Articles tagged as "HIV Treatment"

People who inject drugs living with HIV in Russia face more mental health issues and diminished quality of life

Psychiatric symptoms, quality of life, and HIV status among people using opioids in Saint Petersburg, Russia.

Desrosiers A, Blokhina E, Krupitsky E, Zvartau E, Schottenfeld R, Chawarski M. Drug Alcohol Depend. 2017 Mar 1;172:60-65. doi: 10.1016/j.drugalcdep.2016.12.007. Epub 2017 Jan 23.

Background: The Russian Federation is experiencing a very high rate of HIV infection among people who inject drugs (PWID). However, few studies have explored characteristics of people with co-occurring opioid use disorders and HIV, including psychiatric symptom presentations and how these symptoms might relate to quality of life. The current study therefore explored a.) differences in baseline psychiatric symptoms among HIV+ and HIV- individuals with opioid use disorder seeking naltrexone treatment at two treatment centers in Saint Petersburg, Russia and b.) associations between psychiatric symptom constellations and quality of life.

Methods: Participants were 328 adults enrolling in a randomized clinical trial evaluating outpatient treatments combining naltrexone with different drug counseling models. Psychiatric symptoms and quality of life were assessed using the Brief Symptom Inventory and The World Health Organization Quality of Life-BREF, respectively.

Results: Approximately 60% of participants were HIV+. Those who were HIV+ scored significantly higher on BSI anxiety, depression, psychoticism, somatization, paranoid ideation, phobic anxiety, obsessive-compulsive, and GSI indexes (all p<0.05) than those HIV-. A K-means cluster analysis identified three distinct psychiatric symptom profiles; the proportion of HIV+ was significantly greater and quality of life indicators were significantly lower in the cluster with the highest psychiatric symptom levels.

Conclusion: Higher levels of psychiatric symptoms and lower quality of life indicators among HIV+ (compared to HIV-) individuals injecting drugs support the potential importance of combining interventions that target improving psychiatric symptoms with drug treatment, particularly for HIV+ patients.

Abstract access 

Editor’s notes: The higher prevalence of mental health disorders among people living with HIV is well known. This paper focuses on the association of mental health disorders and HIV among people who inject drugs, in St Petersburg, Russian Federation – the city with the highest prevalence of HIV and drug use in the Russian Federation. HIV positive people who inject drugs had significantly higher prevalence of mental health problems than HIV negative people who inject drugs. They had a lower quality of life according to a validated scale, underscoring the need for strong, combination public health programmes to support this vulnerable group. The population studied was selected through existing service provision. Since these individuals were already seeking treatment on their own, there could be many more who are not engaged in care either for HIV treatment or drug use support. This suggests the need to strengthen awareness and services, especially in areas where clean needles and other risk management methods are not yet available.

Europe
Russian Federation
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Peer support: not a panacea for poor adherence

Use of peers to improve adherence to antiretroviral therapy: a global network meta-analysis.

Kanters S, Park JJ, Chan K, Ford N, Forrest J, Thorlund K, Nachega JB, Mills EJ. J Int AIDS Soc. 2016 Nov 30;19(1):21141. doi: 10.7448/IAS.19.1.21141. eCollection 2016.

Introduction: It is unclear whether using peers can improve adherence to antiretroviral therapy (ART). To construct the World Health Organization's global guidance on adherence interventions, we conducted a systematic review and network meta-analysis to determine the effectiveness of using peers for achieving adequate adherence and viral suppression.

Methods: We searched for randomized clinical trials of peer-based interventions to promote adherence to ART in HIV populations. We searched six electronic databases from inception to July 2015 and major conference abstracts within the last three years. We examined the outcomes of adherence and viral suppression among trials done worldwide and those specific to low- and middle-income countries (LMIC) using pairwise and network meta-analyses.

Results and discussion: Twenty-two trials met the inclusion criteria. We found similar results between pairwise and network meta-analyses, and between the global and LMIC settings. Peer supporter+Telephone was superior in improving adherence than standard-of-care in both the global network (odds-ratio [OR]=4.79, 95% credible intervals [CrI]: 1.02, 23.57) and the LMIC settings (OR=4.83, 95% CrI: 1.88, 13.55). Peer support alone, however, did not lead to improvement in ART adherence in both settings. For viral suppression, we found no difference of effects among interventions due to limited trials.

Conclusions: Our analysis showed that peer support leads to modest improvement in adherence. These modest effects may be due to the fact that in many settings, particularly in LMICs, programmes already include peer supporters, adherence clubs and family disclosures for treatment support. Rather than introducing new interventions, a focus on improving the quality in the delivery of existing services may be a more practical and effective way to improve adherence to ART.

Abstract  Full-text [free] access 

Editor’s notes: Sustained adherence to antiretroviral therapy (ART) is critical to ensure successful treatment outcomes and prevent drug resistance, AIDS-associated illness, death and onward transmission of HIV infection. In recent years, there has been much enthusiasm for use of peer support as a programme to improve adherence. Most high HIV prevalence settings have limited resources. Stigma influences adherence to treatment, and peer-based support may be a practical solution both in terms of being low cost and a mechanism for addressing stigma.

