Articles tagged as "United Republic of Tanzania"

Tenofovir resistance – need for caution but not panic

Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study.

TenoRes Study Group. Lancet Infect Dis. 2016 Jan 28. pii: S1473-3099(15)00536-8. doi: 10.1016/S1473-3099(15)00536-8. [Epub ahead of print]

Background: Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART.

Methods: The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene.

Findings: We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1.50, 95% CI 1.27-1.77 for CD4 cell count <100 cells per µL). Use of lamivudine versus emtricitabine increased the risk of tenofovir resistance across regions (OR 1.48, 95% CI 1.20-1.82). Of 700 individuals with tenofovir resistance, 578 (83%) had cytosine analogue resistance (M184V/I mutation), 543 (78%) had major NNRTI resistance, and 457 (65%) had both. The mean plasma viral load at virological failure was similar in individuals with and without tenofovir resistance (145 700 copies per mL [SE 12 480] versus 133 900 copies per mL [SE 16 650; p=0.626]).

Interpretation: We recorded drug resistance in a high proportion of patients after virological failure on a tenofovir-containing first-line regimen across low-income and middle-income regions. Effective surveillance for transmission of drug resistance is crucial.

Abstract  Full-text [free] access 

Editor’s notes: Global surveillance for tenofovir (TDF) resistance is important at a time of expanding use of TDF-containing regimens for treatment and prevention. This collaborative analysis used data collated from several small studies in different settings. Overall, around one in three people who had failed on TDF-containing treatment had evidence of TDF resistance, although this frequency varied between 20% in Europe to almost 60% in Africa. Mutations associated with NNRTIs and lamivudine/emtricitabine resistance were more common overall and were present in most people with TDF resistance.

The regional variation probably reflects differences in clinical practice and study inclusion criteria. All European studies involved cohorts with frequent viral load monitoring, whereas half of the African cohorts had no routine viral load monitoring. All European studies included people with virologic failure but with low-level viraemia (viral load <1000 copies/ml) whereas almost all African studies included only people with viral load >1000 copies/ml.

While these data provide useful estimates of the frequency of drug resistance mutations in people with virologic failure on first-line ART, there should be caution about extrapolating beyond this. Reports from cohort studies with an accurate denominator of all people starting TDF-containing first-line ART would be useful to give more reliable estimates of overall incidence of acquired TDF resistance. Moreover, there remains a need for representative population-based surveillance for acquired and transmitted drug resistance. So far, global surveillance has detected limited evidence of transmitted TDF-associated mutations, but this needs to be monitored closely, especially in high incidence settings.

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The effects of trauma follow people on the move

A systematic review of HIV risk behaviors and trauma among forced and unforced migrant populations from low and middle-income countries: state of the literature and future directions.

Michalopoulos LM, Aifah A, El-Bassel N. AIDS Behav. 2016 Feb;20(2):243-61. doi: 10.1007/s10461-015-1014-1.

The aim of the current systematic review is to examine the relationship between trauma and HIV risk behaviors among both forced and unforced migrant populations from low and middle income countries (LMIC). We conducted a review of studies published from 1995 to 2014. Data were extracted related to (1) the relationship between trauma and HIV risk behaviors, (2) methodological approach, (3) assessment methods, and (4) differences noted between forced and unforced migrants. A total of 340 records were retrieved with 24 studies meeting inclusion criteria. Our review demonstrated an overall relationship between trauma and HIV risk behaviors among migrant populations in LMIC, specifically with sexual violence and sexual risk behavior. However, findings from 10 studies were not in full support of the relationship. Findings from the review suggest that additional research using more rigorous methods is critically needed to understand the nature of the relationship experienced by this key-affected population.

Abstract access

Editor’s notes: The number of forced and unforced migrants is growing globally. Refugees, asylum seekers, and internally displaced persons (IDP) are forced migrants who often migrate due to political violence or conflict. Labour migrants are seen as unforced migrants who choose to emigrate for economic reasons. About half of labour migrants worldwide are women who are increasingly migrating on their own being the sole income provider for their families. With respect to trauma exposure and HIV risk in settings of long-term political violence and conflict, the distinction between war migrant, non-war migrant, and long-term resident is blurred. This in-depth review of 24 studies related to low-and middle-income countries (LMIC), mostly from sub-Saharan Africa, found findings similar to those from non-migrant populations in high-income countries. These linked traumatic experiences among migrant populations with HIV risk behaviours. Sexual violence was consistently associated with HIV sexual risk behaviours and HIV infection across the studies. But there are big gaps in the scientific literature. For example, the relationship between trauma and HIV risks has been explored for female labour migrants who are sex workers but not among women who have other occupations. Most studies addressed sexual risk and alcohol dependence, but injecting drug risk behaviours and use of any illicit drugs were virtually ignored by most studies. Few studies examined a possible link for trauma that occurred pre-migration and post-migration. Three qualitative studies examined male migrants who have sex with men, finding that violent experiences and discrimination and stigma associated with homophobia, combined with other migrant-associated traumas, can compound their mental health outcomes and subsequent HIV risk behaviours – but all were only conducted in the last four years. No studies were found that focused on HIV prevention programmes to address trauma and HIV risks among migrant workers in LMIC. However, the studies do reveal important factors that prevention programmes would have to consider. For example, concerns among labour migrants about dangerous working conditions may take precedence over HIV risk perceptions and the need for safer sex. This systematic review presents a wealth of information while highlighting the need to improve the quality of scientific research examining the link between HIV and trauma among both forced and unforced migrants in LMIC. 

