Articles tagged as "Thailand"

Men who have sex with men in sub-Saharan Africa: a review of the evidence

Emerging themes for sensitivity training modules of African healthcare workers attending to men who have sex with men: a systematic review.

Dijkstra M, van der Elst EM, Micheni M, Gichuru E, Musyoki H, Duby Z, Lange JM, Graham SM, Sanders EJ. Int Health. 2015 May;7(3):151-162. Epub 2015 Jan 16.

Sensitivity training of front-line African health care workers (HCWs) attending to men who have sex with men (MSM) is actively promoted through national HIV prevention programming in Kenya. Over 970 Kenyan-based HCWs have completed an eight-modular online training free of charge ( since its creation in 2011. Before updating these modules, we performed a systematic review of published literature of MSM studies conducted in sub-Saharan Africa (sSA) in the period 2011-2014, to investigate if recent studies provided: important new knowledge currently not addressed in existing online modules; contested information of existing module topics; or added depth to topics covered already. We used learning objectives of the eight existing modules to categorise data from the literature. If data could not be categorised, new modules were suggested. Our review identified 142 MSM studies with data from sSA, including 34 studies requiring module updates, one study contesting current content, and 107 studies reinforcing existing module content. ART adherence and community engagement were identified as new modules. Recent MSM studies conducted in sSA provided new knowledge, contested existing information, and identified new areas of MSM service needs currently unaddressed in the online training.

Abstract  Full-text [free] access

Editor’s notes: Same sex practices remain criminalised in sub-Saharan Africa. Gay men and other men who have sex with men face stigma, discrimination, harassment and arrest. Health care workers frequently have no training on issues affecting gay men and other men who have sex with men and are ill-prepared to work sensitively with them. Together these can deter these men from accessing health care and HIV/STI services, increasing their risk of HIV and other poor health outcomes.

This study conducted a systematic review of gay men and other men who have sex with men in sub-Saharan Africa. The findings were used to update an on-line training programme for health care workers in Kenya. This previously comprised modules on i) men who have sex with men and HIV in Africa ii) homophobia: stigma and its effects; iii) sexual identity, coming out and disclosure; iv) anal sex and common sexual practices; v) HIV and STIs; vi) condom and lubricant use; vii) mental health: anxiety, depression and substance use; and viii) risk-reduction counselling. The review updated the training programme with new evidence and two new modules were introduced: ix) ART adherence; and x) community engagement.

Health care workers play a crucial role in reducing stigma and discrimination facing gay men and other men who have sex with men. This systematic review provided a valuable step in updating an important, accessible training programme. Reducing homoprejudice and ensuring health care workers have accurate and up-to-date knowledge are key to improving service uptake by gay men and other men who have sex with men.

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Pooled ribonucleic acid testing to maximize detection of acute HIV infection

Impact of nucleic acid testing relative to antigen/antibody combination immunoassay on the detection of acute HIV infection.

De Souza MS, Phanuphak N, Pinyakorn S, Trichavaroj R, Pattanachaiwit S, Chomchey N, Fletcher JL, Kroon ED, Michael NL, Phanuphak P, Kim JH, Ananworanich J, RV254SEARCH 010 Study Group. AIDS. 2015 Apr 24;29(7):793-800. doi: 10.1097/QAD.0000000000000616.

Objective: To assess the addition of HIV nucleic acid testing (NAT) to fourth-generation (4thG) HIV antigen/antibody combination immunoassay in improving detection of acute HIV infection (AHI).

Methods: Participants attending a major voluntary counseling and testing site in Thailand were screened for AHI using 4thG HIV antigen/antibody immunoassay and sequential less sensitive HIV antibody immunoassay. Samples nonreactive by 4thG antigen/antibody immunoassay were further screened using pooled NAT to identify additional AHI. HIV infection status was verified following enrollment into an AHI study with follow-up visits and additional diagnostic tests.

