Articles tagged as "Thailand"

Late antiretroviral therapy start persists for children under two years of age in low- and middle-income countries

Immunodeficiency in children starting antiretroviral therapy in low-, middle-, and high-income countries.

Koller M, Patel K, Chi BH, Wools-Kaloustian K, Dicko F, Chokephaibulkit K, Chimbetete C, Avila D, Hazra R, Ayaya S, Leroy V, Truong HK, Egger M, Davies MA, IeDEA, NISDI, PHACS and IMPAACT 219C studies.  J Acquir Immune Defic Syndr. 2015 Jan 1;68(1):62-72. doi: 10.1097/QAI.0000000000000380.

Background: The CD4 cell count or percent (CD4%) at the start of combination antiretroviral therapy (cART) is an important prognostic factor in children starting therapy and an important indicator of program performance. We describe trends and determinants of CD4 measures at cART initiation in children from low-, middle-, and high-income countries.

Methods: We included children aged <16 years from clinics participating in a collaborative study spanning sub-Saharan Africa, Asia, Latin America, and the United States. Missing CD4 values at cART start were estimated through multiple imputation. Severe immunodeficiency was defined according to World Health Organization criteria. Analyses used generalized additive mixed models adjusted for age, country, and calendar year.

Results: A total of 34 706 children from 9 low-income, 6 lower middle-income, 4 upper middle-income countries, and 1 high-income country (United States) were included; 20 624 children (59%) had severe immunodeficiency. In low-income countries, the estimated prevalence of children starting cART with severe immunodeficiency declined from 76% in 2004 to 63% in 2010. Corresponding figures for lower middle-income countries were from 77% to 66% and for upper middle-income countries from 75% to 58%. In the United States, the percentage decreased from 42% to 19% during the period 1996 to 2006. In low- and middle-income countries, infants and children aged 12-15 years had the highest prevalence of severe immunodeficiency at cART initiation.

Conclusions: Despite progress in most low- and middle-income countries, many children continue to start cART with severe immunodeficiency. Early diagnosis and treatment of HIV-infected children to prevent morbidity and mortality associated with immunodeficiency must remain a global public health priority.

Abstract access 

Editor’s notes: This article describes trends and determinants of CD4 cell measures at antiretroviral therapy (ART) initiation in about 35 000 children in low, middle, and high-income countries. Temporal trends in CD4 measures at ART initiation are a useful indicator of the health system’s ability to identify and treat eligible children in a timely fashion. They are also a useful measure of responsiveness to guideline changes.

Previous WHO guidelines recommended early ART initiation, regardless of immunologic or clinical thresholds. But the authors found that in 2010, approximately two-thirds of children below two years of age, in low- and middle-income countries were still starting ART with severe immunodeficiency.

Delayed country-level implementation of WHO guidelines, poor access to early infant diagnosis, slow turn-around time of test results, and limited ART availability for infants and young children are all contributing factors to this delayed ART initiation. The authors point out that timely diagnosis of paediatric HIV does not necessarily result in timely ART. The main reasons for this diagnosis to treatment gap include HIV diagnostic tests and paediatric ART being located at separate sites without robust referral mechanisms between services. There are challenges with CD4 measurement to determine eligibility. These include access to tests, turn-around time and interpretation of results and health care worker discomfort with treating children.

Currently, only 22% of children living with HIV in sub-Saharan Africa are receiving ART. To decrease the treatment gap among children, WHO 2013 guidelines recommend universal ART for all children living with HIV, aged below five years of age, irrespective of CD4 count or clinical stage. Removing the requirement for a CD4 measurement also removes the time lag while waiting for CD4 results. Thus the guidelines aim both to increase treatment accessibility and to accelerate treatment initiation for all children. 

HIV Treatment
Africa, Asia, Northern America
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Increasing transmitted resistance to antiretroviral therapy in low/middle-income countries - highest prevalence in MSM

Global burden of transmitted HIV drug resistance and HIV-exposure categories: a systematic review and meta-analysis.

Pham QD, Wilson DP, Law MG, Kelleher AD, Zhang L. AIDS. 2014 Nov 28;28(18):2751-62. doi: 10.1097/QAD.0000000000000494.

Objectives: Our aim was to review the global disparities of transmitted HIV drug resistance (TDR) in antiretroviral-naive MSM, people who inject drugs (PWID) and heterosexual populations in both high-income and low/middle-income countries.

Design/methods: We undertook a systematic review of the peer-reviewed English literature on TDR (1999-2013). Random-effects meta-analyses were performed to pool TDR prevalence and compare the odds of TDR across at-risk groups.