Africa, Asia, Europe, Latin America
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Spatial analysis methods to improve localised estimates of HIV prevalence

Evaluation of geospatial methods to generate subnational HIV prevalence estimates for local level planning.

Anderson SJ, Subnational Estimates Working Group of the HIVMC. AIDS. 2016 Feb 25. [Epub ahead of print]

Objective: There is evidence of substantial subnational variation in the HIV epidemic. However, robust spatial HIV data are often only available at high levels of geographic aggregation and not at the finer resolution needed for decision making. Therefore, spatial analysis methods that leverage available data to provide local estimates of HIV prevalence may be useful. Such methods exist but have not been formally compared when applied to HIV.

Design/methods: Six candidate methods - including those used by UNAIDS to generate maps and a Bayesian geostatistical approach applied to other diseases- were used to generate maps and subnational estimates of HIV prevalence across three countries using cluster level data from household surveys. Two approaches were used to assess the accuracy of predictions: (1) internal validation, whereby a proportion of input data is held back (test dataset) to challenge predictions, (2) comparison with location specific data from household surveys in earlier years.

Results: Each of the methods can generate usefully accurate predictions of prevalence at unsampled locations, with the magnitude of the error in predictions similar across approaches. However, the Bayesian geostatistical approach consistently gave marginally the strongest statistical performance across countries and validation procedures.

Conclusions: Available methods may be able to furnish estimates of HIV prevalence at finer spatial scales than the data currently allow. The subnational variation revealed can be integrated into planning to ensure responsiveness to the spatial features of the epidemic. The Bayesian geostatistical approach is a promising strategy for integrating HIV data to generate robust local estimates.

Abstract access  

Editor’s notes: Data from intensively monitored populations indicates that large differences in HIV prevalence can be seen across small geographic spaces. Understanding these localised spatial variations within a generalised epidemic can enable HIV programme resources to be used most effectively. However the data required for such localised estimation are often lacking. As a result modelling strategies must be used to predict local variation based on the best available data.

This study compares six different geospatial methods of estimating local HIV prevalence. The methods can be categorised by whether or not they use ancillary information such as road networks to improve their predictions and also whether they generated continuously changing prevalence surfaces (like map contours) or gave discrete estimates for geographic sub-regions e.g. districts.

While all methods produced reasonable overall levels of performance, those using a Bayesian geostatistical approach illustrated marginally better predictive accuracies. The levels of accuracy appeared more dependent on the national prevalence than the choice of model used.

The authors conclude by setting out a strategy for improvement of the models, principally through integrating additional data from sources such as antiretroviral therapy and prevention of mother-to-child transmission programmes, antenatal clinic surveys and case based reporting. 

Africa
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The power of PEPFAR programmes: estimates of infections averted and life years gained in Africa

Estimating the impact of the US President's Emergency Plan for AIDS Relief on HIV treatment and prevention programmes in Africa.

Heaton LM, Bouey PD, Fu J, Stover J, Fowler TB, Lyerla R, Mahy M. Sex Transm Infect. 2015 Dec;91(8):615-20. doi: 10.1136/sextrans-2014-051991. Epub 2015 Jun 8.

Background: Since 2004, the US President's Emergency Plan for AIDS Relief (PEPFAR) has supported the tremendous scale-up of HIV prevention, care and treatment services, primarily in sub-Saharan Africa. We evaluate the impact of antiretroviral treatment (ART), prevention of mother-to-child transmission (PMTCT) and voluntary medical male circumcision (VMMC) programmes on survival, mortality, new infections and the number of orphans from 2004 to 2013 in 16 PEPFAR countries in Africa.

Methods: PEPFAR indicators tracking the number of persons receiving ART for their own health, ART regimens for PMTCT and biomedical prevention of HIV through VMMC were collected across 16 PEPFAR countries. To estimate the impact of PEPFAR programmes for ART, PMTCT and VMMC, we compared the current scenario of PEPFAR-supported interventions to a counterfactual scenario without PEPFAR, and assessed the number of life years gained (LYG), number of orphans averted and HIV infections averted. Mathematical modelling was conducted using the SPECTRUM modelling suite V.5.03.

Results: From 2004 to 2013, PEPFAR programmes provided support for a cumulative number of     24 565 127 adults and children on ART, 4 154 878 medical male circumcisions, and ART for PMTCT among 4 154 478 pregnant women in 16 PEPFAR countries. Based on findings from the model, these efforts have helped avert 2.9 million HIV infections in the same period. During 2004-2013, PEPFAR ART programmes alone helped avert almost 9 million orphans in 16 PEPFAR countries and resulted in 11.6 million LYG.