Results: Among 74 334 clients screened for HIV infection, HIV prevalence was 10.9% and the overall incidence of AHI (N = 112) was 2.2 per 100 person-years. The inclusion of pooled NAT in the testing algorithm increased the number of acutely infected patients detected, from 81 to 112 (38%), relative to 4thG HIV antigen/antibody immunoassay. Follow-up testing within 5 days of screening marginally improved the 4thG immunoassay detection rate (26%). The median CD4 T-cell count at the enrollment visit was 353 cells/µL and HIV plasma viral load was 598 289 copies/ml.

Conclusion: The incorporation of pooled NAT into the HIV testing algorithm in high-risk populations may be beneficial in the long term. The addition of pooled NAT testing resulted in an increase in screening costs of 22% to identify AHI: from $8.33 per screened patient to $10.16. Risk factors of the testing population should be considered prior to NAT implementation given the additional testing complexity and costs.

Abstract access

Editor’s notes: Acute HIV infection (AHI) is generally defined as the time between HIV acquisition and the appearance of detectable antibodies. Individuals with AHI are highly infectious, at least partly due to high viral load. Effective strategies to identify people with AHI could therefore plausibly reduce transmission, although the extent to which AHI drives transmission at a population level continues to be debated. Although the fourth generation immunoassays, incorporating detection of p24 antigen, have been shown to detect infection earlier, there is still a period during which only HIV ribonucleic acid (RNA) can be detected. High costs limit the routine use of HIV RNA testing for this purpose. Pooling samples is one way to potentially reduce costs.

This research was part of a study aimed at detection and treatment of AHI in an urban population of predominantly gay men and other men who have sex with men in Bangkok. Samples that tested negative on fourth generation immunoassay were pooled (median pool size was 14 samples) before undergoing HIV RNA testing. Some 31 pools were positive (0.5% of pools tested) and one positive specimen was then identified from each of those pools. Overall, this constituted only around a quarter of all AHI cases detected. The remainder were defined as AHI on the basis of positive fourth generation but negative second and third generation antibody tests. Individuals detected only by HIV RNA had somewhat lower viral loads than people detected by immunoassay. Follow-up testing illustrated that this was a time when viral load was increasing rapidly. This highlights the potential impact that detection and treatment at this stage could have on reducing onward transmission.

Although interpretation of the study is somewhat complicated by the use of several different assays during the study and complicated algorithms to define outcomes, the basic message seems clear. Fourth generation immunoassays may detect the majority of acute infections. But there may still be a role for pooled HIV RNA testing in certain key populations to maximize detection of AHI. This study was not really designed to evaluate the real world impact of the testing strategy, as follow-up was very tightly controlled and almost all people initiated ART within one week. Although there was some basic costing analysis included, more detailed cost-effectiveness studies will be important to understand whether or not pooled HIV RNA testing has a role in routine practice.

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Directly observed PrEP among people who inject drugs – useful for improving adherence?

The impact of adherence to preexposure prophylaxis on the risk of HIV infection among people who inject drugs.

Martin M, Vanichseni S, Suntharasamai P, Sangkum U, Mock PA, Leethochawalit M, Chiamwongpaet S, Curlin ME, Na-Pompet S, Warapronmongkholkul A, Kittimunkong S, Gvetadze RJ, McNicholl JM, Paxton LA, Choopanya K, Bangkok Tenofovir Study Group. AIDS. 2015 Apr 24;29(7):819-24. doi: 10.1097/QAD.0000000000000613.

Objective: To describe participant adherence to daily oral tenofovir in an HIV preexposure prophylaxis (PrEP) trial, examine factors associated with adherence, and assess the impact of adherence on the risk of HIV infection.

Design: The Bangkok Tenofovir Study was a randomized, double-blind, placebo-controlled trial conducted among people who inject drugs, 2005-2012.

Methods: Participants chose daily visits or monthly visits. Study nurses observed participants swallow study drug and both initialed a diary. We assessed adherence using the diary. We examined adherence by age group and sex and used logistic regression to evaluate demographics and risk behaviors as predictors of adherence and Cox regression to assess the impact of adherence on the risk of HIV infection.

