Articles tagged as "Asia"

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.

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Poor virologic outcomes persist among children on ART

Suboptimal viral suppression rates among HIV-infected children in low- and middle-income countries: a meta-analysis.

Boerma RS, Boender TS, Bussink AP, Calis JC, Bertagnolio S, Rinke de Wit TF, Boele van Hensbroek M, Sigaloff KC. Clin Infect Dis. 2016 Sep 22. pii: ciw645. [Epub ahead of print]

Background: The 90-90-90 goals aim to achieve viral suppression in 90% of all HIV-infected people on antiretroviral treatment (ART), which is especially challenging in children. Global estimates of viral suppression among children in low- and middle-income countries (LMIC) are lacking. This study summarizes viral suppression rates in children on first-line ART in LMIC since the year 2000.

Methods: We searched for randomized controlled trials and observational studies and analyzed viral suppression rates among children started on ART during three time periods, based on major World Health Organization (WHO) guideline changes: early (2000-2005), intermediate (2006-2009), and current (2010 and later), using random effects meta-analysis.

Results: Seventy-two studies, reporting on 51,347 children and adolescents (<18 years), were included. After 12 months on first-line ART, viral suppression was achieved by 64.7% (95%CI 57.5-71.8) in the early, 74.2% (95%CI 70.2-78.2) in the intermediate, and 72.7% (95% 62.6-82.8) in the current time period. Rates were similar after 6 and 24 months of ART. Using an intention-to-treat analysis, 42.7% (95%CI 33.7-51.7) in the early, 45.7% (95%CI 33.2-58.3) in the intermediate, and 62.5% (95%CI 53.3-72.6) in the current period were suppressed. Long-term follow-up data were scarce.

Conclusion: Viral suppression rates among children on ART in LMIC were low and were considerably poorer than those previously found in adults in LMIC and children in high-income countries. Little progress has been made in improving viral suppression rates over the past years. Without increased efforts to improve pediatric HIV treatment, the 90-90-90 targets for children in LMIC will not be reached.

Abstract access  

Editor’s notes: The authors have undertaken one of the largest meta-analyses to date of viral suppression rates among children and adolescents on first-line ART in low- and middle-income countries (LMIC). The same research group had previously conducted a meta-analysis among adults in LMIC using the same methodology. In this study, they found that viral suppression rates in children in LMIC are well below those previously found in adults in LMIC. The authors had planned to analyse viral suppression rates up to five years after initiation of first-line ART but found very few data on virologic outcomes after more than two years of follow-up. 

The paucity of data on long-term outcomes in children highlights that children have been left behind compared to adults with respect to effective ART delivery. Systems to improve retention in care and adherence to treatment for children are urgently needed. 

HIV Treatment
Africa, Asia, Latin America
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Street children are vulnerable to HIV in Tehran, Iran

Prevalence of HIV, HBV and HCV among street and labour children in Tehran, Iran.

Foroughi M, Moayedi-Nia S, Shoghli A, Bayanolhagh S, Sedaghat A, Mohajeri M, Mousavinasab SN, Mohraz M. Sex Transm Infect. 2016 Sep 6. pii: sextrans-2016-052557. doi: 10.1136/sextrans-2016-052557. [Epub ahead of print]

Objectives: The existence of street and working children in Iran is undeniable. The precarious conditions of these children (including disrupted family, poverty, high prevalence of crime among relatives, family members and peers) cause social harm and high-risk behaviours, including drug addiction, selling sex or having sex with adolescents or peers. Here we explore the HIV, hepatitis B and hepatitis C status of street and working children in Tehran.

Methods: One thousand street and labour children, aged 10-18 years, were recruited by using the time-location sampling method, and semistructured questionnaires were used to find demographic information and information on HIV/AIDS-related high-risk sexual behaviours. Blood samples were collected from children, with use of the dried blood sampling method.

Results: 4.5% of children were HIV infected, 1.7% were infected with hepatitis B virus and 2.6% were infected with hepatitis C virus (HCV). Having parents who used drug, infected with HCV and having experience in trading sex significantly increased the likelihood of getting HIV among the street children of Tehran.

Conclusion: HIV prevalence among street children is much higher than general population (<0.1%), and in fact, the rate of positivity comes close to that among female sex workers in Iran. These findings must be an alarm for HIV policymakers to consider immediate and special interventions for this at-risk group.