Conclusions: Modelling results suggest that the rapid scale-up of PEPFAR-funded ART, PMTCT and VMMC programmes in Africa during 2004-2013 led to substantially fewer new HIV infections and orphaned children during that time and longer lives among people living with HIV. Our estimates do not account for the impact of the PEPFAR-funded non-biomedical interventions such as behavioural and structural interventions included in the comprehensive HIV prevention, care and treatment strategy used by PEPFAR countries. Therefore, the number of HIV infections and orphans averted and LYG may be underestimated by these models.

Abstract access

Editor’s notes: The President’s Emergency Plan for AIDS Relief (PEPFAR) was initiated in 2004 with $42 billion spent up until the end of 2013. Despite limitations in monitoring the overall contribution of PEPFAR to individual programmes, this article attempts to provide an overview of PEPFAR support for ART, prevention of mother to child transmission and voluntary medical male circumcision (VMMC) programmes using the 2014 version of Spectrum Software model. The Spectrum modules used included DemProj, AIDS Impact Model (AIM) and Goals, which interact to model the impact and future course of the HIV epidemic at the population level.  An estimate of PEPFAR’s contribution was obtained by subtracting it from the total for the national programme statistics reported by UNAIDS on ART, PMTCT and VMMC.

The baseline scenario of PEPFAR-supported programmes in 2013 was compared to a counterfactual scenario, which subtracts the direct contribution of PEPFAR. The results estimate that the combined programmes have averted 2.7 million infections in Africa, with over 11.5 million life years gained and the aversion of almost nine million orphans. Other key population programmes that the funding supported including gender equity and health strengthening were not evaluated and therefore, the estimate for impact may be conservative. A limitation of the analysis is that it is unable to predict the national response without PEPFAR and the impact of ART calculated by the model is sensitive to the distribution of new ART patients by CD4 count at the initiation of treatment. In addition, few countries have sufficient death registration systems to validate mortality estimates, which may result in the accomplishments of PEPFAR’s impact being overestimated. However, with the operation of PEPFAR in a larger context of partnership consortiums, an improvement in evaluation methods will be necessary. 

Africa
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Untreated maternal HIV infection and poor perinatal outcomes

Perinatal outcomes associated with maternal HIV infection: a systematic review and meta-analysis.

Wedi CO, Kirtley S, Hopewell S, Corrigan R, Kennedy SH, Hemelaar J. Lancet HIV. 2016 Jan;3(1):e33-48. doi: 10.1016/S2352-3018(15)00207-6. Epub 2015 Nov 27.

Background: The HIV pandemic affects 36.9 million people worldwide, of whom 1.5 million are pregnant women. 91% of HIV-positive pregnant women reside in sub-Saharan Africa, a region that also has very poor perinatal outcomes. We aimed to establish whether untreated maternal HIV infection is associated with specific perinatal outcomes.

Methods: We did a systematic review and meta-analysis of the scientific literature by searching PubMed, CINAHL (Ebscohost), Global Health (Ovid), EMBASE (Ovid), and the Cochrane Central Register of Controlled Trials and four clinical trial databases (WHO International Clinical Trials Registry Platform, the Pan African Clinical Trials Registry, the ClinicalTrials.gov database, and the ISRCTN Registry) for studies published from Jan 1, 1980, to Dec 7, 2014. Two authors independently reviewed the studies retrieved by the scientific literature search, identified relevant studies, and extracted the data. We investigated the associations between maternal HIV infection in women naive to antiretroviral therapy and 11 perinatal outcomes: preterm birth, very preterm birth, low birthweight, very low birthweight, term low birthweight, preterm low birthweight, small for gestational age, very small for gestational age, miscarriage, stillbirth, and neonatal death. We included prospective and retrospective cohort studies and case-control studies reporting perinatal outcomes in HIV-positive women naive to antiretroviral therapy and HIV-negative controls. We used a random-effects model for the meta-analyses of specific perinatal outcomes. We did subgroup and sensitivity analyses and assessed the effect of adjustment for confounders. This systematic review and meta-analysis is registered with PROSPERO, number CRD42013005638.

Findings: Of 60 750 studies identified, we obtained data from 35 studies (20 prospective cohort studies, 12 retrospective cohort studies, and three case-control studies) including 53 623 women. Our meta-analyses of prospective cohort studies show that maternal HIV infection is associated with an increased risk of preterm birth (relative risk 1.50, 95% CI 1.24-1.82), low birthweight (1.62, 1.41-1.86), small for gestational age (1.31, 1.14-1.51), and stillbirth (1.67, 1.05-2.66). Retrospective cohort studies also suggest an increased risk of term low birthweight (2.62, 1.15-5.93) and preterm low birthweight (3.25, 2.12-4.99). The strongest and most consistent evidence for these associations is identified in sub-Saharan Africa. No association was identified between maternal HIV infection and very preterm birth, very small for gestational age, very low birthweight, miscarriage, or neonatal death, although few data were available for these outcomes. Correction for confounders did not affect the significance of these findings.