In this systematic review, the authors evaluated the effectiveness of peer-supporter programmes alone or in combination with other activities, namely telephone calls, device reminders or cognitive behavioural therapy (CBT), globally and in low and middle-income countries (LMIC). The systematic review findings were used to inform the 2015 World Health Organization HIV treatment guidelines.

The study demonstrates that peer support alone did not have any impact on adherence or on viral suppression. It did demonstrate modest improvements on adherence when combined with telephone activities. Several factors need to be considered in interpreting these findings. Firstly, adherence was assessed using a variety of methods including pill counts and the Medication Event Monitoring System (MEMS), which may have introduced heterogeneity. Secondly, few trials (particularly in LMICs) used HIV viral load as an outcome and therefore there may not have been adequate statistical power to detect an effect. Thirdly, populations included in the review were heterogeneous e.g. ART-naïve and experienced, people who inject drugs, non-adherent individuals. Notably, only one trial included children and adolescents among whom adherence is typically poorer. 

Importantly, in many settings particularly in LMICs, programmes already include treatment supporters and adherence clubs and therefore additional peer support would likely not add additional impact. The findings of this study suggest that programmes should focus on improving the quality of existing services rather than introduce new programmes. The review also highlights the need to standardise adherence measures and the need for robust research on adherence, particularly among children.         

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Thymidine analogue mutations associated with extensive resistance in African people failing on tenofovir

Occult HIV-1 drug resistance to thymidine analogues following failure of first-line tenofovir combined with a cytosine analogue and nevirapine or efavirenz in sub-Saharan Africa: a retrospective multi-centre cohort study.

Gregson J, Kaleebu P, Marconi VC, van Vuuren C, Ndembi N, Hamers RL, Kanki P, Hoffmann CJ, Lockman S, Pillay D, de Oliveira T, Clumeck N, Hunt G, Kerschberger B, Shafer RW, Yang C, Raizes E, Kantor R, Gupta RK. Lancet Infect Dis. 2016 Nov 30. pii: S1473-3099(16)30469-8. doi: 10.1016/S1473-3099(16)30469-8. [Epub ahead of print]

Background: HIV-1 drug resistance to older thymidine analogue nucleoside reverse transcriptase inhibitor drugs has been identified in sub-Saharan Africa in patients with virological failure of first-line combination antiretroviral therapy (ART) containing the modern nucleoside reverse transcriptase inhibitor tenofovir. We aimed to investigate the prevalence and correlates of thymidine analogue mutations (TAM) in patients with virological failure of first-line tenofovir-containing ART.

Methods: We retrospectively analysed patients from 20 studies within the TenoRes collaboration who had locally defined viral failure on first-line therapy with tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleoside reverse transcriptase inhibitor (NNRTI; nevirapine or efavirenz) in sub-Saharan Africa. Baseline visits in these studies occurred between 2005 and 2013. To assess between-study and within-study associations, we used meta-regression and meta-analyses to compare patients with and without TAMs for the presence of resistance to tenofovir, cytosine analogue, or NNRTIs.

Findings: Of 712 individuals with failure of first-line tenofovir-containing regimens, 115 (16%) had at least one TAM. In crude comparisons, patients with TAMs had lower CD4 counts at treatment initiation than did patients without TAMs (60.5 cells per µL [IQR 21.0-128.0] in patients with TAMS vs 95.0 cells per µL [37.0-177.0] in patients without TAMs; p=0.007) and were more likely to have tenofovir resistance (93 [81%] of 115 patients with TAMs vs 352 [59%] of 597 patients without TAMs; p<0.0001), NNRTI resistance (107 [93%] vs 462 [77%]; p<0.0001), and cytosine analogue resistance (100 [87%] vs 378 [63%]; p=0.0002). We detected associations between TAMs and drug resistance mutations both between and within studies; the correlation between the study-level proportion of patients with tenofovir resistance and TAMs was 0.64 (p<0.0001), and the odds ratio for tenofovir resistance comparing patients with and without TAMs was 1.29 (1.13-1.47; p<0.0001)

Interpretation: TAMs are common in patients who have failure of first-line tenofovir-containing regimens in sub-Saharan Africa, and are associated with multidrug resistant HIV-1. Effective viral load monitoring and point-of-care resistance tests could help to mitigate the emergence and spread of such strains.

