Articles tagged as "HIV testing and treatment"

Longitudinal HIV viral load measures give insights into disease burden and transmission risk in the USA

Durable viral suppression and transmission risk potential among persons with diagnosed HIV infection: United States, 2012-2013.

Crepaz N, Tang T, Marks G, Mugavero MJ, Espinoza L, Hall HI. Clin Infect Dis. 2016 Oct 1;63(7):976-83. doi: 10.1093/cid/ciw418. Epub 2016 Jun 29.

Background: We examined durable viral suppression, cumulative viral load (VL) burden, and transmission risk potential among human immunodeficiency virus (HIV)-diagnosed persons in care.

Methods: Using data from the National HIV Surveillance System from 17 jurisdictions with complete reporting of VL test results, we determined the percentage of persons in HIV care who achieved durable viral suppression (all VL results <200 copies/mL) and examined viremia copy-years and time spent above VL levels that increase the risk of HIV transmission during 2012-2013.

Results: Of 265 264 persons in HIV care in 2011, 238 641 had at least 2 VLs in 2012-2013. The median number of VLs per individual during the 2-year period was 5. Approximately 62% had durable viral suppression. The remaining 38% had high VL burden (geometric mean of viremia copy-years, 7261) and spent an average of 438 days, 316 days, and 215 days (60%, 43.2%, and 29.5% of the 2-year period) above 200, 1500, and 10 000 copies/mL. Women, blacks/African Americans, Hispanics/Latinos, persons with HIV infection attributed to transmission other than male-to-male sexual contact, younger age groups, and persons with gaps in care had higher viral burden and transmission risk potential.

Conclusions: Two-thirds of persons in HIV care had durable viral suppression during a 2-year period. One-third had high VL burden and spent substantial time above VL levels with increased risk of onward transmission. More intervention efforts are needed to improve retention in care and medication adherence so that more persons in HIV care achieve durable viral suppression.

Abstract access  

Editor’s notes: Virologic suppression is the ultimate goal of HIV care. It determines health outcomes and transmission risk. Most analyses assess viral suppression by considering a single viral load measure. However, adherence to antiretroviral therapy and engagement in HIV care are often not straightforward, but rather complex and dynamic. People living with HIV may transition in and out of treatment and care throughout their lifetime. Therefore, a single undetectable viral load may not equate to true virologic suppression in an individual, but rather only a snapshot. This has the potential for an inaccurate picture of HIV burden and transmission risk in a population.

Within this study, researchers used the longitudinal measures of durable viral suppression, viraemia copy years and time without viral load suppression to assess disease burden and HIV transmission risk in the United States of America. The analysis involved people ages 13 years or older diagnosed with HIV before 2011 and in care in one of 17 jurisdictions that reported complete CD4 and viral load data to the Centers for Disease Control and Prevention’s National HIV Surveillance System. Everyone had at least one viral load test in 2011 and at least two between 2012-2013, and all were alive at the end of 2013.

Of the 251 649 persons included, two thirds had durable viral suppression with all viral load values being <200 copies/mL over the two-year period. Of note, during the same time period an additional 20% (total 83%) of the cohort had a suppressed viral load on their latest test. This would have potentially underestimated disease burden if analysed in isolation. The remaining one-third, without durable viral suppression, had high plasma burden and spent substantial time without virologic suppression, increasing the risk of HIV transmission.  As would be expected, the percentages of persons with durable viral suppression were lower among people with gaps in care. Disparities in disease burden and transmission risk potential were seen in several other subgroups.

The use of longitudinal measures broadens insight into disease burden and transmission risk in this population. Of further interest would have been people that had no evidence of being in care in 2011 but had an unsuppressed viral load between 2012-13, thus contributing to the population disease burden. These people were unfortunately not included in the analyses but may increase overall population transmission risk over the two years.

The findings underscore the recognised need for focused care and treatment efforts to address these disparities in virologic suppression and improve retention in care in the United States of America. The study also encourages the use of longitudinal markers in informing public health planning and resource allocation.

Northern America
United States of America
  • share
0 comments.

Community ART support groups: a partial solution for improving retention in care?

A decade of antiretroviral therapy scale-up in Mozambique: evaluation of outcome trends and new models of service delivery among more than 300 000 patients enrolled during 2004-2013.

Auld AF, Shiraishi RW, Couto A, Mbofana F, Colborn K, Alfredo C, Ellerbrock TV, Xavier C, Jobarteh K. J Acquir Immune Defic Syndr. 2016 Oct 1;73(2):e11-22. doi: 10.1097/QAI.0000000000001137.