Results: A total of 2413 people enrolled and contributed 9665 person-years of follow-up (mean 4.0 years, maximum 6.9 years). The risk of HIV infection decreased as adherence improved, from 48.9% overall to 83.5% for those with at least 97.5% adherence*. In multivariable analysis, men were less adherent than women (P = 0.006) and participants 20-29 years old (P < 0.001) and 30-39 years old (P = 0.01) were less adherent than older participants. Other factors associated with poor adherence included incarceration (P = 0.02) and injecting methamphetamine (P = 0.04).

Conclusion: In this HIV PrEP trial among people who inject drugs, improved adherence to daily tenofovir was associated with a lower risk of HIV infection. This is consistent with trials among MSM and HIV-discordant heterosexual couples and suggests that HIV PrEP can provide a high level of protection from HIV infection.

*The authors mean that effectiveness improved from 48.9% overall to 83.5% in those who were 97.5% adherent.

Abstract access 

Editor’s notes: Randomised controlled trials have illustrated that daily oral tenofovir as pre-exposure prophylaxis (PrEP) can reduce HIV transmission. In this study, using data from the only PrEP trial to be completed among people who inject drugs, the investigators assessed the impact of directly-observed adherence to PrEP on the incidence of HIV infection in the Bangkok Tenofovir Study. Adherence was defined as the proportion of days recorded in the participants’ diaries that the participant took the study drug.  On average, participants took the study drug on 84% of days. Their findings of a strong association of increasing levels of adherence with reduced risk of HIV infection add to existing literature on the importance of adherence for PrEP effectiveness among gay men and other men who have sex with men and HIV-discordant couples. The novelty of this study was to directly observe adherence to PrEP.  Directly observed ART treatment has been used in prisons and drug treatment centres, and the potential of this method to improve adherence estimation is interesting.

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Screening for and treating cryptococcal infection – better evidence of impact necessary

Cryptococcal antigen screening and early antifungal treatment to prevent cryptococcal meningitis: a review of the literature.

Kaplan JE, Vallabhaneni S, Smith RM, Chideya-Chihota S, Chehab J, Park B. J Acquir Immune Defic Syndr. 2015 Apr 15;68 Suppl 3:S331-9. doi: 10.1097/QAI.0000000000000484.

Background: Screening individuals with AIDS for serum cryptococcal antigen (CrAg), followed by treatment of CrAg positives with antifungals, may prevent cryptococcal meningitis. This review examined data on CrAg screening and treatment in resource-limited settings.

Methods: We searched articles published during 2007-2014 on the effectiveness and cost-effectiveness of CrAg screening and treatment on the outcomes of mortality, morbidity, retention in care, quality of life, and/or prevention of ongoing HIV transmission. We rated overall quality of individual articles, summarized the body of evidence, the expected impact, and cost-effectiveness for each outcome.

Results: We identified 2613 articles. Eight met all inclusion criteria. Five studies addressed mortality and/or morbidity outcomes; all were observational and had small sample sizes; 3 lacked a comparison group. Ratings of study quality ranged from "medium" to "weak," and the quality of the overall body of evidence for mortality and morbidity outcomes was rated as "fair." The intervention's expected impact on mortality and morbidity was rated as "moderate." The 4 cost-effectiveness studies included in the analysis showed that CrAg screening and treatment interventions are highly cost-effective. No studies addressed retention in care, quality of life, or HIV transmission.

Conclusions: Although limited, the body of evidence regarding CrAg screening and treatment suggests that the intervention may have an impact on preventing cryptococcal meningitis and death in persons with AIDS. Additional research is needed to quantify the intervention's effectiveness and identify optimal treatment dosing and implementation best practices.

Abstract access 

Editor’s notes: This systematic review was one of a series aimed at evaluating the impact of services supported by the US President’s Emergency Plan for AIDS Relief (PEPFAR). The review set out to assess the evidence around the impact of targeted cryptococcal antigen (CrAg) testing and antifungal treatment for people with advanced HIV disease. In 2011 World Health Organization (WHO) gave a conditional recommendation, based on low quality evidence, that adults with CD4 count <100 cells per μL, in populations where the CrAg prevalence is above 3%, should undergo CrAg screening and be provided with antifungal treatment if CrAg positive.