Abstract  Full-text [free] access 

Editor’s notes: Since 2012, WHO has recommended that tenofovir should be included in first-line antiretroviral therapy, in place of the thymidine analogues, zidovudine and stavudine, which have more significant adverse effects. When therapy fails to maintain virologic control, tenofovir is associated with characteristic resistance mutations that are different from the thymidine analogue mutations (TAMs) associated with the older drugs. This study looked at the resistance patterns of people in Africa with virologic failure after starting on WHO recommended first-line combination including tenofovir and a non-nucleoside reverse transcriptase inhibitor (NNRTI).  TAMs were surprisingly common (16%) for a group who were not known to have received thymidine analogues. This is not what would be expected from this drug combination. The implication is that TAMs may have been present before tenofovir-containing treatment was started, possibly because of undeclared previous therapy. It is well known that TAMs make subsequent therapy with an NNRTI and nucleoside analogues very much more likely to fail. The presence of TAMs was associated with more extensive resistance to other drugs including lamivudine and NNRTIs, some of which may also have been present before the tenofovir based treatment.

Only people with treatment failure were studied. The total number entering into treatment is not recorded. However, based on other reports in Africa the authors speculate a failure rate of 15 to 35% and that they may therefore have found TAMs in two to six percent of people who started treatment. That seems a realistic figure for undeclared prior treatment and gives some perspective to the scale of this problem.

There is continuing concern about drug resistance in low- and middle-income countries.  As the thymidine analogues are phased out, people receiving them may be switched to tenofovir. In situations where there is no access to viral load monitoring, some people will have unrecognised virologic failure and may have developed resistance including TAMs. They are then likely to fail on tenofovir with additional resistance. Realistic strategies are necessary for the prompt detection of treatment failure.

Africa
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At the halfway mark? Community viral suppression in East Africa

Population levels and geographical distribution of HIV RNA in rural Ugandan and Kenyan communities, including serodiscordant couples: a cross-sectional analysis.

Jain V, Petersen ML, Liegler T, Byonanebye DM, Kwarisiima D, Chamie G, Sang N, Black D, Clark TD, Ladai A, Plenty A, Kabami J, Ssemmondo E, Bukusi EA, Cohen CR, Charlebois ED, Kamya MR, Havlir DV. Lancet HIV. 2016 Dec 15. pii: S2352-3018(16)30220-X. doi: 10.1016/S2352-3018(16)30220-X. [Epub ahead of print]

Background: As sub-Saharan Africa transitions to a new era of universal antiretroviral therapy (ART), up-to-date assessments of population-level HIV RNA suppression are needed to inform interventions to optimise ART delivery. We sought to measure population viral load metrics to assess viral suppression and characterise demographic groups and geographical locations with high-level detectable viraemia in east Africa.

Methods: The Sustainable East Africa Research in Community Health (SEARCH) study is a cluster-randomised controlled trial of an HIV test-and-treat strategy in 32 rural communities in Uganda and Kenya, selected on the basis of rural setting, having an approximate population of 10 000 people, and being within the catchment area of a President's Emergency Plan for AIDS Relief-supported HIV clinic. During the baseline population assessment in the SEARCH study, we did baseline HIV testing and HIV RNA measurement. We analysed stable adult (aged 15 years) community residents. We defined viral suppression as a viral load of less than 500 copies per mL. To assess geographical sources of transmission risk, we established the proportion of all adults (both HIV positive and HIV negative) with a detectable viral load (local prevalence of viraemia). We defined transmission risk hotspots as geopolitical subunits within communities with an at least 5% local prevalence of viraemia. We also assessed serodiscordant couples, measuring the proportion of HIV-positive partners with detectable viraemia. The SEARCH study is registered with ClinicalTrials.gov, number NCT01864603.

Findings: Between April 2, 2013, and June 8, 2014, of 303 461 stable residents, we enumerated 274 040 (90.3%), of whom 132 030 (48.2%) were adults. Of these, 117 711 (89.2%) had their HIV status established, of whom 11 964 (10.2%) were HIV positive. Of these, we measured viral load in 8828 (73.8%) people. Viral suppression occurred in 3427 (81.6%) of 4202 HIV-positive adults on ART and 4490 (50.9%) of 8828 HIV-positive adults. Regional viral suppression among HIV-positive adults occurred in 881 (48.2%) of 1827 people in west Uganda, 516 (45.0%) of 1147 in east Uganda, and 3093 (52.8%) of 5854 in Kenya. Transmission risk hotspots occurred in three of 21 parishes in west Uganda and none in east Uganda and in 24 of 26 Kenya geopolitical subunits. In Uganda, 492 (2.9%) of 16 874 couples were serodiscordant: in 287 (58.3%) of these couples, the HIV-positive partner was viraemic (and in 69 [14.0%], viral load was >100 000 copies per mL). In Kenya, 859 (10.0%) of 8616 couples were serodiscordant: in 445 (53.0%) of these couples, the HIV-positive partner was viraemic (and in 129 [15%], viral load was >100 000 copies per mL).

Interpretation: Before the start of the SEARCH trial, 51% of east African HIV-positive adults had viral suppression, reflecting ART scale-up efforts to date. Geographical hotspots of potential HIV transmission risk and detectable viraemia among serodiscordant couples warrant intensified interventions.

