Articles tagged as "Brazil"

When to switch to second-line ART in children?

HIV-1 drug resistance and second-line treatment in children randomized to switch at low versus higher RNA thresholds.

Harrison L, Melvin A, Fiscus S, Saidi Y, Nastouli E, Harper L, Compagnucci A, Babiker A, McKinney R, Gibb D, Tudor-Williams G; PENPACT-1 (PENTA 9PACTG 390) Study Team. J Acquir Immune Defic Syndr. 2015 Sep 1;70(1):42-53. doi: 10.1097/QAI.0000000000000671.

Background: The PENPACT-1 trial compared virologic thresholds to determine when to switch to second-line antiretroviral therapy (ART). Using PENPACT-1 data, we aimed to describe HIV-1 drug resistance accumulation on first-line ART by virologic threshold.

Methods: PENPACT-1 had a 2 x 2 factorial design, randomizing HIV-infected children to start protease inhibitor (PI) versus nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART, and switch at a 1000 copies/mL versus 30 000 copies/mL threshold. Switch criteria were not achieving the threshold by week 24, confirmed rebound above the threshold thereafter, or Center for Disease Control and Prevention stage C event. Resistance tests were performed on samples ≥1000 copies/mL before switch, resuppression, and at 4-years/trial end.

Results: Sixty-seven children started PI-based ART and were randomized to switch at 1000 copies/mL (PI-1000), 64 PIs and 30 000 copies/mL (PI-30 000), 67 NNRTIs and 1000 copies/mL (NNRTI-1000), and 65 NNRTI and 30 000 copies/mL (NNRTI-30 000). Ninety-four (36%) children reached the 1000 copies/mL switch criteria during 5-year follow-up. In 30 000 copies/mL threshold arms, median time from 1000 to 30 000 copies/mL switch criteria was 58 (PI) versus 80 (NNRTI) weeks (P = 0.81). In NNRTI-30 000, more nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations accumulated than other groups. NNRTI mutations were selected before switching at 1000 copies/mL (23% NNRTI-1000, 27% NNRTI-30 000). Sixty-two children started abacavir + lamivudine, 166 lamivudine + zidovudine or stavudine, and 35 other NRTIs. The abacavir + lamivudine group acquired fewest NRTI mutations. Of 60 switched to second-line, 79% PI-1000, 63% PI-30 000, 64% NNRTI-1000, and 100% NNRTI-30 000 were <400 copies/mL 24 weeks later.

Conclusions: Children on first-line NNRTI-based ART who were randomized to switch at a higher virologic threshold developed the most resistance, yet resuppressed on second-line. An abacavir + lamivudine NRTI combination seemed protective against development of NRTI resistance.

Abstract access 

Editor’s notes: Paediatric guidelines recommend that children living with HIV initiate ART early in life. Therefore duration of treatment is likely to be for several decades in children. Children have tended to be maintained on failing therapies longer than adults due to limited treatment options, particularly in resource-limited settings.

The PENPACT-1 trial compared two HIV viral load thresholds, <1000 and <30 000 copies/ml, for switching to second-line ART among children taking non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI)-based first-line regimens. As expected, children starting NNRTIs as their first-line regimen developed more NRTI mutations than children starting on boosted PIs. Importantly, children switching to second line ART at the higher viral load threshold were much more likely to develop resistance if they were taking NNRTI as their first line regimen than if they were taking boosted PIs. The study highlights the more “forgiving” nature of the PI drug class in terms of development of drug resistance. The main implication of this finding is that delayed switching on PI-based ART is a safe option in settings where future drug options are limited, as the risk of development of clinically significant PI or NRTI mutations is low. Interestingly, use of an abacavir + lamivudine nucleoside backbone resulted in fewer thymidine analogue mutations (TAMs) than use of lamivudine + zidovudine or stavudine backbone. This finding was based on analysis of non-randomised data, but supports the current WHO recommendations to use abacavir as the first-line drug of choice in the NRTI backbone.