Background: During 2004-2013 in Mozambique, 455 600 HIV-positive adults (≥15 years old) initiated antiretroviral therapy (ART). We evaluated trends in patient characteristics and outcomes during 2004-2013, outcomes of universal treatment for pregnant women (Option B+) implemented since 2013, and effect on outcomes of distributing ART to stable patients through Community ART Support Groups (CASG) since 2010.

Methods: Data for 306 335 adults starting ART during 2004-2013 at 170 ART facilities were analyzed. Mortality and loss to follow-up (LTFU) were estimated using competing risks models. Outcome determinants were estimated using proportional hazards models, including CASG participation as a time-varying covariate.

Results: Compared with ART enrollees in 2004, enrollees in 2013 were more commonly female (55% vs. 73%), more commonly pregnant if female (<1% vs. 30%), and had a higher median baseline CD4 count (139 vs. 235/µL). During 2004-2013, observed 6-month mortality declined from 7% to 2% but LTFU increased from 24% to 30%. Pregnant women starting ART with CD4 count >350/µL and WHO stage I/II under Option B+ guidelines in 2013 had low 6-month mortality (0.1%) but high 6-month LTFU (38%). During 2010-2013, 6766 patients joined CASGs. In multivariable analysis, compared with nonparticipation in CASG, CASG participation was associated with 35% lower LTFU but similar mortality.

Conclusions: Initiation of ART at earlier disease stages in later calendar years might explain observed declines in mortality. Retention interventions are needed to address trends of increasing LTFU overall and the high LTFU among Option B+ pregnant women specifically. Further expansion of CASG could help reduce LTFU.

Abstract access  

Editor’s notes: The UNAIDS 90–90–90 treatment target for 2020 calls for 90% of all people with HIV to be diagnosed, 90% of people with HIV diagnosed to receive ART and 90% of people on ART to have a suppressed viral load. To maximise the impact of ART, people living with HIV should be diagnosed early, initiated on ART and retained in ART care.  Engagement along the complete treatment cascade will determine the long-term success of the global response to HIV. 

This manuscript describes the trends in patient characteristics and outcomes over the first decade of scale-up of ART in Mozambique (2004-2013). During this period close to half a million people living with HIV were initiated on ART; six-month mortality declined from 7% to 2% but six-month loss to follow-up (LTFU) increased from 24% to 30%. The authors found that later calendar year of ART was associated with higher risk of LTFU; an increase in “silent” transfers (undocumented transfer between health facilities) might have contributed to this. There was an increasing female-to-male ratio over calendar period during the study, most likely due to scale-up of HIV testing during antenatal care and (since 2013) implementation of Option B+ (initiation of lifelong ART for all pregnant women). The authors conclude that increased enrolment among men is necessary to reduce the disproportionally high HIV-associated morbidity and mortality among men.  

Interestingly, this is the first study to report on nationwide outcomes of community ART support groups (CASG), and to quantify the effect of CASG on LTFU. Consistent with the recent systematic review by Nachega and colleagues (included in this issue of HIV This Month), the authors found no difference in mortality between patients who received their ART through CASG and patients who received their ART from facilities. Also consistent with this systematic review, CASG participation was associated with 35% lower LTFU rates. The authors therefore suggest ART distribution through CASG as a potential partial solution. Possible reasons for lower LTFU rates among CASG participants include reduced patient transport cost, reduced patient time at the clinic, increased patient accountability, and improved social support. However, the authors acknowledged that people agreeing to join a CASG might be people who would in any event be retained in care. CASG participants were more commonly unemployed and uneducated than non-participants, which might indicate that CASG participation is more attractive for patients with fewer financial resources.  

Men were less likely to participate in CASGs, emphasizing again the need for male-specific programmes. The authors advocate for further research, and suggest offering male-only CASG as a possible way to improve male participation in CASG.

Africa
Mozambique
  • share
0 comments.

Social constraints on women’s access to HIV treatment cannot be ignored

'Lost to follow up': rethinking delayed and interrupted HIV treatment among married Swazi women.

