Articles tagged as "Brazil"

Do text messaging activities promote adherence to antiretroviral therapy?


Text message intervention designs to promote adherence to antiretroviral therapy (ART): a meta-analysis of randomized controlled trials

Finitsis, D. J. P., J. A. Johnson, B. PLoS One. 2014 Feb 5;9(2):e88166. doi: 10.1371/journal.pone.0088166. eCollection 2014.

Background: The efficacy of antiretroviral therapy depends on patient adherence to a daily medication regimen, yet many patients fail to adhere at high enough rates to maintain health and reduce the risk of transmitting HIV. Given the explosive global growth of cellular-mobile phone use, text-messaging interventions to promote adherence are especially appropriate. This meta-analysis synthesized available text messaging interventions to promote antiretroviral therapy adherence in people living with HIV.

Methods: We performed Boolean searches of electronic databases, hand searches of recent year conference abstracts and reverse searches. Included studies (1) targeted antiretroviral therapy adherence in a sample of people living with HIV, (2) used a randomized-controlled trial design to examine a text messaging intervention, and (3) reported at least one adherence measurement or clinical outcome.

Results: Eight studies, including 9 interventions, met inclusion criteria. Text-messaging interventions yielded significantly higher adherence than control conditions (OR = 1.39; 95% CI = 1.18, 1.64). Sensitivity analyses of intervention characteristics suggested that studies had larger effects when interventions (1) were sent less frequently than daily, (2) supported bidirectional communication, (3) included personalized message content, and (4) were matched to participants' antiretroviral therapy dosing schedule. Interventions were also associated with improved viral load and/or CD4+ count (k = 3; OR = 1.56; 95% CI = 1.11, 2.20).

Conclusions: Text-messaging can support antiretroviral therapy adherence. Researchers should consider the adoption of less frequent messaging interventions with content and timing that is individually tailored and designed to evoke a reply from the recipient. Future research is needed in order to determine how best to optimize efficacy.

Abstract Full-text [free] access

Editor’s notes: Adherence to antiretroviral therapy (ART) is crucial for good clinical outcomes and for reducing the risk of onward HIV transmission. In the last decade, there has been a massive increase in cellular phone ownership. This provides a promising and potentially cost-effective approach to improving ART adherence through short messaging services (SMS). The World Health Organization guidelines recommend using SMS as part of a package of activities to support adherence to ART.

This meta-analysis examined how SMS can be optimally used to promote successful adherence. Eight randomised controlled trials from the USA, Brazil, Kenya and Cameroon investigated nine types of SMS activities. Studies used multiple methods to measure adherence including self-report, electronic drug monitoring and pill counts. Overall, text messaging significantly improved the average adherence outcome. Only three of the eight studies used virologic suppression as an outcome measure; importantly these studies did show an improvement in adherence. The study highlighted the components of SMS activities that were associated with the most effect on adherence. These included less frequent messaging than daily, personalised message content, SMS matched to dosing schedules and bidirectional communication between the care provider and the participant.

In summary, SMS is a promising activity for supporting adherence, although the effect on adherence is modest.  Several questions remain to be answered, namely the optimum way of operationalising this as an adherence support activity, its sustainability and its cost-effectiveness (given the modest effect size). Finally, a major limitation of ART adherence studies is the common use of non-biological measures of adherence, which do not always reflect virologic suppression. Virologic suppression is the most persuasive outcome for evaluations of programmes to improve adherence. 

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Physical as well as sexual partner violence is associated with increased HIV risk

Intimate partner violence and HIV infection among women: a systematic review and meta-analysis

Li Y, Marshall CM, Rees HC, Nunez A, Ezeanolue EE, Ehiri JE. 4 J Int AIDS Soc. 2014 Feb 13;17:18845. doi: 10.7448/IAS.17.1.18845. eCollection 2014.

Introduction: To assess evidence of an association between intimate partner violence (IPV) and HIV infection among women.

Methods: Medline/PubMed, Embase, Web of Science, EBSCO, Ovid, Cochrane HIV/AIDS Group's Specialized Register and Cochrane Central Register of Controlled Trials were searched up to 20 May 2013 to identify studies that examined the association between IPV and HIV infection in women. We included studies on women aged ≥15 years, in any form of sexually intimate relationship with a male partner.

