Articles tagged as "Latin America"

Demand-side activities are essential for achieving population level impact of HIV prevention tools

Interventions to strengthen the HIV prevention cascade: a systematic review of reviews.

Krishnaratne S, Hensen B, Cordes J, Enstone J, Hargreaves JR. Lancet HIV. 2016 Jul;3(7):e307-17. doi: 10.1016/S2352-3018(16)30038-8.

Background: Much progress has been made in interventions to prevent HIV infection. However, development of evidence-informed prevention programmes that translate the efficacy of these strategies into population effect remain a challenge. In this systematic review, we map current evidence for HIV prevention against a new classification system, the HIV prevention cascade.

Methods: We searched for systematic reviews on the effectiveness of HIV prevention interventions published in English from Jan 1, 1995, to July, 2015. From eligible reviews, we identified primary studies that assessed at least one of: HIV incidence, HIV prevalence, condom use, and uptake of HIV testing. We categorised interventions as those seeking to increase demand for HIV prevention, improve supply of HIV prevention methods, support adherence to prevention behaviours, or directly prevent HIV. For each specific intervention, we assigned a rating based on the number of randomised trials and the strength of evidence.

Findings: From 88 eligible reviews, we identified 1964 primary studies, of which 292 were eligible for inclusion. Primary studies of direct prevention mechanisms showed strong evidence for the efficacy of pre-exposure prophylaxis (PrEP) and voluntary medical male circumcision. Evidence suggests that interventions to increase supply of prevention methods such as condoms or clean needles can be effective. Evidence arising from demand-side interventions and interventions to promote use of or adherence to prevention tools was less clear, with some strategies likely to be effective and others showing no effect. The quality of the evidence varied across categories.

Interpretation: There is growing evidence to support a number of efficacious HIV prevention behaviours, products, and procedures. Translating this evidence into population impact will require interventions that strengthen demand for HIV prevention, supply of HIV prevention technologies, and use of and adherence to HIV prevention methods.

Abstract  Full-text [free] access

Editor’s notes: Demand, supply and use of programmes are crucial for the uptake and effective use of HIV prevention strategies. This paper presents an impressive undertaking in which the authors conducted a review of systematic reviews on the evidence for the effectiveness of HIV prevention programmes across the multiple steps in an HIV prevention cascade. This particular prevention cascade allocates programmes into demand-side, supply-side, adherence, and direct HIV prevention technologies. This was published in a separate paper in conjunction with this review. The review found that there is strong evidence with regards to which direct HIV prevention technologies are efficacious, as well as maps where adherence and supply-side programmes have been effective. A primary gap was noted on the demand-side of the cascade (e.g. information, education and communication, and peer-based activities to increase demand for medical male circumcision) where studies have not resulted in reducing HIV incidence or prevalence. There remains a need to understand why, despite supply, there is low uptake of some HIV prevention strategies, and for evaluation of novel activities to increase demand.  

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Negative police activity a structural determinant of HIV

Policing practices as a structural determinant for HIV among sex workers: a systematic review of empirical findings.

Footer KH, Silberzahn BE, Tormohlen KN, Sherman SG. J Int AIDS Soc. 2016 Jul 18;19(4 Suppl 3):20883. doi: 10.7448/IAS.19.4.20883. eCollection 2016.

Introduction: Sex workers are disproportionately infected with HIV worldwide. Significant focus has been placed on understanding the structural determinants of HIV and designing related interventions. Although there is growing international evidence that policing is an important structural HIV determinant among sex workers, the evidence has not been systematically reviewed.

Methods: We conducted a systematic review of quantitative studies to examine the effects of policing on HIV and STI infection and HIV-related outcomes (condom use; syringe use; number of clients; HIV/STI testing and access) among cis and trans women sex workers. Databases included PubMed, Embase, Scopus, Sociological Abstracts, Popline, Global Health (OVID), Web of Science, IBSS, IndMed and WHOLIS. We searched for studies that included police practices as an exposure for HIV or STI infection or HIV-related outcomes.

Results: Of the 137 peer-reviewed articles identified for full text review, 14 were included, representing sex workers' experiences with police across five settings. Arrest was the most commonly explored measure with between 6 and 45% of sex workers reporting having ever been arrested. Sexual coercion was observed between 3 and 37% of the time and police extortion between 12 and 28% across studies. Half the studies used a single measure to capture police behaviours. Studies predominantly focused on "extra-legal policing practices," with insufficient attention to the role of "legal enforcement activities". All studies found an association between police behaviours and HIV or STI infection, or a related risk behaviour.

