Articles tagged as "Zimbabwe"

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.

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Effective, long-term programmes for alcohol and sexual risk reduction are yet to be shown

HIV-alcohol risk reduction interventions in sub-Saharan Africa: a systematic review of the literature and recommendations for a way forward.

Carrasco MA, Esser MB, Sparks A, Kaufman MR. AIDS Behav. 2015 Oct 29. [Epub ahead of print]

Sub-Saharan Africa bears 69% of the global burden of HIV, and strong evidence indicates an association between alcohol consumption, HIV risk behavior, and HIV incidence. However, characteristics of efficacious HIV-alcohol risk reduction interventions are not well known. The purpose of this systematic review is to summarize the characteristics and synthesize the findings of HIV-alcohol risk reduction interventions implemented in the region and reported in peer-reviewed journals. Of 644 citations screened, 19 met the inclusion criteria for this review. A discussion of methodological challenges, research gaps, and recommendations for future interventions is included. Relatively few interventions were found, and evidence is mixed about the efficacy of HIV-alcohol risk reduction interventions. There is a need to further integrate HIV-alcohol risk reduction components into HIV prevention programming and to document results from such integration. Additionally, research on larger scale, multi-level interventions is needed to identify effective HIV-alcohol risk reduction strategies.

Abstract access

Editor’s notes: Alcohol and risk of HIV have been shown to be linked, yet little is known about which programmes are best at reducing this risk. This paper features a systematic review updating a previous review published by the authors in 2011. While this update found several more programmes aimed at reducing risky behaviour caused by alcohol use and in more countries than just the one previously, South Africa, the results of the review are largely the same. Most programmes had limited follow-up time of participants and found a dissipating effect over time. Additionally, older models of behaviour change were primarily used as the frameworks upon which these programmes were built. These models focus only on individual behaviour and not on the structural factors further affecting consumption of alcohol and risky sexual behaviour. On a positive note, some studies found moderate success based on location of the programme, clinic versus bar or tavern setting for instance. This review clearly demonstrates the need for further efforts to integrate alcohol risk reduction components into HIV prevention programmes, particularly for populations in which alcohol consumption is common.

Angola, Nigeria, South Africa, Uganda, Zambia, Zimbabwe
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Routine opt-out HIV testing reduces missed diagnoses in children

The effectiveness of routine opt-out HIV testing for children in Harare, Zimbabwe.

Ferrand RA, Meghji J, Kidia K, Dauya E, Bandason T, Mujuru H, Ncube G, Mungofa S, Kranzer K. J Acquir Immune Defic Syndr. 2015 Oct 12. [Epub ahead of print]

Objective: HIV testing is the entry point to access HIV care. For HIV-infected children who survive infancy undiagnosed, diagnosis usually occurs on presentation to health care services. We investigated the effectiveness of routine opt-out HIV testing (ROOT) compared to conventional opt-in provider-initiated testing and counselling (PITC) for children attending primary care clinics.

Methods: Following an evaluation of PITC services for children aged 6 to 15 years in six primary health care facilities in Harare, Zimbabwe, ROOT was introduced through a combination of interventions. The change in the proportion of eligible children offered and receiving HIV tests, reasons for not testing, and yield of HIV positive diagnoses were compared between the two HIV testing strategies. Adjusted risk ratios for having an HIV test in the ROOT compared to the PITC period were calculated.

Results: There were 2831 and 7842 children eligible for HIV testing before and after the introduction of ROOT. The proportion of eligible children offered testing increased from 76% to 93% and test uptake improved from 71% to 95% in the ROOT compared to the PITC period. The yield of HIV diagnoses increased from 2.9% to 4.5%, and a child attending the clinics post intervention had a 1.99 increased adjusted risk (95% CI 1.85-2.14) of receiving an HIV test in the ROOT period compared to the pre-intervention period.

Conclusion: ROOT increased the proportion of children undergoing HIV-testing, resulting in an overall increased yield of positive diagnoses, compared to PITC. ROOT provides an effective approach to reduce missed HIV diagnosis in this age-group.

Abstract access 

Editor’s notes: The policy and practice of HIV testing in high HIV prevalence settings has evolved over the years, from a more cautious approach in the early years of the HIV epidemic to a more proactive one with the scale up of antiretroviral therapy (ART). Despite a marked increase in HIV testing following the introduction of provider-initiated testing and counselling (PITC) in clinical settings, coverage remains suboptimal. Routine opt-out testing (ROOT) describes a strategy of HIV testing as part of the routine clinical ‘work-up’, unless a person explicitly refuses to test. To date, ROOT has been confined to specialist clinical services, such as prevention of mother-to-child HIV transmission programmes, sexual health clinics and tuberculosis services.

