(ARV-) Free State? The moratorium's threat to patients' adherence and the development of drug-resistant HIV.
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ABSTRACT: Introduction: Hope is an essential dimension of successful coping in the context of illnesses such as HIV/AIDS, because positive expectations for the future alleviate emotional distress, enhance quality of life and have been linked to the capacity for behavioural change. The social environment (e.g. family, peers) is a regulator of hope for people living with HIV/AIDS (PLWHA). In this regard, the dual aim of this article is (1) to analyze the influence of a peer adherence support (PAS) intervention and the family environment on the state of hope in PLWHA and (2) to investigate the interrelationship between the two determinants. Methods: The Effective AIDS Treatment and Support in the Free State study is a prospective randomized controlled trial. Participants were recruited from 12 public antiretroviral treatment (ART) clinics across five districts in the Free State Province of South Africa. Each of these patients was assigned to one of the following groups: a control group receiving standard care, a group receiving additional biweekly PAS or a group receiving PAS and nutritional support. Latent cross-lagged modelling (Mplus) was used to analyse the impact of PAS and the family environment on the level of hope in PLWHA. Results: The results of the study indicate that neither PAS nor the family environment has a direct effect on the level of hope in PLWHA. Subsequent analysis reveals a positive significant interaction between family functioning and PAS at the second follow-up, indicating that better family functioning increases the positive effect of PAS on the state of hope in PLWHA. Conclusions: The interplay between well-functioning families and external PAS generates higher levels of hope, which is an essential dimension in the success of lifelong treatment. This study provides additional insight into the important role played by family dynamics in HIV/AIDS care, and it underscores the need for PAS interventions that are sensitive to the contexts in which they are implemented.Journal of the International AIDS Society 04/2014; 17(1):18802. · 4.21 Impact Factor
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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). Although the findings may not be generalizable to all HIV patients in Rwanda, our data suggest that first-line ART regimen changes are currently not warranted. However, the accumulation of acquired HIVDR mutations in some participants underscores the need to reinforce HIVDR prevention strategies, such as increasing the availability and appropriate use of VL testing to monitor ART response, ensuring high quality adherence counseling, and promoting earlier identification of HIV patients and enrollment into HIV care and treatment programs.PLoS ONE 08/2013; 8(8):e64345. · 3.53 Impact Factor
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ABSTRACT: The primary objective was to measure HIV incidence in two prospective cohorts of HIV-negative women. Secondary objectives included measuring pregnancy rates and participant retention rates. Cross-sectional HIV screening of women selected for higher risk behaviours, with a subsequent prospective study of uninfected women, followed monthly for up to 6 months. Clinics established for research purposes in Bloemfontein and Rustenburg, South Africa. The authors enrolled women 18-35 years old and presumed at higher risk of sexual acquisition of HIV as indicated by self-reported sexual behaviour or recent sexually transmitted infection symptoms. In Bloemfontein, 1364 women were screened, 1154 were eligible for HIV testing and 1145 agreed to be tested. The prospective study enrolled 401 HIV-negative women. In Rustenburg, 946 women were screened, 540 were eligible and underwent HIV testing and 223 HIV-negative women entered the prospective study. PRIMARY AND SECONDARY OUTCOMES: Baseline prevalences of HIV infection and HIV incidence rates in the prospective cohorts, according to a double rapid test algorithm with a third rapid test for discrepant or indeterminate results. Pregnancy prevalences and pregnancy incidence rate in Bloemfontein. Participant retention rates in the prospective cohort until the study end. In Bloemfontein, 1145 women were tested, 391 entered follow-up and 92.3% of participants completed six study visits. In Rustenburg, 540 women were tested, 194 entered follow-up and retention up to the point of early study termination was 88.6%. Overall HIV prevalence was 21.2% (95% CI 18.9% to 23.6%) in Bloemfontein and 23.5% (95% CI 19.9% to 27.1%) in Rustenburg. Overall HIV incidence was 5.5/100 person-years (95% CI 2.5 to 10.4) in Bloemfontein and 3.0/100 person-years (95% CI 0.4 to 10.8) in Rustenburg. Cross-sectional pregnancy prevalences were 6.5% in Bloemfontein and 8.6% in Rustenburg. The authors observed substantial HIV incidence rates in both cohorts. Vigorous prevention efforts are needed in these smaller cities.BMJ Open 01/2012; 2(1):e000626. · 2.06 Impact Factor
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.
Department of Community Health
University of KwaZulu-Natal
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.
Division of Global Health (IHCAR)
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
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.
6. 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;
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
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