Articles tagged as "Asia"

Does pregnancy accelerate HIV progression?

Pregnancy and HIV disease progression: a systematic review and meta-analysis.

Calvert C, Ronsmans C. Trop Med Int Health. 2014 Oct 31. doi: 10.1111/tmi.12412. [Epub ahead of print]

Objective: To assess whether pregnancy accelerates HIV disease progression.

Methods: Studies comparing progression to HIV-related illness, low CD4 count, AIDS-defining illness, HIV-related death, or any death in HIV-infected pregnant and non-pregnant women were included. Relative risks (RR) for each outcome were combined using random effects meta-analysis and were stratified by antiretroviral therapy (ART) availability.

Results: 15 studies met the inclusion criteria. Pregnancy was not associated with progression to HIV-related illness [summary RR: 1.32, 95% confidence interval (CI): 0.66-2.61], AIDS-defining illness (summary RR: 0.97, 95%CI: 0.74-1.25) or mortality (summary RR: 0.97, 95%CI: 0.62-1.53), but there was an association with low CD4 counts (summary RR: 1.41, 95%CI: 0.99-2.02) and HIV-related death (summary RR: 1.65, 95%CI: 1.06-2.57). In settings where ART was available, there was no evidence that pregnancy accelerated progress to HIV/AIDS-defining illnesses, death and drop in CD4 count. In settings without ART availability, effect estimates were consistent with pregnancy increasing the risk of progression to HIV/AIDS-defining illnesses and HIV-related or all-cause mortality, but there were too few studies to draw meaningful conclusions.

Conclusions: In the absence of ART, pregnancy is associated with small but appreciable increases in the risk of several negative HIV outcomes, but the evidence is too weak to draw firm conclusions. When ART is available, the effects of pregnancy on HIV disease progression are attenuated and there is little reason to discourage healthy HIV-infected women who desire to become pregnant from doing so.

Abstract access 

Editor’s notes: The suppression of cell-mediated immunity during pregnancy is associated with increased susceptibility to and/or severity of many infections. Therefore the question of whether pregnancy accelerates HIV disease progression in HIV-positive women is pertinent. A previous systematic review published in the late 1990s found weak evidence that the odds of acquiring an AIDS-defining illness or death were higher among HIV-positive pregnant women than HIV-positive non-pregnant women. The findings from this meta-analysis also suggest that in the absence of antiretroviral therapy (ART), pregnancy is associated with an increase in the risk of several negative HIV outcomes. Fortunately ART appears to diminish the effects of pregnancy on HIV progression.  The authors also draw attention to the methodological weaknesses of the studies included and highlight the need for better quality data, examining whether pregnancy aggravates HIV progression.

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High frequency of drug-resistant TB in HIV clinics in India

Alarming levels of drug-resistant tuberculosis in HIV-infected patients in metropolitan Mumbai, India.

Isaakidis P, Das M, Kumar AM, Peskett C, Khetarpal M, Bamne A, Adsul B, Manglani M, Sachdeva KS, Parmar M, Kanchar A, Rewari BB, Deshpande A, Rodrigues C, Shetty A, Rebello L, Saranchuk P. PLoS One. 2014 Oct 21;9(10):e110461. doi: 10.1371/journal.pone.0110461. eCollection 2014.

Background: Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India.

Methods: A cross-sectional survey was conducted among adults and children ART-center attendees. Smear microscopy, culture and drug-susceptibility-testing (DST) against all first and second-line TB-drugs using phenotypic liquid culture (MGIT) were conducted on all presumptive tuberculosis patients. Analyses were performed to determine DR-TB prevalence and resistance patterns separately for new and previously treated, culture-positive TB-cases.

Results: Between March 2013 and January 2014, ART-center attendees were screened during 14 135 visits, of whom 1724 had presumptive TB. Of 1724 attendees, 72 (4%) were smear-positive and 202 (12%) had a positive culture for Mycobacterium tuberculosis. Overall DR-TB was diagnosed in 68 (34%, 95% CI: 27%-40%) TB-patients. The proportions of DR-TB were 25% (29/114) and 44% (39/88) among new and previously treated cases respectively. The patterns of DR-TB were: 21% mono-resistant, 12% poly-resistant, 38% multidrug-resistant (MDR-TB), 21% pre-extensively-drug-resistant (MDR-TB plus resistance to either a fluoroquinolone or second-line injectable), 6% extensively drug-resistant (XDR-TB) and 2% extremely drug-resistant TB (XDR-TB plus resistance to any group-IV/V drug). Only previous history of TB was significantly associated with the diagnosis of DR-TB in multivariate models.

