. Demissie A, Leyten EM, Abebe M, et al. Recognition of stage-specific mycobacterial antigens
differentiates between acute and latent infections with Mycobacterium tuberculosis. Clin Vaccine
Immunol 2006; 13(2): 179-186.
2. Hussain R, Talat N, Shahid F, Dawood G. Longitudinal tracking of cytokines after acute
exposure to tuberculosis: association of distinct cytokine patterns with protection and disease
development. Clin Vaccine Immunol 2007; 14(12): 1578-1586.
(ARV-) Free State? The moratorium’s
threat to patients’ adherence and the
development of drug-resistant HIV
To the Editor: Despite early fears that people living with
HIV (PLWHs) in Africa would not be able to adhere to
antiretrovirals (ARVs),1,2 research has shown that the
proportion of PLWHs reporting 95% adherence in sub-
Saharan Africa is higher than that in North America.3 However,
maintaining adherence is complex, and several factors
affect patient ability to access and adhere to ARVs: patient
characteristics and context, ARV regimen, clinical situation and
the patient/health staff relationship.4
In October 2008, the new Minister of Health announced
that 550 000 PLWHs – the highest number in the world – were
on ARVs in South Africa.5 This achievement was recently
tarnished by increasing alarm over Free State province’s public
sector ARV programme. The Free State has the third-highest
HIV prevalence (of 31%) in the country.6 Since December 2008,
the province’s Department of Health stopped initiating new
patients on ARVs7 because of out-of-stock drugs and lack of
funds. An estimated 30 PLWHs are dying every day in the
province while this hiatus continues.8 The moratorium will
increase morbidity and mortality, but the loss of trust in the
health system and the potential impact of the ARV crisis on
existing patient adherence also need to be considered.
Campero et al. reported that patients already on ARVs share
their medication with neighbours, relatives or friends who
experience delays in receiving ARVs.9 This practice could
lead to the development of drug resistance in people sharing
medication if they consequently have differential exposure to
ARVs,10-13 and raises serious public health concerns about drug
failure, subsequent and more expensive drug regimens, and the
spread of drug-resistant strains of HIV.
Patients’ perceptions of staff attitudes and waiting times
were reported to be key factors for patients’ ARV adherence.14
Conceivably, PLWHs will seek care in other provinces, and
would consequently be required to return monthly to outlying
clinics to pick up their ARVs. Transport costs and the time
needed to reach clinics are risk factors to adherence and
retention in care.15,16 Patients currently on treatment – in the
Free State and elsewhere – are understandably anxious about
the health system’s ability to guarantee lifelong access to ARVs.
An estimated 300 000 people might not have died of AIDS
if the South African government had responded to the AIDS
crisis quickly and in a coherent manner.17 How the government
proceeds to contain and repair the damage being done in the
Free State will be a litmus test for the long-term success of
South Africa’s ARV programme.
Ziad El-Khatib
Division of Global Health (IHCAR)
Karolinska Institutet
Marlise Richter
Steve Biko Centre for Bioethics
University of the Witwatersrand
June 2009, Vol. 99, No. 6 SAMJ
1. Moatti JP, Spire B, Kazatchkine M. Drug resistance and adherence to HIV/AIDS antiretroviral
treatment: against a double standard between the north and the south. AIDS 2004; 18 (suppl
3): S55-61.
2. Check E. Staying the course. Nature 2006; 442: 617-619.
3. Mills EJ, Nachega JB, Buchan I, et al. Adherence to antiretroviral therapy in sub-Saharan
Africa and North America. JAMA 2006; 296: 679-690.
4. Bangsberg DR, Ware N, Simoni JM. Adherence without access to antiretroviral therapy in
sub-Saharan Africa? AIDS 2006; 20: 140-141.
5. Speech by the Minister of Health Ms Barbara Hogan at the HIV Vaccine Research Conference
(http://www.doh.gov.za/docs/sp/sp1013-f.html). In: Vaccine Research Conference; Cape
Town 13 - 16 October 2008. Pretoria, Department of Health.
National HIV and Syphilis Antenatal Sero-Prevalence Survey in South Africa 2006. Pretoria:
Department of Health, 2007.
7. ART crisis − Free State province, Dec. 2008. http://www.sahivsoc.org. (accessed 18 March
8. Thom A. 30 dying every day in the Free State − HIV Clinicians (http://www.health-e.org.
za/news/article.php?uid=20032192). Health-e (accessed 19 February 2009).
9. Campero L, Herrera C, Kendall T, Caballero M. Bridging the gap between antiretroviral
access and adherence in Mexico. Qualitative Health Research 2007; 17: 599-611.