HIV Treatment
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Better integration of programmes against alcohol use necessary at every step of the HIV treatment cascade

The impact of alcohol use and related disorders on the HIV continuum of care: a systematic review: alcohol and the HIV continuum of care.

Vagenas P, Azar MM, Copenhaver MM, Springer SA, Molina PE, Altice FL. Curr HIV/AIDS Rep. 2015 Sep 28. [Epub ahead of print]

Alcohol use is highly prevalent globally with numerous negative consequences to human health, including HIV progression, in people living with HIV (PLH). The HIV continuum of care, or treatment cascade, represents a sequence of targets for intervention that can result in viral suppression, which ultimately benefits individuals and society. The extent to which alcohol impacts each step in the cascade, however, has not been systematically examined. International targets for HIV treatment as prevention aim for 90% of PLH to be diagnosed, 90% of them to be prescribed with antiretroviral therapy (ART), and 90% to achieve viral suppression; currently, only 20% of PLH are virally suppressed. This systematic review, from 2010 through May 2015, found 53 clinical research papers examining the impact of alcohol use on each step of the HIV treatment cascade. These studies were mostly cross-sectional or cohort studies and from all income settings. Most (77 %) found a negative association between alcohol consumption on one or more stages of the treatment cascade. Lack of consistency in measurement, however, reduced the ability to draw consistent conclusions. Nonetheless, the strong negative correlations suggest that problematic alcohol consumption should be targeted, preferably using evidence-based behavioral and pharmacological interventions, to indirectly increase the proportion of PLH achieving viral suppression, to achieve treatment as prevention mandates, and to reduce HIV transmission.

Abstract access 

Editor’s notes: This systematic review examined the impact of alcohol consumption on each step of the HIV treatment cascade. This covered HIV diagnosis, linkage to care, retention in care, ART initiation and adherence, and sustained virologic suppression. Overall, there was an association between alcohol consumption and negative consequences on various steps of the treatment cascade. The majority of studies focused on the effect of alcohol use disorders and ART adherence, and on viral suppression. There was fairly consistent evidence of reduced adherence among people with alcohol use disorders. Key findings of this review include the lack of consistency in studies of alcohol consumption. Many studies are not using standardised, validated, measures such as the AUDIT, and there is the lack of studies on the association of alcohol use with earlier stages of the cascade, including testing uptake and linkage to care. Further studies in this area would be useful, to identify whether programmes focused on problematic alcohol use are necessary at HIV testing centres.

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START trial illustrates benefit of ART start with CD4>500

Initiation of antiretroviral therapy in early asymptomatic HIV infection.

Lundgren J, Babiker A,  Gordin F, Emery S, Grund B, Sharma S, Avihingsanon A, Cooper D, Fätkenheuer G, Llibre J, Molina J, Munderi P, Schechter M, Wood R, Klingman K, Collins S, Lane H, Phillips A,  Neaton J. INSIGHT START Study Group. N Engl J Med. 2015 Jul 20. [Epub ahead of print]

Background: Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter.

Methods: We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause.

Results: A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12 759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions.

Conclusions: The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter.

Abstract  Full-text [free] access

Editor’s notes: Guidelines on when to start antiretroviral therapy (ART) are rapidly evolving. The major point of uncertainty, and disagreement between guidelines, has been whether the benefits to individuals of starting ART outweigh the risks for people with high CD4 counts, where the absolute risk of morbidity and mortality is relatively low.

The START study addressed this question among people with CD4 counts greater than 500 cells per µl. Study participants were recruited across the global regions, with the largest number from Europe (33%) followed by Latin America (25%) and Africa (21%). Some 55% were gay men and other men who have sex with men. Retention in the study was very good, and virologic outcomes among people who started ART were excellent (98% and 97% had virologic suppression by 12 months in the immediate versus deferred study arms). There was a 57% reduction in the hazard of the primary outcome, a composite of serious AIDS-associated events, serious non-AIDS associated events or death from any cause. The most common AIDS-associated events were tuberculosis (mostly seen in African participants), malignant lymphoma and Kaposi’s sarcoma. Among the serious non-AIDS events, cancers unrelated to AIDS were reduced by 50%, but interestingly there was no change in cardiovascular events. There was no increase in risk of serious adverse events. Interestingly the magnitude of risk reduction for the primary outcome was similar in high- and low-income countries.