Conclusion: The burden of DR-TB among HIV-infected patients attending public ART-centers in Mumbai was alarmingly high, likely representing ongoing transmission in the community and health facilities. These data highlight the need to promptly diagnose drug-resistance among all HIV-infected patients by systematically offering access to first and second-line DST to all patients with 'presumptive TB' rather than 'presumptive DR-TB' and tailor the treatment regimen based on the resistance patterns.

Abstract  Full-text [free] access

Editor’s notes: Drug-resistant tuberculosis (TB) is a major threat to public health. It is associated with substantial morbidity and mortality, particularly among people with advanced HIV disease. Standard drug regimens for multi- and extensively drug-resistant TB are unsatisfactory, requiring long courses of treatment with drugs which often have unpleasant and sometimes serious side effects. For TB programmes, treating drug-resistant TB requires substantial resources, and presents a risk to health care workers unless infection control measures are rigorously applied. 

In this study at five HIV treatment centres in Mumbai, India, adults and children attending for HIV care were systematically screened for TB by a research nurse. Individuals reporting one or more TB symptom (any of cough, weight loss, night sweats or fever, referred to in the article as people with “presumptive TB”) had sputum sent for microscopy, culture and drug susceptibility testing. Among individuals who had Mycobacterium tuberculosis on culture, some 34% had resistance to any drug. Among individuals who had never previously been treated for TB, 11% had resistance to at least rifampicin and isoniazid (multidrug-resistant tuberculosis), and several had more extensive resistance patterns. Among 15 children with culture-positive TB, seven had resistance to at least one drug, and six had at least multidrug-resistant TB. This is particularly concerning because it implies transmission of drug-resistant tuberculosis either in the community or in health care facilities or both.

As the authors illustrate, the absolute number of TB cases was relatively small, and the findings may not be generalisable to other settings in India. Nonetheless, the findings indicate transmission of drug-resistant TB among people living with HIV attending these clinics. This study underlines the need for early detection and prompt initiation of effective treatment for people with TB, including individuals with drug-resistant TB, and for infection control measures to protect individuals and staff within clinics.

Avoid TB deaths
Comorbidity
Asia
India
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Targeted HIV prevention is extremely cost-effective at scale

Cost-effectiveness of HIV prevention for high-risk groups at scale: an economic evaluation of the Avahan programme in south India.

Vassall A, Pickles M, Chandrashekar S, Boily MC, Shetty G, Guinness L, Lowndes CM, Bradley J, Moses S, Alary M, Charme India G, Vickerman P. Lancet Glob Health. 2014 Sep;2(9):e531-40. doi: 10.1016/S2214-109X(14)70277-3. Epub 2014 Aug 27.

Background: Avahan is a large-scale, HIV preventive intervention, targeting high-risk populations in south India. We assessed the cost-effectiveness of Avahan to inform global and national funding institutions who are considering investing in worldwide HIV prevention in concentrated epidemics.

Methods: We estimated cost effectiveness from a programme perspective in 22 districts in four high-prevalence states. We used the UNAIDS Costing Guidelines for HIV Prevention Strategies as the basis for our costing method, and calculated effect estimates using a dynamic transmission model of HIV and sexually transmitted disease transmission that was parameterised and fitted to locally observed behavioural and prevalence trends. We calculated incremental cost-effective ratios (ICERs), comparing the incremental cost of Avahan per disability-adjusted life-year (DALY) averted versus a no-Avahan counterfactual scenario. We also estimated incremental cost per HIV infection averted and incremental cost per person reached.

Findings: Avahan reached roughly 150 000 high-risk individuals between 2004 and 2008 in the 22 districts studied, at a mean cost per person reached of US$327 during the 4 years. This reach resulted in an estimated 61 000 HIV infections averted, with roughly 11 000 HIV infections averted in the general population, at a mean incremental cost per HIV infection averted of $785 (SD 166). We estimate that roughly 1 million DALYs were averted across the 22 districts, at a mean incremental cost per DALY averted of $46 (SD 10). Future antiretroviral treatment (ART) cost savings during the lifetime of the cohort exposed to HIV prevention were estimated to be more than $77 million (compared with the slightly more than $50 million spent on Avahan in the 22 districts during the 4 years of the study).

Interpretation: This study provides evidence that the investment in targeted HIV prevention programmes in south India has been cost effective, and is likely to be cost saving if a commitment is made to provide ART to all that can benefit from it. Policy makers should consider funding and sustaining large-scale targeted HIV prevention programmes in India and beyond.