Abstract access 

Editor’s notes: Relatively few studies have been published on the prevalence of HIV and other communicable diseases in vulnerable populations in Iran. This paper presents results from a prevalence study among street children in Tehran, Iran. Researchers were able to survey 1000 street children, and children exploited by labour between the ages of 10-18, finding an HIV prevalence of 4.5%. The survey data revealed high rates of physical abuse, drug use, and school dropout, but it is not clear whether any of the children were already aware of their HIV status, or how many had acquired HIV perinatally. These important findings point to the imperative for programmes to address the needs of street children in Tehran, and additional research in other areas within the country where similar issues may be prevalent. 

Asia
Iran (Islamic Republic of)
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The limits of HIV disclosure for women in 27 countries

The association between HIV disclosure status and perceived barriers to care faced by women living with HIV in Latin America, China, central/eastern Europe, and western Europe/Canada.

Loutfy M, Johnson M, Walmsley S, Samarina A, Vasquez P, Hao-Lan H, Madihlaba T, Martinez-Tristani M, van Wyk J. AIDS Patient Care STDS. 2016 Sep;30(9):435-44. doi: 10.1089/apc.2016.0049. Epub 2016 Aug 23.

Generally, women are less likely than men to disclose their HIV status. This analysis examined the relationship between HIV disclosure and (1) perceived barriers to care and (2) quality of life (QoL) for women with HIV. The ELLA (EpidemioLogical study to investigate the popuLation and disease characteristics, barriers to care, and quAlity of life for women living with HIV) study enrolled HIV-positive women aged ≥18 years. Women completed the 12-item Barriers to Care Scale (BACS) questionnaire. QoL was assessed using the Health Status Assessment. BACS and QoL were stratified by dichotomized HIV disclosure status (to anyone outside the healthcare system). Multilevel logistic regression analysis was used to identify factors associated with disclosure. Of 1945 patients enrolled from Latin America, China, central/eastern Europe, and western Europe/Canada between July 2012 and September 2013, 1929 were included in the analysis (disclosed, n = 1724; nondisclosed, n = 205). Overall, 55% of patients lived with a husband/partner, 53% were employed, and 88% were receiving antiretroviral therapy. Patients who were with a serodiscordant partner were more likely to disclose (p = 0.0003). China had a disproportionately higher percentage of participants who did not disclose at all (nearly 30% vs. <15% for other regions). Mean BACS severity scores for medical/psychological service barriers and most personal resource barriers were significantly lower for the disclosed group compared with the nondisclosed group (p ≤ 0.02 for all). Compared with the disclosed group, the nondisclosed group reported statistically significantly higher (p ≤ 0.03) BACS item severity scores for 8 of the 12 potential barriers to care. The disclosed group reported better QoL. Overall, HIV nondisclosure was associated with more severe barriers to accessing healthcare by women with HIV.

Abstract Full-text [free] access

Editor’s notes: This study drew women participants from Latin America, China, central and eastern Europe and from western Europe and Canada.  China was the only Asian country included and no African countries were included. This is important background information since the first sentence of the abstract ‘women are less likely than men to disclose HIV status’ is less likely to be true for, for example, parts of Africa. The study did not include men. So, no comparison can therefore be made with men’s disclosure behaviour. Nevertheless, the paper draws on data from 27 countries. Most women in the study did have access to ‘efficacious, well-tolerated’ antiretroviral therapy. A number of women, most notably in China, did not disclose their HIV status outside the health care system. Many women disclosed their status to a limited extent (only to some family and close friends). Non-disclosure affected access to health care as well as more general support. This pattern of non- or limited disclosure and barriers to access to care is replicated in many other places. The findings in this paper point to the importance globally of tackling stigma and providing a supportive health care and social setting for people living with HIV, so they can benefit fully from the treatment and care that is available.

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HIV treatment during acute infection can lead to false negative HIV antibody tests

Initiation of antiretroviral therapy during acute HIV-1 infection leads to a high rate of nonreactive HIV serology.

de Souza MS, Pinyakorn S, Akapirat S, Pattanachaiwit S, Fletcher JL, Chomchey N, Kroon ED, Ubolyam S, Michael NL, Robb ML, Phanuphak P, Kim JH, Phanuphak N, Ananworanich J. Clin Infect Dis. 2016 Aug 15;63(4):555-61. doi: 10.1093/cid/ciw365. Epub 2016 Jun 17.