Results: Twenty-eight studies [(19 cross-sectional, 5 cohorts and 4 case-control studies) involving 331 468 individuals in 16 countries - the US (eight studies), South Africa (four studies), East Africa (10 studies), India (three studies), Brazil (one study) and multiple low-income countries (two studies)] were included. Results were pooled using RevMan 5.0. To moderate effect estimates, we analyzed all data using the random effects model, irrespective of heterogeneity level. Pooled results of cohort studies indicated that physical IPV [pooled RR (95% CI): 1.22 (1.01, 1.46)] and any type of IPV [pooled RR (95% CI): 1.28 (1.00, 1.64)] were significantly associated with HIV infection among women. Results of cross-sectional studies demonstrated significant associations of physical IPV with HIV infection among women [pooled OR (95% CI): 1.44 (1.10, 1.87)]. Similarly, results of cross-sectional studies indicated that combination of physical and sexual IPV [pooled OR (95% CI): 2.00 (1.24, 3.22) and any type of IPV [pooled OR (95% CI): 1.41 (1.16, 1.73)] were significantly associated with HIV infection among women.

Conclusions: Available evidence suggests a moderate statistically significant association between IPV and HIV infection among women. To further elucidate the strength of the association between IPV and HIV infection among women, there is a need for high-quality follow-up studies conducted in different geographical regions of the world, and among individuals of diverse racial/cultural backgrounds and varying levels of HIV risks.

Abstract Full-text [free] access

Editor’s notes: Globally, an estimated 30% of partnered women will experience physical and/or sexual violence. As well as being a violation of human rights, there is growing evidence about the different ways in which violence and the fear of violence may limit women’s ability to prevent themselves from acquiring infection, or access services. This paper presents a systematic review and meta-analysis of current evidence on whether exposures to violence by an intimate partner increase women’s HIV risk. Commonly, debates on this issue focus on forced sex. The findings suggest that the issue is more complex – with exposures to physical violence also being associated with increased HIV risk. Exposures to both physical and sexual violence by partners, which is an indicator of more severe partner violence, found stronger effect estimates. The pathways underlying the documented associations may be multiple: as well as forced sex, women may have difficulties negotiating condom use or accessing services. Other studies have suggested that there may also be other characteristics of the relationship.  These are that men who are violent are also more likely to have other risk behaviours such as problematic alcohol use or multiple sexual partners. These result in them being more likely to be HIV positive than non-violent men. The findings suggest that violence prevention activities may reduce HIV risk. They also highlight the need to ensure that HIV services are sensitive to, and able to support, women who have experienced or fear violence.

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CD4 counts at antiretroviral therapy start rising globally, but could do better!

Immunodeficiency at the start of combination antiretroviral therapy in low-,  middle-, and high-income countries.

The IeDEA and ART Cohort Collaborations. J Acquir Immune Defic Syndr 2014 Jan 1;65(1):e8-e16. doi: 10.1097/QAI.0b013e3182a39979.

Objective: To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC), and high-income (HIC) countries.

Methods: Patients aged 16 years or older starting cART in a clinic participating in a multicohort collaboration spanning 6 continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multilevel linear regression models were adjusted for age, gender, and calendar year; missing CD4 counts were imputed.

Results: In total, 379 865 patients from 9 LIC, 4 LMIC, 4 UMIC, and 6 HIC were included. In LIC, the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/µL between 2002 and 2009. Corresponding increases in LMIC, UMIC, and HIC were from 87 to 155 cells/µL (76% increase), 88 to 135 cells/µL (53%), and 209 to 274 cells/µL (31%). In 2009, compared with LIC, median counts were 13 cells/µL [95% confidence interval (CI): -56 to +30] lower in LMIC, 22 cells/µL (-62 to +18) lower in UMIC, and 112 cells/µL (+75 to +149) higher in HIC. They were 23 cells/µL (95% CI: +18 to +28 cells/µL) higher in women than men. Median counts were 88 cells/µL (95% CI: +35 to +141 cells/µL) higher in countries with an estimated national cART coverage >80%, compared with countries with <40% coverage.

