Articles tagged as "HIV testing and treatment"

Abacavir: a safe first line drug for children

Adverse events associated with abacavir use in HIV-infected children and adolescents: a systematic review and meta-analysis.

Jesson J, Dahourou DL, Renaud F, Penazzato M, Leroy V. Lancet HIV. 2016 Feb;3(2):e64-75. doi: 10.1016/S2352-3018(15)00225-8. Epub 2015 Dec 7.

Background: Concerns exist about the toxicity of drugs used in the implementation of large-scale antiretroviral programmes, and documentation of antiretroviral toxicity is essential. We did a systematic review and meta-analysis of adverse events among children and adolescents receiving regimens that contain abacavir, a widely used antiretroviral drug.

Methods: We searched bibliographic databases and abstracts from relevant conferences from Jan 1, 2000, to March 1, 2015. All experimental and observational studies of HIV-infected patients aged 0-18 years who used abacavir, were eligible. Incidence of adverse outcomes in patients taking abacavir (number of new events in a period divided by population at risk at the beginning of the study) and relative risks (RR) compared with non-abacavir regimens were pooled with random effects models.

Findings: Of 337 records and 21 conference abstracts identified, nine studies (eight full-text articles and one abstract) collected information about 2546 children, of whom 1769 (69%) were on abacavir regimens. Among children and adolescents taking abacavir, hypersensitivity reactions (eight studies) had a pooled incidence of 2.2% (95% CI 0.4-5.2); treatment switching or discontinuation (seven studies) pooled incidence was 10.9% (2.1-24.3); of grade 3-4 adverse events (six studies) pooled incidence was 9.9% (2.4-20.9); and adverse events other than hypersensitivity reaction (six studies) pooled incidence was 21.5% (2.8-48.4). Between-study inconsistency was significant for all outcomes (p<0.0001 for all inconsistencies). Incidence of death (four studies) was 3.3% (95% CI 1.5-5.6). In the three randomised clinical trials with comparative data, no increased risk of hypersensitivity reaction (pooled RR 1.08; 95% CI 0.19-6.15), grade 3 or 4 events (0.79 [0.44-1.42]), or death (1.72 [0.77-3.82]) was noted for abacavir relative to non-abacavir regimens. None of the reported deaths were related to abacavir.

Interpretation: Abacavir-related toxicity occurs early after ART initiation and is manageable. Abacavir can be safely used for first-line or second-line antiretroviral regimens in children and adolescents, especially in sub-Saharan Africa where HLA B5701 genotype is rare.

Abstract access

Editor’s notes: Abacavir is a nucleoside reverse transciptase inhibitor (NRTI), available as a paediatric formulation. Abacavir in combination with lamivudine is the preferred NRTI backbone for children aged three to ten years and for adolescents weighing under 35 kilograms. It is thus part of both first- and second-line antiretroviral therapy (ART) regimens recommended for children by World Health Organization (WHO), American and European guidelines.  

In the context of implementation of large-scale ART programmes where abacavir is recommended as the NRTI of choice, understanding its toxicity is crucial. In adults the main concern is the increased risk of hypersensitivity reactions, particularly among people with the HLA B5701 genotype, and of myocardial infarction. Children have specific characteristics that affect both the pharmacokinetic profiles of drugs, and also drug tolerability in the short and the long term. Despite the widespread use of abacavir, there has been no systematic evaluation of the toxicity profile of abacavir in children. 

This systematic review of nine studies conducted between 2000 and 2015 demonstrates that there is a low risk of hypersensitivity reactions, especially for children living in sub-Saharan Africa, where 90% of children with HIV live. This is consistent with studies in adults which illustrates that the frequency of the HLAB5701 allele genotype in African populations is low, estimated to be less than two percent.

Other adverse events such as gastrointestinal symptoms and laboratory abnormalities were common. Rates of adverse events should be interpreted with caution as these could depend on factors such as other drugs in the regimen, adherence and so on. Furthermore, data on adverse events were obtained from cohort studies that were not blinded and selection or recall bias cannot be excluded.

Notwithstanding this, most adverse events occurred early after initiation of abacavir, were no more common than with other NRTI regimens, and were manageable. Importantly, there were no deaths associated with abacavir in any of the reported studies. This study supports the use of abacavir as a preferred drug in the NRTI backbone for treatment of children living with HIV. 