Abstract  Full-text [free] access

Editor’s notes: This study evaluates the cost-effectiveness of Avahan, one of the largest targeted HIV prevention programmes in the world. The authors find that prevention activities targeted to high-risk populations is extremely cost-effective, and likely to be cost-saving in the long run. Although there have been previous studies to the same effect on small projects or pilot programmes, these results are important for several reasons. First, the large scale of the study provides solid evidence on the cost-effectiveness of this activity in the real world, and at scale. Second, the inclusion of costs above the NGO level is unique, and reflects a vital investment for countries seeking to scale up HIV prevention activities. Further, the precision of estimates due to the comprehensive original data collection and fitting of the model is unparalleled. This study should encourage confidence in policy makers of the continuing strength of ‘prevention as prevention’ in the effort to stem the HIV epidemic in the context of scarce resources for HIV programmes. 

Asia
India
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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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Do not ignore higher level costs - only 35% of programme costs for service delivery in Indian HIV prevention programmes

The costs of scaling up HIV prevention for high risk groups: lessons learned from the Avahan programme in India.

Chandrashekar S, Guinness L, Pickles M, Shetty GY, Alary M, Vickerman P, Group C-E, Vassall A. PLoS One. 2014 Sep 9;9(9):e106582. doi: 10.1371/journal.pone.0106582. eCollection 2014.

Objective: The study objective is to measure, analyse costs of scaling up HIV prevention for high-risk groups in India, in order to assist the design of future HIV prevention programmes in South Asia and beyond.

Design: Prospective costing study.

Methods: This study is one of the most comprehensive studies of the costs of HIV prevention for high-risk groups to date in both its scope and size. HIV prevention included outreach, sexually transmitted infections (STI) services, condom provision, expertise enhancement, community mobilisation and enabling environment activities. Economic costs were collected from 138 non-government organisations (NGOs) in 64 districts, four state level lead implementing partners (SLPs), and the national programme level (Bill and Melinda Gates Foundation (BMGF)) office over four years using a top down costing approach, presented in US$ 2011.

Results: Mean total unit costs (2004-08) per person reached at least once a year and per monthly contact were US$ 235(56-1864) and US$ 82(12-969) respectively. 35% of the cost was incurred by NGOs, 30% at the state level SLP and 35% at the national programme level. The proportion of total costs by activity were 34% for expertise enhancement, 37% for programme management (including support and supervision), 22% for core HIV prevention activities (outreach and STI services) and 7% for community mobilisation and enabling environment activities. Total unit cost per person reached fell sharply as the programme expanded due to declining unit costs above the service level (from US$ 477 per person reached in 2004 to US$ 145 per person reached in 2008). At the service level also unit costs decreased slightly over time from US$ 68 to US$ 64 per person reached.

Conclusions: Scaling up HIV prevention for high risk groups requires significant investment in expertise enhancement and programme administration. However, unit costs decreased with programme expansion in spite of an increase in the scope of activities.

Abstract  Full-text [free] access

Editor’s notes: This paper captures the costs of one of the largest HIV prevention programmes among key populations to date. In the four states of study, Avahan focussed on a comprehensive set of activities among female sex workers and men who have sex with men. In addition to intervening with key populations the programme also focussed on strengthening technical expertise among providers. Most costing studies have focussed on costs at the service delivery level. It is widely acknowledged that the costs incurred at higher levels of the system are largely unknown. This study applies a top down cost allocation, which followed funding from the national, state and district levels as well the service delivery level. Only 35% of programme costs were at the service level, though this increases as programmes mature and scale up. This emphasises how detrimental ignoring higher level costs can be when making projections of budget impact and may provide insights into why so many new programmes and individual activities are not sustained.

Asia
India
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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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Treatment of HIV-2, where is the evidence?

Antiretroviral therapy response among HIV-2 infected patients: a systematic review.

Ekouevi DK, Tchounga BK, Coffie PA, Tegbe J, Anderson AM, Gottlieb GS, Vitoria M, Dabis F, Eholie SP. BMC Infect Dis. 2014 Aug 26;14:461. doi: 10.1186/1471-2334-14-461.

Methods: Data were extracted from articles that were selected after screening of PubMed/MEDLINE up to November 2012 and abstracts of the 1996-2012 international conferences. Observational cohorts, clinical trials and program reports were eligible as long as they reported data on ART response (clinical, immunological or virological) among HIV-2 infected patients. The determinants investigated included patients' demographic characteristics, CD4 cell count at baseline and ART received.