Conclusions: The review points to a small body of evidence that confirms policing practices as an important structural HIV determinant for sex workers, but studies lack generalizability with respect to identifying those police behaviours most relevant to women's HIV risk environment.

Abstract  Full-text [free] access 

Editor’s notes: The paper reports on a systematic review, which explored how quantitative research to date has operationalized the measurement of law enforcement practices as a structural determinant of HIV for female (including transgender) sex workers. The authors reviewed 14 quantitative studies using policing practices as a micro-structural determinant for HIV risk among sex workers. They found substantial heterogeneity in both the police measures and the health outcomes considered by the different studies. Overall, the studies found that police measures were regularly reported by sex workers, with an average of 34% of sex workers experiencing at least one police measure. They found that arrest was the most commonly explored measure in the studies. Following this, sexual coercion and then police extortion were important.

The studies reported that these police measures were consistently, positively, associated with either HIV infection or STI symptoms or with inconsistent condom use. Having ever been arrested, sexual coercion, police extortion, and syringe confiscation was associated with an increased risk of acquiring an HIV infection or an STI. These measures, and displacement by the police, were also associated with inconsistent condom use. Intervening on interactions between sex workers and the police reduced HIV risk over the time of the programme.

The authors argue that these findings point to the potentially pivotal role that the police have as a structural determinant for HIV in vulnerable populations. However, they argue that nearly all the papers identified in this review fail to take account of the complexities of the risk environment in which law enforcement occurs. The authors thus suggest a need for better measures for legal and extra-legal enforcement practices as mechanisms through which sex workers’ HIV risk is mediated.

Africa, Asia, Europe, Latin America
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The negative health impacts of HIV-associated stigma

Examining the associations between HIV-related stigma and health outcomes in people living with HIV/AIDS: a series of meta-analyses.

Rueda S, Mitra S, Chen S, Gogolishvili D, Globerman J, Chambers L, Wilson M, Logie CH, Shi Q, Morassaei S, Rourke SB. BMJ Open. 2016 Jul 13;6(7):e011453. doi: 10.1136/bmjopen-2016-011453.

Objective: To conduct a systematic review and series of meta-analyses on the association between HIV-related stigma and health among people living with HIV.

Data sources: A structured search was conducted on 6 electronic databases for journal articles reporting associations between HIV-related stigma and health-related outcomes published between 1996 and 2013.

Study eligibility criteria: Controlled studies, cohort studies, case-control studies and cross-sectional studies in people living with HIV were considered for inclusion.

Outcome measures: Mental health (depressive symptoms, emotional and mental distress, anxiety), quality of life, physical health, social support, adherence to antiretroviral therapy, access to and usage of health/social services and risk behaviours.

Results: 64 studies were included in our meta-analyses. We found significant associations between HIV-related stigma and higher rates of depression, lower social support and lower levels of adherence to antiretroviral medications and access to and usage of health and social services. Weaker relationships were observed between HIV-related stigma and anxiety, quality of life, physical health, emotional and mental distress and sexual risk practices. While risk of bias assessments revealed overall good quality related to how HIV stigma and health outcomes were measured on the included studies, high risk of bias among individual studies was observed in terms of appropriate control for potential confounders. Additional research should focus on elucidating the mechanisms behind the negative relationship between stigma and health to better inform interventions to reduce the impact of stigma on the health and well-being of people with HIV.

Conclusions: This systematic review and series of meta-analyses support the notion that HIV-related stigma has a detrimental impact on a variety of health-related outcomes in people with HIV. This review can inform the development of multifaceted, intersectoral interventions to reduce the impact of HIV-related stigma on the health and well-being of people living with HIV.

Abstract  Full-text [free] access 

Editor’s notes: There is a growing body of research documenting the negative impact of stigma and discrimination on the health of people living with HIV. Stigma is associated with poorer mental health, including emotional distress, depression and reduced psychological functioning. It has also been linked to intermediate health outcomes such as seeking healthcare and adherence to antiretroviral therapy. This paper reports a comprehensive systematic review and meta-analyses summarising the published evidence on the relationship between HIV-associated stigma and a wide range of health outcomes, including intermediate health outcomes. Results illustrate associations between HIV-associated stigma and depressive symptoms, lower levels of social support, ART adherence and use of health services. However, the majority of studies in the review were cross-sectional and longitudinal studies are necessary to explore the complex relationship between these factors, including the role of moderating factors, such as coping strategies. In addition, more research is necessary from low- and middle-income countries given that much of the published research is from North America. Further, there is also a need to better understand the intersection of HIV-associated stigma with other types of stigma experienced by people living with HIV, including homophobia, racism and gender discrimination. 