Abstract access  

Editor’s notes: Half of all people living with HIV with a valid viral load measurement in these East African communities had viral suppression (<500 copies/mL) at the start of this cluster randomised trial in 2013-14. These results already provided good evidence of the effectiveness and impact of antiretroviral programmes in East Africa. However, at the AIDS conference in July 2016 the study group presented updated results following two years of a universal test and treat (UTT) strategy with expansion of community-based HIV testing services (access abstract here). By this point, the UNAIDS 90-90-90 treatment target had been exceeded in the study communities and, overall, 82% of people living with HIV had viral suppression. 

These results highlight the role of community viral load metrics as indicators of programme impact. What gives rise to more debate is the role of these metrics in estimating the risk of ongoing HIV transmission in the community. Consensus seems to be emerging that the population prevalence of viraemia may be the metric best suited for this purpose. In this study, the estimated population prevalence of viraemia varied quite widely from 0.5 to 14.1% at the level of local communities (of between around 500 and 5000 people). This measure was also used to define several transmission hotspots, based on an arbitrary cut-off of five percent prevalence of viraemia.

Additional research is necessary in different epidemiological contexts to understand the association between these metrics and risk of HIV transmission. There is also some way to go to understand if such metrics can have practical public health implications for HIV prevention. Whether revealing such heterogeneity in transmission risk within generalized epidemics can inform the application of geographically focussed programmes is a question that now should be addressed.

Africa
Kenya, Uganda
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ART has dramatically improved life expectancy for people living with HIV in KwaZulu-Natal, South Africa

Trends in the burden of HIV mortality after roll-out of antiretroviral therapy in KwaZulu-Natal, South Africa: an observational community cohort study.

Reniers G, Blom S, Calvert C, Martin-Onraet A, Herbst AJ, Eaton JW, Bor J, Slaymaker E, Li ZR, Clark SJ, Barnighausen T, Zaba B, Hosegood V Lancet HIV. 2016 Dec 9. pii: S2352-3018(16)30225-9. doi: 10.1016/S2352-3018(16)30225-9

Background: Antiretroviral therapy (ART) substantially decreases morbidity and mortality in people living with HIV. In this study, we describe population-level trends in the adult life expectancy and trends in the residual burden of HIV mortality after the roll-out of a public sector ART programme in KwaZulu-Natal, South Africa, one of the populations with the most severe HIV epidemics in the world.

Methods: Data come from the Africa Centre Demographic Information System (ACDIS), an observational community cohort study in the uMkhanyakude district in northern KwaZulu-Natal, South Africa. We used non-parametric survival analysis methods to estimate gains in the population-wide life expectancy at age 15 years since the introduction of ART, and the shortfall of the population-wide adult life expectancy compared with that of the HIV-negative population (ie, the life expectancy deficit). Life expectancy gains and deficits were further disaggregated by age and cause of death with demographic decomposition methods.

Findings: Covering the calendar years 2001 through to 2014, we obtained information on 93 903 adults who jointly contribute 535 428 person-years of observation to the analyses and 9992 deaths. Since the roll-out of ART in 2004, adult life expectancy increased by 15.2 years for men (95% CI 12.4-17.8) and 17.2 years for women (14.5-20.2). Reductions in pulmonary tuberculosis and HIV-related mortality account for 79.7% of the total life expectancy gains in men (8.4 adult life-years), and 90.7% in women (12.8 adult life-years). For men, 9.5% is the result of a decline in external injuries. By 2014, the life expectancy deficit had decreased to 1.2 years for men (-2.9 to 5.8) and to 5.3 years for women (2.6-7.8). In 2011-14, pulmonary tuberculosis and HIV were responsible for 84.9% of the life expectancy deficit in men and 80.8% in women.

Interpretation: The burden of HIV on adult mortality in this population is rapidly shrinking, but remains large for women, despite their better engagement with HIV-care services. Gains in adult life-years lived as well as the present life expectancy deficit are almost exclusively due to differences in mortality attributed to HIV and pulmonary tuberculosis.

Abstract access

Editor’s notes: Health and demographic surveillance system (HDSS) sites allow for monitoring of population health through the collection of detailed data on tens of thousands of individuals. Such sites in countries with high HIV prevalence have played an important role in measuring the effects of large-scale programmes, such as the global roll-out of antiretroviral therapy (ART). The data presented in this paper, from the Africa Centre Demographic Information System (ACDIS) in KwaZulu-Natal, South Africa, span 13 years (2001–14) and represent over 93 000 individuals living in an area with extremely high HIV prevalence (29% in adults aged 15–49 years in 2011). At least 15 000 of people studied were HIV-positive, of whom at least 2000 died. ART was first made available to people living with HIV (PLHIV) in this area in 2004.