Background: Third- and fourth-generation immunoassays (IAs) are widely used in the diagnosis of human immunodeficiency virus (HIV) infection. Antiretroviral therapy (ART) during acute HIV infection (AHI) may impact HIV-specific antibodies, with failure to develop antibody or seroreversion. We report on the ability of diagnostic tests to detect HIV-specific antibodies in Thai participants initiating ART during AHI.

Methods: Participants with detectable plasma HIV RNA but nonreactive HIV-specific immunoglobulin G, enrolled in an AHI study, were offered immediate initiation of ART. Participants were tested at initiation and at 12 and 24 weeks following treatment using standard second-, third-, and fourth-generation IAs and Western blot (WB).

Results: Participants (N = 234) initiating ART at a median of 19 days (range, 1-62 days) from HIV exposure demonstrated different frequencies of reactivity prior to and following 24 weeks of ART depending on the IA. Third-generation IA nonreactivity prior to ART was 48%, which decreased to 4% following ART (P < .001). Fourth-generation IA nonreactivity was 18% prior to ART and 17% following ART (P = .720). Negative WB results were observed in 89% and 12% of participants prior to and following 24 weeks of ART, respectively (P < .001). Seroreversion to nonreactivity during ART was observed to at least one of the tests in 20% of participants, with fourth-generation IA demonstrating the highest frequency (11%) of seroreversion.

Conclusions: HIV-specific antibodies may fail to develop and, when detected, may decline when ART is initiated during AHI. Although fourth-generation IA was the most sensitive at detecting AHI prior to ART, third-generation IA was the most sensitive during treatment.

Clinical trials registration: NCT00796146 and NCT00796263.

Abstract access  

Editor’s notes: Antibodies to HIV become detectable around three weeks after HIV infection. Fourth generation HIV tests detect both HIV antibodies and the p24 HIV antigen, and can therefore detect HIV infection earlier than second and third-generation tests, which are based on detection of antibodies. Fourth generation tests therefore allow for earlier initiation of antiretroviral therapy (ART) relative to second- and third-generation HIV tests.

There have been sporadic reports of seroreversion from being HIV antibody positive to negative, or failure to seroconvert to being HIV antibody positive, following initiation of ART, particularly from paediatric populations. This study examined the impact of ART initiation during acute HIV infection on HIV diagnostic test results. Although the fourth-generation HIV test was the most sensitive at detecting acute HIV infection, it also had the highest frequency of seroreversion. Conversely, third generation HIV tests were positive prior to the start of ART in just over half of participants, compared to nearly all by 12 weeks after ART initiation. Notably, the Western blot, which was historically used as a confirmatory test for HIV, had high rates of non-reactivity in acute infection and 12% of tests were negative at 24 weeks after treatment, demonstrating that this test is not informative as a confirmatory assay in the context of acutely-treated HIV infection.   

The recent WHO guidelines recommend ART for all HIV-positive people regardless of age and disease stage.  Initiating ART as early as possible following HIV infection has also been recommended as a means to limit the size of the viral reservoir and improve prognosis. It is therefore likely that increasing numbers of individuals will start ART during early infection. There may be instances where individuals on ART may retest either due to doubts about results, or when they relocate to other HIV services. Clinicians need to be aware of the possibility of false-negative HIV antibody tests among people taking ART, particularly among individuals who initiated treatment during acute infection.    

Asia
Thailand
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Mental health as a barrier to HIV testing and care

Pathways to HIV testing and care in Goa, India: exploring psychosocial barriers and facilitators using mixed methods.

Mayston R, Lazarus A, Patel V, Abas M, Korgaonkar P, Paranjape R, Rodrigues S, Prince M. BMC Public Health. 2016 Aug 11;16(1):765. doi: 10.1186/s12889-016-3456-4.

Background: Despite recognition of the importance of timely presentation to HIV care, research on pathways to care is lacking. The adverse impact of depression upon adherence to antiretroviral therapy is established. There is emerging evidence to suggest depression may inhibit initial engagement with care. However, the effect of depression and other psychosocial factors upon the pathway to care is unknown.