Results: A total of 212 studies were included in this review. Areas with greatest TDR prevalence were North America (MSM: 13.7%, PWID: 9.1%, heterosexuals: 10.5%); followed by western Europe (MSM: 11.0%, PWID: 5.7%, heterosexuals: 6.9%) and South America (MSM: 8.3%, PWID: 13.5%, heterosexuals: 7.5%). Our data indicated disproportionately high TDR burdens in MSM in Oceania (Australia 15.5%), eastern Europe/central Asia (10.2%) and east Asia (7.8%). TDR epidemics have stabilized in high-income countries, with a higher prevalence (range 10.9-12.6%) in MSM than in PWID (5.2-8.3%) and heterosexuals (6.4-9.0%) over 1999-2013. In low/middle-income countries, TDR prevalence in all at-risk groups in 2009-2013 almost doubled than that in 2004-2008 (MSM: 7.8 vs. 4.2%, P = 0.011; heterosexuals: 4.1 vs. 2.6%, P < 0.001; PWID: 4.8 vs. 2.4%, P = 0.265, respectively). The risk of TDR infection was significantly greater in MSM than that in heterosexuals and PWID. We observed increasing trends of resistance to non-nucleoside reverse transcriptase and protease inhibitors among MSM.

Conclusion: TDR prevalence is stabilizing in high-income countries, but increasing in low/middle-income countries. This is likely due to the low, but increasing, coverage of antiretroviral therapy in these settings. Transmission of TDR is most prevalent among MSM worldwide.

Abstract access 

Editor’s notes: HIV mutates very rapidly, and many early antiretroviral agents had a low genetic barrier to the development of resistance. Thus the emergence of virus resistant to antiretroviral agents, particularly to early drug classes, was inevitable. Surveillance for drug-resistant virus among people with no prior history of taking antiretroviral drugs (transmitted drug resistance) is essential to monitor the spread of drug resistance at population level.

This systematic review aimed to compare transmitted drug resistance in different geographical regions and between subpopulations of HIV-positive people by likely route of transmission. Transmitted resistance was most prevalent in high income settings. This is not surprising given wide use of suboptimal drug regimens before effective triple therapy was available. Reassuringly, the prevalence of transmitted resistance seems to have stabilised in high-income settings. The increase in transmitted resistance in low and middle income countries is of more concern. It is not surprising, given that first-line regimens comprising two nucleoside reverse transcriptase inhibitors and a non-nucleoside reverse transcriptase inhibitor are vulnerable to the development of resistance if the drug supply is interrupted or adherence is suboptimal. In addition, if viral load monitoring is not available, people remain on failing drug regimens for longer, and thus have more risk of transmitting resistant virus.

Within the subpopulations examined in this review, transmitted resistance was consistently higher in men who have sex with men, suggesting that resistance testing prior to treatment is particularly valuable for this population.

Limitations of the review include exclusion of studies that did not compare transmitted resistance between the specified subpopulations, and small sample size in many subgroups.

Continued surveillance for transmitted drug resistance is critical. This is most important in settings where individualised resistance testing is not available. This will ensure that people starting antiretroviral therapy receive treatment that will suppress their viral load effectively. Wider use of viral load monitoring, combined with access to effective second and third line regimens, will also help limit spread of drug resistance.

HIV Treatment
Angola, Argentina, Australia, Austria, Belgium, Benin, Botswana, Brazil, Burkina Faso, Cambodia, Cameroon, Canada, Central African Republic, Chad, China, Côte d'Ivoire, Croatia, Cuba, Cyprus, Denmark, Dominican Republic, El Salvador, Estonia, Ethiopia, France, Gabon, Georgia, Germany, Greece, Guatemala, Honduras, Hong Kong Special Administrative Region of China, Hungary, India, Indonesia, Ireland, Israel, Italy, Japan, Kazakhstan, Kenya, Latvia, Malawi, Malaysia, Moldova, Mozambique, Netherlands, Peru, Philippines, Poland, Portugal, Republic of Korea, Romania, Russia, Rwanda, Slovenia, South Africa, Spain, Swaziland, Sweden, Switzerland, Taiwan, Thailand, Uganda, United Kingdom of Great Britain and Northern Ireland, United Republic of Tanzania, United States of America, Viet Nam, Zambia, Zimbabwe
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Diagnosis of syphilis as an entry point for PrEP initiation among men who have sex with men

Syphilis predicts HIV incidence among men and transgender women who have sex with men in a preexposure prophylaxis trial.