10. Bangsberg DR. Preventing HIV antiretroviral resistance through better monitoring of
treatment adherence. J Infect Dis 2008; 197: S272-S278.
11. Bangsberg DR, Acosta EP, Gupta R, et al. Adherence-resistance relationships for protease and
non-nucleoside reverse transcriptase inhibitors explained by virological fitness. AIDS 2006;
20: 223-231.
12. Boulle A, Ford N. Scaling up antiretroviral therapy in developing countries: what are the
benefits and challenges? Sex Transm Inf 2007; 83: 503-505.
13. Gardner EM, Sharma S, Peng G, et al. Differential adherence to combination antiretroviral
therapy is associated with virological failure with resistance. AIDS 2008; 22: 75-82.
14. Dahab M, Charalambous S, Hamilton R, et al. ‘That is why I stopped the ART’: Patients’ &
providers’ perspectives on barriers to and enablers of HIV treatment adherence in a South
African workplace programme. BMC Public Health 2008; 8:doi:10.1186/471-2458-8-63.
15. Murray LK, Semrau K, McCurley E, et al. Barriers to acceptance and adherence of
antiretroviral therapy in urban Zambian women: a qualitative study. AIDS Care 2009; 21:
16. Tuller DM, Bangsberg DR, Senkungu J, Ware NC, Emenyonu N, Weiser SD. Transportation
costs impede sustained adherence and access to HAART in a clinic population in
southwestern Uganda: A qualitative study. AIDS Behav 2009; 13 March [Epub ahead of print].
17. Chigwedere P, Seage GR 3rd, Gruskin S, Lee TH, Essex M. Estimating the lost benefits of
antiretroviral drug use in South Africa. J Acquir Immune Defic Syndr 2008; 49(4): 410-415.
Are investigators satisfied with contract
clinical research in South Africa?
To the Editor: In October 2008, I surveyed 75 principal
investigators in South Africa with whom I had worked since
2004. I emailed to each a covering letter, a survey sheet with
tick boxes for answers to 13 questions, and a comment sheet. I
received completed surveys from 35 investigators. I could find
no similar surveys in the literature.
The respondents are experienced investigators, of whom
66% had more than 5 years’ experience in clinical trials, and a
further 24% 2 - 5 years’ experience; 37% had taken part in more
than 5 trials in the previous 12 months, and a further 49% had
taken part in 2 - 5 trials in the same period.
Investigator meetings were rated as ‘good’ by 51% of the
investigators, and as ‘average’ by 43%; the supply of study
materials to the site was rated as ‘good’ by 37% and ‘average’
by 57%. Most respondents felt that the general conduct of the
study was ‘good’ (71%), with nobody rating the conduct as
‘bad’. The conduct of monitors was rated as ‘good’ by 63% of
investigators, with nobody rating them as ‘bad’.
Only 14% of investigators rated recruitment at their site as
‘bad’, while 6% described the sponsor’s expectations of their
site as ‘bad’. The process of closing a study at the site was rated
as ‘good’ by 74%.
A preference for electronic case report forms was stated by
59%, the rest preferring paper forms. Investigator fees were
described as ‘good’ by 26% of investigators, and ‘average’ by
Only 3% of investigators felt that the time to Medicines
Control Council (MCC) approval was ‘good’, with 80% rating
the time as ‘bad’.
Contract clinical research in South Africa has grown steadily
in the last 5 years. This is the only survey that has been
conducted to determine investigator satisfaction with the
clinical trial industry. Investigators are generally satisfied with
the process of conducting clinical research in South Africa, and
are willing to utilise enhanced technology to stay abreast of the
rest of the developing world in clinical trials. The time to MCC
approval remains a concern but, with steps that are under way,
I am certain that the dissatisfaction will change in the near
E Mitha
Newtown Clinical Research
Kebble or quibble?
Dear Aunt Ethel,
To those skilled at matters surgical, a lost orchid is the
euphemism for an ectopic testis or undescended testicle. Makes
Tretchikoff’s originals/collectors’ pieces sound like priceless
balderdash, perhaps?