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Accurate country-level data necessary to inform HIV incidence estimates

Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015: the Global Burden of Disease Study 2015.

Wang H, Wolock TM, Carter A, Nguyen G, Kyu HH, Gakidou E, Hay SI, Mills EJ, Trickey A, Msemburi W, Coates MM, Mooney MD, Fraser MS, Sligar A, Salomon J, Larson HJ, Friedman J, Abajobir AA, Abate KH, Abbas KM, Razek MM, Abd-Allah F, Abdulle AM, Abera SF, Abubakar I, Abu-Raddad LJ, Abu-Rmeileh NM, Abyu GY, Adebiyi AO, Adedeji IA, Adelekan AL, Adofo K, Adou AK, Ajala ON, Akinyemiju TF, Akseer N, Lami FH, Al-Aly Z, Alam K, Alam NK, Alasfoor D, Aldhahri SF, Aldridge RW, Alegretti MA, Aleman AV, Alemu ZA, Alfonso-Cristancho R, Ali R, Alkerwi A, Alla F, Mohammad R, Al-Raddadi S, Alsharif U, Alvarez E, Alvis-Guzman N, Amare AT, Amberbir A, Amegah AK, Ammar W, Amrock SM, Antonio CA, Anwari P, Arnlov J, Artaman A, Asayesh H, Asghar RJ, Assadi R, Atique S, Atkins LS, Avokpaho EF, Awasthi A, Quintanilla BP, Bacha U, Badawi A, Barac A, Barnighausen T, Basu A, Bayou TA, Bayou YT, Bazargan-Hejazi S, Beardsley J, Bedi N, Bennett DA, Bensenor IM, Betsu BD, Beyene AS, Bhatia E, Bhutta ZA, Biadgilign S, Bikbov B, Birlik SM, Bisanzio D, Brainin M, Brazinova A, Breitborde NJ, Brown A, Burch M, Butt ZA, Campuzano JC, Cardenas R, Carrero JJ, Castaneda-Orjuela CA, Rivas JC, Catala-Lopez F, Chang HY, Chang JC, Chavan L, Chen W, Chiang PP, Chibalabala M, Chisumpa VH, Choi JY, Christopher DJ, Ciobanu LG, Cooper C, Dahiru T, Damtew SA, Dandona L, Dandona R, das Neves J, de Jager P, De Leo D, Degenhardt L, Dellavalle RP, Deribe K, Deribew A, Des Jarlais DC, Dharmaratne SD, Ding EL, Doshi PP, Driscoll TR, Dubey M, Elshrek YM, Elyazar I, Endries AY, Ermakov SP, Eshrati B, Esteghamati A, Faghmous ID, Farinha CS, Faro A, Farvid MS, Farzadfar F, Fereshtehnejad SM, Fernandes JC, Fischer F, Fitchett JR, Foigt N, Fullman N, Furst T, Gankpe FG, Gebre T, Gebremedhin AT, Gebru AA, Geleijnse JM, Gessner BD, Gething PW, Ghiwot TT, Giroud M, Gishu MD, Glaser E, Goenka S, Goodridge A, Gopalani SV, Goto A, Gugnani HC, Guimaraes MD, Gupta R, Gupta R, Gupta V, Haagsma J, Hafezi-Nejad N, Hagan H, Hailu GB, Hamadeh RR, Hamidi S, Hammami M, Hankey GJ, Hao Y, Harb HL, Harikrishnan S, Haro JM, Harun KM, Havmoeller R, Hedayati MT, Heredia-Pi IB, Hoek HW, Horino M, Horita N, Hosgood HD, Hoy DG, Hsairi M, Hu G, Huang H, Huang JJ, Iburg KM, Idrisov BT, Innos K, Iyer VJ, Jacobsen KH, Jahanmehr N, Jakovljevic MB, Javanbakht M, Jayatilleke AU, Jeemon P, Jha V, Jiang G, Jiang Y, Jibat T, Jonas JB, Kabir Z, Kamal R, Kan H, Karch A, Karema CK, Karletsos D, Kasaeian A, Kaul A, Kawakami N, Kayibanda JF, Keiyoro PN, Kemp AH, Kengne AP, Kesavachandran CN, Khader YS, Khalil I, Khan AR, Khan EA, Khang YH, Khubchandani J, Kim YJ, Kinfu Y, Kivipelto M, Kokubo Y, Kosen S, Koul PA, Koyanagi A, Defo BK, Bicer BK, Kulkarni VS, Kumar GA, Lal DK, Lam H, Lam JO, Langan SM, Lansingh VC, Larsson A, Leigh J, Leung R, Li Y, Lim SS, Lipshultz SE, Liu S, Lloyd BK, Logroscino G, Lotufo PA, Lunevicius R, Razek HM, Mahdavi M, Majdan M, Majeed A, Makhlouf C, Malekzadeh R, Mapoma CC, Marcenes W, Martinez-Raga J, Marzan MB, Masiye F, Mason-Jones AJ, Mayosi BM, McKee M, Meaney PA, Mehndiratta MM, Mekonnen AB, Melaku YA, Memiah P, Memish ZA, Mendoza W, Meretoja A, Meretoja TJ, Mhimbira FA, Miller TR, Mikesell J, Mirarefin M, Mohammad KA, Mohammed S, Mokdad AH, Monasta L, Moradi-Lakeh M, Mori R, Mueller UO, Murimira B, Murthy GV, Naheed A, Naldi L, Nangia V, Nash D, Nawaz H, Nejjari C, Ngalesoni FN, de Dieu Ngirabega J, Nguyen QL, Nisar MI, Norheim OF, Norman RE, Nyakarahuka L, Ogbo FA, Oh IH, Ojelabi FA, Olusanya BO, Olusanya JO, Opio JN, Oren E, Ota E, Padukudru MA, Park HY, Park JH, Patil ST, Patten SB, Paul VK, Pearson K, Peprah EK, Pereira CC, Perico N, Pesudovs K, Petzold M, Phillips MR, Pillay JD, Plass D, Polinder S, Pourmalek F, Prokop DM, Qorbani M, Rafay A, Rahimi K, Rahimi-Movaghar V, Rahman M, Rahman MH, Rahman SU, Rai RK, Rajsic S, Ram U, Rana SM, Rao PV, Remuzzi G, Rojas-Rueda D, Ronfani L, Roshandel G, Roy A, Ruhago GM, Saeedi MY, Sagar R, Saleh MM, Sanabria JR, Santos IS, Sarmiento-Suarez R, Sartorius B, Sawhney M, Schutte AE, Schwebel DC, Seedat S, Sepanlou SG, Servan-Mori EE, Shaikh. Lancet HIV. 2016 Aug;3(8):e361-87. doi: 10.1016/S2352-3018(16)30087-X. Epub 2016 Jul 19.