Interpretation: Maternal HIV infection in women who have not received antiretroviral therapy is associated with preterm birth, low birthweight, small for gestational age, and stillbirth, especially in sub-Saharan Africa. Research is needed to assess how antiretroviral therapy regimens affect these perinatal outcomes.

Abstract access 

Editor’s notes:  Maternal HIV infection is associated with maternal morbidity and mortality and risk of mother-to-child transmission of HIV. Whether maternal HIV infection affects perinatal outcomes, which are major contributors to poor health worldwide, is less well understood. This systematic review and meta-analysis of retrospective and prospective cohort studies and case-control studies demonstrates that untreated maternal HIV infection is associated with increased risk of pre-term birth, low birthweight, small for gestational age and stillbirth. The risk of adverse perinatal outcomes appeared to increase with more advanced HIV disease, although only three of the 35 studies reported perinatal outcomes according to HIV disease stage. These findings persisted even after controlling for potential confounding factors and irrespective of the method used for determining gestational age. None of the studies used a first trimester ultrasound scan, the gold standard for determining gestational age. The association of perinatal outcomes with the infant’s HIV status was not investigated. The strongest evidence for these associations was found in sub-Saharan Africa, where the majority of the studies were conducted.

These findings suggest that HIV is an important contributor to the global burden of perinatal and child morbidity and mortality particularly in countries with the highest burden of maternal HIV infection.     Sub-Saharan Africa has the highest rates of stillbirths and neonatal deaths and is also the region where more than 90% of the world’s pregnant women living with HIV reside.

This study has important implications. Firstly, the coverage of antiretroviral therapy (ART) among pregnant women worldwide still remains suboptimal (estimated to be 68% in 2013), exposing women living with untreated HIV to an increased risk of adverse perinatal outcomes. The biological mechanisms underlying adverse perinatal outcomes in the context of HIV infection are not understood. ART in pregnancy may also adversely affect perinatal outcomes, and there is a pressing need to investigate this as ART is rapidly scaled up.     

Africa, Europe, Northern America
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How gender norms and power may impact on the acceptability, access and adherence to microbicides

Optimizing HIV prevention for women: a review of evidence from microbicide studies and considerations for gender-sensitive microbicide introduction.

Doggett EG, Lanham M, Wilcher R, Gafos M, Karim QA, Heise L. J Int AIDS Soc. 2015 Dec 21;18(1):20536. doi: 10.7448/IAS.18.1.20536. eCollection 2015.

Introduction: Microbicides were conceptualized as a product that could give women increased agency over HIV prevention. However, gender-related norms and inequalities that place women and girls at risk of acquiring HIV are also likely to affect their ability to use microbicides. Understanding how gendered norms and inequalities may pose obstacles to women's microbicide use is important to inform product design, microbicide trial implementation and eventually microbicide and other antiretroviral-based prevention programmes. We reviewed published vaginal microbicide studies to identify gender-related factors that are likely to affect microbicide acceptability, access and adherence. We make recommendations on product design, trial implementation, positioning, marketing and delivery of microbicides in a way that takes into account the gender-related norms and inequalities identified in the review.

Methods: We conducted PubMed searches for microbicide studies published in journals between 2000 and 2013. Search terms included trial names (e.g. "MDP301"), microbicide product names (e.g. "BufferGel"), researchers' names (e.g. "van der Straten") and other relevant terms (e.g. "microbicide"). We included microbicide clinical trials; surrogate studies in which a vaginal gel, ring or diaphragm was used without an active ingredient; and hypothetical studies in which no product was used. Social and behavioural studies implemented in conjunction with clinical trials and surrogate studies were also included. Although we recognize the importance of rectal microbicides to women, we did not include studies of rectal microbicides, as most of them focused on men who have sex with men. Using a standardized review template, three reviewers read the articles and looked for gender-related findings in key domains (e.g. product acceptability, sexual pleasure, partner communication, microbicide access and adherence).

Results and discussion: The gendered norms, roles and relations that will likely affect women's ability to access and use microbicides are related to two broad categories: norms regulating women's and men's sexuality and power dynamics within intimate relationships. Though norms about women's and men's sexuality vary among cultural contexts, women's sexual behaviour and pleasure are typically less socially acceptable and more restricted than men's. These norms drive the need for woman-initiated HIV prevention, but also have implications for microbicide acceptability and how they are likely to be used by women of different ages and relationship types. Women's limited power to negotiate the circumstances of their intimate relationships and sex lives will impact their ability to access and use microbicides. Men's role in women's effective microbicide use can range from opposition to non-interference to active support.

Conclusions: Identifying an effective microbicide that women can use consistently is vital to the future of HIV prevention for women. Once such a microbicide is identified and licensed, positioning, marketing and delivering microbicides in a way that takes into account the gendered norms and inequalities we have identified would help maximize access and adherence. It also has the potential to improve communication about sexuality, strengthen relationships between women and men and increase women's agency over their bodies and their health.