Yours affectionately
Robert-Ian Caldwell
Hilton, KwaZulu-Natal
    • "In 2010, more than five million HIV-infected Africans were estimated to receive life-saving ART, with Rwanda reporting treatment coverage of 80% [3]. However, ART scale up in resource-poor settings could accelerate HIVDR emergence [4,5,6,7] due to insufficient viral load (VL) monitoring [8], inconsistent drug supply [9], and possible unregulated use of antiretroviral drugs (ARV) [10]. HIVDR can develop because of the error prone nature of HIV replication resulting in a high mutation rate in combination with the ongoing presence of drug-selective pressures. "
    [Show abstract] [Hide abstract] ABSTRACT: Treatment outcomes of HIV patients receiving antiretroviral therapy (ART) in Rwanda are scarcely documented. HIV viral load (VL) and HIV drug-resistance (HIVDR) outcomes at month 12 were determined in a prospective cohort study of antiretroviral–naïve HIV patients initiating first-line therapy in Kigali. Treatment response was monitored clinically and by regular CD4 counts and targeted HIV viral load (VL) to confirm drug failure. VL measurements and HIVDR genotyping were performed retrospectively on baseline and month 12 samples. One hundred and fifty-eight participants who completed their month 12 follow-up visit had VL data available at month 12. Most of them (88%) were virologically suppressed (VL≤1000 copies/mL) but 18 had virological failure (11%), which is in the range of WHO-suggested targets for HIVDR prevention. If only CD4 criteria had been used to classify treatment response, 26% of the participants would have been misclassified as treatment failure. Pre-therapy HIVDR was documented in 4 of 109 participants (3.6%) with an HIVDR genotyping results at baseline. Eight of 12 participants (66.7%) with virological failure and HIVDR genotyping results at month 12 were found to harbor mutation(s), mostly NNRTI resistance mutations, whereas 4 patients had no HIVDR mutations. Almost half (44%) of the participants initiated ART at CD4 count ≤200cell/µl and severe CD4 depletion at baseline (<50 cells/µl) was associated with virological treatment failure (p = 0.008).
    Full-text · Article · Aug 2013
    • "More than a quarter (27%) had not managed to take at least 95% of their treatment on time, while 30% showed a rebounding viral load. Treatment free of charge facilitates patient uptake of HAART, but failures in the supply line for antiretrovirals may also interrupt adherence[30]. In June 2011, Ghana had to draw down emergency supplies of ARVs priced at USD1.5 million[31], and in July 2011 protests occurred in Algeria[32] and Swaziland[33] over ARV supply problems. "
    [Show abstract] [Hide abstract] ABSTRACT: ABSTRACT: This paper reviews the healthcare issues facing nations which have a substantial caseload of chronic HIV cases. It considers the challenges of extending antiretroviral coverage to an expanding caseload as supplier price rises and international trade agreements come into force to reduce the availability of affordable antiretrovirals just as the economic downturn restricts donor funding. It goes on to review the importance in this context of supporting adherence to drug regimens in order to preserve access to affordable antiretrovirals for those already on treatment, and of removing key barriers such as patient fees and supply interruptions. The demands of those with chronic HIV for health services other than antiretroviral therapy are considered in the light of the fearful or discriminatory attitudes of non-specialist healthcare staff due to HIV-related stigma, which is linked with the weakness of infection control measures in many health facilities. The implications for prevention strategies including those involving criminalisation of HIV transmission or exposure are briefly summarised for the current context, in which the caseload of those whose chronic HIV infection must be controlled with antiretrovirals will continue to rise for the foreseeable future.
    Full-text · Article · Oct 2011
    • "In addition to traditional understanding of effective treatment, the sharing of ARVs was cited by community participants as a barrier to adherence. This phenomenon has been documented elsewhere515253. Patients may have resorted to sharing medication during " stock-outs " that have occurred, especially early in ART roll-out. "
    [Show abstract] [Hide abstract] ABSTRACT: HIV is treated as a chronic disease, but high lost-to-follow-up rates and poor adherence to medication result in higher mortality, morbidity, and viral mutation. Within 18 clinical sites in rural Zambézia Province, Mozambique, patient adherence to antiretroviral therapy has been sub-optimal. To better understand barriers to adherence, we conducted 18 community and clinic focus groups in six rural districts. We interviewed 76 women and 88 men, of whom 124 were community participants (CP; 60 women, 64 men) and 40 were health care workers (HCW; 16 women, 24 men) who provide care for those living with HIV. While there was some consensus, both CP and HCW provided complementary insights. CP focus groups noted a lack of confidentiality and poor treatment by hospital staff (42% CP vs. 0% HCW), doubt as to the benefits of antiretroviral therapy (75% CP vs. 0% HCW), and sharing medications with family members (66% CP vs. 0%HCW). Men expressed a greater concern about poor treatment by HCW than women (83% men vs. 0% women). Health care workers blamed patient preference for traditional medicine (42% CP vs. 100% HCW) and the side effects of medication for poor adherence (8% CP vs. 83% CHW). Perspectives of CP and HCW likely reflect differing sociocultural and educational backgrounds. Health care workers must understand community perspectives on causes of suboptimal adherence as a first step toward effective intervention.
    Full-text · Article · Aug 2011
Show more