Background: Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.

Methods: For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification.

Findings: Global HIV incidence reached its peak in 1997, at 3.3 million new infections (95% uncertainty interval [UI] 3.1-3.4 million). Annual incidence has stayed relatively constant at about 2.6 million per year (range 2.5-2.8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38.8 million (95% UI 37.6-40.4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1.8 million deaths (95% UI 1.7-1.9 million) in 2005, to 1.2 million deaths (1.1-1.3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections.

Interpretation: Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030.

Abstract  Full-text [free] access

Editor’s notes: The global estimates for HIV incidence, prevalence, and deaths produced by the Global Burden of Disease (GBD) mathematical modelling approach for 2015 are somewhat higher than those published by UNAIDS in June 2016 prior to the International Conference on AIDS held in Durban in July. Both GBD and UNAIDS agree that as the scale-up of antiretroviral treatment (ART) continues, HIV-associated mortality is declining with the result that HIV prevalence is rising as the number of people living with HIV continues to grow. The metric of critical interest to policy makers and programme planners is HIV incidence, the number of new infections. Each new infection means ART for life, starting from HIV diagnosis now rather than later in disease progression. Both GBD and UNAIDS estimates suggest that globally annual HIV incidence stopped declining after 2005 and has remained persistently high at 2.5 million (2.2-2.7 million) according to GDB and 2.1 million (1.8-2.4 million) according to UNAIDS. Where the estimates differ is at country level, precisely where they can make the most difference to decision making. GBD estimates for HIV incidence for countries in the regions of northern America, Europe, Australasia, and central Asia are significantly lower than the reported numbers of newly diagnosed cases (see the comparison table in the Lancet commentary by Supervie and Costagliola. For example, 85 252 people were newly diagnosed with HIV in the Russian federation in 2014 whereas the GBD estimate for people newly acquiring HIV in 2015 was only 57 340, albeit with a wide range of uncertainly. For the United States of America, the uncertainly bounds around the GBD estimate of 23 040 do not include 44,073, the number of newly diagnosed cases. Furthermore, new diagnoses likely underestimate actual HIV incidence as they include people who acquired HIV in previous years. Estimates for some high prevalence countries are significantly higher than those produced by those countries with UNAIDS support. For example, http://aidsinfo.unaids.org/ illustrates South Africa as having 380 000 (330 000-430 000) new infections while GBD estimates 529 670 (440 940 to 630 390). Modelling estimates are simply estimates but they cannot be confirmatory or even complementary when they are so different. UNAIDS and IHME (GBD) are already working to understand the differences in the two mathematical modelling approaches - their methodologies, parameters, and assumptions - in order to explain important discrepancies at country level. More importantly, improved data collection by countries of the numbers of HIV diagnoses, people accessing and staying on ART, and the proportion of people living with HIV who achieve viral suppression is necessary to monitor progress towards the UNAIDS 90-90-90 treatment target. Enhanced clinical and epidemiological surveillance systems are also key to the creation of more accurate estimates of country HIV incidence, the metric that reflects HIV prevention programme progress and informs budget allocations and programme planning for HIV treatment. 