Conclusions: Median CD4 cell counts at the start of cART increased 2000-2009 but remained below 200 cells/µL in LIC and MIC and below 300 cells/µL in HIC. Earlier start of cART will require substantial efforts and resources globally.

Abstract access 

Editor’s notes: In this multi-cohort analysis spanning six continents, median CD4 counts at initiation of combination antiretroviral therapy were substantially higher in high-income compared to low- or middle-income countries. Median CD4 counts at initiation increased between 2002 and 2009 in most countries studied, but these increases were greater in low- and middle-income than high-income countries and were greater among men than women. Baseline CD4 counts in low- and middle-income countries were higher among countries with national antiretroviral therapy coverage of 80% or above. Nevertheless, despite the massive scale-up of antiretroviral therapy in low-income countries since 2002, the increases in median CD4 count at the start of antiretroviral therapy have been modest. Substantial efforts and resources are needed to achieve earlier implementation of antiretroviral therapy globally.

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Renewed prevention efforts needed for key populations in Latin America and the Caribbean

Epidemiology of HIV in Latin America and the Caribbean.

De Boni R, Veloso VG, Grinsztejn B. Curr Opin HIV AIDS. 2014 Jan 3. [Epub ahead of print]

Purpose of review: The aim of the present review is to update HIV/AIDS Epidemiology in Latin America and the Caribbean highlighting the concentrated aspect of epidemic in the region.

Recent findings: Among general population, HIV prevalence in Latin America is at stable levels (0.2-0.7%). The Caribbean still has one of the highest HIV prevalence rates in the world (<0.1-3%), but incidences have declined around 49%. This is not the current situation for high-risk key populations; most incident cases occur among MSM. Available data on transgender women suggest that they are the most-at-risk group. Female sex workers still have a 12-fold chance of being HIV positive compared with other women. IDU prevalence was revised to 0.45%, but non-IDU has been suggested as a mediator between sexual risk and HIV.

Summary: The increase in treatment coverage (mean is at 63%) resulted in modifications of HIV/AIDS epidemiology. New strategies to seek, test and link key populations to care are urgently needed and targeted interventions to prevent HIV expansion among them must be adopted. These strategies should consider the particular situation regarding social inequalities, discrimination and violence that pervade the HIV epidemic among key populations.

Abstract access 

Editor’s notes: This review highlights recently published data on key populations in Latin America and the Caribbean, including men who have sex with men (MSM), transgender women, female sex workers and people who inject drugs. HIV remains a concentrated epidemic in Latin America and the Caribbean with MSM and transgender women being the most vulnerable populations. Although antiretroviral therapy (ART) coverage has increased to over 80% in several countries, a renewed focus on prevention, especially among key populations, is needed. It is estimated that prevention efforts currently only receive 15% of HIV public spending in this region. Culturally appropriate efforts are needed to identify and prevent HIV infection among key populations, and to better understand transmission dynamics of neglected groups such as transgender women. 

Latin America
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An integrated investment approach for women’s and children’s health

Advancing social and economic development by investing in women's and children's health: a new Global Investment Framework.

Stenberg K, Axelson H, Sheehan P, Anderson I, Gülmezoglu AM, Temmerman M, Mason E, Friedman HS, Bhutta ZA, Lawn JE, Sweeny K, Tulloch J, Hansen P, Chopra M, Gupta A, Vogel JP, Ostergren M, Rasmussen B, Levin C, Boyle C, Kuruvilla S, Koblinsky M, Walker N, de Francisco A, Novcic N, Presern C, Jamison D, Bustreo F; on behalf of the Study Group for the Global Investment Framework for Women's Children's Health. Lancet. 2013 Nov 18. doi: S0140-6736(13)62231-X. pii: 10.1016/S0140-6736(13)62231-X. [Epub ahead of print]

A new Global Investment Framework for Women's and Children's Health demonstrates how investment in women's and children's health will secure high health, social, and economic returns. We costed health systems strengthening and six investment packages for: maternal and newborn health, child health, immunisation, family planning, HIV/AIDS, and malaria. Nutrition is a cross-cutting theme. We then used simulation modelling to estimate the health and socioeconomic returns of these investments. Increasing health expenditure by just $5 per person per year up to 2035 in 74 high-burden countries could yield up to nine times that value in economic and social benefits. These returns include greater gross domestic product (GDP) growth through improved productivity, and prevention of the needless deaths of 147 million children, 32 million stillbirths, and 5 million women by 2035. These gains could be achieved by an additional investment of $30 billion per year, equivalent to a 2% increase above current spending.