Abstract  Full-text [free] access

Editor’s notes: This paper presents a review of the evidence of microbicides research to understand gender-associated factors that could impact on acceptability, access and adherence. These gender norms include women and men’s sexual norms and power differentials in intimate partner relationships. This review included studies conducted between 2000 and 2013 and thus only includes papers on hypothetical research and clinical trials. While the studies were conducted in a variety of contexts the authors found a number of similar norms and power differentials.

In relation to sexual norms, the review revealed findings on sexual risk, sexual pleasure, and sexual preferences. In terms of sexual risk there were differing opinions across the studies of which women were most likely to need microbicides. Some studies suggested that microbicides should be focused on women in steady partnerships where condom negotiation is difficult, while others suggested focusing on key populations such as sex workers. Across many studies the potential for promoting sexual pleasure for both women and men emerged as an advantage of microbicides, and had an impact on acceptability. However, many of the studies highlighted how men’s sexual pleasure takes precedence. In relation to sexual preferences, the much touted idea that men prefer ‘dry’ or ‘tight’ sex was challenged by some of the studies, which found that the lubricating effect of the gel was acceptable.

The review also uncovered issues associated to power inequalities in intimate partner relationships, including power to control time of sex, male partner engagement and communication, and intimate-partner violence. Women reported in many studies their lack of power to control the timing of sex and this is seen as likely to impact on their ability to use coitally-dependant microbicides. However, there is some evidence that men supported women’s use of the gel, although this depended on the type of relationship. While microbicides have been promoted as products that women can use without a partner’s knowledge the review illustrated that women do prefer to communicate with their partners about their use and there is evidence of joint-decision making. Further, there was evidence of women experiencing intimate partner violence in relation to trial participation. There is also some evidence that women were less likely to discuss or use microbicides in violent relationships.

This highly comprehensive review concludes that while microbicides will not empower women they do have the potential to enhance women’s agency in relation to their health and sexuality and may improve communication in their relationships. However, the authors conclude that gender norms and power differentials may impact on acceptability, access and adherence.

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Violence experience of women living with HIV: a global study

Violence. Enough already: findings from a global participatory survey among women living with HIV.

Orza L, Bewley S, Chung C, Crone ET, Nagadya H, Vazquez M, Welbourn A. J Int AIDS Soc. 2015 Dec 1;18(6 Suppl 5):20285. doi: 10.7448/IAS.18.6.20285. eCollection 2015.

Introduction: Women living with HIV are vulnerable to gender-based violence (GBV) before and after diagnosis, in multiple settings. This study's aim was to explore how GBV is experienced by women living with HIV, how this affects women's sexual and reproductive health (SRH) and human rights (HR), and the implications for policymakers.

Methods: A community-based, participatory, user-led, mixed-methods study was conducted, with women living with HIV from key affected populations. Simple descriptive frequencies were used for quantitative data. Thematic coding of open qualitative responses was performed and validated with key respondents.

Results: In total, 945 women living with HIV from 94 countries participated in the study. Eighty-nine percent of 480 respondents to an optional section on GBV reported having experienced or feared violence, either before, since and/or because of their HIV diagnosis. GBV reporting was higher after HIV diagnosis (intimate partner, family/neighbours, community and health settings). Women described a complex and iterative relationship between GBV and HIV occurring throughout their lives, including breaches of confidentiality and lack of SRH choice in healthcare settings, forced/coerced treatments, HR abuses, moralistic and judgemental attitudes (including towards women from key populations), and fear of losing child custody. Respondents recommended healthcare practitioners and policymakers address stigma and discrimination, training, awareness-raising, and HR abuses in healthcare settings.

Conclusions: Respondents reported increased GBV with partners and in families, communities and healthcare settings after their HIV diagnosis and across the life-cycle. Measures of GBV must be sought and monitored, particularly within healthcare settings that should be safe. Respondents offered policymakers a comprehensive range of recommendations to achieve their SRH and HR goals. Global guidance documents and policies are more likely to succeed for the end-users if lived experiences are used.

Abstract  Full-text [free] access

Editor’s notes: Violence against women who are living with HIV is common globally. This paper reports on a study of 832 women living with HIV from 94 countries who participated in an online survey, recruited through a non-random snowball sampling model. The survey comprised quantitative and qualitative (free text) components. Participants included women who had ever or were currently using injection drugs (14%), who had ever or were currently selling sex (14%), and who had ever or were currently homeless (14%). Lifetime experience of violence among respondents was high (86%). Perpetrators included: intimate partner (59%), family member / neighbour (45%), community member (53%), health care workers (53%) and police, military, prison or detention services (17%). Findings suggest that violence is not a one off occurrence and cannot easily be packaged as a cause or a consequence of HIV. Instead violence occurs throughout women’s lives, takes multiple forms, and has a complex and iterative relationship with HIV.

The study population did not represent all women living with HIV, and was biased towards women with internet access who have an activist interest. Nonetheless, the study provides further evidence of the breadth and frequency of gender based violence experienced by women living with HIV. Key recommendations for policy makers include training of health care workers working in sexual and reproductive services to offer non-discriminatory services to women living with HIV and to effectively respond to disclosures of gender based violence (such as intimate partner violence) as part of the package of care.