195 countries
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A booster dose of HIV prevention

Adolescent HIV risk reduction in the Bahamas: results from two randomized controlled intervention trials spanning elementary school through high school.

Stanton B, Dinaj-Koci V, Wang B, Deveaux L, Lunn S, Li X, Rolle G, Brathwaite N, Marshall S, Gomez P. AIDS Behav. 2016 Jun;20(6):1182-96. doi: 10.1007/s10461-015-1225-5.

To address global questions regarding the timing of HIV-prevention efforts targeting youth and the possible additional benefits of parental participation, researchers from the USA and The Bahamas conducted two sequential longitudinal, randomized trials of an evidence-based intervention spanning the adolescent years. The first trial involved 1360 grade-6 students and their parents with three years of follow-up and the second 2564 grade-10 students and their parents with two years of follow-up. Through grade-12, involvement in the combined child and parent-child HIV-risk reduction interventions resulted in increased consistent condom-use, abstinence/ protected sex, condom-use skills and parent-child communication about sex. Receipt of the grade-6 HIV-prevention intervention conferred lasting benefits regarding condom-use skills and self-efficacy. Youth who had not received the grade-six intervention experienced significantly greater improvement over baseline as a result of the grade-10 intervention. The HIV-risk reduction intervention delivered in either or both grade-6 and grade-10 conferred sustained benefits; receipt of both interventions appears to confer additional benefits.

Abstract access

Editor’s notes: Prevention of HIV infection in adolescents is key to combating HIV. In the Bahamas, two school-based programmes for adolescents were evaluated to answer key questions about the effect of school-based activities at different ages in adolescence, and the effect of including parental participation. This paper focused on the additional effect of a programme in mid-adolescence (age 15 to16) following an earlier programme (at age 10 to11). The early- and mid-adolescent programmes were similar. There were eight-sessions based on Protection Motivation Theory, using discussion and role play to increase knowledge and skills regarding sexual-risk avoidance, with the aim of changing behaviour. Both included a component for parents and children together, and both were effective at improving HIV knowledge, and reported condom-use skills and intentions.

Results illustrated that the early-adolescent programme had sustained effects throughout the following six years, and the mid-adolescent programme acted as a ‘booster’, conferring additional benefits including increased rates of reported consistent condom use and abstinence/protected sexual intercourse and increased condom-use skills. Participants who did not receive the early-adolescent programme gained more benefit from the mid-adolescent programme but had lower scores than youth who had both. Parental involvement was important, especially regarding condom-use skills. Although the results are promising, there is potential for biased reporting of self-reported behavioural outcomes, and it would be good to confirm these findings with biological outcomes including unplanned pregnancy and HSV-2 infection. 

Latin America
Bahamas
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Minimal evidence for serious adverse events resulting from in utero ARV exposure

The PHACS SMARTT Study: assessment of the safety of in utero exposure to antiretroviral drugs.

Van Dyke RB, Chadwick EG, Hazra R, Williams PL, Seage GR, 3rd. Front Immunol. 2016 May 23;7:199. doi: 10.3389/fimmu.2016.00199. eCollection 2016.