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Editor’s notes: Over the past 20 years there have been substantial gains in maternal and child health (MCH). However, much still needs to be done – assuming a continuation of current rates of progress, there would nevertheless be shortfalls in the achievement of MDG 4 and 5 targets. Especially in sub-Saharan Africa, HIV is an important underlying cause of maternal and child ill health. This paper models the costs and benefits of an accelerated action on MCH, including for HIV, the prevention of mother to child HIV transmission; first line treatment for pregnant women; cotrimoxazole for children, and the provision of paediatric antiretroviral therapy (ART). These HIV services are complemented by health systems strengthening; increased family planning provision; and packages for malaria, immunisation, and child health. The paper is interesting for many reasons, including both the breadth of its intervention focus, and the detailed modelling of the likely health, social and economic benefits of such investments.

Although the direct HIV related benefits are not described in detail in the main paper, it is likely that these result both from increased contraceptive use (prong 2 for preventing vertical HIV transmission), as well as ART and cotrimoxazole provision. It also illustrates the potential value of developing a cross-disease investment approach, as a means to ensure that services effectively respond to the breadth of women’s and children’s health needs. This more ‘joined up’, integrated perspective on strategies for health investment can support core investments in health systems strengthening. It can also potentially achieve important cross-disease synergies, e.g., ensuring that a child who has not acquired HIV at birth does not then die from malaria. 

Africa, Asia, Latin America, Oceania
Afghanistan, Angola, Azerbaijan, Bangladesh, Benin, Bolivia, Botswana, Brazil, Burkina Faso, Burundi, Cambodia, Cameroon, Central African Republic, Chad, China, Comoros, Congo, Côte d'Ivoire, Democratic People's Republic of Korea, Democratic Republic of the Congo, Djibouti, Egypt, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Gambia, Ghana, Guatemala, Guinea, Guinea-Bissau, Haiti, India, Indonesia, Iraq, Kenya, Kyrgyzstan, Lao People's Democratic Republic, Lesotho, Liberia, Madagascar, Malawi, Mali, Mauritania, Mexico, Morocco, Mozambique, Myanmar, Nepal, Niger, Nigeria, Pakistan, Papua New Guinea, Peru, Philippines, Rwanda, Sao Tome and Principe, Senegal, Sierra Leone, Solomon Islands, Somalia, South Africa, Sudan, Swaziland, Tajikistan, Togo, Turkmenistan, Uganda, United Republic of Tanzania, Uzbekistan, Viet Nam, Yemen, Zambia, Zimbabwe
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Intrauterine infections, but not obstetric complications, more common among pregnant women with HIV

HIV and the Risk of Direct Obstetric Complications: A Systematic Review and Meta-Analysis. 

Calvert C, Ronsmans C. PLoS One. 2013 Oct 4;8(10):e74848. doi:10.1371/journal.pone.0074848.

Background: Women of reproductive age in parts of sub-Saharan Africa are faced both with high levels of HIV and the threat of dying from the direct complications of pregnancy. Clinicians practicing in such settings have reported a high incidence of direct obstetric complications among HIV-infected women, but the evidence supporting this is unclear. The aim of this systematic review is to establish whether HIV-infected women are at increased risk of direct obstetric complications.

Methods and findings: Studies comparing the frequency of obstetric haemorrhage, hypertensive disorders of pregnancy, dystocia and intrauterine infections in HIV-infected and uninfected women were identified. Summary estimates of the odds ratio (OR) for the association between HIV and each obstetric complication were calculated through meta-analyses. In total, 44 studies were included providing 66 data sets; 17 on haemorrhage, 19 on hypertensive disorders, five on dystocia and 25 on intrauterine infections. Meta-analysis of the OR from studies including vaginal deliveries indicated that HIV-infected women had over three times the risk of a puerperal sepsis compared with HIV-uninfected women [pooled OR: 3.43, 95% confidence interval (CI): 2.00-5.85]; this figure increased to nearly six amongst studies only including women who delivered by caesarean (pooled OR: 5.81, 95% CI: 2.42-13.97). For other obstetric complications the evidence was weak and inconsistent.