The quality of the evidence was rated using a system adapted from the US Preventive Services Task Force. Five observational studies that evaluated the impact of the CrAg screening and antifungal treatment approach on mortality were included. Most of these did not have a comparator. One study used a historical control group from the same facility and another study compared mortality in people who received fluconazole following a positive CrAg, to people who did not. All studies had a very small number of deaths. In the five studies, mortality in people testing CrAg positive and receiving fluconazole varied between 0 and 29%. Based on these studies it would be difficult to evaluate the true impact of the strategy on mortality.

Four cost-effectiveness studies from different settings were also reviewed. All four studies suggested that a strategy with CrAg screening and antifungal treatment would be cost-effective. However, the cost-effectiveness modelling was based on data from the observational studies mentioned above and required other assumptions based on low quality evidence, leading to substantial uncertainty around the cost-effectiveness estimates.

Although a few countries have already implemented CrAg screening and antifungal treatment strategies, better quality evidence is necessary to inform management more broadly in countries with a high burden of cryptococcal disease. Some evidence has already appeared, with a randomised controlled trial in Tanzania and Zambia demonstrating a reduction in mortality with a CrAg screening strategy combined with a community support package during the early phase of antiretroviral therapy (see HIV This Month Issue 4). In addition there are three other randomised controlled trials exploring the impact of CrAg screening, ongoing or planned in Uganda, Zimbabwe and Viet Nam (NCT01535469, NCT02434172, and NCT02334670). It is hoped that the evidence generated by these studies will improve our understanding of the impact of a CrAg screening strategy and also give further insight into how best to implement this in different health care settings.   

Avoid TB deaths
Africa, Asia
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Economic strengthening programmes for people living with HIV may increase their quality of life

The impact of social services interventions in developing countries: a review of the evidence of impact on clinical outcomes in people living with HIV.

Bateganya MH, Dong M, Oguntomilade J, Suraratdecha C. J Acquir Immune Defic Syndr. 2015 Apr 15;68 Suppl 3:S357-67. doi: 10.1097/QAI.0000000000000498.

Background: Social service interventions have been implemented in many countries to help people living with HIV (PLHIV) and household members cope with economic burden as a result of reduced earning or increased spending on health care. However, the evidence for specific interventions-economic strengthening and legal services-on key health outcomes has not been appraised.

Methods: We searched electronic databases from January 1995 to May 2014 and reviewed relevant literature from resource-limited settings on the impact of social service interventions on mortality, morbidity, retention in HIV care, quality of life, and ongoing HIV transmission and their cost-effectiveness.

Results: Of 1685 citations, 8 articles reported the health impact of economic strengthening interventions among PLHIV in resource-limited settings. None reported on legal services. Six of the 8 studies were conducted in sub-Saharan Africa: 1 reported on all 5 outcomes and 2 reported on 4 and 2 outcomes, respectively. The remaining 5 reported on 1 outcome each. Seven studies reported on quality of life. Although all studies reported some association between economic strengthening interventions and HIV care outcomes, the quality of evidence was rated fair or poor because studies were of low research rigor (observational or qualitative), had small sample size, or had other limitations. The expected impact of economic strengthening interventions was rated as high for quality of life but uncertain for all the other outcomes.

Conclusions: Implementation of economic strengthening interventions is expected to have a high impact on the quality of life for PLHIV but uncertain impact on mortality, morbidity, retention in care, and HIV transmission. More rigorous research is needed to explore the impact of more targeted intervention components on health outcomes.

Abstract access 

Editor’s notes: To mitigate the impact of HIV on people living with HIV and their households, economic strengthening programmes and legal services have often been implemented. However, few have been rigorously evaluated in terms of their impact on HIV outcomes. This review of the literature reveals a limited and weak evidence base on the impact of such social services programmes for people living with HIV on mortality, morbidity, retention in HIV care, quality of life, and ongoing HIV transmission. It only identifies eight studies, all of them on economic strengthening activities, and most of them qualitative or observational in design. The authors conclude that the evidence suggests a high impact of such programmes on the quality of life for people living with HIV, which was consistently reported in the studies identified. Access to other confounding services, such as ART and broader community-based support, requires these findings to be interpreted with caution.     