Methods: We used mixed methods to explore pathways to care of people accessing testing and treatment in Goa, India. Questionnaires including measures of common mental disorder, hazardous alcohol use, cognition and assessment of pathways to care (motivations for testing, time since they were first aware of this reason for testing, whether they had been advised to test, who had given this advice, time elapsed since this advice was given) were administered to 1934 participants at the time of HIV testing. Qualitative interviews were carried out with 15 study participants who attended the antiretroviral therapy treatment centre. Interview topic guides were designed to elicit responses that discussed barriers and facilitators of accessing testing and care.

Results: Pathways were often long and complex. Quantitative findings revealed that Common Mental Disorder was associated with delayed testing when advised by a Doctor (the most common pathway to testing) (AOR = 6.18, 2.16-17.70). Qualitative results showed that triggers for testing (symptoms believed to be due to HIV, and for women, illness or death of their husband) suggested that poor health, rather than awareness of risk was a key stimulus for testing. The period immediately before and after diagnosis was characterised by distress and fear. Stigma was a prominent backdrop to narratives. However, once participants had made contact with care and support (HIV services and non-governmental organisations), these systems were often effective in alleviating fear and promoting confidence in treatment and self-efficacy.

Conclusion: The effectiveness of formal and informal systems of support around the time of diagnosis in supporting people with mental disorder is unclear. Ways of enhancing these systems should be explored, with the aim of achieving timely presentation at HIV care for all those diagnosed with the disease.

Abstract  Full-text [free] access 

Editor’s notes: Late presentation to HIV care is associated with poorer outcomes for individuals living with HIV (increased risk of morbidity and death) and for treatment programmes (increased costs). The focus of this mixed methods study was to improve understanding of the impact of common mental disorders, hazardous alcohol use and cognitive impairment on accessing HIV testing and care in India. Although the investigators report that common mental disorders increased the possibility of delayed testing, internalised stigma and fear of discrimination was a common theme in the qualitative narratives. Stigma is associated with poorer mental health, including emotional distress, depression and reduced psychological functioning. It has also been linked to intermediate health outcomes such as seeking healthcare and adherence to antiretroviral therapy. These results reinforce the need to develop and evaluate programmes to address HIV-associated stigma so that people living with HIV can access care and benefit from treatment. However, development of appropriate programmes requires a better understanding of the complexities of HIV-associated stigma. These include the relationship between stigma, depression and social support and the intersection of HIV-associated stigma and other types of stigma experienced by people living with HIV, such as homophobia and gender discrimination.

Asia
India
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Challenges in assessing quality in HIV outpatient care

Structure and quality of outpatient care for people living with an HIV infection.

Engelhard EA, Smit C, Nieuwkerk PT, Reiss P, Kroon FP, Brinkman K, Geerlings SE. AIDS Care. 2016 Aug;28(8):1062-72. doi: 10.1080/09540121.2016.1153590. Epub 2016 Mar 13.

Policy-makers and clinicians are faced with a gap of evidence to guide policy on standards for HIV outpatient care. Ongoing debates include which settings of care improve health outcomes, and how many HIV-infected patients a health-care provider should treat to gain and maintain expertise. In this article, we evaluate the studies that link health-care facility and care provider characteristics (i.e., structural factors) to health outcomes in HIV-infected patients. We searched the electronic databases MEDLINE, PUBMED, and EMBASE from inception until 1 January 2015. We included a total of 28 observational studies that were conducted after the introduction of combination antiretroviral therapy in 1996. Three aspects of the available research linking the structure to quality of HIV outpatient care were evaluated: (1) assessed structural characteristics (i.e., health-care facility and care provider characteristics); (2) measures of quality of HIV outpatient care; and (3) reported associations between structural characteristics and quality of care. Rather than scarcity of data, it is the diversity in methodology in the identified studies and the inconsistency of their results that led us to the conclusion that the scientific evidence is too weak to guide policy in HIV outpatient care. We provide recommendations on how to address this heterogeneity in future studies and offer specific suggestions for further reading that could be of interest for clinicians and researchers.

Abstract access

Editor’s notes: The availability of antiretroviral therapy has resulted in remarkable decreases in HIV-associated mortality.  Complexity in the management of HIV infection has however grown along with these advances in treatment. Health-care providers are confronted with challenges associated with antiretroviral therapy including toxicities; drug-drug interactions and drug resistance; and comorbidities and aging among the population living with HIV. In order to achieve optimal health outcomes, care for people living with HIV should be provided at health-care facilities and by care providers with sufficient expertise. A variety of different delivery models have been attempted to achieve this. There are a growing number of studies assessing care delivery models and programmes in outpatient HIV care.  In this article the authors provide an overview of the scientific literature linking health-care facility and care provider characteristics to the quality of HIV outpatient care.