Conclusions: The higher risk of intrauterine infections in HIV-infected pregnant and postpartum women may require targeted strategies involving the prophylactic use of antibiotics during labour. However, as the huge excess of pregnancy-related mortality in HIV-infected women is unlikely to be due to a higher risk of direct obstetric complications, reducing this mortality will require non obstetric interventions involving access to ART in both pregnant and non-pregnant women.

Abstract  Full-text [free] access

Editor’s notes: Women with HIV are thought to have a higher risk of adverse outcomes during pregnancy. This review is valuable in summarizing available data on this topic. Many of the included studies predated the wide availability of antiretroviral therapy. There was a clear association between HIV infection and intrauterine infections, but not with the other obstetric complications, e.g., obstetric haemorrhage, hypertensive disorders of pregnancy, dystocia, examined in the review. Considering individual conditions analysed, HIV infection was associated with antepartum haemorrhage, (but not postpartum haemorrhage). It was also found to be associated with pregnancy-induced hypertension (but not pre-eclampsia or eclampsia), and uterine rupture or prolonged labour (but not other complications of dystocia). The authors note that the studies were generally of low quality, and there were too few studies to examine the effect of antiretroviral therapy on these complications.  

Given the excess of intrauterine infections in women with HIV, the authors suggest that these might be preventable with prophylactic antibiotics. Overall, where causes of maternal mortality are documented, pregnant women with HIV are more likely to die of non-pregnancy related infections, than of obstetric complications. Specifically, non-pregnancy related infections are tuberculosis, pneumonia or meningitis. Pregnant women living with HIV need access to antenatal services and a skilled attendant at delivery. But, the top priority with respect to reducing maternal mortality is effective antiretroviral therapy.

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Promising treatment outcomes with dolutegravir

Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study.

Cahn P, Pozniak AL, Mingrone H, Shuldyakov A, Brites C, Andrade-Villanueva JF, Richmond G, Buendia CB, Fourie J, Ramgopal M, Hagins D, Felizarta F, Madruga J, Reuter T, Newman T, Small CB, Lombaard J, Grinsztejn B, Dorey D, Underwood M, Griffith S, Min S; extended SAILING Study Team. Lancet. 2013 Aug 24;382(9893):700-8. doi: 10.1016/S0140-6736(13)61221-0. Epub 2013 Jul 3.

Background: Dolutegravir (GSK1349572), a once-daily HIV integrase inhibitor, has shown potent antiviral response and a favourable safety profile. We evaluated safety, efficacy, and emergent resistance in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV-1 with at least two-class drug resistance.

Methods:  ING111762 (SAILING) is a 48 week, phase 3, randomised, double-blind, active-controlled, non-inferiority study that began in October, 2010. Eligible patients had two consecutive plasma HIV-1 RNA assessments of 400 copies per mL or higher (unless >1 000 copies per mL at screening), resistance to two or more classes of antiretroviral drugs, and had one to two fully active drugs for background therapy. Participants were randomly assigned (1:1) to once-daily dolutegravir 50 mg or twice-daily raltegravir 400 mg, with investigator-selected background therapy. Matching placebo was given, and study sites were masked to treatment assignment. The primary endpoint was the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL at week 48, evaluated in all participants randomly assigned to treatment groups who received at least one dose of study drug, excluding participants at one site with violations of good clinical practice. Non-inferiority was prespecified with a 12% margin; if non-inferiority was established, then superiority would be tested per a prespecified sequential testing procedure. A key prespecified secondary endpoint was the proportion of patients with treatment-emergent integrase-inhibitor resistance. The trial is registered at, NCT01231516.