HIV Treatment
Africa, Europe, Latin America
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Fear of HIV test deters Ethiopians from getting malaria treatment

Concerns about covert HIV testing are associated with delayed presentation in Ethiopian adults with suspected malaria: a cross-sectional study.

Tadesse F, Deressa W, Fogarty AW. BMC Public Health. 2016 Feb 1;16(1):102. doi: 10.1186/s12889-016-2773-y

Background: Although early diagnosis and prompt treatment is important in preventing mortality from malaria, presentation of symptomatic individuals is often relatively late. One possible contributing factor is that fear of covert human immunodeficiency virus (HIV) testing delays presentation in adults. We aimed to survey the magnitude of such concerns and their association with delayed presentation with suspected malaria.

Methods: The study design was a health facility-based cross-sectional survey. The study population consisted of adults with suspected malaria who presented to health centres in central Ethiopia. Data were collected on attitudes to HIV testing and the duration between onset of symptoms and treatment seeking for suspected malaria.

Results: Eight hundred and ten individuals provided data. Of these, 406 (50 %) perceived that HIV testing was routinely done on blood donated for malaria diagnosis, and 327 (40 %) considered that community members delayed seeking medical advice because of these concerns. Concerns about HIV testing were associated with delays in attending for malaria diagnosis and treatment, with 117 individuals (29 %) of those with concerns about covert HIV testing waiting for 4 days or more, compared to 89 (22 %) of those who did not have any such concerns (p = 0.03). One hundred and twenty nine (16 %) individuals stated that concern about HIV testing was the main reason for the delay in seeking treatment, and 46 % of these individuals presented after experiencing symptoms of malaria infection for three days or more compared to 22 % of the 681 individuals who had no such concerns (p < 0.001). Analysis stratified by health centre demonstrated that these associations were a consequence of Meki health centre (odds ratio for duration of symptoms greater than 3 days if patient has concerns about HIV testing was 8.72; 95 % confidence intervals 3.63 to 20.97).

Conclusions: In adults living in central Ethiopia, the perception that HIV testing accompanied the investigation of suspected malaria was common. This is likely to impede presentation for early medical treatment in some areas and represents a reversible risk factor that deserves further study.

Abstract  Full-text [free] access 

Editor’s notes: This study addresses a relatively under-studied issue of concerns about HIV testing among adults with malaria. Previously, the authors of this paper found that about half of guardians of children with malaria symptoms in central Ethiopia thought the children’s blood samples were tested for HIV without consent. Guardians who believed this were more likely to delay bringing children for treatment. In this paper, the authors illustrate that the same is true for adults. In a representative survey of adults presenting with malaria symptoms at five health centres, about half of participants were concerned that their blood sample was secretly tested for HIV without their consent and about one in three thought that many or almost all members of their community believed this. Concern about covert HIV testing was associated with delayed presentation for management of suspected malaria overall, although this was largely due to the issue in one specific health centre. Electricity in the home, better education and urban versus rural home were not associated with this belief, although people in rural areas were more likely to delay treatment-seeking.

Beliefs about health care are culturally specific, so the results may not be generalizable to other contexts, but the belief that blood taken at health centres is secretly tested for HIV has been found in different cultural settings. Prompt treatment for suspected malaria is key and strategies to address these concerns are necessary. Possible strategies include investigations to clarify whether, in fact, blood is being tested for HIV without fully informed consent, and improved confidentiality of blood test results. 

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We need to listen to people living with HIV who refuse or delay starting ART: lessons from Australia

On the margins of pharmaceutical citizenship: not taking HIV medication in the "treatment revolution" era.

Persson A, Newman CE, Mao L, de Wit J. Med Anthropol Q. 2016 Jan 12. doi: 10.1111/maq.12274. [Epub ahead of print]

With the expanding pharmaceuticalization of public health, anthropologists have begun to examine how biomedicine's promissory discourses of normalization and demarginalization give rise to new practices of and criteria for citizenship. Much of this work focuses on the biomedicine-citizenship nexus in less-developed, resource-poor contexts. But how do we understand this relationship in resource-rich settings where medicines are readily available, often affordable, and a highly commonplace response to illness? In particular, what does it mean to not use pharmaceuticals for a treatable infectious disease in this context? We are interested in these questions in relation to the recent push for early and universal treatment for HIV infection in Australia for the twin purposes of individual and community health. Drawing on Ecks's concept of pharmaceutical citizenship, we examine the implications for citizenship among people with HIV who refuse or delay recommended medication. We find that moral and normative expectations emerging in the new HIV "treatment revolution" have the capacity to both demarginalize and marginalize people with HIV.