Algeria, Angola, Argentina, Armenia, Australia, Austria, Azerbaijan, Belarus, Belgium, Belize, Bolivarian Republic of Venezuela, Bolivia, Botswana, Burkina Faso, Burundi, Cambodia, Cameroon, Canada, Chile, China, Colombia, Costa Rica, Côte d'Ivoire, Czech Republic, Democratic Republic of the Congo, Denmark, Dominican Republic, Ecuador, El Salvador, Estonia, Ethiopia, France, Gabon, Germany, Ghana, Greece, Guatemala, Honduras, Hungary, India, Indonesia, Ireland, Italy, Jamaica, Kazakhstan, Kenya, Kyrgyzstan, Lesotho, Malawi, Mali, Mexico, Moldova, Morocco, Mozambique, Myanmar, Namibia, Nepal, Netherlands, New Zealand, Nicaragua, Nigeria, Norway, Panama, Paraguay, Peru, Poland, Republic of the Congo, Romania, Russian Federation, Rwanda, Serbia, South Africa, Spain, Sri Lanka, Sudan, Swaziland, Switzerland, Tajikistan, Togo, Transdniestria, Turkey, Uganda, Ukraine, United Kingdom, United Republic of Tanzania, United States of America, Uruguay, Uzbekistan, Viet Nam, Zambia, Zimbabwe
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Condoms are highly effective at preventing HSV-2 acquisition, especially for women

Effect of condom use on per-act HSV-2 transmission risk in HIV-1, HSV-2-discordant couples.

Magaret AS, Mujugira A, Hughes JP, Lingappa J, Bukusi EA, DeBruyn G, Delany-Moretlwe S, Fife KH, Gray GE, Kapiga S, Karita E, Mugo NR, Rees H, Ronald A, Vwalika B, Were E, Celum C, Wald A, Partners in Prevention HSVHIVTST. Clin Infect Dis. 2015 Nov 17. pii: civ908. [Epub ahead of print]

Background: The efficacy of condoms for protection against transmission of herpes simplex virus type 2 (HSV-2) has been examined in a variety of populations with different effect measures. Often the efficacy has been assessed as change in hazard of transmission with consistent vs inconsistent use, independent of the number of acts. Condom efficacy has not been previously measured on a per-act basis.

Methods: We examined the per-act HSV-2 transmission rates with and without condom use among 911 African HSV-2 and human immunodeficiency virus type 1 (HIV-1) serodiscordant couples followed for an average of 18 months in an HIV prevention study. Infectivity models were used to associate the log10 probability of HSV-2 transmission over monthly risk periods with reported numbers of protected and unprotected sex acts. Condom efficacy was computed as the proportionate reduction in transmission risk for protected relative to unprotected sex acts.

Results: Transmission of HSV-2 occurred in 68 couples, including 17 with susceptible women and 51 with susceptible men. The highest rate of transmission was from men to women: 28.5 transmissions per 1000 unprotected sex acts. We found that condoms were differentially protective against HSV-2 transmission by sex; condom use reduced per-act risk of transmission from men to women by 96% (P < .001) and marginally from women to men by 65% (P = .060).

Conclusions: Condoms are recommended as an effective preventive method for heterosexual transmission of HSV-2.

Abstract access

Editor’s notes: HSV-2 is extremely prevalent in sub-Saharan Africa, and an important co-factor in HIV transmission. Although condoms are recommended for preventing HSV-2 infection, there have been no previous studies of their effectiveness on a per-sex act basis. This study in HIV and HSV-2 discordant couples participating in an HIV prevention trial examined the risk of HSV-2 transmission for each sex act with and without male condoms. At enrolment, index partners were living with both HIV and HSV-2 infections; susceptible partners were negative for both infections.

The authors found that condoms provided greater protection against HSV-2 acquisition for women than for men, reducing the risk of transmission by 96% from men to women, and by 65% from women to men. However, the overall risk of HSV-2 infection was much higher for women – for each condomless sex act, women were nearly 20 times more likely than men to become infected. As a result, even when using condoms, susceptible women had only a slightly lower risk of infection than men did without condoms. Interestingly, HSV-2 suppressive therapy with acyclovir did not have any effect on HSV-2 transmission, for either sex. Although the authors were not able to confirm that the HSV-2 transmissions occurred within the partnership (e.g. by sequencing the HSV2 DNA), an analysis restricted to couples who never reported sex outside the partnership illustrated very similar results.

The difference in the protection provided by condoms between the sexes may be explained by the fact that, in men, HSV-2 viral shedding is primarily from the penile shaft whereas in women the virus is shed from the wider area of the perineum, and hence condoms are less effective for female-male transmission. These findings indicate that, in individuals who are both HIV and HSV-2 positive, male condoms are extremely effective in preventing male-to-female transmission of HSV-2, and also provide some protection against female-to-male transmission. Although condoms may not provide the same level of protection in populations who are HIV negative, their promotion remains an important public health activity for preventing HSV-2 infection.