The Surveillance Monitoring for ART Toxicities (SMARTT) cohort of the Pediatric HIV/AIDS Cohort Study includes over 3500 HIV-exposed but uninfected infants and children at 22 sites in the US, including Puerto Rico. The goal of the study is to determine the safety of in utero exposure to antiretrovirals (ARVs) and to estimate the incidence of adverse events. Domains being assessed include metabolic, growth and development, cardiac, neurological, neurodevelopmental (ND), behavior, language, and hearing. SMARTT employs an innovative trigger-based design as an efficient means to identify and evaluate adverse events. Participants who met a predefined clinical or laboratory threshold (trigger) undergo additional evaluations to define their case status. After adjusting for birth cohort and other factors, there was no significant increase in the likelihood of meeting overall case status (case in any domain) with exposure to combination ARVs (cARVs), any ARV class, or any specific ARV. However, several individual ARVs were significantly associated with case status in individual domains, including zidovudine for a metabolic case, first trimester stavudine for a language case, and didanosine plus stavudine for a ND case. We found an increased rate of preterm birth with first trimester exposure to protease inhibitor-based cARV. Although there was no overall increase in congenital anomalies with first trimester cARV, a significant increase was seen with exposure to atazanavir, ritonavir, and didanosine plus stavudine. Tenofovir exposure was associated with significantly lower mean whole-body bone mineral content in the newborn period and a lower length and head circumference at 1 year of age. With ND testing at 1 year of age, specific ARVs (atazanavir, ritonavir-boosted lopinavir, nelfinavir, and tenofovir) were associated with lower performance, although all groups were within the normal range. No ARVs or classes were associated with lower performance between 5 and 13 years of age. Atazanavir and saquinavir exposure were associated with late language emergence at 1 year, but not at 2 years of age. The results of the SMARTT study are generally reassuring, with little evidence for serious adverse events resulting from in utero ARV exposure. However, several findings of concern warrant further evaluation, and new ARVs used in pregnancy need to be evaluated.

Abstract  Full-text [free] access 

Editor’s notes: The SMARTT study set out to determine the safety of in utero exposure to antiretroviral (ARV) therapy using a trigger-based surveillance design to identify adverse events in a cohort of HIV-positive mothers and their HIV-exposed but HIV-negative children in the United States of America and Puerto Rico. A ‘trigger’ was set off if participants met a predefined clinical or laboratory threshold, with additional specified evaluations to determine if they met a predefined adverse event “case” definition.  After adjusting for birth cohort and other factors, there was no significant increase in the likelihood of meeting overall case status (case in any domain, such as growth and development or language etc.) with exposure to combination ARVs or any ARV class. No single ARV prophylaxis was associated with an increased risk of overall case status on adjusted analysis. However, several ARVs had significant associations in unadjusted analysis, namely between (1) maternal PI-based ARV prophylaxis during pregnancy and premature delivery and low birth weight; and (2) exposure to atazanavir and a twofold-higher risk of congenital anomalies. Overall the results from this study are reassuring, but some of the findings warrant further evaluation.

Latin America, Northern America
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Oral PrEP reduces risk of HIV and does not result in riskier sex

Effectiveness and safety of oral HIV pre-exposure prophylaxis (PrEP) for all populations: A systematic review and meta-analysis.

Fonner VA, Dalglish SL, Kennedy CE, Baggaley R, O'Reilly K R, Koechlin FM, Rodolph M, Hodges-Mameletzis I, Grant RM. AIDS. 2016 May 5. [Epub ahead of print]

Objective: Pre-exposure prophylaxis (PrEP) offers a promising new approach to HIV prevention. This systematic review and meta-analysis evaluated the evidence for use of oral PrEP containing tenofovir disoproxil fumarate (TDF) as an additional HIV prevention strategy in populations at substantial risk for HIV based on HIV acquisition, adverse events, drug resistance, sexual behavior, and reproductive health outcomes.

Design: Rigorous systematic review and meta-analysis.

Methods: A comprehensive search strategy reviewed three electronic databases and conference abstracts through April 2015. Pooled effect estimates were calculated using random-effects meta-analysis.

Results: Eighteen studies were included, comprising data from 39 articles and six conference abstracts. Across populations and PrEP regimens, PrEP significantly reduced the risk of HIV acquisition compared to placebo. Trials with PrEP use >70% demonstrated the highest PrEP effectiveness (RR = 0.30, 95% CI: 0.21-0.45, p < 0.001) compared to placebo. Trials with low PrEP use did not show a significantly protective effect. Adverse events were similar between PrEP and placebo groups. More cases of drug-resistant HIV infection were found among PrEP users who initiated PrEP while acutely HIV-infected, but incidence of acquiring drug-resistant HIV during PrEP use was low. Studies consistently found no association between PrEP use and changes in sexual risk behavior. PrEP was not associated with increased pregnancy-related adverse events or hormonal contraception effectiveness.