The study clearly highlights the need for more rigorous impact and economic evaluations in this area. Indeed, the review did not identify any studies considering costs or cost-effectiveness. The authors also recommend more research into the feasibility and sustainability of these programmes, as well as greater focus of the implemented programmes on population groups in the greatest need.  

Africa, Asia, Latin America
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Can a simple risk score predict chronic kidney disease among people living with HIV?

Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study.

Mocroft A, Lundgren JD, Ross M, Law M, Reiss P, Kirk O, Smith C, Wentworth D, Neuhaus J, Fux CA, Moranne O, Morlat P, Johnson MA, Ryom L, D:A:D study group, the Royal Free Hospital Clinic Cohort, and the INSIGHT, SMART, and ESPRIT study groups. PLoS Med. 2015 Mar 31;12(3):e1001809. doi: 10.1371/journal.pmed.1001809. eCollection 2015.

Background: Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice.

Methods and findings: A total of 17 954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR >60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR ≤60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103 185 person-years of follow-up (PYFU; incidence 6.2/1000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score <0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0-4, 103 events) and high risk groups (risk score ≥5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1702 (95% CI 1166-3367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2548 individuals, of whom 94 individuals developed CKD (3.7%) during 18 376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria.

Conclusions: Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.

Abstract  Full-text [free] access

Editor’s notes: The nephrotoxicity of antiretroviral drugs, particularly tenofovir, is of concern, particularly where there is limited access to laboratory monitoring of kidney function. The development of kidney impairment among people with HIV is associated with poor outcomes, and in low resource settings where dialysis is not available this can be catastrophic.

This study, like previous work, attempts to address this problem by developing a risk score for the development of chronic kidney disease (CKD). The strength of this study is the availability of data for over 17 000 men and women living with HIV enrolled in cohort studies for many years, and in over 40 countries globally. The resulting risk score uses nine simple clinical variables which predict CKD both overall, and after starting potentially nephrotoxic antiretrovirals. A short risk score, not including cardiovascular risk factors, which may be more suitable for low resource settings, shows almost as good a prediction of CKD.

So will this risk score become widely used in clinical decision making? For high income countries this tool may be useful to identify people where strategies to prevent cardiovascular and renal disease are best focussed. It may also be useful to identify people at high risk of developing CKD for whom use of tenofovir may be unacceptable, especially when monitoring of kidney function is limited. However, few of the enrolled people were from low and middle income countries, and there was limited information on the race of participants. Therefore, the risk score may need to be validated in low resource settings before it can be widely used. Whether the use of the tool would help to improve clinical outcomes where kidney function is frequently monitored is unclear.

Meanwhile, a new drug formulation, tenofovir alafenamide (TAF), is currently in clinical trials. This appears to be associated with less renal toxicity, and to be safe and well tolerated among adults with decreased kidney function. If future trial results support this evidence, and tenofovir alafenamide becomes widely available, concern about drug nephrotoxicity may become a less pressing clinical issue.

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Potential for psychological programmes for mental disorders among people living with HIV: further studies necessary in sub-Saharan Africa

Psychological interventions for common mental disorders for people living with HIV in low- and middle-income countries: systematic review.

Chibanda D, Cowan FM, Healy JL, Abas M, Lund C. Trop Med Int Health. 2015 Mar 7. doi: 10.1111/tmi.12500. [Epub ahead of print]

Objective: To assess the effectiveness of structured psychological interventions against common mental disorders (CMD) in people living with HIV infection (PLWH), in low- and middle-income countries (LMIC).

Methods: Systematic review of psychological interventions for CMD from LMIC for PLWH, with two-stage screening carried out independently by 2 authors.

Results: Of 190 studies, 5 met inclusion criteria. These were randomised-controlled trials based on the principles of cognitive behaviour therapy (CBT) and were effective in reducing CMD symptoms in PLWH. Follow-up of study participants ranged from 6 weeks to 12 months with multiple tools utilised to measure the primary outcome. Four studies showed a high risk of bias, while 1 study from Iran met low risk of bias in all 6 domains of the Cochrane risk of bias tool and all 22 items of the CONSORT instrument.