Dlamini-Simelane TT, Moyer E. Health Policy Plan. 2016 Oct 13. pii: czw117. [Epub ahead of print]

Through various campaigns and strategies, more women are being tested for HIV in countries with a high prevalence of the virus. Despite the ready availability of treatment at government clinics in sub-Saharan African countries like Swaziland, women consistently report difficulty in maintaining access to treatment. Drawing on two individual case studies selected from a larger study of the so-called leaky cascade in Swaziland, we illustrate the protracted journeys married women undertake to initiate treatment. We demonstrate how women manoeuvre tactically after diagnosis, highlight factors that influence their decisions related to initiating treatment, and detail the actors involved in the decision-making process. Our research shows the persistence of structural factors that inhibit access, including economic constraints, gender inequality and patriarchal social norms. Patients referred as 'lost to follow up' are in many cases actively pursuing treatment within a context that includes the biomedical health system, but also extends well beyond it. We argue that the phrase 'lost to follow up' conceals the complex social navigation required by women to initiate and maintain access to treatment. Further, we suggest that many of the logistical challenges of monitoring and tracking people with HIV can be better addressed by taking into account the structural and social aspects of delayed treatment initiative.

Abstract access 

Editor’s notes: With new global guidelines for the treatment of HIV, in Swaziland, as elsewhere, there has been a focus on increasing access to point-of-care diagnostics. This paper uses case studies to examine the complex social and logistical factors that contribute to HIV-positive women ‘falling out’ of HIV treatment healthcare in Swaziland.  These losses are despite an enhanced logistical system. In particular, the authors argue that terms such as ‘treatment defaulters’ or ‘lost to follow up’ only define patients from the perspective of the healthcare system. Such terms, they suggest, hide the social and economic challenges that women living with HIV face in trying to start treatment. These challenges include family power structures, lack of autonomy, gender norms, and constraints on married women to access treatment.

The authors reveal that women’s decision making around initiating treatment in Swaziland involves navigating multiple social terrains. They demonstrate that when a married woman has been diagnosed with HIV in Swaziland, she is often not free to initiate treatment. Nor can she decide on her own to visit the clinic, especially if doing so requires money. Further to this they demonstrate that women’s ability to seek treatment is impacted by gender and generational power relations. Treatment access may also be affected by preserving the family honour. The husband, mother in-law and wider kinship network can constitute a ‘therapy management group’ and either accompany women to treatment or influence the routes taken. Where concerns arise for how a woman might be perceived or rejected by this group, women are at times compelled to conceal their HIV status. This might be deemed necessary to avoid dishonour for her birth family, thus ‘the therapy management group’ goes beyond providing advice and information. The group also prescribes the route a woman should follow as a good wife or daughter-in-law. The authors suggest that that labelling women who are actively seeking ways to access care as ‘lost to follow up’ ‘or ‘treatment defaulters’ obscures these challenges.

The authors conclude that married women’s decision making around HIV treatment in Swaziland is contingent upon social and economic circumstances.  Being diagnosed with HIV is not sufficient motivation to take up treatment. They argue that, in the light of this, programme implementers should focus on building women’s capacity to navigate the social constraints. This could include providing expert counsellors in each clinic to support such issues.

HIV Treatment, treatment
Africa
Swaziland
  • share
0 comments.

Evaluating strategies to improve HIV care outcomes

Evaluating strategies to improve HIV care outcomes in Kenya: a modelling study.

Olney JJ, Braitstein P, Eaton JW, Sang E, Nyambura M, Kimaiyo S, McRobie E, Hogan JW, Hallett TB. Lancet HIV. 2016 Dec;3(12):e592-e600. pii: S2352-3018(16)30120-5. doi: 10.1016/S2352-3018(16)30120-5. Epub 2016 Oct 19.

Background: With expanded access to antiretroviral therapy (ART) in sub-Saharan Africa, HIV mortality has decreased, yet life-years are still lost to AIDS. Strengthening of treatment programmes is a priority. We examined the state of an HIV care programme in Kenya and assessed interventions to improve the impact of ART programmes on population health.

Methods: We created an individual-based mathematical model to describe the HIV epidemic and the experiences of care among adults infected with HIV in Kenya. We calibrated the model to a longitudinal dataset from the Academic Model Providing Access To Healthcare (known as AMPATH) programme describing the routes into care, losses from care, and clinical outcomes. We simulated the cost and effect of interventions at different stages of HIV care, including improvements to diagnosis, linkage to care, retention and adherence of ART, immediate ART eligibility, and a universal test-and-treat strategy.

Findings: We estimate that, of people dying from AIDS between 2010 and 2030, most will have initiated treatment (61%), but many will never have been diagnosed (25%) or will have been diagnosed but never started ART (14%). Many interventions targeting a single stage of the health-care cascade were likely to be cost-effective, but any individual intervention averted only a small percentage of deaths because the effect is attenuated by other weaknesses in care. However, a combination of five interventions (including improved linkage, point-of-care CD4 testing, voluntary counselling and testing with point-of-care CD4, and outreach to improve retention in pre-ART care and on-ART) would have a much larger impact, averting 1.10 million disability-adjusted life-years (DALYs) and 25% of expected new infections and would probably be cost-effective (US$571 per DALY averted). This strategy would improve health more efficiently than a universal test-and-treat intervention if there were no accompanying improvements to care ($1760 per DALY averted).