Findings:  Analysis included 715 patients (354 dolutegravir; 361 raltegravir). At week 48, 251 (71%) patients on dolutegravir had HIV-1 RNA less than 50 copies per mL versus 230 (64%) patients on raltegravir (adjusted difference 7·4%, 95% CI 0·7 to 14·2); superiority of dolutegravir versus raltegravir was then concluded (p=0·03). Significantly fewer patients had virological failure with treatment-emergent integrase-inhibitor resistance on dolutegravir (four vs 17 patients; adjusted difference -3·7%, 95% CI -6·1 to -1·2; p=0·003). Adverse event frequencies were similar across groups; the most commonly reported events for dolutegravir versus raltegravir were diarrhoea (71 [20%] vs 64 [18%] patients), upper respiratory tract infection (38 [11%] vs 29 [8%]), and headache (33 [9%] vs 31 [9%]). Safety events leading to discontinuation were infrequent in both groups (nine [3%] dolutegravir, 14 [4%] raltegravir).

Interpretation: Once-daily dolutegravir, in combination with up to two other antiretroviral drugs, is well tolerated with greater virological effect compared with twice-daily raltegravir in this treatment-experienced patient group.

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Editor’s notes: This trial shows that once a day dolutegravir, together with an optimized treatment backbone, is an effective, well- tolerated option for treatment-experienced patients with dual class resistance.  In fact, in this trial it was superior to twice daily raltegravir both in terms of the proportion of patients achieving viral suppression (VL <50 copies/ml) at 48 weeks and in terms of emergent resistance.  Once daily-dosing has potential advantages in terms of reducing pill burden and optimizing adherence. Also, as dolutegravir does not significantly induce or inhibit cytochrome P450, the risk of drug interactions is low. Dolutegravir is therefore a very promising addition to current treatment options. However, the cost, which has been estimated to be greater than its equivalent weight in gold, will limit its widespread use, particularly in resource-limited settings.

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Isoniazid preventive therapy reduces tuberculosis incidence and death in Brazil

Effect of improved tuberculosis screening and isoniazid preventive therapy on incidence of tuberculosis and death in patients with HIV in clinics in Rio de Janeiro, Brazil: a stepped wedge, cluster-randomised trial.

Durovni B, Saraceni V, Moulton LH, Pacheco AG, Cavalcante SC, King BS, Cohn S, Efron A, Chaisson RE, Golub JE. Lancet Infect Dis. 2013 Aug 14. doi:pii: S1473-3099(13)70187-7. 10.1016/S1473-3099(13)70187-7. [Epub ahead of print]

Background:  Preventive therapy for tuberculosis in patients with HIV is effective, but it has not been widely implemented in moderate or high-burden settings. We assessed the effect of widespread use of isoniazid preventive therapy on rates of tuberculosis and death in people with HIV in Brazil.

Methods:  We did a stepped wedge, cluster-randomised trial with patients actively enrolled in 29 HIV clinics in Rio de Janeiro. Clinic staff were trained in tuberculosis screening, use of tuberculin skin tests, and use of isoniazid preventive therapy. Clinics were randomly allocated a date to begin the intervention period, with two clinics beginning the intervention every 2 months starting from Sept 1, 2005. The primary outcome was tuberculosis incidence alone or combined with death in the control versus intervention periods until Aug 31, 2009. This trial is registered at, number NCT00107887.

Results:  Of 17 413 patients in the cohort, 12 816 were eligible for the intervention. Overall, there were 475 tuberculosis cases and 838 deaths. The intervention increased the rate of patients receiving skin tests from 19 per 100 person-years to 59 per 100 person-years, and from 36 per 100 person-years to 144 per 100 person-years for those eligible for isoniazid preventive therapy. In the control period, 221 cases of tuberculosis were diagnosed (1·31 per 100 person-years) compared with 254 (1·10 per 100 person-years) in the intervention period (unadjusted hazard ratio [HR] 0·87; 95% CI 0·69-1·10). Rates of tuberculosis incidence or death were 3·64 and 3·04 per 100 person-years, respectively (0·76; 95% CI 0·66-0·87). When adjusted for age, sex, entry CD4 count, and use of antiretroviral therapy, the HR for tuberculosis was 0·73 (95% CI 0·54-0·99) and for tuberculosis or death was 0·69 (0·57-0·83).

Interpretation:  Operational training aimed at increasing tuberculosis screening, provision of tuberculin skin tests, and use of isoniazid preventive therapy in Brazilian HIV clinics significantly reduced incident tuberculosis and death. Thus, scale-up of preventive therapy for HIV-infected patients in settings of moderate tuberculosis incidence is achievable and should be widely implemented in Brazil and elsewhere.