These results will be very important as ART guidelines are reviewed and are likely to lead to recommendations for ART initiation, regardless of CD4 count in most settings. The authors note that, with a relatively low absolute risk of serious events, some people with high CD4 counts may opt to defer treatment, and this trial has produced very useful data to inform this discussion. Benefits from earlier ART initiation are dependent on earlier testing.  With an estimated 50% of people with HIV globally unaware of their status, the uptake of testing by asymptomatic people will need to be increased. In addition, retention in care will need to be optimised if the potential benefits of ART demonstrated by this study are to be realised.

HIV Treatment
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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 (http://www.marps-africa.org) 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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Combination harm reduction may be more effective and cost-effective than partial approaches alone

The cost-effectiveness of harm reduction.

Wilson DP, Donald B, Shattock AJ, Wilson D, Fraser-Hurt N. Int J Drug Policy. 2015 Feb;26 Suppl 1:S5-11. doi: 10.1016/j.drugpo.2014.11.007. Epub 2014 Dec 1.

HIV prevalence worldwide among people who inject drugs (PWID) is around 19%. Harm reduction for PWID includes needle-syringe programs (NSPs) and opioid substitution therapy (OST) but often coupled with antiretroviral therapy (ART) for people living with HIV. Numerous studies have examined the effectiveness of each harm reduction strategy. This commentary discusses the evidence of effectiveness of the packages of harm reduction services and their cost-effectiveness with respect to HIV-related outcomes as well as estimate resources required to meet global and regional coverage targets. NSPs have been shown to be safe and very effective in reducing HIV transmission in diverse settings; there are many historical and very recent examples in diverse settings where the absence of, or reduction in, NSPs have resulted in exploding HIV epidemics compared to controlled epidemics with NSP implementation. NSPs are relatively inexpensive to implement and highly cost-effective according to commonly used willingness-to-pay thresholds. There is strong evidence that substitution therapy is effective, reducing the risk of HIV acquisition by 54% on average among PWID. OST is relatively expensive to implement when only HIV outcomes are considered; other societal benefits substantially improve the cost-effectiveness ratios to be highly favourable. Many studies have shown that ART is cost-effective for keeping people alive but there is only weak supportive, but growing evidence, of the additional effectiveness and cost-effectiveness of ART as prevention among PWID. Packages of combined harm reduction approaches are highly likely to be more effective and cost-effective than partial approaches. The coverage of harm reduction programs remains extremely low across the world. The total annual costs of scaling up each of the harm reduction strategies from current coverage levels, by region, to meet WHO guideline coverage targets are high with ART greatest, followed by OST and then NSPs. But scale-up of all three approaches is essential. These interventions can be cost-effective by most thresholds in the short-term and cost-saving in the long-term.

Abstract   Full-text [free] access

Editor’s notes: The spread of HIV among people who inject drugs has driven epidemics throughout regions of eastern Europe, and central and South-East Asia. In eastern Europe and central Asia, the majority of HIV infections have been attributed to injecting drug use. Some countries in the Middle East and North Africa region have also been experiencing rapidly emerging HIV epidemics among people who inject drugs. Harm reduction refers to methods of reducing health risks when eliminating them may not be possible. This paper provides a comprehensive review of evidence on the effectiveness and cost-effectiveness of different harm reduction approaches. These include needle- syringe programmes, opioid substitution therapy (OST), and antiretroviral therapy (ART), when implemented in different settings. Importantly, alongside considering the potential benefits of each approach separately, it makes the case that combination  prevention strategies are synergistic, and may achieve multiple impacts. Sadly still however, the coverage of harm reduction remains very low across the world. An estimated 90% of people who inject drugs worldwide are not accessing needle-syringe programmes, despite this being a highly effective and cost-effective programme. Along with the need for a greater investment in harm reduction, there are socio-political and legislative reasons for poor coverage of harm reduction. This cannot be improved without first addressing the stigma, discrimination and intolerance that restricts the expansion of harm reduction programmes in many settings. Addressing these barriers remains of paramount importance for facilitating effective harm reduction programmes. Encouragingly however, high OST coverage has been reported in Iran, Czech Republic and western Europe, and several countries in Asia and the Middle East have begun to scale-up their programmes. China has recently had the largest OST scale-up programme in the world. Uptake of ART by people living with HIV who inject drugs illustrates the largest disparities with what is required or deemed to be appropriate access. Only 14% of people living with HIV who inject drugs globally, have access to ART, with the largest gaps in ART provision in eastern Europe and central Asia. The further expansion of harm reduction is urgently needed, both to meet WHO targets, and to achieve the UNAIDS 90-90-90 target.