Solomon MM, Mayer KH, Glidden DV, Liu AY, McMahan VM, Guanira JV, Chariyalertsak S, Fernandez T, Grant RM, iPrEx Study Team. Clin Infect Dis. 2014 Oct;59(7):1020-6. doi: 10.1093/cid/ciu450. Epub 2014 Jun 13.

Background: Syphilis infection may potentiate transmission of human immunodeficiency virus (HIV). We sought to determine the extent to which HIV acquisition was associated with syphilis infection within an HIV preexposure prophylaxis (PrEP) trial and whether emtricitabine/tenofovir (FTC/TDF) modified that association.

Methods: The Preexposure Prophylaxis Initiative (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily FTC/TDF or placebo. Syphilis prevalence at screening and incidence during follow-up were measured. Hazard ratios for the effect of incident syphilis on HIV acquisition were calculated. The effect of FTC/TDF on incident syphilis and HIV acquisition was assessed.

Results: Of 2499 individuals, 360 (14.4%) had a positive rapid plasma reagin test at screening; 333 (92.5%) had a positive confirmatory test, which did not differ between the arms (FTC/TDF vs placebo, P = .81). The overall syphilis incidence during the trial was 7.3 cases per 100 person-years. There was no difference in syphilis incidence between the study arms (7.8 cases per 100 person-years for FTC/TDF vs 6.8 cases per 100 person-years for placebo, P = .304). HIV incidence varied by incident syphilis (2.8 cases per 100 person-years for no syphilis vs 8.0 cases per 100 person-years for incident syphilis), reflecting a hazard ratio of 2.6 (95% confidence interval, 1.6-4.4; P < .001). There was no evidence for interaction between randomization to the FTC/TDF arm and incident syphilis on HIV incidence.

Conclusions: In HIV-seronegative MSM, syphilis infection was associated with HIV acquisition in this PrEP trial; a syphilis diagnosis should prompt providers to offer PrEP unless otherwise contraindicated.

Abstract  Full-text [free] access

Editor’s notes: The Preexposure Prophylaxis Initiative (iPrEx) trial and other recent trials have illustrated clearly that preexposure prophylaxis (PrEP) with emtricitabine/tenofovir (FTC/TDF) dramatically reduces the risk of HIV when used correctly and consistently. There is current discussion about the practical implications of these findings. This paper confirms a strong association between incident syphilis and HIV acquisition among men who have sex with men (MSM), and illustrates that syphilis did not attenuate the protective benefit of FTC/TDF against HIV. Syphilis continues to be prevalent among MSM in many settings, and the screening prevalence of 13% in this study is consistent with global estimates. These results highlight that individuals with syphilis are a key group for HIV acquisition. The results suggest that a new diagnosis of syphilis is an important opportunity for PrEP initiation, unless contraindications are present. This would be in addition to immediate syphilis treatment, and treatment for sexual partners. 

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Counting and classifying global deaths

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

Murray CJ, Ortblad KF, Guinovart C, et al. Lancet. 2014 Sep 13;384(9947):1005-70. doi: 10.1016/S0140-6736(14)60844-8. Epub 2014 Jul 22.

Background: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occurred since the Millennium Declaration.

Methods: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets.

Findings: Globally in 2013, there were 1.8 million new HIV infections (95% uncertainty interval 1.7 million to 2.1 million), 29.2 million prevalent HIV cases (28.1 to 31.7), and 1.3 million HIV deaths (1.3 to 1.5). At the peak of the epidemic in 2005, HIV caused 1.7 million deaths (1.6 million to 1.9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19.1 million life-years (16.6 million to 21.5 million) have been saved, 70.3% (65.4 to 76.1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$ 4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7.5 million (7.4 million to 7.7 million), prevalence was 11.9 million (11.6 million to 12.2 million), and number of deaths was 1.4 million (1.3 million to 1.5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7.1 million (6.9 million to 7.3 million), prevalence was 11.2 million (10.8 million to 11.6 million), and number of deaths was 1.3 million (1.2 million to 1.4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64.0% of cases (63.6 to 64.3) and 64.7% of deaths (60.8 to 70.3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1.2 million deaths (1.1 million to 1.4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31.5% (15.7 to 44.1). Outside of Africa, malaria mortality has been steadily decreasing since 1990.

Interpretation: Our estimates of the number of people living with HIV are 18.7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action.