This study in primary care facilities in Harare compared the effectiveness of ROOT with PITC in children aged six to 15 years, a group for whom opportunities to receive HIV testing have been limited. The authors found that a 22% increase in the proportion of eligible children offered testing following the introduction of ROOT; a 34% increase in the proportion of HIV test uptake; and a 55% increase in proportion of children testing HIV positive (yield).  Importantly, the increase in proportion of children to whom testing was offered, test uptake and yield compared to opt-in PITC was sustained over the 1.5 years follow-up period. Factors postulated to have resulted in improved testing and uptake included the removal of the decision of whether to test from the guardian and healthcare worker and decreased stigma associated with opt-out testing. The authors also acknowledge that investment in training and human resource capacity likely contributed to improvements seen. Further, as stated by the authors, HIV testing must be accompanied by effective strategies to ensure linkage to care in order to improve health outcomes in this population.

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AIDS and bacterial disease remain leading causes of hospital admission

Causes of hospital admission among people living with HIV worldwide: a systematic review and meta-analysis.

Ford N, Shubber Z, Meintjes G, Grinsztejn B, Eholie S, Mills EJ, Davies MA, Vitoria M, Penazzato M, Nsanzimana S, Frigati L, O'Brien D, Ellman T, Ajose O, Calmy A, Doherty M. Lancet HIV. 2015 Oct;2(10):e438-44. doi: 10.1016/S2352-3018(15)00137-X. Epub 2015 Aug 11.

Background: Morbidity associated with HIV infection is poorly characterised, so we aimed to investigate the contribution of different comorbidities to hospital admission and in-hospital mortality in adults and children living with HIV worldwide.

Methods: Using a broad search strategy combining terms for hospital admission and HIV infection, we searched MEDLINE via PubMed, Embase, Web of Science, LILACS, AIM, IMEMR and WPIMR from inception to Jan 31, 2015, to identify studies reporting cause of hospital admission in people living with HIV. We focused on data reported after 2007, the period in which access to antiretroviral therapy started to become widespread. We estimated pooled proportions of hospital admissions and deaths per disease category by use of random-effects models. We stratified data by geographical region and age.

Findings: We obtained data from 106 cohorts, with reported causes of hospital admission for  313 006 adults and 6182 children living with HIV. For adults, AIDS-related illnesses (25 119 patients, 46%, 95% CI 40-53) and bacterial infections (14 034 patients, 31%, 20-42) were the leading causes of hospital admission. These two categories were the most common causes of hospital admission for adults in all geographical regions and the most common causes of mortality. Common region-specific causes of hospital admission included malnutrition and wasting, parasitic infections, and haematological disorders in the Africa region; respiratory disease, psychiatric disorders, renal disorders, cardiovascular disorders, and liver disease in Europe; haematological disorders in North America; and respiratory, neurological, digestive and liver-related conditions, viral infections, and drug toxicity in South and Central America. For children, AIDS-related illnesses (783 patients, 27%, 95% CI 19-34) and bacterial infections (1190 patients, 41%, 26-56) were the leading causes of hospital admission, followed by malnutrition and wasting, haematological disorders, and, in the African region, malaria. Mortality in individuals admitted to hospital was 20% (95% CI 18-23, 12 902 deaths) for adults and 14% (10-19, 643 deaths) for children.

Interpretation: This review shows the importance of prompt HIV diagnosis and treatment, and the need to reinforce existing recommendations to provide chemoprophylaxis and vaccination against major preventable infectious diseases to people living with HIV to reduce serious AIDS and non-AIDS morbidity.

Abstract access 

Editor’s notes: Despite the widening availability of antiretroviral therapy (ART), HIV-associated disease remains an important cause of illness and death. In this systematic review the authors summarise published data concerning causes of hospital admission among HIV-positive people since 2007. This date was selected on the basis that access to ART was limited prior to 2007.