Interpretation: When resources are limited, combinations of interventions to improve care should be prioritised over high-cost strategies such as universal test-and-treat strategy, especially if this is not accompanied by improvements to the care cascade. International guidance on ART should reflect alternative routes to programme strengthening and encourage country programmes to evaluate the costs and population-health impact in addition to the clinical benefits of immediate initiation.

Abstract  Full-text (free) access

Editor’s notes: Antiretroviral therapy has substantially reduced HIV-associated morbidity and mortality. However, maintaining a strong care cascade is challenging. A mathematical model for HIV transmission and care cascade was used to quantify the previous experience of people dying from HIV in a setting with an established antiretroviral therapy programme. The model was also used to simulate the cost and effect of HIV care programmes. The model was parameterised with data from HIV care programme in western Kenya supported by the Academic Model Providing Access To Healthcare. The model was analysed to assess: the impact of individual HIV programmes on the care cascade and the effect on outcomes of people living with HIV. These were compared with the baseline scenario without any programme. Disability-adjusted life-years (DALYs) averted, cost of care and HIV-associated deaths were used to quantify the effects of the programmes. The authors found that, strengthening each part of the care cascade through a combination of programmes could cost-effectively improve ART programmes. This is a very interesting study which suggest the need to prioritise HIV programmes to improve care in ART programmes over high-cost strategies.

Africa
Kenya
  • share
0 comments.

Improving programmes: a thematic synthesis of qualitative studies of treatment adherence programmes

Barriers and facilitators of interventions for improving antiretroviral therapy adherence: a systematic review of global qualitative evidence.

Ma Q, Tso LS, Rich ZC, Hall BJ, Beanland R, Li H, Lackey M, Hu F, Cai W, Doherty M, Tucker JD. J Int AIDS Soc. 2016 Oct 17;19(1):21166. doi: 10.7448/IAS.19.1.21166. eCollection 2016.

Introduction: Qualitative research on antiretroviral therapy (ART) adherence interventions can provide a deeper understanding of intervention facilitators and barriers. This systematic review aims to synthesize qualitative evidence of interventions for improving ART adherence and to inform patient-centred policymaking.

Methods: We searched 19 databases to identify studies presenting primary qualitative data on the experiences, attitudes and acceptability of interventions to improve ART adherence among PLHIV and treatment providers. We used thematic synthesis to synthesize qualitative evidence and the CERQual (Confidence in the Evidence from Reviews of Qualitative Research) approach to assess the confidence of review findings.

Results: Of 2982 references identified, a total of 31 studies from 17 countries were included. Twelve studies were conducted in high-income countries, 13 in middle-income countries and six in low-income countries. Study populations focused on adults living with HIV (21 studies, n=1025), children living with HIV (two studies, n=46), adolescents living with HIV (four studies, n=70) and pregnant women living with HIV (one study, n=79). Twenty-three studies examined PLHIV perspectives and 13 studies examined healthcare provider perspectives. We identified six themes related to types of interventions, including task shifting, education, mobile phone text messaging, directly observed therapy, medical professional outreach and complex interventions. We also identified five cross-cutting themes, including strengthening social relationships, ensuring confidentiality, empowerment of PLHIV, compensation and integrating religious beliefs into interventions. Our qualitative evidence suggests that strengthening PLHIV social relationships, PLHIV empowerment and developing culturally appropriate interventions may facilitate adherence interventions. Our study indicates that potential barriers are inadequate training and compensation for lay health workers and inadvertent disclosure of serostatus by participating in the intervention.

Conclusions: Our study evaluated adherence interventions based on qualitative data from PLHIV and health providers. The study underlines the importance of incorporating social and cultural factors into the design and implementation of interventions. Further qualitative research is needed to evaluate ART adherence interventions.