Abstract  Full-text [free] access

Editor’s notes: The Global Burden of Disease (GBD) study uses standard methods to compare and track over time national distributions of deaths by cause, and the prevalence of disease and disability.  This detailed report focuses on HIV, TB and Malaria. It presents regional summaries of incidence, prevalence and mortality rates, and national estimates of the number of male and female deaths and new infections. Point estimates are shown for 2013, and annualised rates of change for 1990-2000 and 2000-2013. These highlight the contrasting trends in disease impact before and after the formulation of the Millennium Development Goal to combat these diseases.  The global peak of HIV mortality occurred in 2005, but regional annualised rates of change for 2000-2013 indicate that HIV deaths are still increasing significantly in east Asia, southern Africa, and most rapidly in eastern Europe.

The GBD 2013 global estimates of new infections and deaths agree closely with the corresponding estimates made by UNAIDS. But there are significant differences in the respective estimates of the number of people currently living with HIV (UNAIDS estimates are some 18% higher), and historical trends in AIDS deaths, with UNAIDS judging that the recent fall has been steeper. These differences are attributed primarily to methods used in the GBD study to ensure that the sum of deaths from specific causes fits the estimated all cause total, and to varying assumptions about historical survival patterns following HIV infection. 

It may be worthwhile to look at a comment by Michel Sidibé, Mark Dybul, and Deborah Birx in the Lancet on MDG 6 and beyond: from halting and reversing AIDS to ending the epidemic which refers to this study.

Epidemiology
Afghanistan, Albania, Algeria, Andorra, Angola, Antigua and Barbuda, Argentina, Australia, Austria, Bahamas, Bahrain, Bangladesh, Barbados, Belarus, Belgium, Belize, Benin, Bhutan, Bolivia, Bosnia and Herzegovina, Botswana, Brazil, Bulgaria, Burkina Faso, Burundi, Cambodia, Cameroon, Canada, Cape Verde, Central African Republic, Chad, Chile, China, Colombia, Comoros, Congo, Costa Rica, Côte d'Ivoire, Croatia, Cuba, Cyprus, Czech Republic, Democratic People's Republic of Korea, Democratic Republic of the Congo, Democratic Republic of Timor-Leste, Denmark, Djibouti, Dominica, Dominican Republic, Ecuador, Egypt, El Salvador, Equatorial Guinea, Eritrea, Estonia, Ethiopia, Fiji, Finland, France, Gabon, Gambia, Germany, Ghana, Greece, Grenada, Guatemala, Guinea, Guinea-Bissau, Guyana, Haiti, Honduras, Hungary, Iceland, India, Indonesia, Iran (Islamic Republic of), Iraq, Ireland, Israel, Italy, Jamaica, Jordan, Kazakhstan, Kenya, Kiribati, Kuwait, Kyrgyzstan, Lao People's Democratic Republic, Latvia, Lebanon, Lesotho, Liberia, Libyan Arab Jamahiriya, Lithuania, Luxembourg, Madagascar, Malawi, Malaysia, Maldives, Mali, Malta, Marshall Islands, Mauritania, Mauritius, Mexico, Micronesia (Federated States of), Monaco, Mongolia, Morocco, Mozambique, Myanmar, Namibia, Nepal, Netherlands, New Zealand, Nicaragua, Niger, Nigeria, Norway, Oman, Pakistan, Palestinian Territory, Occupied, Panama, Papua New Guinea, Paraguay, Peru, Philippines, Poland, Portugal, Qatar, Romania, Russian Federation, Rwanda, Saint Lucia, Saint Vincent and the Grenadines, Samoa, Sao Tome and Principe, Saudi Arabia, Senegal, Serbia and Montenegro, Seychelles, Sierra Leone, Slovakia, Slovenia, Solomon Islands, Somalia, South Africa, Spain, Sri Lanka, Sudan, Suriname, Swaziland, Sweden, Switzerland, Syrian Arab Republic, Taiwan, Tajikistan, Thailand, Togo, Tonga, Trinidad and Tobago, Tunisia, Turkey, Turkmenistan, Uganda, Ukraine, United States of America, Uruguay, Uzbekistan, Vanuatu, Venezuela, Viet Nam, Yemen, Zimbabwe
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More data needed from routine programme data on antiretroviral therapy cascade outcomes among female sex workers

Antiretroviral therapy uptake, attrition, adherence and outcomes among HIV-infected female sex workers: a systematic review and meta-analysis.

Mountain E, Mishra S, Vickerman P, Pickles M, Gilks C, Boily MC. PLoS One. 2014 Sep 29;9(9):e105645. doi: 10.1371/journal.pone.0105645. eCollection 2014.

Purpose: We aimed to characterize the antiretroviral therapy (ART) cascade among female sex workers (FSWs) globally.