Asia, Europe, Oceania
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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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Assessing risk behaviour and uptake of HIV care using an online network among MSM in Latin America

Engagement in HIV care and sexual transmission risk behavior among men who have sex with men using online social/sexual networking in Latin America.

Magidson JF, Biello KB, Safren SA, Rosenberger JG, Novak DS, Mayer KH, Mimiaga MJ. AIDS Care. 2015 Mar 4:1-8. [Epub ahead of print]

HIV/AIDS in Latin America is concentrated among men who have sex with men (MSM). However, accurate estimates of engagement in HIV care in this population can be difficult to ascertain because many do not self-identify as MSM. Given evidence of decreased HIV transmissibility in the context of antiretroviral therapy (ART) adherence, identifying individuals not in care who are engaging in HIV transmission risk behavior is crucial for secondary prevention. Primary aims of this study were to examine engagement in care from testing to ART adherence among MSM using online social/sexual networking across Latin America, and whether individuals not in care at each step reported greater sexual transmission risk behavior than those in care. In the overall sample (n = 28 779), approximately 75% reported ever being tested for HIV, and 9% reported having received an HIV diagnosis. Among known HIV-infected individuals, 20% reported not being in care, 30% reported not taking ART, and 55% reported less than 100% ART adherence. Over one-third of HIV-infected individuals reported sexual HIV transmission risk behavior, defined as unprotected anal intercourse (UAI) with a male partner of different/unknown HIV serostatus in the past three months. HIV-infected individuals not engaged in care more often reported UAI compared to those in care (OR = 1.29; 95% CI = 1.01-1.66). Although not statistically significant, HIV-infected individuals not on ART more often reported UAI compared to those on ART (OR = 1.18; 95% CI = 0.94-1.47). Individuals who reported less than 100% ART adherence more often reported UAI compared to individuals with 100% adherence (OR = 1.55; 95% CI = 1.26-1.90). Findings demonstrate that a substantial portion of HIV-infected MSM in Latin America who are likely not virologically suppressed from lack of ART use or adherence report sexual HIV transmission risk. Tailoring secondary HIV prevention for MSM in Latin America who are not in HIV care or adherent to ART may be warranted.

Abstract access

Editor’s notes: The prevalence of HIV among gay men and other men who have sex with men in Latin America and the Caribbean is among the highest in the world. Stigma and discrimination towards gay men and other men who have sex with men  in these settings mean that many do not reveal their sexual preference, do not acknowledge their HIV risk, and do not access HIV diagnosis, care and treatment. This paper describes a large cross-sectional study of almost 30 000 gay men and other men who have sex with men from 17 countries in Latin America, recruited via a social/sexual networking website that they had recently used. The study highlights the substantial difficulty in fully engaging gay men and other men who have sex with men living with HIV, into treatment and care services in this region. This in turn contributes to high HIV prevalence and incidence, through unsafe sexual behaviour and unsuppressed viral load in gay men and other men who have sex with men living with HIV. The authors note that the highest proportion of participants receiving HIV care lived in Brazil, where national efforts have been made to reduce homophobia and to include gay men and other men who have sex with men in HIV prevention initiatives. Similar efforts are required in other Latin American countries if their high levels of HIV transmission in these communities, are to be reduced. This includes innovative methods such as using social networking sites as a platform for delivering programmes.  