Among adults aged 15–49 years, the authors report an overall reduction in death rate from 2001–14.  This translates into large increases in life expectancy (i.e., the expected number of years lived from age 15) of 15 and 17 years for men and women, respectively, between 2001 and 2014.  The changes in life expectancy are greater in people who were confirmed HIV-positive: 18 and 21 years for men and women, respectively, from 2007–14.  The large difference in life expectancies between the sexes that still exists (31 versus 44 years in HIV-positive men and women, respectively) are consistent with previously published estimates from Rwanda and Uganda. This study, however, illustrates that HIV-positive men are catching up to their HIV-negative counterparts faster than women are. The ‘deficit’ in 2014 - the gap in life expectancies between HIV-positive and HIV-negative individuals, was 1.2 years in men but still 5.3 years in women.

The authors propose that increased access to ART is the primary driver of the gains in life expectancy seen in this cohort. To further support this, they include data from verbal autopsies (VAs), which suggest that reductions in deaths due to HIV and pulmonary tuberculosis were responsible for 80% and 90% of the increases in life expectancy in men and women, respectively. VAs have limitations, however, particularly in areas of high HIV prevalence, but the overall mortality patterns suggested by these findings are likely to be accurate, even if the precise estimates differ.

The dramatic increases in life expectancy, in only seven years, for HIV-positive individuals in this cohort add to the encouraging observations from other low- and middle-income countries that many people receiving ART can expect to live for nearly as long as HIV-negative individuals.  Of course, people with advanced disease starting ART are still at high risk of death and there remain considerable challenges in getting treatment to all people in need of it. 

Africa
South Africa
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The hope and reality of injecting drug use among people living with HIV in Ukraine

Attitudes toward addiction, methadone treatment, and recovery among HIV-infected Ukrainian prisoners who inject drugs: incarceration effects and exploration of mediators.  

Polonsky M, Rozanova J, Azbel L, Bachireddy C, Izenberg J, Kiriazova T, Dvoryak S, Altice FL. AIDS Behav. 2016 Dec;20(12):2950-2960.

In this study, we use data from a survey conducted in Ukraine among 196 HIV-infected people who inject drugs, to explore attitudes toward drug addiction and methadone maintenance therapy (MMT), and intentions to change drug use during incarceration and after release from prison. Two groups were recruited: Group 1 (n = 99) was currently incarcerated and Group 2 (n = 97) had been recently released from prison. This paper's key finding is that MMT treatment and addiction recovery were predominantly viewed as mutually exclusive processes. Group comparisons showed that participants in Group 1 (pre-release) exhibited higher optimism about changing their drug use, were less likely to endorse methadone, and reported higher intention to recover from their addiction. Group 2 participants (post-release), however, reported higher rates of HIV stigma. Structural equation modeling revealed that in both groups, optimism about recovery and awareness of addiction mediated the effect of drug addiction severity on intentions to recover from their addiction.

Abstract access 

Editor’s notes: Despite reductions in HIV incidence and mortality globally, the epidemic in Ukraine remains volatile and continues to expand, especially among people who inject drugs.  People who inject drugs account for more than 40% of people living with HIV.  At 20%, HIV prevalence among Ukrainian people living in prisons is the highest in Europe, with drug injection of opioids being the major driver of transmission. This is due to a concentration of people who inject drugs among prisoners and other incarcerated people, especially people living with HIV. Programmes focusing on prisoners and other incrcerated people may play a central role in HIV prevention since nearly all of them transition back to the community. Opioid agonist therapies including methadone maintenance therapy have been shown to have many benefits including reducing HIV transmission by over 50% among people who inject drugs.  Despite these benefits, moral biases, stigma and ideological prejudices are barriers to opioid agonist therapies scale-up globally including in Ukraine.  Opioid agonist therapies are available free of charge through national and external Global Fund support. However, scale up of opioid agonist therapies and treatment retention in Ukraine have been low, with only about 2.7% of people who inject drugs enrolled. This has constrained HIV prevention efforts.  Adoption of opioid agonist therapies has been especially slow among criminal justice populations. This study compares attitudes towards opioid agonist therapies among currently and previously incarcerated opioid-dependent people living with HIV in Ukraine.

The study uses data from a survey of people living with HIV conducted in Ukraine to explore attitudes to methadone treatment and intentions to change drug use behaviour before and after release from prison.

This study has important implications for future management of people who inject drugs who are living with HIV.  While staff attitudes may undermine the successful opioid agonist therapies delivery in prisons, the findings of this study suggest that prisoners and other incarcerated people are important foci for programmes that should be done in parallel with staff-based activities. The findings also suggest that optimism about recovery while in prison is falsely elevated. This may contribute to individual inability to comprehend addiction as a chronic relapsing condition, which in the absence of treatment, results in 85% relapsing within 12 months of release. Future programmes should take advantage of individuals’ sobriety while in prison and cultivate their ability to recognise the cycle of addiction and incarceration. This optimism should also be channelled to focus on evidence-based programmes, e.g., methadone maintenance therapy that has been associated with reduced illicit drug relapse, HIV risk-taking and reincarceration. Considerable health marketing work also needs to be done to focus on negative attitudes and prejudices about methadone maintenance therapy at both individual and societal level. This would importantly involve rebranding methadone maintenance therapy as a medical treatment for a chronic relapsing condition.