Methods: We systematically searched PubMed, Embase and MEDLINE in March 2014 to identify studies reporting on ART uptake, attrition, adherence, and outcomes (viral suppression or CD4 count improvements) among HIV-infected FSWs globally. When possible, available estimates were pooled using random effects meta-analyses (with heterogeneity assessed using Cochran's Q test and I2 statistic).

Results: 39 studies, reporting on 21 different FSW study populations in Asia, Africa, North America, South America, and Central America and the Caribbean, were included. Current ART use among HIV-infected FSWs was 38% (95% CI: 29%-48%, I2 = 96%, 15 studies), and estimates were similar between high-, and low- and middle-income countries. Ever ART use among HIV-infected FSWs was greater in high-income countries (80%; 95% CI: 48%-94%, I2 = 70%, 2 studies) compared to low- and middle-income countries (36%; 95% CI: 7%-81%, I2 = 99%, 3 studies). Loss to follow-up after ART initiation was 6% (95% CI: 3%-11%, I2 = 0%, 3 studies) and death after ART initiation was 6% (95% CI: 3%-11%, I2 = 0%, 3 studies). The fraction adherent to ≥95% of prescribed pills was 76% (95% CI: 68%-83%, I2 = 36%, 4 studies), and 57% (95% CI: 46%-68%, I2 = 82%, 4 studies) of FSWs on ART were virally suppressed. Median gains in CD4 count after 6 to 36 months on ART, ranged between 103 and 241 cells/mm3 (4 studies).

Conclusions: Despite global increases in ART coverage, there is a concerning lack of published data on HIV treatment for FSWs. Available data suggest that FSWs can achieve levels of ART uptake, retention, adherence, and treatment response comparable to that seen among women in the general population, but these data are from only a few research settings. More routine programme data on HIV treatment among FSWs across settings should be collected and disseminated.

Abstract  Full-text [free] access

Editor’s notes: Female sex workers remain a key population for HIV prevention, treatment and care. This is the first paper to systematically review and quantify the HIV treatment cascade among sex workers globally. The review highlights the scarcity of published data on HIV treatment among sex workers. For example, data were identified from only five countries in sub-Saharan Africa (Benin, Burkina Faso, Kenya, Rwanda and Zimbabwe) and a lack of data from routine (non research) settings. Further, most studies presented data on current antiretroviral therapy (ART) or CD4 count at initiation rather than follow-up data on attrition, adherence or viral suppression. The results suggest that research cohorts have been largely successful at enrolling and retaining female sex workers on ART, but there may be an issue with adherence. Adherence, in the few studies where it was measured (usually by self-report or pill counts) was high, and similar to estimates from the general population. But just over half of the participants initiating ART achieved viral suppression in the four studies which looked at this. This indicates scope for improvements in adherence (and adherence measurement) in these populations. This is possibly due to individual-level and structural-level barriers that sex workers face when receiving HIV treatment and care

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Rural-urban migration associated with earlier sexual debut in Thailand

Rural-to-urban migration and sexual debut in Thailand.

Anglewicz P, VanLandingham M, Phuengsamran D. Demography. 2014 Aug 22. [Epub ahead of print]

Migration from one's parents' home and sexual debut are common features of the transition to adulthood. Although many studies have described both of these features independently, few have examined the relationship between migration and sexual debut in a systematic manner. In this study, we explore this link for young adults in Thailand. With relatively high rates of internal migration, rapid modernization, a moderate HIV epidemic, and a declining average age of sexual debut, Thailand presents an instructive environment in which to examine migration and sexual debut. We use two waves of a longitudinal data set (2005 and 2007) that includes a subsample of young adults who migrated to urban areas during that period. We identify characteristics and behaviors associated with sexual debut and examine the role of migration on debut. Our approach reduces several common sources of bias that hamper existing work on both migration and sexual debut: (1) the longitudinal nature of the data enables us to examine the effects of characteristics that predate both behaviors of interest; (2) the survey on sexual behavior employed a technique that reduces response bias; and (3) we examine differences in debut by marital status. We find that migrants have a higher likelihood of sexual debut than nonmigrants.