Latin America
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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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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.

Abstract access 

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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Is genotype resistance testing cost-effective for the ART naïve?

Cost-effectiveness of genotype testing for primary resistance in Brazil.

Luz PM, Morris BL, Grinsztejn B, Freedberg KA, Veloso VG, Walensky RP, Losina E, Nakamura YM, Girouard MP, Sax PE, Struchiner CJ, Paltiel AD. J Acquir Immune Defic Syndr. 2015 Feb 1;68(2):152-61. doi: 10.1097/QAI.0000000000000426.

Objective: HIV genotype-resistance testing can help identify more effective antiretroviral treatment (ART) regimens for patients, substantially increasing the likelihood of viral suppression and immune recovery. We sought to evaluate the cost-effectiveness of genotype-resistance testing before first-line ART initiation in Brazil.

Design: We used a previously published microsimulation model of HIV disease (CEPAC-International) and data from Brazil to compare the clinical impact, costs, and cost-effectiveness of initial genotype testing (Genotype) with no initial genotype testing (No genotype).

Methods: Model parameters were derived from the HIV Clinical Cohort at the Evandro Chagas Clinical Research Institute and from published data, using Brazilian sources whenever possible. Baseline patient characteristics included 69% male, mean age of 36 years (SD, 10 years), mean CD4 count of 347 per microliter (SD, 300/µL) at ART initiation, annual ART costs from 2012 US $1400 to US $13 400, genotype test cost of US $230, and primary resistance prevalence of 4.4%. Life expectancy and costs were discounted 3% per year. Genotype was defined as "cost-effective" compared with No Genotype if its incremental cost-effectiveness ratio was less than 3 times the 2012 Brazilian per capita GDP of US $12 300.

Results: Compared with No genotype, Genotype increased life expectancy from 18.45 to 18.47 years and reduced lifetime cost from US $45 000 to $44 770; thus, in the base case, Genotype was cost saving. Genotype was cost-effective at primary resistance prevalence as low as 1.4% and remained cost-effective when subsequent-line ART costs decreased to 30% of baseline value. Cost-inefficient results were observed only when simultaneously holding multiple parameters to extremes of their plausible ranges.

Conclusions: Genotype-resistance testing in ART-naive individuals in Brazil will improve survival and decrease costs and should be incorporated into HIV treatment guidelines in Brazil.

Abstract  Full-text [free] access

Editor’s notes: This study aims to provide guidance on when HIV genotype-resistance testing should be used during the course of antiretroviral therapy (ART). Previous studies in high income countries suggest that use prior to ART initiation may be cost-effective. In more resource constrained settings, two previous studies suggest that genotype-resistance testing may be cost-effective following first-line treatment failure. But none have examined use of these tests on the ART-naïve.

This study compares genotype-resistance testing prior to ART initiation to the current policy of testing post treatment failure, for the population of Brazil. The study finds that genotype-resistance testing is likely to be cost saving in Brazil. The authors predict modest increases in life expectancy for individuals on ART. Cost savings are achieved from predicted reductions in complications and the duration of expensive ART regimens. Costs savings are primarily incurred for non-nucleoside reverse-transcriptase inhibitors (NNRTI) resistant people. These savings outweigh the cost of the genotype-resistance test. The study usefully highlights that the extent of cost savings (and cost-effectiveness) depends primarily on test cost, future ART costs and prevalence of NNRTI resistance in the study population. For most plausible ranges of NNRTI prevalence and costs observed in Brazil, genotype-resistance testing prior to ART initiation is likely to be cost-effective. However, both costs and NNRTI prevalence vary by setting; as does the threshold by which technologies are judged to be cost-effective. These factors therefore need to be considered before applying these results to policy change around the use of genotype-resistance testing more broadly.

Latin America
Brazil
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