Europe
Ukraine
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Adolescents’ concerns: psychosocial needs of young people living with HIV in Thailand

Psychosocial needs of perinatally HIV-infected youths in Thailand: lessons learnt from instructive counseling.

Manaboriboon B, Lolekha R, Chokephaibulkit K, Leowsrisook P, Naiwatanakul T, Tarugsa J, Durier Y, Aunjit N, Punpanich Vandepitte W, Boon-Yasidhi V. AIDS Care. 2016 Dec;28(12):1615-1622. Epub 2016 Jun 26.

Identifying psychosocial needs of perinatally HIV-infected (pHIV) youth is a key step in ensuring good mental health care. We report psychosocial needs of pHIV youth identified using the "Youth Counseling Needs Survey" (YCS) and during individual counseling (IC) sessions. pHIV youth receiving care at two tertiary-care hospitals in Bangkok or at an orphanage in Lopburi province were invited to participate IC sessions. The youths' psychosocial needs were assessed using instructive IC sessions in four main areas: general health, reproductive health, mood, and psychosocial concerns. Prior to the IC session youth were asked to complete the YCS in which their concerns in the four areas were investigated. Issues identified from the YCS and the IC sessions were compared. During October 2010-July 2011, 150 (68.2%) of 220 eligible youths participated in the IC sessions and completed the YCS. Median age was 14 (range 11-18) years and 92 (61.3%) were female. Mean duration of the IC sessions was 36.5 minutes. One-hundred and thirty (86.7%) youths reported having at least one psychosocial problem discovered by either the IC session or the YCS. The most common problems identified during the IC session were poor health attitude and self-care (48.0%), lack of life skills (44.0%), lack of communication skills (40.0%), poor antiretroviral (ARV) adherence (38.7%), and low self-value (34.7%). The most common problems identified by the YCS were lack of communication skills (21.3%), poor health attitude and self-care (14.0%), and poor ARV adherence (12.7%). Youth were less likely to report psychosocial problems in the YCS than in the IC session. Common psychosocial needs among HIV-infected youth were issues about life skills, communication skills, knowledge on self-care, ARV adherence, and self-value. YCS can identify pHIV youths' psychosocial needs but might underestimate issues. Regular IC sessions are useful to detect problems and provide opportunities for counseling.

Abstract access  

Editor’s notes: The study reports on the psychological needs of young people who acquired HIV in the perinatal period.  The needs were highlighted during counselling sessions and in a survey conducted as part of the Happy-Teen Programme in Thailand. Young people (age 11-18) who have perinatally acquired HIV were recruited in two hospitals and from a service run by an orphanage linked to one of the hospitals. Young people took part in two individual ‘instructive counselling’ sessions, and two survey sessions for a needs-assessment questionnaire. Participants reported higher levels of needs in the counselling sessions compared to the questionnaire. Key areas of need identified included: health attitudes and self-care (e.g., diet, sleep, drug use); issues with sexual risk and difficulties communicating with sexual partners; HIV treatment adherence problems; concerns about HIV-associated stigma; and concerns about peer pressure. The study illustrates the difference in the quality of findings obtained from data collected via the questionnaire in comparison with data collected via sessions with counsellors. The counsellors were people that the young people knew for some time and trusted. The study highlights the importance of counselling with young people to improve self-esteem and health-associated behaviours.  Counsellors are also important to provide referrals for more severe mental health issues. 

Asia
Thailand
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Improving ART adherence: what works?

Interventions to improve adherence to antiretroviral therapy: a systematic review and network meta-analysis.

Kanters S, Park JJ, Chan K, Socias ME, Ford N, Forrest JI, Thorlund K, Nachega JB, Mills EJ. Lancet HIV. 2017 Jan;4(1):e31-e40. doi: 10.1016/S2352-3018(16)30206-5. Epub 2016 Nov 16.

Background: High adherence to antiretroviral therapy is crucial to the success of HIV treatment. We evaluated comparative effectiveness of adherence interventions with the aim of informing the WHO's global guidance on interventions to increase adherence.

Methods: For this systematic review and network meta-analysis, we searched for randomised controlled trials of interventions that aimed to improve adherence to antiretroviral therapy regimens in populations with HIV. We searched Cochrane Central Register of Controlled Trials, Embase, and MEDLINE for reports published up to July 16, 2015, and searched major conference abstracts from Jan 1, 2013, to July 16, 2015. We extracted data from eligible studies for study characteristics, interventions, patients' characteristics at baseline, and outcomes for the study populations of interest. We used network meta-analyses to compare adherence and viral suppression for all study settings (global network) and for studies in low-income and middle-income countries only (LMIC network).