Abstract access 

Editor’s notes: Much of the research on sexual behaviour comes from sub-Saharan Africa. It is useful to see a study on rural-urban migration and sexual debut in Thailand, a rapidly urbanizing country. The share of the urban population is expected to double by 2050. Rural-urban migration has become part of the experience of many young men and women, growing up. In this study of 4 000 young people aged 15-29 years, 16% of respondents at baseline had migrated within a two-year period. Thailand has been successful in reducing HIV incidence, but there are now concerns over reduced awareness of sexually transmitted infections in young people, increased sexual activity, and reductions in the age of sexual debut. Using a longitudinal dataset, the authors found that rural-urban migration was associated with higher likelihood of sexual debut.  It seems this is not solely due to non-residence with a parent, as this was not associated with sexual debut. The findings raise a number of interesting hypotheses about the implications for HIV prevention, and about the mechanisms that produce this association between migration and sexual debut. These include ideational changes, weakening of the social control mechanisms, a larger pool of potential partners in urban areas, or reverse causality. 

Asia
Thailand
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No evidence that antiretroviral therapy increases risk taking behaviour

Effects of HIV antiretroviral therapy on sexual and injecting risk-taking behaviour: a systematic review and meta-analysis.

Doyle JS, Degenhardt L, Pedrana AE, McBryde ES, Guy R, Stoove MA, Weaver E, Grulich AE, Lo YR, Hellard ME. Clin Infect Dis. 2014 Aug 4. pii: ciu602. [Epub ahead of print]

Background:  Increased global access and use of HIV antiretroviral therapy (ART) has been postulated to undermine HIV prevention efforts by changing individual risk-taking behaviour. This review aims to determine whether ART use is associated with changes in sexual or injecting risk-taking behaviour or diagnosis of sexually transmitted infections (STIs).

Methods: A systematic review and meta-analysis was conducted of HIV-seropositive participants receiving ART compared to no ART use in experimental or observational studies. Primary outcomes included: (1) any unprotected sexual intercourse; (2) STI diagnoses; and (3) any unsafe injecting behaviour.

Results: Fifty-eight studies met the selection criteria. Fifty-six studies containing 32 857 participants reported unprotected sex; eleven studies containing 16 138 participants reported STI diagnoses; and four studies containing 1 600 participants reported unsafe injecting behaviour. All included studies were observational. Unprotected sex was lower in those receiving ART than those not receiving ART (odds ratio (OR) 0.73, 95%CI 0.64-0.83, p<0.001; heterogeneity I2=79%) in both high-income (n=38) and low-/middle-income country (n=18) settings, without any evidence of publication bias. STI diagnoses were also lower among individuals on ART (OR 0.58, 95%CI 0.33-1.01, p=0.053; I2=92%), however there was no difference in injecting risk-taking behaviour with antiretroviral use (OR 0.90, 95%CI 0.60-1.35, p=0.6; I2=0%).

Conclusions: Despite concerns that use of ART might increase sexual or injecting risk-taking, available research suggests unprotected sex is reduced among HIV-infected individuals on treatment. The reasons for this are not yet clear, though self-selection and mutually reinforcing effects of HIV treatment and prevention messages among people on ART are likely.

Abstract access 

Editor’s notes: Use of antiretroviral therapy (ART) may modify risk perception, leading to increases in risk-taking behaviour and HIV transmission. This has important implications for HIV prevention. In particular in low and middle-income countries, where the global burden of HIV is greatest and where access to, and use of, ART is rapidly increasing. This systematic review identified observational studies comparing risk-taking behaviour in people living with HIV using ART, compared with people not using ART. The review found that ART does not appear to increase reported unprotected anal or vaginal intercourse, newly diagnosed sexually transmitted infections, or unsafe injecting behaviour among people on treatment. The observation that reductions in unprotected sex are associated with ART use should be interpreted cautiously as limited data are available to accurately assess a causal relationship. The current practice of providing ART with counselling, education and ongoing clinical care probably offers the optimal strategy of ensuring that individuals on ART minimise risks associated with unsafe sex. 

Africa, Asia, Europe, Northern America, Oceania
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Model estimates large global burden of childhood tuberculosis infection and potentially preventable future tuberculosis disease

Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study.

Dodd PJ, Gardiner E, Coghlan R, Seddon JA. Lancet Glob Health. 2014 Aug;2(8):e453-9. doi: 10.1016/S2214-109X(14)70245-1. Epub 2014 Jul 8.

Background: Confirmation of a diagnosis of tuberculosis in children (aged <15 years) is challenging; under-reporting can result even when children do present to health services. Direct incidence estimates are unavailable, and WHO estimates build on paediatric notifications, with adjustment for incomplete surveillance by the same factor as adult notifications. We aimed to estimate the incidence of infection and disease in children, the prevalence of infection, and household exposure in the 22 countries with a high burden of the disease.