The authors conducted a systematic review of articles that reported an original observational research study with an adult population living with HIV, were conducted after 1996, and that did not focus exclusively on interventions.

The authors acknowledge the limitations of their research. These included a disproportionate number of studies based in the USA and sub-Saharan Africa (thus limited generalisability); diversity in the definition of structural variables; a wide scope of measures of quality of care used in studies; and limited inclusion of peoples’ healthcare experiences. The authors summarise two main implications of their research.  First, they note that their findings suggest that health-care provider experience improves outcomes among people living with HIV although they are unable to make recommendations regarding facility volume requirements for outpatient care. Second, they advocate for the need for research to extend to regions outside the USA and sub-Saharan Africa.  They also note the need for researchers to align their methods of measuring quality including by going beyond HIV-associated morbidity in the evaluation of health outcomes.  Peoples’ preferences and retention in care should also play an important role in the evaluation of the quality of care.

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Antiretroviral therapy dramatically reduces transmission of HIV to sexual partners

Antiretroviral therapy for the prevention of HIV-1 transmission.

Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Cottle L, Zhang XC, Makhema J, Mills LA, Panchia R, Faesen S, Eron J, Gallant J, Havlir D, Swindells S, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano DD, Essex M, Hudelson SE, Redd AD, Fleming TR. N Engl J Med. 2016 Jul 18. [Epub ahead of print]

Background: An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission.

Methods: We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis.

Results: Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant.

Conclusions: The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 ClinicalTrials.gov number, NCT00074581.).

Abstract access

Editor’s notes: The HPTN 052 trial has been a landmark study in establishing antiretroviral therapy as a strategy for preventing onward transmission of HIV. It was a study of more than 800 couples. More than half of the couples were in African countries. In each couple, one sexual partner was HIV positive and the other HIV negative.  The participants living with HIV were randomised either to receive immediate antiretroviral therapy or to delay until their CD4 count fell to 350, an approved approach at that time. The HIV negative partners were then monitored for acquisition of HIV.  When new HIV infections occurred, the virus was studied for genetic similarity to the virus of the known positive partner. The interim analysis was published in 2011.  It illustrated the programme to be so effective that the randomisation was ended and all the participants living with HIV were offered antiretroviral therapy. 

This article presents data after five years of follow-up, and if anything the results are even more remarkable. In more than 10 000 person-years of follow up, there were only eight transmissions of genetically linked virus from participants receiving antiretroviral therapy. Of these transmissions, four occurred early in treatment when the viral load would not be expected to be suppressed.  The other four occurred after treatment failure. In this enormous study, there were therefore no linked transmissions from participants who were stable on treatment without detectable viraemia. The study provides powerful support for the UNAIDS 90-90-90 treatment target.  The widest possible effective use of antiretroviral therapy will not only improve the health of people treated but could have a dramatic effect on new HIV infections.

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Weekend breaks on efavirenz-based ART non-inferior in adolescents

BREATHER (PENTA 16) short-cycle therapy (SCT) (5 days on/2 days off) in young people with chronic human immunodeficiency virus infection: an open, randomised, parallel-group Phase II/III trial.

Butler K, Inshaw J, Ford D, Bernays S, Scott K, Kenny J, Klein N, Turkova A, Harper L, Nastouli E, Paparini S, Choudhury R, Rhodes T, Babiker A, Gibb D. Health Technol Assess. 2016 Jun;20(49):1-108. doi: 10.3310/hta20490.

Background: For human immunodeficiency virus (HIV)-infected adolescents facing lifelong antiretroviral therapy (ART), short-cycle therapy (SCT) with long-acting agents offers the potential for drug-free weekends, less toxicity, better adherence and cost savings.

Objectives: To determine whether or not efavirenz (EFV)-based ART in short cycles of 5 days on and 2 days off is as efficacious (in maintaining virological suppression) as continuous EFV-based ART (continuous therapy; CT). Secondary objectives included the occurrence of new clinical HIV events or death, changes in immunological status, emergence of HIV drug resistance, drug toxicity and changes in therapy.

Design: Open, randomised, non-inferiority trial.