Editor’s notes: Following the release of WHO ‘Guidelines on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV’ at the end of September 2015, there has been growing momentum to roll out treatment to all people living with HIV. This important paper highlights an important issue affecting the provision of antiretroviral therapy (ART) to all people living with HIV, regardless of CD4 cell count. Not everyone wants to start treatment promptly. The authors interviewed 27 people in Australia who had declined to start ART. Ten of these people had never used ART, while the remaining 17 had started and then stopped therapy. There were many reasons why these people chose not to start or continue with ART. These reasons included fears over side-effects and the commitment to life-long therapy. Some doubted that they needed ‘treatment’ because they were well. A few were sceptical about the efficacy of the drugs.  These reasons for delaying treatment are being echoed in research from other parts of the world. The authors of this paper note that if treatment is promoted as ‘normal’, then people who decline ART risk marginalisation for ‘not doing the right thing’. This, they suggest, is particularly the case in places where ART are readily and freely available, like Australia. The authors conclude by highlighting the importance of listening to people who do not want to start ART, and understanding their reservations, while ensuring they do not become marginalised.

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Time to consider older adults on ART

Risk factors for mortality during antiretroviral therapy in older populations in resource-limited settings.

O'Brien D, Spelman T, Greig J, McMahon J, Ssonko C, Casas E, Mesic A, Du Cros P, Ford N. J Int AIDS Soc. 2016 Jan 14;19(1):20665. doi: 10.7448/IAS.19.1.20665. eCollection 2016.

Introduction: An increasing proportion of adult patients initiating antiretroviral therapy (ART) in resource-limited settings are aged >50 years. Older populations on ART appear to have heightened risk of death, but little is known about factors influencing mortality in this population.

Methods: We performed a retrospective observational multisite cohort study including all adult patients (≥15 years) initiating ART between 2003 and 2013 in programmes supported by Medecins Sans Frontieres across 12 countries in Asia, Africa and Europe. Patients were stratified into two age groups, >50 years and 15 to 50 years. A Cox proportional hazards model was used to explore factors associated with mortality.

Results: The study included 41 088 patients: 2591 (6.3%) were aged >50 years and 38 497 (93.7%) were aged 15 to 50 years. The mortality rate was significantly higher in the age group >50 years [367 (14.2%) deaths; mortality rate 7.67 deaths per 100 person-years (95% confidence interval, CI: 6.93 to 8.50)] compared to the age group 15 to 50 years [3788 (9.8%) deaths; mortality rate 4.18 deaths per 100 person-years (95% CI: 4.05 to 4.31)], p<0.0001. Higher CD4 levels at baseline were associated with significantly reduced mortality rates in the 15 to 50 age group but this association was not seen in the >50 age group. WHO Stage 4 conditions were more strongly associated with increased mortality rates in the 15 to 50 age group compared to populations >50 years. WHO Stage 3 conditions were associated with an increased mortality rate in the 15 to 50 age group but not in the >50 age group. Programme region did not affect mortality rates in the >50 age group; however being in an Asian programme was associated with a 36% reduced mortality rate in populations aged 15 to 50 years compared to being in an African programme. There was a higher overall incidence of Stage 3 WHO conditions in people >50 years (12.8/100 person-years) compared to those 15 to 50 years (8.1/100 person-years) (p<0.01). The rate of Stage 4 WHO conditions was similar (5.8/100 versus 6.1/100 respectively, p=0.52). Mortality rates on ART associated with the majority of specific WHO conditions were similar between the 15 to 50 and >50 age groups.

Conclusions: Older patients on ART in resource-limited settings have increased mortality rates, but compared to younger populations this appears to be less influenced by baseline CD4 count and WHO clinical stage. HIV treatment programmes in resource-limited settings need to consider risk factors associated with mortality on ART in older populations, which may differ to those related to younger adults.

Abstract Full-text [free] access

Editor’s notes: This article reports on a retrospective multisite cohort analysis that examined mortality rates and factors associated with mortality on ART for older individuals (> 50 years). The authors found that mortality was nearly two times greater in populations aged >50 years compared with people aged 15 to 50 years.