Africa
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Expanding ART access: increasing costs

The HIV treatment gap: estimates of the financial resources needed versus available for scale-up of antiretroviral therapy in 97 countries from 2015 to 2020.

Dutta A, Barker C, Kallarakal A. PLoS Med. 2015 Nov 24;12(11):e1001907. doi: 10.1371/journal.pmed.1001907. eCollection 2015.

Background: The World Health Organization (WHO) released revised guidelines in 2015 recommending that all people living with HIV, regardless of CD4 count, initiate antiretroviral therapy (ART) upon diagnosis. However, few studies have projected the global resources needed for rapid scale-up of ART. Under the Health Policy Project, we conducted modeling analyses for 97 countries to estimate eligibility for and numbers on ART from 2015 to 2020, along with the facility-level financial resources required. We compared the estimated financial requirements to estimated funding available.

Methods and findings: Current coverage levels and future need for treatment were based on country-specific epidemiological and demographic data. Simulated annual numbers of individuals on treatment were derived from three scenarios: (1) continuation of countries' current policies of eligibility for ART, (2) universal adoption of aspects of the WHO 2013 eligibility guidelines, and (3) expanded eligibility as per the WHO 2015 guidelines and meeting the Joint United Nations Programme on HIV/AIDS "90-90-90" ART targets. We modeled uncertainty in the annual resource requirements for antiretroviral drugs, laboratory tests, and facility-level personnel and overhead.

We estimate that 25.7 (95% CI 25.5, 26.0) million adults and 1.57 (95% CI 1.55, 1.60) million children could receive ART by 2020 if countries maintain current eligibility plans and increase coverage based on historical rates, which may be ambitious. If countries uniformly adopt aspects of the WHO 2013 guidelines, 26.5 (95% CI 26.0 27.0) million adults and 1.53 (95% CI 1.52, 1.55) million children could be on ART by 2020. Under the 90-90-90 scenario, 30.4 (95% CI 30.1, 30.7) million adults and 1.68 (95% CI 1.63, 1.73) million children could receive treatment by 2020. The facility-level financial resources needed for scaling up ART in these countries from 2015 to 2020 are estimated to be US$45.8 (95% CI 45.4, 46.2) billion under the current scenario, US$48.7 (95% CI 47.8, 49.6) billion under the WHO 2013 scenario, and US$52.5 (95% CI 51.4, 53.6) billion under the 90-90-90 scenario. After projecting recent external and domestic funding trends, the estimated 6-y financing gap ranges from US$19.8 billion to US$25.0 billion, depending on the costing scenario and the U.S. President's Emergency Plan for AIDS Relief contribution level, with the gap for ART commodities alone ranging from US$14.0 to US$16.8 billion. The study is limited by excluding above-facility and other costs essential to ART service delivery and by the availability and quality of country- and region-specific data.

Conclusions: The projected number of people receiving ART across three scenarios suggests that countries are unlikely to meet the 90-90-90 treatment target (81% of people living with HIV on ART by 2020) unless they adopt a test-and-offer approach and increase ART coverage. Our results suggest that future resource needs for ART scale-up are smaller than stated elsewhere but still significantly threaten the sustainability of the global HIV response without additional resource mobilization from domestic or innovative financing sources or efficiency gains. As the world moves towards adopting the WHO 2015 guidelines, advances in technology, including the introduction of lower-cost, highly effective antiretroviral regimens, whose value are assessed here, may prove to be "game changers" that allow more people to be on ART with the resources available.

Abstract Full-text [free] access

Editor’s notes: This is a complex and important paper that seeks to understand the financial requirements necessary to: a) continue countries’ current policies of eligibility for ART, b) roll out universal adoption of certain aspects of WHO 2013 eligibility guidelines, and c) expand eligibility as per WHO 2015 guidelines and meeting the Joint United Nations Programme on HIV/AIDS ‘90-90-90’ targets.

The authors estimated the number of adults and children eligible for and receiving HIV treatment, as well as the cost of providing ART in 97 countries across six regions, covering different income levels. They estimated that 25.7 million adults and 1.57 million children could receive ART by 2020 if countries maintain the current eligibility strategies. If countries adopted WHO 2013 eligibility guidelines, 26.5 million adults and 1.53 million children would be on ART by 2020, and if they adopted the 90-90-90 scenario, 30.4 million adults and 1.68 million children could receive treatment by then. The financial resources necessary for this scale up are estimated to be US$ 45.8 billion under current eligibility, US$ 48.7 billion under WHO 2013 scenario and US$ 52.5 billion under the 90-90-90 scenario. The estimated funding gap for the six year period ranges between US$ 20 and US$ 25 billion. In this study, the costs of commodities were taken directly from data collated by other organisations.  No empirical cost estimates of service delivery were made.  Nor was there an attempt to understand the cost implications of the development synergies and social and programme enablers that may be needed to increase the number of people living with HIV knowing their status.  The new WHO recommendations need to be actively pursued if we are to meet targets, rather than passively continuing with “business as usual”. 