Methods: Within a mechanistic mathematical model, we combined estimates of adult tuberculosis prevalence in 2010, with aspects of the natural history of paediatric tuberculosis. In a household model, we estimated household exposure and infection. We accounted for the effects of age, BCG vaccination, and HIV infection. Additionally, we tested sensitivity to key structural assumptions by repeating all analyses without variation in BCG efficacy by latitude.

Findings: The median number of children estimated to be sharing a household with an individual with infectious tuberculosis in 2010 was 15 319 701 (IQR 13 766 297-17 061 821). In 2010, the median number of Mycobacterium tuberculosis infections in children was 7 591 759 (5 800 053-9 969 780), and 650 977 children (424 871-983 118) developed disease. Cumulative exposure meant that the median number of children with latent infection in 2010 was 53 234 854 (41 111 669-68 959 804). The model suggests that 35% (23-54) of paediatric cases of tuberculosis in the 15 countries reporting notifications by age in 2010 were detected. India is predicted to account for 27% (22-33) of the total burden of paediatric tuberculosis in the 22 countries. The predicted proportion of tuberculosis burden in children for each country correlated with incidence, varying between 4% and 21%.

Interpretation: Our model has shown that the incidence of paediatric tuberculosis is higher than the number of notifications, particularly in young children. Estimates of current household exposure and cumulative infection suggest an enormous opportunity for preventive treatment.

Abstract  Full-text [free] access 

Editor’s notes: Estimating the burden of childhood tuberculosis has been largely neglected until recently. Children with tuberculosis rarely transmit and therefore from a control perspective, childhood tuberculosis does not notably contribute to the continuation of the tuberculosis epidemic. This modelling paper attempts to estimate the global burden of childhood tuberculosis infection and disease. Incidence estimates are made by using adult tuberculosis prevalence data to tackle the known limitations of using paediatric notification data. A second model estimates the prevalence of infection in children and household exposure, ignoring exposure outside of the household.  As with all mathematical model predictions, precision of estimates are dependent on the data used as inputs in the model. Despite these limitations, the paper draws attention to the fact that the burden of childhood tuberculosis infection and disease is significant and reflects failure of tuberculosis control in the 22 high-burden countries. The paper also highlights the fact that household contact tracing and preventive therapy in tuberculosis-exposed children could substantially reduce future tuberculosis-related morbidity.

Avoid TB deaths
Comorbidity, Epidemiology
Africa, Asia, Latin America
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How can we improve the UNAIDS modes of transmission model?

The HIV modes of transmission model: a systematic review of its findings and adherence to guidelines.

Shubber Z, Mishra S, Vesga JF, Boily MC. J Int AIDS Soc. 2014 Jun 23;17:18928. doi: 10.7448/IAS.17.1.18928. eCollection 2014.

Introduction: The HIV Modes of Transmission (MOT) model estimates the annual fraction of new HIV infections (FNI) acquired by different risk groups. It was designed to guide country-specific HIV prevention policies. To determine if the MOT produced context-specific recommendations, we analyzed MOT Results by region and epidemic type, and explored the factors (e.g. data used to estimate parameter inputs, adherence to guidelines) influencing the differences.

Methods: We systematically searched MEDLINE, EMBASE and UNAIDS reports, and contacted UNAIDS country directors for published MOT Results from MOT inception (2003) to 25 September 2012.

Results: We retrieved four journal articles and 20 UNAIDS reports covering 29 countries. In 13 countries, the largest FNI (range 26 to 63%) was acquired by the low-risk group and increased with low-risk population size. The FNI among female sex workers (FSWs) remained low (median 1.3%, range 0.04 to 14.4%), with little variability by region and epidemic type despite variability in sexual behaviour. In India and Thailand, where FSWs play an important role in transmission, the FNI among FSWs was 2 and 4%, respectively. In contrast, the FNI among men who have sex with men (MSM) varied across regions (range 0.1 to 89%) and increased with MSM population size. The FNI among people who inject drugs (PWID, range 0 to 82%) was largest in early-phase epidemics with low overall HIV prevalence. Most MOT studies were conducted and reported as per guidelines but data quality remains an issue.

Conclusions: Although countries are generally performing the MOT as per guidelines, there is little variation in the FNI (except among MSM and PWID) by region and epidemic type. Homogeneity in MOT FNI for FSWs, clients and low-risk groups may limit the utility of MOT for guiding country-specific interventions in heterosexual HIV epidemics.