Abstract  Full-text [free] access 

Editor’s notes: This is a review of studies using qualitative methods to explore the experiences of people living with HIV and healthcare providers involved in programmes to support antiretroviral treatment adherence. The thematic synthesis is presented in two ways. First, the reviewed studies are categorised by types of adherence programmes, such as task shifting, education, or directly observed therapy. Secondly, the authors present themes that are common across all reviewed studies. These include: the benefits and challenges of employing lay healthcare workers; the need to maintain confidentiality in adherence programmes; the benefits of supporting empowerment and social relationships for people living with HIV; and the need for culturally appropriate information and practice. Overall the review illustrates that adherence programmes can have more impact if they address confidentiality, strengthen social ties among people living with HIV and their communities; provide adequate compensation and training for lay healthcare workers; and sensitively reflect local social, cultural and religious norms and beliefs. 

  • share
0 comments.

Success in accelerating ART initiation in Uganda

Effects of a multicomponent intervention to streamline initiation of antiretroviral therapy in Africa: a stepped-wedge cluster-randomised trial.

Amanyire G, Semitala FC, Namusobya J, Katuramu R, Kampiire L, Wallenta J, Charlebois E, Camlin C, Kahn J, Chang W, Glidden D, Kamya M, Havlir D, Geng E. Lancet HIV. 2016 Nov;3(11):e539-e548. pii: S2352-3018(16)30090-X. doi: 10.1016/S2352-3018(16)30090-X. [Epub 2016 Aug 27]

Background: In Africa, up to 30% of HIV-infected patients who are clinically eligible for antiretroviral therapy (ART) do not start timely treatment. We assessed the effects of an intervention targeting prevalent health systems barriers to ART initiation on timing and completeness of treatment initiation.

Methods: In this stepped-wedge, non-blinded, cluster-randomised controlled trial, 20 clinics in southwestern Uganda were randomly assigned in groups of five clinics every 6 months to the intervention by a computerised random number generator. This procedure continued until all clinics had crossed over from control (standard of care) to the intervention, which consisted of opinion-leader-led training and coaching of front-line health workers, a point-of-care CD4 cell count testing platform, a revised counselling approach without mandatory multiple pre-initiation sessions, and feedback to the facilities on their ART initiation rates and how they compared with other facilities. Treatment-naive, HIV-infected adults (aged ≥18 years) who were clinically eligible for ART during the study period were included in the study population. The primary outcome was ART initiation 14 days after first clinical eligibility for ART. This study is registered with ClinicalTrials.gov, number NCT01810289.

Findings: Between April 11, 2013, and Feb 2, 2015, 12 024 eligible patients visited one of the 20 participating clinics. Median CD4 count was 310 cells per µL (IQR 179-424). 3753 of 4747 patients (weighted proportion 80%) in the intervention group had started ART by 2 weeks after eligibility compared with 2585 of 7066 patients (38%) in the control group (risk difference 41.9%, 95% CI 40.1-43.8). Vital status was ascertained in a random sample of 208 patients in the intervention group and 199 patients in the control group. Four deaths (2%) occurred in the intervention group and five (3%) occurred in the control group.

Interpretation: A multicomponent intervention targeting health-care worker behaviour increased the probability of ART initiation 14 days after eligibility. This intervention consists of widely accessible components and has been tested in a real-world setting, and is therefore well positioned for use at scale.

Abstract access  

Editor’s notes: As noted in another article in this month’s digest, early mortality remains high among people starting antiretroviral therapy (ART). People with advanced disease are at particularly high risk. Previous research has illustrated that mortality was even higher during the period between entering care and starting ART. ART start may be delayed for many reasons, some attributable to the person and others to the health system. Some of the health system delays date from practice early in ART roll-out. Great emphasis was placed on ART counselling, usually requiring people to attend several counselling sessions prior to initiating treatment, because of concerns about poor adherence. This practice has persisted despite evidence that treatment outcomes are no worse if ART is initiated rapidly with concurrent counselling rather than delaying ART initiation until after counselling has been completed.

In this study, the investigators tested a complex activity aiming to accelerate ART initiation in primary health care clinics in Uganda. This was developed based on health promotion literature, and was a combination of training led by opinion-leaders to counter the widespread belief that delays to ART initiation are not harmful. There was also a more flexible approach to ART counselling and the need for treatment supporters; introduction of point of care CD4 machines so that ART eligibility could be assessed in-session; and feedback to facilities concerning their performance compared to other clinics. The programme was successful in accelerating ART initiation. This approach holds promise as an effective method to implement change in health facilities. However, as more countries adopt the WHO guidance to offer ART regardless of CD4 count, the contribution of point of care CD4 machines in similar approaches may diminish.  This is a common challenge for generalisability from randomised trials at a time of rapid policy changes. Cost and cost-effectiveness analyses will be reported later. The study was not primarily designed to determine the effect of the activity on patient-relevant outcomes, which were measured in a small subset of people, and illustrated no difference in mortality after one year. Of note, mortality was very low in both groups (2% programme versus 3% control), which may be partly explained by the relatively high median CD4 count at enrolment, and around one-quarter of participants being pregnant women. It would be very interesting to see whether this programme has an effect on early mortality in settings and populations where early survival is less good.  