Results: Seventeen reports (involving 976 HIV-2 only and 454 HIV1&2 dually reactive patients) were included in the final review, and the analysis presented in this report are related to HIV-2 infected patients only in 17 reports. There was no randomized controlled trial and only two cohorts had enrolled more than 100 HIV-2 only infected patients. The median CD4 count at ART initiation was 165 cells /mm3, [IQR; 137-201] and the median age at ART initiation was 44 years (IQR: 42-48 years). Ten studies included 103 patients treated with three nucleoside reverse transcriptase inhibitors (NRTI). Protease inhibitor (PI) based regimens were reported by 16 studies. Before 2009, the most frequent PIs used were Nelfinavir and Indinavir, whereas it was Lopinavir/ritonavir thereafter. The immunological response at month-12 was reported in six studies and the mean CD4 cell count increase was +118 cells /µL (min-max: 45-200 cells/µL).

Conclusion: Overall clinical and immuno-virologic outcomes in HIV-2 infected individuals treated with ART are suboptimal. There is a need of randomized controlled trials to improve the management and outcomes of people living with HIV-2 infection.

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Editor’s notes: HIV-2 accounts for between 10-20% of HIV infections in West Africa. With a longer asymptomatic period, lower plasma viral load and slower decline in CD4 count, it is often seen as a less aggressive virus than HIV-1. However, people with HIV-2 still experience clinical progression and AIDS-related deaths. WHO recommends initiating a boosted protease inhibitor regimen or a triple nucleoside reverse transcriptase (NRTI)-based regimen in people living with HIV-2 when their CD4 count falls below 500 cells/mm3. However, as clearly demonstrated in this systematic review, the evidence underlying when to start antiretroviral therapy (ART) and the optimal treatment options for people living with HIV-2, is weak. Only 17 observational studies (15 cohort studies and two case series) were identified. Overall immune recovery was sub-optimal and, given the small sample sizes of these studies, there was limited power to detect any differences in outcomes by treatment regimen. Further evidence is urgently needed to guide optimal treatment of people living with HIV-2. 

Africa, Asia, Europe, Northern America
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Cotrimoxazole appears safe in pregnant women living with HIV, despite poor quality evidence

Safety of cotrimoxazole in pregnancy: a systematic review and meta-analysis.

Ford N, Shubber Z, Jao J, Abrams EJ, Frigati L, Mofenson L. J Acquir Immune Defic Syndr. 2014 Aug 15;66(5):512-21. doi: 10.1097/QAI.0000000000000211.

Introduction: Cotrimoxazole is widely prescribed to treat a range of infections, and for HIV-infected individuals it is administered as prophylaxis to protect against opportunistic infections. Some reports suggest that fetuses exposed to cotrimoxazole during early pregnancy may have an increased risk of congenital anomalies. We carried out this systematic review to update the evidence of cotrimoxazole safety in pregnancy.

Methods: Three databases and 1 conference abstract site were searched in duplicate up to October 31, 2013, for studies reporting adverse maternal and infant outcomes among women receiving cotrimoxazole during pregnancy. This search was updated in MEDLINE via PubMed to April 28, 2014. Studies were included irrespective of HIV infection status or the presence of other coinfections. Our primary outcome was birth defects of any kind. Secondary outcomes included spontaneous abortions, terminations of pregnancy, stillbirths, preterm deliveries, and drug-associated toxicity.

Results: Twenty-four studies were included for review. There were 232 infants with congenital anomalies among 4 196 women receiving cotrimoxazole during pregnancy, giving an overall pooled prevalence of 3.5% (95% confidence interval: 1.8% to 5.1%; τ² = 0.03). Three studies reported 31 infants with neural tube defects associated with first trimester exposure to cotrimoxazole, giving a crude prevalence of 0.7% (95% confidence interval: 0.5% to 1.0%) with most data (29 neural tube defects) coming from a single study. The majority of adverse drug reactions were mild. The quality of the evidence was very low.

Conclusions: The findings of this review support continued recommendations for cotrimoxazole as a priority intervention for HIV-infected pregnant women. It is critical to improve data collection on maternal and infant outcomes.

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Editor’s notes: Cotrimoxazole significantly reduces morbidity and increases survival in people living with HIV (including people on antiretroviral therapy) in resource-limited settings.  However, there is some concern of potential human foetal risk when cotrimoxazole is taken during pregnancy. This systematic review found very limited evaluable data on maternal and infant outcomes associated with cotrimoxazole exposure during pregnancy. Cotrimoxazole is likely to be of most benefit in high HIV burden, low-income settings. In this context, the known benefit of treatment outweighs the potential risk to the foetus, in HIV-positive pregnant women.  Importantly, this paper highlights the need for better pregnancy outcome surveillance in women living with HIV, in resource-poor settings, which includes evaluation of exposure to cotrimoxazole and antiretroviral treatment.  

Africa, Asia, Europe, Northern America, Oceania
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