Conclusion: PrEP is protective against HIV infection across populations, presents few significant safety risks, and no evidence of behavioral risk compensation. The effective and cost-effective use of PrEP will require development of best practices for fostering uptake and adherence among people at substantial HIV-risk.

Abstract access

Editor’s notes: This systematic review is the first to aggregate data from across oral pre-exposure prophylaxis (PrEP) studies, including randomized control trials and observational studies, to present clear evidence on the effectiveness of oral PrEP use. The findings confirm that oral PrEP significantly reduces the risk of acquiring HIV if taken consistently and correctly across populations, countries, and most age groups. Differences in efficacy directly correlate with adherence, which accounts for the lower efficacy seen in some subgroups. Perhaps two of the most compelling analyses presented in this paper relate to resistance and behavioural disinhibition. The risk of resistance was shown to be quite low, and study participants exhibiting resistant HIV either enrolled in the studies during an acute infection stage or acquired resistant strains during the course of the research. Regarding behavioural disinhibition, indicators measured such as rates of sexually transmitted infections revealed that PrEP use in the efficacy trials was not associated with behavioural disinhibition and in some studies, resulted in even safer sexual behaviour than what was reported at baseline. Recently completed demonstration projects have reported increased rates of STIs among gay men and other men who have sex with men. However, in the open-label extensions included in this review, where counselling was more intensive, safer sex practices were maintained, thus suggesting that counselling can be effective in preventing behavioural disinhibition. 

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What works to link people living with HIV to care - a review

Facilitators and barriers in HIV linkage to care interventions: a qualitative evidence review.

Tso LS, Best J, Beanland R, Doherty M, Lackey M, Ma Q, Hall BJ, Yang B, Tucker JD. AIDS. 2016 Apr 6. [Epub ahead of print]

Objective: To synthesize qualitative evidence on linkage to care interventions for people living with HIV.

Design: Systematic literature review.

Methods: We searched nineteen databases for studies reporting qualitative evidence on linkage interventions. Data extraction and thematic analysis were used to synthesize findings. Quality was assessed using the CASP tool and certainty of evidence was evaluated using the CERQual approach.

Results: Twenty-five studies from eleven countries focused on adults (24 studies), adolescents (8 studies), and pregnant women (4 Facilitators included community-level factors (i.e. task-shifting, mobile outreach, integrated HIV and primary services, supportive cessation programs for substance users, active referrals, and dedicated case management teams) and individual-level factors (encouragement of peers/family and positive interactions with healthcare providers in transitioning into care). One key barrier for people living with HIV was perceived inability of providers to ensure confidentiality as part of linkage to care interventions. Providers reported difficulties navigating procedures across disparate facilities and having limited resources for linkage to care interventions.

Conclusions: Our findings extend the literature by highlighting the importance of task-shifting, mobile outreach, and integrated HIV and primary services. Both community and individual level factors may increase the feasibility and acceptability of HIV linkage to care interventions. These findings may inform policies to increase the reach of HIV services available in communities.

Abstract access  

Editor’s notes: As the authors of this paper observe, most evaluations of linkage to care programmes have focused on quantitative assessment. This useful paper provides a thorough overview of the findings from 25 studies which used qualitative methods for assessment. Linkage-to- care programmes feasible in different country settings were identified in this review.  The authors also highlight gaps, most notably a lack of information on linkage-to-care programmes for men. They also note the need for longitudinal assessments that look at changes over time.

This paper is a useful synthesis of findings. But it is also an excellent example of how to carry out a systematic review of qualitative research. The description of the qualitative meta-synthesis the authors performed adds additional value to this paper. 

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What works to link people living with HIV to care - a review

Facilitators and barriers in HIV linkage to care interventions: a qualitative evidence review.

Tso LS, Best J, Beanland R, Doherty M, Lackey M, Ma Q, Hall BJ, Yang B, Tucker JD. AIDS. 2016 Apr 6. [Epub ahead of print]

Objective: To synthesize qualitative evidence on linkage to care interventions for people living with HIV.

Design: Systematic literature review.

Methods: We searched nineteen databases for studies reporting qualitative evidence on linkage interventions. Data extraction and thematic analysis were used to synthesize findings. Quality was assessed using the CASP tool and certainty of evidence was evaluated using the CERQual approach.