Conclusion: There is a need for more robust and adequately powered studies to further explore CBT-based interventions in PLWH. Future studies should report on components of the psychological interventions, fidelity measurement and training, including supervision of delivering agents, particularly where lay health workers are the delivering agent.

Abstract   Full-text [free] access

Editor’s notes: Common mental disorders (CMD) including depression and anxiety, are highly prevalent among people living with HIV and contribute to poor HIV outcomes, including treatment failure. However, the lack of mental health professionals in many low- and middle-income countries means that lay health workers can play an important role in treating CMD. This has been well-documented from non-HIV settings, but not among people living with HIV. This systematic review found that few studies have rigorously evaluated the effectiveness of psychological programmes for CMD among people living with HIV (and only one from sub-Saharan Africa), but all of these reported benefits in the activity arm compared to the control arm. This suggests that further, large, well-designed trials are necessary to evaluate such activities especially in countries most severely affected by HIV in southern and eastern Africa. Key points raised by this review include the need for locally validated tools to assess mental health outcomes in future trials. The importance of formative work to develop and finalise the programme for the trial setting, including local stakeholders, systems for assessing the fidelity of the activity, and a referral or supervision plan, is ever more emphasized.  

Africa, Asia
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Barriers and facilitators of safer sexual behaviour for people living with HIV on ART

Intimacy versus isolation: a qualitative study of sexual practices among sexually active HIV-infected patients in HIV care in Brazil, Thailand, and Zambia.

Closson EF, Mimiaga MJ, Sherman SG, Tangmunkongvorakul A, Friedman RK, Limbada M, Moore AT, Srithanaviboonchai K, Alves CA, Roberts S, Oldenburg CE, Elharrar V, Mayer KH, Safren SA, HPTN063 study team. PLoS One. 2015 Mar 20;10(3):e0120957. doi: 10.1371/journal.pone.0120957. eCollection 2015.

The success of global treatment as prevention (TasP) efforts for individuals living with HIV/AIDS (PLWHA) is dependent on successful implementation, and therefore the appropriate contribution of social and behavioral science to these efforts. Understanding the psychosocial context of condomless sex among PLWHA could shed light on effective points of intervention. HPTN 063 was an observational mixed-methods study of sexually active, in-care PLWHA in Thailand, Zambia, and Brazil as a foundation for integrating secondary HIV prevention into HIV treatment. From 2010-2012, 80 qualitative interviews were conducted with PLWHA receiving HIV care and reported recent sexual risk. Thirty men who have sex with women (MSW) and 30 women who have sex with men (WSM) participated in equal numbers across the sites. Thailand and Brazil also enrolled 20 biologically-born men who have sex with men (MSM). Part of the interview focused on the impact of HIV on sexual practices and relationships. Interviews were recorded, transcribed, translated into English and examined using qualitative descriptive analysis. The mean age was 25 (SD = 3.2). There were numerous similarities in experiences and attitudes between MSM, MSW and WSM across the three settings. Participants had a high degree of HIV transmission risk awareness and practiced some protective sexual behaviors such as reduced sexual activity, increased use of condoms, and external ejaculation. Themes related to risk behavior can be categorized according to struggles for intimacy and fears of isolation, including: fear of infecting a sex partner, guilt about sex, sexual communication difficulty, HIV-stigma, and worry about sexual partnerships. Emphasizing sexual health, intimacy and protective practices as components of nonjudgmental sex-positive secondary HIV prevention interventions is recommended. For in-care PLWHA, this approach has the potential to support TasP. The overlap of themes across groups and countries indicates that similar intervention content may be effective for a range of settings.

Abstract   Full-text [free] access

Editor’s notes: Antiretroviral therapy has transformed the lives of many people living with HIV, holding the promise of sustaining health well into older age. Yet, as the authors of this paper remind us, HIV remains a stigmatised condition. Because of the fear and prejudice which continue to surround HIV, living with the infection while on antiretroviral therapy remains challenging not least because of its impact on intimate relationships. Using qualitative data from three very different cultural settings, the authors illustrate the continuing impact of HIV infection on the lives of people taking antiretroviral therapy. Many people in the study were keen to reduce the risk of infecting others through risky sexual behaviour. As a consequence, some struggled to establish and sustain intimate relationships trapped in feelings of shame about their infection and guilt about sexual enjoyment. The findings in this paper are not new. But what is interesting is how similar the experience of women and men living with HIV was across the different settings. As the health of more and more people living with HIV is sustained through antiretroviral therapy, there is a continuing and urgent need for programmes that address the fears and concerns that they may have about sexual behaviour. 