Findings: We obtained data from 85 trials with 16 271 participants. Short message service (SMS; text message) interventions were superior to standard of care in improving adherence in both the global network (odds ratio [OR] 1.48, 95% credible interval [CrI] 1.00-2.16) and in the LMIC network (1.49, 1.04-2.09). Multiple interventions showed generally superior adherence to single interventions, indicating additive effects. For viral suppression, only cognitive behavioural therapy (1.46, 1.05-2.12) and supporter interventions (1.28, 1.01-1.71) were superior to standard of care in the global network; none of the interventions improved viral response in the LMIC network. For the global network, the time discrepancy (whether the study outcome was measured during or after intervention was withdrawn) was an effect modifier for both adherence to antiretroviral therapy (coefficient estimate -0.43, 95% CrI -0.75 to -0.11) and viral suppression (-0.48; -0.84 to -0.12), suggesting that the effects of interventions wane over time.

Interpretation: Several interventions can improve adherence and viral suppression; generally, their estimated effects were modest and waned over time.

Abstract access  

Editor’s notes: Maintaining adherence to self-administered medications is difficult. On average, people who are prescribed medications for chronic diseases take fewer than half the prescribed doses. Evidence suggests that in most settings adherence to antiretroviral therapy (ART) is better than this, but there will always be people that struggle to maintain the high levels of adherence required for durable virologic suppression. In this analysis, there was some evidence that specific activities or combinations of activities improved virologic suppression. However, the effect sizes were small and when the analysis was confined to studies in low-income and middle-income countries, there was no evidence to suggest an effect on virologic suppression. Overall the evidence to support any particular activity or combination of activities was not compelling.     

Findings from this analysis have been incorporated into most recent consolidated ART guidelines from the World Health Organization. Trying to summarize complex evidence in this way creates many challenges. Trials were conducted in different populations. Some with all people starting ART, others with people considered to have high risk of suboptimal adherence, and others with people who already had adherence problems. The trials also naturally would have differed in content and quality of the usual package of care to support adherence (the comparator for most programme). 60% of the trials were conducted exclusively in the United States, while others were conducted across different settings.

These are just some of the things that make it difficult to synthesize this evidence into guidance that can be applicable to people living with HIV worldwide. HIV programmes in countries have to decide whether or not to adopt any of these activities that are recommended by WHO on the basis of relatively weak evidence. Would we expect activities aimed at improving adherence to be generalizable across different settings? One might argue probably not. Adherence is a multifactorial, dynamic process and there is unlikely to be a ‘one size fits all’ approach to supporting adherence. In the absence of better evidence for any specific activity, we should perhaps focus on improving the quality of the basic package of adherence support offered to all people receiving ART, while also developing better ways to identify when certain people might benefit from enhanced support.        

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Dolutegravir in the real world – more intolerance than first thought?

Intolerance of dolutegravir-containing combination antiretroviral therapy regimens in real-life clinical practice.

de Boer MG, van den Berk GE, van Holten N, Oryszcyn JE, Dorama W, Moha DA, Brinkman K. AIDS. 2016 Nov 28;30(18):2831-2834.

Objective: Dolutegravir (DGV) is one of the preferred antiretroviral agents in first-line combination antiretroviral therapy (cART). Though considered to be a well tolerated drug, we aimed to determine the actual rate, timing and detailed motivation of stopping DGV in a real-life clinical setting.

Design: A cohort study including all patients who started DGV in two HIV treatment centers in The Netherlands.

Methods: All cART-naive and cART-experienced patients who had started DGV were identified from the institutional HIV databases. Clinical data, including motivation and timing of discontinuation of DGV, were extracted from the patient files. Factors that potentially influenced discontinuation of DGV were compared between patients who stopped or continued DGV by multivariate and Kaplan-Meier analyses.

Results: In total, 556 patients were included, of whom 102 (18.4%) were cART-naive at initiation of DGV. Median follow-up time was 225 days. Overall, in 85 patients (15.3%), DGV was stopped. In 76 patients (13.7%), this was due to intolerability. Insomnia and sleep disturbance (5.6%), gastrointestinal complaints (4.3%) and neuropsychiatric symptoms such as anxiety, psychosis and depression (4.3%) were the predominant reasons for switching DGV. In regimens that included abacavir, DGV was switched more frequently (adjusted relative risk 1.92, 95% confidence interval 1.09-3.38, P log-rank 0.01). No virologic failures were observed.

Conclusion: A relatively high rate of preliminary discontinuation of DGV due to intolerability was detected in our patient population. In particular, DGV was stopped more frequently if the regimen included abacavir. Multiple factors may explain these unexpected postmarketing observations, which warrant further investigation.

Abstract access  

Editor’s notes: The integrase inhibitor dolutegravir has been billed as a very important milestone in the treatment of HIV. Randomized controlled trials reported that not only was it a highly effective antiviral agent, but it also had a high barrier to resistance. Trial data also suggested an excellent safety profile. Trial participants experienced fewer side effects with dolutegravir use compared to many other drugs. For these reasons, dolutegravir is recommended as one of the preferred options for first-line treatment in European and United States treatment guidelines. In addition, it is increasingly becoming a key component in global efforts to expand access to HIV-positive people in low-income countries.