Setting: Europe, Thailand, Uganda, Argentina and the USA.

Participants: Young people (aged 8-24 years) on EFV plus two nucleoside reverse transcriptase inhibitors and with a HIV-1 ribonucleic acid level [viral load (VL)] of < 50 copies/ml for > 12 months.

Interventions: Young people were randomised to continue daily ART (CT) or change to SCT (5 days on, 2 days off ART).

Main outcome measures: Follow-up was for a minimum of 48 weeks (0, 4 and 12 weeks and then 12-weekly visits). The primary outcome was the difference between arms in the proportion with VL > 50 copies/ml (confirmed) by 48 weeks, estimated using the Kaplan-Meier method (12% non-inferiority margin) adjusted for region and age.

Results: In total, 199 young people (11 countries) were randomised (n = 99 SCT group, n = 100 CT group) and followed for a median of 86 weeks. Overall, 53% were male; the median age was 14 years (21% ≥ 18 years); 13% were from the UK, 56% were black, 19% were Asian and 21% were Caucasian; and the median CD4% and CD4 count were 34% and 735 cells/mm3, respectively. By week 48, only one participant (CT) was lost to follow-up. The SCT arm had a 27% decreased drug exposure as measured by the adherence questionnaire and a MEMSCap Medication Event Monitoring System (MEMSCap Inc., Durham, NC, USA) substudy (median cap openings per week: SCT group, n = 5; CT group, n = 7). By 48 weeks, six participants in the SCT group and seven in the CT group had a confirmed VL > 50 copies/ml [difference -1.2%, 90% confidence interval (CI) -7.3% to 4.9%] and two in the SCT group and four in the CT group had a confirmed VL > 400 copies/ml (difference -2.1%, 90% CI -6.2% to 1.9%). All six participants in the SCT group with a VL > 50 copies/ml resumed daily ART, of whom five were resuppressed, three were on the same regimen and two with a switch; two others on SCT resumed daily ART for other reasons. Overall, three participants in the SCT group and nine in the CT group (p = 0.1) changed ART regimen, five because of toxicity, four for simplification reasons, two because of compliance issues and one because of VL failure. Seven young people (SCT group, n = 2; CT group, n = 5) had major non-nucleoside reverse transcriptase inhibitor mutations at VL failure, of whom two (n = 1 SCT group, n = 1 CT group) had the M184V mutation. Two young people had new Centers for Disease Control B events (SCT group, n = 1; CT group, n = 1). There were no significant differences between SCT and CT in grade 3/4 adverse events (13 vs. 14) or in serious adverse events (7 vs. 6); there were fewer ART-related adverse events in the SCT arm (2 vs. 14; p = 0.02). At week 48 there was no evidence that SCT led to increased inflammation using an extensive panel of markers. Young people expressed a strong preference for SCT in a qualitative substudy and in pre- and post-trial questionnaires. In total, 98% of the young people are taking part in a 2-year follow-up extension of the trial.

Conclusions: Non-inferiority of VL suppression in young people on EFV-based first-line ART with a VL of < 50 copies/ml was demonstrated for SCT compared with CT, with similar resistance, safety and inflammatory marker profiles. The SCT group had fewer ART-related adverse events. Further evaluation of the immunological and virological impact of SCT is ongoing. A limitation of the trial is that the results cannot be generalised to settings where VL monitoring is either not available or infrequent, nor to use of low-dose EFV. Two-year extended follow-up of the trial is ongoing to confirm the durability of the SCT strategy. Further trials of SCT in settings with infrequent VL monitoring and with other antiretroviral drugs such as tenofovir alafenamide, which has a long intracellular half-life, and/or dolutegravir, which has a higher barrier to resistance, are planned.

Trial registration: Current Controlled Trials ISRCTN97755073; EUDRACT 2009-012947-40; and CTA 27505/0005/001-0001.

Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (projects 08/53/25 and 11/136/108), the European Commission through EuroCoord (FP7/2007/2015), the Economic and Social Research Council, the PENTA Foundation, the Medical Research Council and INSERM SC10-US19, France, and will be published in full in Health Technology Assessment; Vol. 20, No. 49. See the NIHR Journals Library website for further project information.