Africa, Asia, Latin America
Brazil, Thailand, Zambia
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Boosted protease inhibitor monotherapy as second-line ART: a strategy for resource-limited settings?

Lopinavir/ritonavir monotherapy as second-line antiretroviral treatment in resource-limited settings - week 104 analysis of ACTG A5230.

Kumarasamy N, Aga E, Ribaudo HJ, Wallis CL, Katzenstein DA, Stevens WS, Norton MR, Klingman KL, Hosseinipour MC, Crump JA, Supparatpinyo K, Badal-Faesen S, Bartlett JA. Clin Infect Dis. 2015 Feb 18. pii: civ109. [Epub ahead of print]

Objective: ACTG A5230 evaluated lopinavir/ritonavir (LPV/r) monotherapy following virologic failure on first-line regimens in Africa and Asia.

Methods: Eligible subjects had received first-line regimens for at least 6 months and had plasma HIV-1 RNA levels 1000-200 000copies/mL. All subjects received LPV/r 400/100mg twice daily. Virologic failure (VF) was defined as failure to suppress to <400 copies/mL by week 24, or confirmed rebound to >400 copies/mL at or after week 16 following confirmed suppression. Subjects with VF added emtricitabine 200mg/tenofovir 300mg (FTC/TDF) once daily. The probability of continued HIV-1 RNA <400 copies/mL on LPV/r-monotherapy through week 104 was estimated with a 95% confidence interval (CI); predictors of treatment success were evaluated with Cox proportional hazards models.

Results: 123 subjects were enrolled. Four subjects died and 2 discontinued prematurely; 117 /123 (95%) completed 104 weeks. Through week 104, 49 subjects met the primary endpoint; 47 had VF, and 2 intensified treatment without VF. Of the 47 subjects with VF, 41 (33%) intensified treatment, and 39/41 subsequently achieved levels <400 copies/mL. The probability of continued suppression <400copies/mL over 104 weeks on LPV/r-monotherapy was 60% [95% CI 50%, 68%]; 80-85% maintained levels <400 copies/mL with FTC/TDF intensification as needed. Ultrasensitive assays on specimens with HIV-1 RNA level<400 copies/mL at weeks 24, 48 and 104 revealed that 61%, 62% and 65% were suppressed to <40 copies/mL, respectively.

Conclusion: LPV/r monotherapy after first-line virologic failure with FTC/TDF intensification when needed provides durable suppression of HIV-1 RNA over 104 weeks.

Abstract access 

Editor’s notes: First-line antiretroviral therapy failure is increasingly encountered in resource-limited settings. However limited access to viral load monitoring means that treatment failure is often not recognised until immunological or clinical failure occurs. Late switching can lead to the accumulation of resistance mutations. Resistance to nucleoside reverse transcriptase inhibitors (NRTI) is of particular concern as this class remains a component of second-line, boosted protease inhibitor (bPI)-based regimens. Several studies have now looked at boosted protease inhibitor monotherapy as an alternative strategy. A strategy which aims to limit the toxicity and additional cost associated with NRTIs. In general boosted protease inhibitor monotherapy has been found to have inferior virologic outcomes when compared to bPI plus two NRTIs or bPI plus raltegravir.

In this study, while short term virologic outcomes were favourable (87% probability of continued virologic suppression over 24 weeks); longer term outcomes with bPI monotherapy were less good. However, with frequent viral load monitoring, 4-12 weekly, early detection of virologic failure and intensification with two NRTIs, outcomes in the bPI monotherapy arm improved substantially. This strategy warrants further investigation. But without markedly increasing access to viral load monitoring and lowering the cost to allow frequent testing, it is difficult to see how this strategy could be implemented in practice in resource-constrained settings. 