Funding:  Bill & Melinda Gates Foundation and the National Institutes of Health.

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Editor’s notes: There is a wealth of evidence supporting the efficacy of isoniazid preventive therapy in preventing tuberculosis among people with HIV, but implementation has been disappointingly slow. In Brazil, isoniazid preventive therapy is recommended in guidelines but has not been widely implemented. In this large, pragmatic trial with a stepped wedge design, clinic staff were trained to deliver isoniazid preventive therapy for HIV-positive people with a positive tuberculin skin test, in line with national guidelines. Coverage of antiretroviral therapy was relatively high (60% at baseline). Tuberculosis incidence and death was lower in the intervention period, supporting the wider use of isoniazid preventive therapy as part of care for people living with HIV. More than one-third of tuberculosis cases in the intervention period occurred among people who had not yet had a tuberculin skin test. This underlines the need for increased coverage of HIV testing, aiming to reduce the number of people living with HIV who first present for care with active tuberculosis, and that screening for tuberculosis and provision of isoniazid for those without active disease is a priority for people entering HIV care. The study also illustrates that tuberculin skin tests are cumbersome to administer, highlighting the need for tests to identify individuals at highest risk of developing active tuberculosis which are easier to deploy.

Avoid TB deaths
Latin America
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Encouraging results of community empowerment interventions among female sex workers

Community empowerment among female sex workers is an effective HIV prevention intervention: a systematic review of the peer-reviewed evidence from low- and middle-income countries.

Kerrigan DL, Fonner VA, Stromdahl S, Kennedy CE., AIDS Behav. 2013 Jul;17(6):1926-40. doi: 10.1007/s10461-013-0458-4.

We conducted a systematic review and meta-analysis of community empowerment interventions for HIV prevention among sex workers in low- and middle-income countries from 1990-2010. Two coders abstracted data using standardized forms. Of 6 664 citations screened, ten studies met inclusion criteria. For HIV infection, two observational studies showed a significantly protective combined effect [odds ratio (OR): 0.84, 95 % confidence interval (CI): 0.709-0.988]. For STI infection, one longitudinal study showed reduced gonorrhoea/chlamydia (OR: 0.51, 95 % CI: 0.26-0.99). Observational studies showed reduced gonorrhoea (OR: 0.65, 95 % CI: 0.47-0.90), but non-significant effects on chlamydia and syphilis. For condom use, one randomized controlled trial showed improvements with clients (ß: 0.3447, p = 0.002). One longitudinal study showed improvements with regular clients (OR: 1.9, 95 % CI: 1.1-3.3), but no change with new clients. Observational studies showed improvements with new clients (OR: 3.04, 95 % CI: 1.29-7.17), regular clients (OR: 2.20, 95 % CI: 1.41-3.42), and all clients (OR: 5.87, 95 % CI: 2.88-11.94), but not regular non-paying partners. Overall, community empowerment-based HIV prevention was associated with significant improvements across HIV outcomes and settings.

Abstract access

Editor’s notes: In contrast to individual behaviour change interventions, community empowerment is a structural intervention which seeks to address and alter social, political and material conditions surrounding sex work in a given setting.  This is the first systematic review to evaluate the impact of community empowerment as an HIV prevention strategy among sex worker in low- and middle-income countries. This systematic review was conducted as part of a larger World Health Organization (WHO) effort to develop technical guidelines for HIV/STI prevention among sex workers. The results were encouraging, with positive effects of empowerment interventions on outcomes including HIV/STI infection and consistent condom use with clients (but not with regular partners, with whom condom use is generally low).  Encouragingly, all of the studies involved included not only the community empowerment intervention elements as described above, but also core HIV prevention elements: HIV/STI peer education, some form of condom distribution (free or via social marketing), and STI screening, treatment and management. Of the 10 included studies, seven were from India, two from Brazil and one from the Dominican Republic.  The lack of such studies in southeast Asia, or Africa, is striking, and a rigorous evaluation of community empowerment among sex workers in sub-Saharan Africa is warranted.