 Abstract  Full-text [free] access

Editor’s notes: In 2002, the HIV Modes of Transmission model (MoT) was developed by UNAIDS to inform and focus, country-specific HIV prevention policies. The idea behind the model was to use simple mathematical modelling approaches, in combination with country specific data, to predict what the distribution of new HIV infection may look like. In this way, countries would be able to better focus their HIV response. Since its development and through 2012, the MoT has been applied in 29 countries, with the findings being used in many settings to shape priorities. In this study, the authors assess the degree to which the MoT produces different outputs in different epidemic contexts. They explore whether there are key parameters in the model that seem to drive similarities and/or differences in projections between countries. Surprisingly, across a broad range of epidemic settings, they found limited variability in the predicted annual fraction of new HIV infections (FNI) acquired by female sex workers (FSW) (0.04-14.4%). There were higher levels of variability between countries in the projected fraction of new HIV infections among men who have sex with men (0.01-89%) and people who inject drugs (0-82%).

The differences in the MoT projections were largely dependent on whether the country in question was categorised as having a concentrated / low-level epidemic, versus generalised epidemic, as defined by UNAIDS. Differences also arose depending upon whether ‘low risk groups’ were also included in the model. Indeed, for 22 of the 25 studies that included a low-risk group, this group was predicted to have a large annual fraction of new HIV infections (11.8-62.9%). This phenomenon arose, not because of high transmission rates in this group (in comparison to others such as MSM or PWIDs) but because these ‘low risk groups’ are large. They are one third of the total population. These findings may be misleading, as the projected high fraction of transmission is dependent on the assumption that everyone in this ‘low risk group’ does have some risk.

It appears that although the MoT was designed to address an important need, it is likely to have limited utility to guide programming in heterosexually driven epidemics.  To address this limitation, UNAIDS is supporting the HIV Modelling Consortium in their development of a revised MoT model that takes into better consideration risk categorization, data constraints and programmatic needs. The revised model is currently undergoing field testing and will be available for country use in 2015.

Africa, Asia, Europe, Latin America
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Per-act HIV transmission risk during anal sex may be higher than previously thought

Estimating per-act HIV transmission risk: a systematic review.

Patel P, Borkowf CB, Brooks JT, Lasry A, Lansky A, Mermin J. AIDS. 2014 Jun 19;28(10):1509-19. doi: 10.1097/QAD.0000000000000298.

Background: Effective HIV prevention programs rely on accurate estimates of the per-act risk of HIV acquisition from sexual and parenteral exposures. We updated the previous risk estimates of HIV acquisition from parenteral, vertical, and sexual exposures, and assessed the modifying effects of factors including condom use, male circumcision, and antiretroviral therapy.

Methods: We conducted literature searches to identify new studies reporting data regarding per-act HIV transmission risk and modifying factors. Of the 7 339 abstracts potentially related to per-act HIV transmission risk, three meta-analyses provided pooled per-act transmission risk probabilities and two studies provided data on modifying factors. Of the 8 119 abstracts related to modifying factors, 15 relevant articles, including three meta-analyses, were included. We used fixed-effects inverse-variance models on the logarithmic scale to obtain updated estimates of certain transmission risks using data from primary studies, and employed Poisson regression to calculate relative risks with exact 95% confidence intervals for certain modifying factors.

Results: Risk of HIV transmission was greatest for blood transfusion, followed by vertical exposure, sexual exposures, and other parenteral exposures. Sexual exposure risks ranged from low for oral sex to 138 infections per 10 000 exposures for receptive anal intercourse. Estimated risks of HIV acquisition from sexual exposure were attenuated by 99.2% with the dual use of condoms and antiretroviral treatment of the HIV-infected partner.

Conclusion: The risk of HIV acquisition varied widely, and the estimates for receptive anal intercourse increased compared with previous estimates. The risk associated with sexual intercourse was reduced most substantially by the combined use of condoms and antiretroviral treatment of HIV-infected partners.

Abstract access 

Editor’s notes: The study updates the 2005 Centres for Disease Control (CDC) per-act HIV transmission risks with estimates from recent publications. In addition, it summarizes the effects of various co-factors that modify the transmission risks during sexual exposure. These include genital ulcer disease, viral load, disease stage, use of antiretrovirals, condom use and male circumcision. However, estimates from low-income countries on sexual and mother-to-child transmission are very heterogeneous and not included in the analyses. In general, the updated estimates of transmission risks are comparable to figures from the 2005 CDC study. But they also suggest that the transmission probabilities for both receptive and insertive anal intercourse could be higher than previously thought. Further, the study reasserts that the per-act risk for all sexual exposures is substantially attenuated through the use of condoms and antiretrovirals. These new estimates will be important for both modelling studies and prevention programmes. But a better understanding of HIV transmission risks in low-income countries is needed. 

Asia, Northern America, Oceania
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