HIV Treatment
Africa, Asia
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Adolescent adherence to antiretroviral therapy: what matters?

Factors associated with adherence to antiretroviral therapy among adolescents living with HIV/AIDS in low- and middle-income countries: a systematic review.

Hudelson C, Cluver L. AIDS Care. 2015 Feb 23:1-12. [Epub ahead of print]

Adolescents living in low- and middle-income countries (LMICs) are disproportionately burdened by the global HIV/AIDS pandemic. Maintaining medication adherence is vital to ensuring that adolescents living with HIV/AIDS receive the benefits of antiretroviral therapy (ART), although this group faces unique challenges to adherence. Knowledge of the factors influencing adherence among people during this unique developmental period is needed to develop more targeted and effective adherence-promoting strategies. This systematic review summarizes the literature on quantitative observational studies examining correlates, including risk and resilience-promoting factors, of ART adherence among adolescents living with HIV/AIDS in LMICs. A systematic search of major electronic databases, conference-specific databases, gray literature, and reference lists of relevant reviews and documents was conducted in May 2014. Included studies examined relationships between at least one factor and ART adherence as an outcome and were conducted in primarily an adolescent population (age 10-19) in LMICs. The search identified 7948 unique citations from which 15 studies fit the inclusion criteria. These 15 studies identified 35 factors significantly associated with ART adherence representing a total of 4363 participants across nine different LMICs. Relevant studies revealed few consistent relationships between measured factors and adherence while highlighting potentially important themes for ART adherence including the impact of (1) adolescent factors such as gender and knowledge of serostatus, (2) family structure, (3) the burdensome ART regimens, route of administration, and attitudes about medication, and (4) health care and environmental factors, such as rural versus urban location and missed clinic appointments. Rates of adherence across studies ranged from 16% to 99%. This review identifies unique factors significantly related to ART adherence among adolescents living in LMICs. More research using longitudinal designs and rigorous measures of adherence is required in order to identify the range of factors influencing ART adherence as adolescents living with HIV/AIDS in LMICs grow into adulthood.

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Editor’s notes: Expanded access to antiretroviral therapy (ART) and scale-up of programmes to prevent mother-to-child HIV transmission has resulted in the burden of paediatric HIV infection shifting onto adolescents, in low- and middle-income countries. Adolescents and young adults account for 41% of incident infections globally and are the only age group for which AIDS-associated deaths have risen in the past decade.

As the number of adolescents on ART increases, sustaining optimal adherence has emerged as the key challenge. While there are limited adolescent-specific data available, estimates of ART adherence suggest that adolescents have much poorer adherence than adults. This leads to increased risk of disease progression, transmission to sexual partners and antiretroviral drug resistance.

There is a growing body of literature that has examined factors affecting adherence, but to date the focus has been on adults and young children. Therefore, this systematic review of factors associated with good and suboptimal adherence specifically among adolescents aged 10 to 19 years, is timely.

There were a diverse range of factors associated with adherence across the fifteen studies considered. These include knowledge of serostatus, the influence of family structure, burdensome regimens, route of administration (caregiver giving medication versus adolescent self-medicating), and attitudes about medication and missed appointments. These factors likely interact with the complexities faced during adolescence to increase the risk of suboptimal adherence.   

The studies considered in this review had significant weaknesses. Firstly, most studies were cross-sectional. Therefore the extent to which causality between the considered factors and adherence can be inferred is limited. Secondly, not all studies reported on the strengths of the relationship between the factors and adherence or accounted for confounding. Thirdly, the method of measuring adherence varied between studies. Only one study in the review used a gold standard, objective treatment outcome measure, HIV viral load.

Notwithstanding these limitations, this is the first study to examine correlates of adherence to ART in adolescence. Although there were few consistent relationships between these factors and adherence, the study does suggest potential activities to improve adherence.

Given the central role of adolescents in determining the trajectory of the HIV epidemic, there is a need for more rigorous research to define factors affecting adherence behaviours among adolescents. Programmes addressing important risk- and resilience-promoting factors such as caregiver support and less burdensome regimens have potential to improve adherence. 

Africa, Asia, Europe, Latin America
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