Nonetheless, the findings of this study highlight the gap between guidelines written by WHO and very real programmatic obstacles on the ground. There is evidence to suggest that universal test-and-treat strategies could lead to substantially improved health outcomes at the population level, as well as potentially being cost-saving in the long-term. However, as the authors have illustrated, it would require increased levels of funding. What needs to be explored further now is how to overcome the logistical hurdles of rolling out such an initiative. Changing systems and practices is costly and takes time. Health workers will have to be retrained, data collection strategies will have to be revised. Expanding treatment may also mean increasing the number of health staff working on this initiative, which has an opportunity cost that may reverberate in other parts of the health system. Substantially altering health service provision, particularly in weak health systems, may have knock-on effects with unexpected and unintended consequences.

WHO guidelines serve a vital purpose of giving us a goal to aim for. But studies like this one help us know if and how we can get there. 

Africa, Asia, Europe, Latin America, Oceania
Algeria, Angola, Armenia, Azerbaijan, Bahamas, Bangladesh, Barbados, Belarus, Belize, Benin, Bhutan, Bolivia, Botswana, Bulgaria, Burkina Faso, Burundi, Cambodia, Cameroon, Central African Republic, Chad, China, Comoros, Côte d'Ivoire, Cuba, Democratic Republic of the Congo, Djibouti, Dominican Republic, Egypt, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Gambia, Georgia, Ghana, Guatemala, Guinea, Guinea-Bissau, Guyana, Haiti, Honduras, India, Indonesia, Iran (Islamic Republic of), Jamaica, Kazakhstan, Kenya, Kyrgyzstan, Lao People's Democratic Republic, Lesotho, Liberia, Madagascar, Malawi, Malaysia, Mali, Mauritania, Mauritius, Moldova, Mongolia, Morocco, Mozambique, Myanmar, Namibia, Nepal, Nicaragua, Niger, Nigeria, Pakistan, Papua New Guinea, Philippines, Republic of the Congo, Romania, Russia, Rwanda, Senegal, Serbia and Montenegro, Sierra Leone, Somalia, South Africa, Sri Lanka, Sudan, Suriname, Swaziland, Tajikistan, Thailand, Togo, Trinidad and Tobago, Tunisia, Uganda, Ukraine, United Republic of Tanzania, Uzbekistan, Viet Nam, Yemen, Zambia, Zimbabwe
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Vulnerabilities of children living with HIV positive adults

Children living with HIV-infected adults: estimates for 23 countries in sub-Saharan Africa.

Short SE, Goldberg RE. PLoS One. 2015 Nov 17; 10(11): e0142580.

Background: In sub-Saharan Africa many children live in extreme poverty and experience a burden of illness and disease that is disproportionately high. The emergence of HIV and AIDS has only exacerbated long-standing challenges to improving children's health in the region, with recent cohorts experiencing pediatric AIDS and high levels of orphan status, situations which are monitored globally and receive much policy and research attention. Children's health, however, can be affected also by living with HIV-infected adults, through associated exposure to infectious diseases and the diversion of household resources away from them. While long recognized, far less research has focused on characterizing this distinct and vulnerable population of HIV-affected children.

Methods: Using Demographic and Health Survey data from 23 countries collected between 2003 and 2011, we estimate the percentage of children living in a household with at least one HIV-infected adult. We assess overlaps with orphan status and investigate the relationship between children and the adults who are infected in their households.

Results: The population of children living in a household with at least one HIV-infected adult is substantial where HIV prevalence is high; in Southern Africa, the percentage exceeded 10% in all countries and reached as high as 36%. This population is largely distinct from the orphan population. Among children living in households with tested, HIV-infected adults, most live with parents, often mothers, who are infected; nonetheless, in most countries over 20% live in households with at least one infected adult who is not a parent.

Conclusion: Until new infections contract significantly, improvements in HIV/AIDS treatment suggest that the population of children living with HIV-infected adults will remain substantial. It is vital to on-going efforts to reduce childhood morbidity and mortality to consider whether current care and outreach sufficiently address the distinct vulnerabilities of these children.

Abstract Full-text [free] access

Editor’s notes: This paper is an important contribution to the literature on the impact of the HIV epidemic. Using Demographic and Health Survey (DHS) data from 23 countries it highlights the considerable number of children living with HIV-positive adults in sub-Saharan Africa. However, notable exceptions from the analysis (no DHS data available) included South Africa. This, coupled with specific issues related to DHS data collection methods and response rates, means that the number of children living with HIV-positive adults is much higher. Reductions in mortality from HIV due to increased treatment availability and the addition of adults newly acquiring HIV means that population of children living with an HIV-positive adult will continue to increase in the near future.

Children living with HIV-positive adults are clearly vulnerable and like all vulnerable children should be focussed on in efforts to promote child wellbeing. The authors suggest, however, that children living with HIV-positive adults may have distinct vulnerabilities that need to be considered. These include direct exposure to opportunistic infections, social stigma and disrupted networks, as well as increases in poverty. The challenge for many countries is how to identify these children and ensure that focussed programmes are delivered effectively.

Africa
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