Africa
Uganda
  • share
0 comments.

High mortality persists among people presenting with advanced HIV disease

Mortality in the first 3 months on antiretroviral therapy among HIV-positive adults in low- and middle-income countries: a meta-analysis.

Brennan AT, Long L, Useem J, Garrison L, Fox MP. J Acquir Immune Defic Syndr. 2016 Sep 1;73(1):1-10. doi: 10.1097/QAI.0000000000001112.

Previous meta-analyses reported mortality estimates of 12-month post-antiretroviral therapy (ART) initiation; however, 40%-60% of deaths occur in the first 3 months on ART, a more sensitive measure of averted deaths through early ART initiation. To determine whether early mortality is dropping as treatment thresholds have increased, we reviewed studies of 3 months on ART initiation in low- to middle-income countries. Studies of 3-month mortality from January 2003 to April 2016 were searched in 5 databases. Articles were included that reported 3-month mortality from a low- to middle-income country; nontrial setting and participants were ≥15. We assessed overall mortality and stratified by year using random effects models. Among 58 included studies, although not significant, pooled estimates show a decline in mortality when comparing studies whose enrollment of patients ended before 2010 (7.0%; 95% CI: 6.0 to 8.0) with the studies during or after 2010 (4.0%; 95% CI: 3.0 to 5.0). To continue to reduce early HIV-related mortality at the population level, intensified efforts to increase demand for ART through active testing and facilitated referral should be a priority. Continued financial investments by multinational partners and the implementation of creative interventions to mitigate multidimensional complex barriers of accessing care and treatment for HIV are needed.

Abstract access  

Editor’s notes: Early mortality among people initiating antiretroviral therapy (ART) remains high, presumed to be because many people living with HIV present when already very sick with advanced HIV disease. This systematic review included 43 studies from Africa and 13 from Asia. Its main aim was to see whether the evolution of guidelines recommending ART initiation at progressively higher CD4 counts over this period had reduced early mortality (defined as death within three months of ART start) and, by implication, the proportion of people starting ART who had advanced disease. To investigate this, the authors compared studies where enrolment ended before 2010 with studies that had started later.

Overall early mortality was six percent.  Because of the large numbers lost to follow up this will be an underestimate. The authors attempted to compensate for this, and calculated an adjusted overall figure of more than 10%. There was a fall in early mortality from seven percent to four percent (unadjusted) between the early and late periods but although the trend was consistent the difference was not significant.

In only four of the 58 studies was the median CD4 count at ART initiation above 200x106/l. It seems likely that even when policies to initiate ART at high CD4 counts are adopted, additional efforts will be necessary to promote initiation of ART and retention in care for people who feel well.  This is in order to reduce the number of people starting ART with advanced disease and consequently at very high risk of early death.   

Africa, Asia, Latin America
  • share
0 comments.

Weekends off ART: a strategy to maintain adherence in children and adolescents?

Weekends-off efavirenz-based antiretroviral therapy in HIV-infected children, adolescents, and young adults (BREATHER): a randomised, open-label, non-inferiority, phase 2/3 trial.

The BREATHER (PENTA 16) Trial Group. Lancet HIV. 2016 Sep;3(9):e421-30. doi: 10.1016/S2352-3018(16)30054-6. Epub 2016 Jun 20.

Background: For HIV-1-infected young people facing lifelong antiretroviral therapy (ART), short cycle therapy with long-acting drugs offers potential for drug-free weekends, less toxicity, and better quality-of-life. We aimed to compare short cycle therapy (5 days on, 2 days off ART) versus continuous therapy (continuous ART).

Methods: In this open-label, non-inferiority trial (BREATHER), eligible participants were aged 8-24 years, were stable on first-line efavirenz with two nucleoside reverse transcriptase inhibitors, and had HIV-1 RNA viral load less than 50 copies per mL for 12 months or longer. Patients were randomly assigned (1:1) to remain on continuous therapy or change to short cycle therapy according to a computer-generated randomisation list, with permuted blocks of varying size, stratified by age and African versus non-African sites; the list was prepared by the trial statistician and randomisation was done via a web service accessed by site clinician or one of the three coordinating trials units. The primary outcome was the proportion of participants with confirmed viral load 50 copies per mL or higher at any time up to the 48 week assessment, estimated with the Kaplan-Meier method. The trial was powered to exclude a non-inferiority margin of 12%. Analyses were intention to treat. The trial was registered with EudraCT, number 2009-012947-40, ISRCTN, number 97755073, and CTA, number 27505/0005/001-0001.