Contrary to other recent research, they did not find that the effect of age on mortality was stronger at lower CD4 cell counts. However, the analysis used pooled data from very diverse settings, with the great majority of patients (77%) from Asian programmes, and only 22% from Africa (and from nine different countries). This makes it difficult to tease out risk factors for mortality.

Interestingly they found that being in an Asian programme was associated with a 36% reduction in mortality (aHR: 0.64, 95%CI 0.59-0.69) among populations between 15 and 50 years compared to being in an African programme. The authors suggest that this might be due to a lower incidence of co-morbidities including opportunistic infections in Asian populations below 50 years compared to African populations.

As little is known about what it is like living with HIV for older people in resource-limited settings, the authors conclude with suggesting further social science research to address this issue. 

Africa, Asia, Europe
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The power of PEPFAR programmes: estimates of infections averted and life years gained in Africa

Estimating the impact of the US President's Emergency Plan for AIDS Relief on HIV treatment and prevention programmes in Africa.

Heaton LM, Bouey PD, Fu J, Stover J, Fowler TB, Lyerla R, Mahy M. Sex Transm Infect. 2015 Dec;91(8):615-20. doi: 10.1136/sextrans-2014-051991. Epub 2015 Jun 8.

Background: Since 2004, the US President's Emergency Plan for AIDS Relief (PEPFAR) has supported the tremendous scale-up of HIV prevention, care and treatment services, primarily in sub-Saharan Africa. We evaluate the impact of antiretroviral treatment (ART), prevention of mother-to-child transmission (PMTCT) and voluntary medical male circumcision (VMMC) programmes on survival, mortality, new infections and the number of orphans from 2004 to 2013 in 16 PEPFAR countries in Africa.

Methods: PEPFAR indicators tracking the number of persons receiving ART for their own health, ART regimens for PMTCT and biomedical prevention of HIV through VMMC were collected across 16 PEPFAR countries. To estimate the impact of PEPFAR programmes for ART, PMTCT and VMMC, we compared the current scenario of PEPFAR-supported interventions to a counterfactual scenario without PEPFAR, and assessed the number of life years gained (LYG), number of orphans averted and HIV infections averted. Mathematical modelling was conducted using the SPECTRUM modelling suite V.5.03.

Results: From 2004 to 2013, PEPFAR programmes provided support for a cumulative number of     24 565 127 adults and children on ART, 4 154 878 medical male circumcisions, and ART for PMTCT among 4 154 478 pregnant women in 16 PEPFAR countries. Based on findings from the model, these efforts have helped avert 2.9 million HIV infections in the same period. During 2004-2013, PEPFAR ART programmes alone helped avert almost 9 million orphans in 16 PEPFAR countries and resulted in 11.6 million LYG.

Conclusions: Modelling results suggest that the rapid scale-up of PEPFAR-funded ART, PMTCT and VMMC programmes in Africa during 2004-2013 led to substantially fewer new HIV infections and orphaned children during that time and longer lives among people living with HIV. Our estimates do not account for the impact of the PEPFAR-funded non-biomedical interventions such as behavioural and structural interventions included in the comprehensive HIV prevention, care and treatment strategy used by PEPFAR countries. Therefore, the number of HIV infections and orphans averted and LYG may be underestimated by these models.

Abstract access

Editor’s notes: The President’s Emergency Plan for AIDS Relief (PEPFAR) was initiated in 2004 with $42 billion spent up until the end of 2013. Despite limitations in monitoring the overall contribution of PEPFAR to individual programmes, this article attempts to provide an overview of PEPFAR support for ART, prevention of mother to child transmission and voluntary medical male circumcision (VMMC) programmes using the 2014 version of Spectrum Software model. The Spectrum modules used included DemProj, AIDS Impact Model (AIM) and Goals, which interact to model the impact and future course of the HIV epidemic at the population level.  An estimate of PEPFAR’s contribution was obtained by subtracting it from the total for the national programme statistics reported by UNAIDS on ART, PMTCT and VMMC.