However, with increased use of dolutegravir beyond clinical trials, evidence is growing to suggest that the incidence of side effects is greater than trial data would predict. This study describes the two-year experience of a cohort spanning two medical centres in the Netherlands. It explores the rate and cause of discontinuation of dolutegravir-containing regimes in both antiretroviral therapy naïve and experienced individuals. Of 556 receiving a dolutegravir-containing regimen, just over 15% stopped its use over two years. Adverse effects were cited as the cause in a sizeable 13%. These rates of discontinuation are over five times higher than was reported from clinical trials. The predominant side effects were sleep disturbance and insomnia. Other reactions included gastrointestinal disturbances, anxiety, depression and general malaise. In terms of factors associated with increased risk of discontinuation, only the concomitant use of abacavir was identified.

These results do not detract from the importance of dolutegravir as an antiretroviral agent. Indeed, it is reassuring that in this cohort no virologic failure occurred as result of its discontinuation. The results instead highlight the need for caution concerning recommendations for dolutegravir as a universal first line agent until further data are accrued from real-world experience.

Europe
Netherlands
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Antiretroviral therapy in pregnancy is not associated with an increased risk of preterm delivery

PMTCT Option B+ does not increase preterm birth risk and may prevent extreme prematurity: A retrospective cohort study in Malawi.

Chagomerana MB, Miller WC, Pence BW, Hosseinipour MC, Hoffman IF, Flick RJ, Tweya H, Mumba S, Chibwandira F, Powers KA. J Acquir Immune Defic Syndr. 2016 Nov 21. [Epub ahead of print]

Objective: To estimate preterm birth risk among infants of HIV-infected women in Lilongwe, Malawi according to maternal antiretroviral therapy (ART) status and initiation time under Option B+.

Design: Retrospective cohort study of HIV-infected women delivering at ≥27 weeks of gestation, April 2012- November 2015. Among women on ART at delivery, we restricted our analysis to those who initiated ART before 27 weeks of gestation.

Methods: We defined preterm birth as a singleton live birth at ≥27 and <37 weeks of gestation, with births at <32 weeks classified as extremely to very preterm. We used log-binomial models to estimate risk ratios (RR) and 95% confidence intervals (CIs) for the association between ART and preterm birth.

Results: Among 3074 women included in our analyses, 731 preterm deliveries were observed (24%). Overall preterm birth risk was similar in women who had initiated ART at any point before 27 weeks and those who never initiated ART (RR = 1.14; 95% CI: 0.84 - 1.55), but risk of extremely to very preterm birth was 2.33 (1.39 - 3.92) times as great in those who never initiated ART compared to those who did at any point before 27 weeks. Among women on ART before delivery, ART initiation before conception was associated with the lowest preterm birth risk.

Conclusions: ART during pregnancy was not associated with preterm birth, and it may in fact be protective against severe adverse outcomes accompanying extremely to very preterm birth. As pre-conception ART initiation appears especially protective, long-term retention on ART should be a priority to minimize preterm birth in subsequent pregnancies.

Abstract access  

Editor’s notes: Effectively delivered antiretroviral therapy (ART) in pregnancy virtually eliminates the risk of mother-to-child HIV transmission and has been widely adopted. Option B+ is a strategy to start all HIV-positive pregnant women on ART regardless of their CD4 count or other HIV parameters and to continue it indefinitely after delivery to further protect the mother’s health. Balanced against the substantial health gains from the use of ART in pregnancy have been concerns that they may make some adverse pregnancy outcomes more common. Concerns about teratogenicity and birth defects with commonly-used drugs have largely gone as more data has accumulated but prematurity has remained an issue. There has been conflicting evidence from previous studies. Some have suggested an increased risk of preterm birth but others, including meta-analysis, have not. Many earlier studies were predominantly of women with advanced HIV disease, a group with an already-increased risk of preterm birth, and included single- or dual-drug regimens that are no longer recommended. Thus, the results of earlier studies may not be generalizable to women with early stage HIV disease who are being offered newer ART regimens in the context of Option B+.

This study has shown no increase in preterm birth associated with ART in pregnancy, and in fact a statistically and clinically significant protective effect for very early birth (before 32 weeks gestational age). It is a large, thorough and impressive piece of work but has the limitations of any observational study. The risk of unmeasured confounders can never be eliminated; in this case perhaps economic status or level of education. No precise data are presented on the ARV combinations used but it is implied that the great majority of women received efavirenz-based treatment, in accordance with national guidelines in Malawi. Previous studies have suggested that protease inhibitors may be responsible for increased preterm birth. The present study cannot address this question.

This large study of pregnancy outcomes from Option B+ should reassure HIV-positive women and their clinicians that no significant harms were found to be associated with this strategy.  

Africa
Malawi
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