Results: Twenty-five studies from eleven countries focused on adults (24 studies), adolescents (8 studies), and pregnant women (4 Facilitators included community-level factors (i.e. task-shifting, mobile outreach, integrated HIV and primary services, supportive cessation programs for substance users, active referrals, and dedicated case management teams) and individual-level factors (encouragement of peers/family and positive interactions with healthcare providers in transitioning into care). One key barrier for people living with HIV was perceived inability of providers to ensure confidentiality as part of linkage to care interventions. Providers reported difficulties navigating procedures across disparate facilities and having limited resources for linkage to care interventions.

Conclusions: Our findings extend the literature by highlighting the importance of task-shifting, mobile outreach, and integrated HIV and primary services. Both community and individual level factors may increase the feasibility and acceptability of HIV linkage to care interventions. These findings may inform policies to increase the reach of HIV services available in communities.

Abstract access  

Editor’s notes: As the authors of this paper observe, most evaluations of linkage to care programmes have focused on quantitative assessment. This useful paper provides a thorough overview of the findings from 25 studies which used qualitative methods for assessment. Linkage-to- care programmes feasible in different country settings were identified in this review.  The authors also highlight gaps, most notably a lack of information on linkage-to-care programmes for men. They also note the need for longitudinal assessments that look at changes over time.

This paper is a useful synthesis of findings. But it is also an excellent example of how to carry out a systematic review of qualitative research. The description of the qualitative meta-synthesis the authors performed adds additional value to this paper. 

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Profound effect of ART on mortality through reduction of opportunistic infections

Incidence of opportunistic infections and the impact of antiretroviral therapy among HIV-infected adults in low and middle income countries: a systematic review and meta-analysis. 

Low A, Gavriilidis G, Larke N, Lajoie MR, Drouin O, Stover J, Muhe L, Easterbrook P. Clin Infect Dis. 2016 Mar 6. pii: ciw125. [Epub ahead of print]

Background: To understand regional burdens and inform delivery of health services, we conducted a systematic review and meta-analysis to evaluate the effect of antiretroviral therapy (ART) on incidence of key opportunistic infections (OIs) in HIV-infected adults in low and middle-income countries (LMIC).

Methods: Eligible studies describing the cumulative incidence of OIs and proportion on ART from 1990 to November 2013 were identified using multiple databases. Summary incident risks for the ART-naive period, and during and after the first year of ART, were calculated using random effects meta-analyses. Summary estimates from ART subgroups were compared using meta-regression. The number of OI cases and associated costs averted if ART was initiated at CD4 ≥200 cells/µl was estimated using UNAIDS country estimates and global average OI treatment cost per case.

Results: We identified 7965 citations, and included 126 studies describing 491 608 HIV-infected persons. In ART-naive patients, summary risk was highest (>5%) for oral candidiasis, tuberculosis, herpes zoster, and bacterial pneumonia. The reduction in incidence was greatest for all OIs during the first 12 months of ART (range 57-91%) except for tuberculosis, and was largest for oral candidiasis, PCP and toxoplasmosis. Earlier ART was estimated to have averted 857 828 cases in 2013 (95% confidence interval [CI], 828 032-874 853), with cost savings of $46.7 million (95% CI, 43.8-49.4).

Conclusions: There was a major reduction in risk for most OIs with ART use in LMICs, with the greatest effect seen in the first year of treatment. ART has resulted in substantial cost savings from OIs averted.

Abstract  Full-text [free] access

Editor’s notes: Opportunistic infections (OIs) remain the major cause of HIV-associated mortality. OIs account for substantially higher mortality in low and middle income countries (LMICs) compared to high income countries (HICs).

This paper describes the results of a systematic review and meta-analysis including about 500 000 people on ART in LMICs across three regions (sub-Saharan Africa, Asia, and Latin America). These large numbers enabled the investigators to look at the effect of ART on the incidence of key OIs during and after the first year of treatment.

Not surprisingly they found that the effect of ART reduced the risk of all OIs during the first year after ART initiation, although the reduction was less for tuberculosis. The authors attribute this to the occurrence of tuberculosis across a wide range of CD4 cell counts, a smaller effect of early immune restoration and the contribution of TB as a manifestation of immune reconstitution syndrome during the first months after ART initiation. Beyond one year after ART initiation, the reduction in tuberculosis was greater.

They conclude that the effect of ART on the incidence of most HIV-associated OIs is the key reason for the global decline in HIV-associated mortality. However, a significant proportion of HIV-positive persons still continue to present with advanced disease. Besides timely ART initiation, additional measures such as CTX prophylaxis, screening for TB and cryptococcal disease, and the use of isoniazid and fluconazole prophylaxis should be considered for late presenters. 

Africa, Asia, Latin America
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