The baseline scenario of PEPFAR-supported programmes in 2013 was compared to a counterfactual scenario, which subtracts the direct contribution of PEPFAR. The results estimate that the combined programmes have averted 2.7 million infections in Africa, with over 11.5 million life years gained and the aversion of almost nine million orphans. Other key population programmes that the funding supported including gender equity and health strengthening were not evaluated and therefore, the estimate for impact may be conservative. A limitation of the analysis is that it is unable to predict the national response without PEPFAR and the impact of ART calculated by the model is sensitive to the distribution of new ART patients by CD4 count at the initiation of treatment. In addition, few countries have sufficient death registration systems to validate mortality estimates, which may result in the accomplishments of PEPFAR’s impact being overestimated. However, with the operation of PEPFAR in a larger context of partnership consortiums, an improvement in evaluation methods will be necessary. 

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When are children ‘mature enough’ to know their HIV status? Caregivers’ and children’s perspectives on discussing HIV and ART at home in Jinja District, Uganda

Tensions in communication between children on antiretroviral therapy and their caregivers: a qualitative study in Jinja district, Uganda.

Kajubi P, Whyte SR, Kyaddondo D, Katahoire AR. PLoS One. 2016 Jan 19;11(1):e0147119. doi: 10.1371/journal.pone.0147119. eCollection 2016.

Introduction: HIV treatment and disclosure guidelines emphasize the importance of communicating diagnosis and treatment to infected children in ways that are appropriate to children's developmental stage and age. Minimal attention, however, has been given to communication challenges confronted by HIV-infected children and their caregivers. This study examined the tensions between children and their caregivers arising from differing perspectives regarding when and what to communicate about antiretroviral therapy (ART).

Methods: This qualitative study was conducted between November 2011 and December 2012 and involved 29 HIV-infected children aged 8-17 years on ART and their caregivers. Data were collected through observations and in-depth interviews, which took place in homes, treatment centres and post-test clubs. Children and caregivers were sampled from among the 394 HIV-infected children and (their) 393 caregivers who participated in the cross-sectional survey that preceded the qualitative study. ATLAS.ti. Version 7 was used in the management of the qualitative data and in the coding of the emerging themes. The data were then analyzed using content thematic analysis.

Results: While the children felt that they were mature enough to know what they were suffering and what the medications were for, the caregivers wanted to delay discussions relating to the children's HIV diagnosis and medication until they felt that the children were mature enough to deal with the information and keep it a secret and this caused a lot of tension. The children employed different tactics including refusing to take the medicines, to find out what they were suffering from and what the medications were for. Children also had their own ideas about when, where and with whom to discuss their HIV condition, ideas that did not necessarily coincide with those of their caregivers, resulting in tensions.

Conclusions: Guidelines should take into consideration differing perceptions of maturity when recommending ages at which caregivers should communicate with their children about diagnosis and ART. Health care providers should also encourage caregivers to recognize and respect children's efforts to learn about and manage their condition. Children's questions and expressions of feelings should be treated as openings for communication on these issues.

Abstract  Full-text [free] access

Editor’s notes: Caregivers’ ideas of when children are ready to know about their HIV status can often differ from children’s own views. This qualitative study explored children’s and caregivers’ views about HIV status disclosure in the Jinja District in eastern Uganda. A purposive sample of 29 children living with HIV (aged 8-17) was recruited. Participants who were aware of their own HIV status were interviewed (21/29). Great care was taken to avoid accidental disclosure during the study. Caregivers’ views on children’s maturity were not linked to a specific age. Caregivers considered children ‘mature enough’ to know about their status when they believed that children could: 1) understand the implications of their diagnosis; 2) keep secrets 3) take responsibility for their antiretroviral therapy (ART) and 4) begin sexual activity. Some carers thought their child was not mature, but the child saw themselves as being mature enough. Children wanted to know what health condition they had and why they were taking treatment. Children perceived caregivers’ reticence as betrayal. Children deployed strategies such as refusing to take ART or go to the clinic unless they were told what the medication was for. However, children who had been told their status became responsible for their own ART adherence. Older children who were independent often did not discuss HIV or ART with anyone in the household. This could mean they lacked support with adherence issues they might have. The study offers an important and detailed account of the complicated question of disclosure and of communication about HIV and ART in the home. The authors advance our understanding of the importance of age in this process. They highlight the strengths and weaknesses of different approaches to managing adherence in children. The study illustrates the need to improve and extend communication about HIV within and beyond the clinic. The authors highlight that discussions about HIV and ART should be revisited at different points in time to ensure comprehension. This useful paper adds to research exploring children’s agency and resilience strategies in the context of silence and stigma about their HIV status. 

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