Findings: Between April 1, 2011, and June 28, 2013, 199 participants from 11 countries worldwide were randomly assigned, 99 to the short cycle therapy and 100 to continuous therapy, and were followed up until the last patient reached 48 weeks. 105 (53%) were men, median age was 14 years (IQR 12-18), and median CD4 cell count was 735 cells per µL (IQR 576-968). Six percent (6%) patients assigned to the short cycle therapy versus seven percent (7%) assigned to continuous therapy had confirmed viral load 50 copies per mL or higher (difference -1.2%, 90% CI -7.3 to 4.9, non-inferiority shown). 13 grade 3 or 4 events occurred in the short cycle therapy group and 14 in the continuous therapy group (p=0.89). Two ART-related adverse events (one gynaecomastia and one spontaneous abortion) occurred in the short cycle therapy group compared with 14 (p=0.02) in the continuous therapy group (five lipodystrophy, two gynaecomastia, one suicidal ideation, one dizziness, one headache and syncope, one spontaneous abortion, one neutropenia, and two raised transaminases).

Interpretation: Non-inferiority of maintaining virological suppression in children, adolescents, and young adults was shown for short cycle therapy versus continuous therapy at 48 weeks, with similar resistance and a better safety profile. This short cycle therapy strategy is a viable option for adherent HIV-infected young people who are stable on efavirenz-based ART.

Abstract  Full-text [free] access 

Editor’s notes: Increasing number of children born with HIV infection, who would otherwise have died in infancy, are now reaching adolescence because of the scale-up of antiretroviral therapy (ART). Adherence to treatment for chronic illnesses often drops as children approach adolescence, and unfortunately HIV is no exception.  

BREATHER is an open-label, non-inferiority trial comparing continuous daily ART (CT) with short cycle treatment (SCT) enabling two days off treatment every week. The participants were aged 8 to 24 years and had to have been virally suppressed for at least one year prior to enrolment on an ART regimen containing efavirenz. At 48 weeks, 6.1% of children in the SCT arm versus 7.3% in the CT arm had virologic rebound (defined as an HIV viral load > 50 copies/ml), demonstrating that SCT is non-inferior to CT. There was no statistical difference between arms in the proportion who developed major resistance mutations or in proportion of adverse events.

This is the first trial to demonstrate that controlled interruption appears to be safe in terms of maintaining viral suppression and lack of emergence of drug resistance mutations. Notably, the trial was conducted in geographically diverse settings (11 countries) and achieved an impressive retention rate with only one participant being lost to follow-up. In addition, the strategy was highly acceptable to participants, particularly as it provided a legitimate way of missing doses. Children are expected to take ART for 20 years longer on average than adults and strategies that enable time off ART may be an effective way to reduce treatment fatigue. In addition, reduced ART usage may provide potential cost savings. 

A concern, however, is that such a strategy may give out the detrimental message that missing doses is acceptable and may not affect the viral load. Therefore, appropriate counselling is important to ensure that people understand that there is a maximum break in treatment of two designated days per week. It is also important to note that the findings of this study are only generalisable to people who are stable on ART, who have not experienced treatment failure and who are taking efavirenz-based regimens. The trial was carried out with intensive viral load monitoring and further research is required to work out how such a strategy could be safely implemented in settings where routine viral load monitoring may not be available.

Viral suppression is the ultimate goal to improve health outcomes and reduce HIV transmission. Consistent adherence to ART is critical to ensure sustained virologic suppression. Children and adolescents face multiple challenges to adhere to treatment and a number of different approaches to address this are required- this trial now provides an innovative and promising option to offer to children.

  • share
0 comments.

Improving retention in HIV care

Barriers and facilitators to interventions improving retention in HIV care: a qualitative evidence meta-synthesis.