Abstract  Full-text [free] access 

Editor’s notes: Adherence to ART has been shown to deteriorate in adolescence, with missed doses occurring particularly at weekends. Pharmacokinetic properties of some ART drugs, such as efavirenz, allow for a break in pill taking without a break in effective treatment. Non-inferiority trials evaluating five days on, two days off in adults have shown continuous ART to be non-inferior with low rates of virologic rebound.  This formed the rationale for this global, randomised Phase II/III trial in young people.

In the BREATHER trial, non-inferiority of viral suppression in adolescents on efavirenz-based first-line ART was shown for short-cycle treatment compared with continuous treatment. Overall 93% of adolescents remained virally suppressed. Findings from the two-year long-term follow-up phase will confirm if short-cycle treatment is effective and safe in this population.  Further studies are required to confirm the applicability of this strategy in real-life settings where viral load monitoring is likely to be less frequent than in a trial setting.

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Getting to 90-90-90 in China: where are the gaps?

Disparities in HIV care along the path from infection to viral suppression: a cross-sectional study of HIV/AIDS patient records in 2013, Shandong province, China.

Zhang N, Bussell S, Wang G, Zhu X, Yang X, Huang T, Qian Y, Tao X, Kang D, Wang N. Clin Infect Dis. 2016 Jul 1;63(1):115-21. doi: 10.1093/cid/ciw190. Epub 2016 Mar 29.

Background: The 90-90-90 targets recommended by the Joint United Nations Programme on HIV/AIDS require strengthening human immunodeficiency virus (HIV) care, which includes diagnosis, linkage to and retention in care, assessment for treatment suitability, and optimization of HIV treatment. We sought to quantify patient engagement along the continuum, 10 years after introduction of Chinese HIV care policies.

Methods: We included patients from Shandong, China, who were diagnosed with HIV from 1992 to 2013. Records were obtained from the HIV/AIDS Comprehensive Response Information Management System to populate a 7-step HIV care continuum. Pearson chi2 test and multivariate logistic regression were used for analysis.

Results: Of 6500 estimated HIV-infected persons, 60.1% were diagnosed, of whom 41.9% received highly active antiretroviral therapy (HAART). Only 59.6% of patients on HAART and 15% of all infected persons achieved viral suppression. Children infected by mother-to-child transmission (MTCT) and persons infected by intravenous drug use were less likely to be linked to and retained in care (odds ratio [OR], 0.33 [95% confidence interval {CI}, .14-.80] and OR, 0.58 [95% CI, .40-.90], respectively). Persons tested in custodial institutions were substantially less likely to be on HAART (OR, 0.22 [95% CI, .09-.59]) compared with those tested in medical facilities. Patients on HAART infected by homosexual or heterosexual transmission and those infected by MTCT were less likely to achieve viral suppression (OR, 0.18 [95% CI, .09-.34]; OR, 0.12 [95% CI, .06-.22]; OR, 0.07 [95% CI, .02-.20], respectively).

Conclusions: Our report suggests, at the current rate, Shandong Province has to accelerate HIV care efforts to close disparities in HIV care and achieve the 90-90-90 goals equitably.

Abstract access

Editor’s notes: The UNAIDS treatment target set for 2020 aim for at least 90 percent of all people living with HIV to be diagnosed, at least 90 percent of people diagnosed to receive antiretroviral therapy, and for treatment to be effective and consistent enough in at least 90 percent of those people on treatment to suppress the virus. This would result in about 73% of all people living with HIV being virally suppressed.

This study estimated coverage of HIV diagnosis, antiretroviral treatment and viral suppression in Shandong Province in 2013, 10 years after the introduction of a Chinese HIV care policy.

The authors found that overall, only about 60% of people on ART and 15% of all people living with HIV achieved viral suppression (defined in this analysis as having a viral load of less than HIV RNA 50 copies per mL). This is in sharp contrast with recently published figures from Botswana where 97% of people on ART, and about 70% of persons living with HIV were virally suppressed (there defined as having a viral load of less than 400 copies per mL).

With only 15% of persons with HIV being virally suppressed in Shandong Province, a big gap remains for reaching the UNAIDS target of 73%. The authors demonstrate that despite a free, inclusive, nationwide HIV care policy, significant inequalities in HIV testing and treatment exist in Shandong Province. For example people who inject drugs and people in custodial institutions were much less likely to be initiated on ART.

The authors conclude that to achieve the 90-90-90 UNAIDS treatment target, Shandong Province needs to close these disparities in HIV care. 

Asia
China
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