Asia, Latin America
Brazil, Dominican Republic, India
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Efavirenz dose adjustments are probably not required in patients taking concurrent rifampicin

Relationship between weight, efavirenz exposure and virologic suppression in HIV-infected patients on rifampin-based TB treatment in the ACTG A5221 STRIDE study

Luetkemeyer AF, Rosenkranz SL, Lu D, Marzan F, Ive P, Hogg E, et al. Adult AIDS Clinical Trials Group A5221 Study Team. Clinical Infectious Diseases Advance Access published April 19, 2013.

Background: Rifampin (RIF) upregulates CYP 450 isoenzymes potentially lowering efavirenz (EFV) exposure. The US EFV package insert recommends EFV dose increase for patients on RIF weighing ≥50 kg. We conducted a pharmacokinetic study to evaluate EFV trough concentrations (Cmin) and HIV virologic suppression in patients on EFV (600 mg) and RIFbased TB treatment as part of a multicenter randomized trial (ACTG A5221)

Methods: EFV Cmin was measured using HPLC 20‐28 hours post‐EFV dose at weeks 4,8,16,24 on‐RIF and weeks 4,8 off‐RIF. Results evaluated with two‐sided Wilcoxon rank‐sum, chi‐square and Fisher's Exact tests and logistic regression (5% Type I error rate).

Results: 780 patients from 11 countries received EFV, 543 provided ≥ 1 EFV Cmin. Median (IQR) weight was 52.8 kg (48.0,59.5), BMI 19.4 kg/m2 (17.5,21.6), age 34 (29,41), 63% male, race Black (74%), Hispanic (20%), non‐Hispanic White (5%), Asian (1%). Median Cmin was 1.96μg/mL onRIF vs. 1.80 offRIF (p=0.067). EFV concentrations were significantly higher onRIF vs. offRIF in Blacks (2.08 vs. 1.75, p=0.005). Weight ≥60 kg onRIF, compared to <60 kg, was associated with lower EFV Cmin (1.68 vs. 2.02, p=0.021). However, weight ≥60 kg was associated with more frequent HIV RNA<400 copies/mL at week 48, compared to weight <60 kg (81.9% vs. 73.8%, p=0.023).

Conclusions: Coadministration of EFV and RIFbased TB therapy was associated with a trend toward higher, not lower, EFV Cmin compared to EFV alone, which was statistically significant in Black patients. Patients weighing ≥60 kg had lower median EFV Cmin vs. those <60 kg, but there was no association of higher weight with reduced virologic suppression. These data do not support weightbased dosing of EFV with RIF co-administration.

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Editor’s notes: Effective treatment of HIV-TB co-infection is complicated by drug-drug interactions. Rifampicin, the key component of effective anti-TB therapy, is a potent inducer of the cytochrome P450 enzymes which metabolize many antiretrovirals including efavirenz. Appropriate dosing of efavirenz in patients taking concomitant TB treatment has been debated, with both US and British national treatment guidelines recommending efavirenz dose increases. The WHO does not recommend adjusting dosing. This study, an analysis of efavirenz levels from 543 participants in the STRIDE study of ART timing in TB co-infected patients, suggests that efavirenz dose adjustments are not required in patients taking concurrent rifampicin based TB treatment. Efavirenz levels were not reduced in patients who were taking TB treatment. In fact trough efavirenz levels were slightly increased in patients during TB treatment. This increase in efavirenz levels was most marked in black patients. Virological outcomes with efavirenz based ART in this cohort of patients on TB treatment were good, with 76% fully suppressed at 48 weeks.  Perhaps unsurprisingly, efavirenz levels were slightly lower in patients weighing over 60 kg compared to those below 60 kg, but this did not translate into worse virological outcomes. Given the racial differences seen in efavirenz metabolism in this study there is a question about the generalisability of the study to certain populations, notably Caucasians who only made up 5% of the study population. However the demographics were representative of the vast majority of HIV-TB co-infected patients worldwide. These results strongly suggest that efavirenz at standard doses can be safely used in patients receiving rifampicin based TB treatment, avoiding the need to complicate ART treatment regimens in the large number of individuals receiving TB treatment in resource-limited public health programmes.

Avoid TB deaths
Comorbidity, HIV Treatment
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