Hall BJ, Sou KL, Beanland R, Lacky M, Tso LS, Ma Q, Doherty M, Tucker JD. AIDS Behav. 2016 Aug 31. [Epub ahead of print]

Retention in HIV care is vital to the HIV care continuum. The current review aimed to synthesize qualitative research to identify facilitators and barriers to HIV retention in care interventions. A qualitative evidence meta-synthesis utilizing thematic analysis. Prospective review registration was made in PROSPERO and review procedures adhered to PRISMA guidelines. Nineteen databases were searched to identify qualitative research conducted with individuals living with HIV and their caregivers. Quality assessment was conducted using CASP and the certainty of the evidence was evaluated using CERQual. A total of 4419 citations were evaluated and 11 were included in the final meta-synthesis. Two studies were from high-income countries, 3 from middle-income countries, and 6 from low-income countries. A total of eight themes were identified as facilitators or barriers for retention in HIV care intervention: (1) stigma and discrimination, (2) fear of HIV status disclosure, (3) task shifting to lay health workers, (4) human resource and institutional challenges, (5) mobile health (mHealth), (6) family and friend support, (7) intensive case management, and, (8) relationships with caregivers. The current review suggests that task shifting interventions with lay health workers were feasible and acceptable. mHealth interventions and stigma reduction interventions appear to be promising interventions aimed at improving retention in HIV care. Future studies should focus on improving the evidence base for these interventions. Additional research is needed among women and adolescents who were under-represented in retention interventions.

Abstract access 

Editor’s notes: Retention in HIV care is defined as the continued engagement in health services from enrolment in care to discharge or death of an individual living with HIV. There is strong evidence for the clinical and public health benefits of early antiretroviral therapy initiation. Individuals retained in care have lower mortality and a higher likelihood of viral suppression. Universal test and treat strategies are dependent on successful retention in HIV care.

A qualitative evidence meta-synthesis utilising thematic analysis was conducted. Some 11 studies were ultimately included in the review. Task shifting to non-specialist community caregivers was the most common activity identified in the review. Other programmes included home-based care, case management, primary HIV medical care, counselling, and mHealth.

The findings of the meta-synthesis highlight eight themes that were identified as facilitators or barriers for retention in HIV care programmes. This offers important insights for improving retention in care. However, more research is necessary to understand the experience of important sub populations including pregnant women, children and adolescents and key populations including gay men and other men who have sex with men.  The authors also emphasise the need for studies to provide particular emphasis on the perspectives of individuals living with HIV and providers involved in programme delivery. This, they argue, would greatly enhance subsequent implementation and development of tailored programmes to retain individuals living with HIV in care.

Africa, Northern America
  • share
0 comments.

She looks healthy so is she dangerous to me? Unintended consequences of HIV treatment through the eyes of men in the community

They are looking just the same: antiretroviral treatment as social danger in rural Malawi.

Kaler A, Angotti N, Ramaiya A. Soc Sci Med. 2016 Oct;167:71-8. doi: 10.1016/j.socscimed.2016.08. 023. Epub 2016 Aug 18.

Research on the social impact of ART pivots on questions of individual adherence and community acceptability of treatment programmes. In this paper we examine unexpected and unintended consequences of the scale-up of treatment in rural Malawi, using a unique dataset of more than 150 observational journals from three sites, spanning 2010 to 2013, focusing on men's everyday conversations. Through thematic content analysis, we explore the emerging perception that the widespread availability of ART constitutes a form of social danger, as treatment makes it difficult to tell who does or does not have AIDS. This ambiguity introduced through ART is interpreted as putting individuals at risk, because it is no longer possible to tell who might be infected - indeed, the sick now look healthier and "plumper" than the well. This ambivalence over the social impact of ART co-exists with individual demand for and appreciation of the benefits of treatment.

Abstract access  

Editor’s notes: Widespread uptake of lifelong antiretroviral therapy means that our focus on its impact on communities should no longer be on its novelty but its consequences. This is a really interesting qualitative paper which reflects on how men in a rural community in Malawi consider the social dangers that women who are on HIV treatment, specifically, pose to men. Through the content analysis of journal entries, which captured men’s informal conversations, the researchers draw out this sub group’s ambivalence towards antiretroviral therapy. Women who have HIV can become appealing sexual partners through projecting a healthy attractiveness. Thus treatment is portrayed as disruptive by putting men, attracted to plump/ healthy women, at risk. It is revealing that two of the key tenets of current prevention policy are relatively silent within these findings. Neither the message of the prevention benefits of treatment, in which people successfully adhering to treatment pose a minimal transmission risk, nor the message that sex should be protected, because anyone’s status should be considered unknown, appears to have a significant influence on either discourse or practice. By paying attention to the ‘hum’ and ‘chatter’ of everyday life we can learn about how treatment opportunities are interpreted. We can also gain insights into how they are understood in accordance with concerns around sexual opportunities and sexual appeal. These may change but they continue to be heavily shaped by gender.  

Africa
Malawi
  • share
0 comments.