Overall the most common causes of admission among adults, across all geographical regions, were AIDS-associated illness and bacterial infections. Tuberculosis was the most common cause among adults, accounting for 18% of all admissions, followed by bacterial pneumonia (15%). Among children, similarly AIDS-associated illnesses (particularly tuberculosis and Pneumocystis pneumonia) and bacterial infections were the most common causes of admission. Among the 20% of adults who died during their admission, the most common causes of death were tuberculosis, bacterial infections, cerebral toxoplasmosis and cryptococcal meningitis. Among children the most common causes of death were tuberculosis, bacterial infections and Pneumocystis pneumonia. Tuberculosis is likely to have been underestimated in these studies. Autopsy studies consistently illustrate that around half of HIV-positive people who have tuberculosis identified at autopsy had not been diagnosed prior to death.

The review highlights that the majority of severe HIV-associated disease remains attributable to advanced immunosuppression. This is reflected by a median CD4 count at admission among adults of 168 cells per µl. Some 30% of people first tested HIV positive at the time of the admission. The review underlines the need to promote HIV testing so that HIV-positive people can access ART, and prevent the complications of advanced HIV disease. It also underscores the need for better coverage of screening for tuberculosis and preventive therapy for people without active disease.  

Avoid TB deaths
Comorbidity, Epidemiology
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Comparing strategies for HIV testing and counselling for children and adolescents

Uptake and yield of HIV testing and counselling among children and adolescents in sub-Saharan Africa: a systematic review.

Govindasamy D, Ferrand RA, Wilmore SM, Ford N, Ahmed S, Afnan-Holmes H, Kranzer K. J Int AIDS Soc. 2015 Oct 14;18(1):20182. doi: 10.7448/IAS.18.1.20182. eCollection 2015.

Introduction: In recent years children and adolescents have emerged as a priority for HIV prevention and care services. We conducted a systematic review to investigate the acceptability, yield and prevalence of HIV testing and counselling (HTC) strategies in children and adolescents (5 to 19 years) in sub-Saharan Africa.

Methods: An electronic search was conducted in MEDLINE, EMBASE, Global Health and conference abstract databases. Studies reporting on HTC acceptability, yield and prevalence and published between January 2004 and September 2014 were included. Pooled proportions for these three outcomes were estimated using a random effects model. A quality assessment was conducted on included studies.

Results and discussion: A total of 16 380 potential citations were identified, of which 21 studies (23 entries) were included. Most studies were conducted in Kenya (n=5) and Uganda (n=5) and judged to provide moderate (n=15) to low quality (n=7) evidence, with data not disaggregated by age. Seven studies reported on provider-initiated testing and counselling (PITC), with the remainder reporting on family-centred (n=5), home-based (n=5), outreach (n=5) and school-linked HTC among primary schoolchildren (n=1). PITC among inpatients had the highest acceptability (86.3%; 95% confidence interval [CI]: 65.5 to 100%), yield (12.2%; 95% CI: 6.1 to 18.3%) and prevalence (15.4%; 95% CI: 5.0 to 25.7%). Family-centred HTC had lower acceptance compared to home-based HTC (51.7%; 95% CI: 10.4 to 92.9% vs. 84.9%; 95% CI: 74.4 to 95.4%) yet higher prevalence (8.4%; 95% CI: 3.4 to 13.5% vs. 3.0%; 95% CI: 1.0 to 4.9%). School-linked HTC showed poor acceptance and low prevalence.

Conclusions: While PITC may have high test acceptability priority should be given to evaluating strategies beyond healthcare settings (e.g. home-based HTC among families) to identify individuals earlier in their disease progression. Data on linkage to care and cost-effectiveness of HTC strategies are needed to strengthen policies.

Abstract  Full-text [free] access

Editor’s notes: In sub-Saharan Africa children and adolescents are a priority group for HIV prevention and care services. Children and adolescents living with HIV are less likely than adults to know their HIV status, to access treatment and to achieve virologic suppression. As with adults, the first essential step to managing HIV in children and adolescents is to provide appropriate HIV testing and counselling services. This is the first systematic review to assess HIV testing and counselling strategies in this age group, 5-19 years. One key finding is the lack of data on testing and counselling services for this age group. Most services replicate strategies developed for adults with little consideration for the specific needs of children and adolescents. The studies illustrated that health care facility-based provider-initiated testing and counselling had relatively high acceptance, yield and linkage-to-care, but tended to identify individuals at a late stage of disease. In contrast, community-based approaches had the potential to diagnose asymptomatic children. Further work on innovative approaches, family-centred and mobile-based, should be assessed.  

HIV testing
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HIV self-testing: A cost-saving approach?

Assessment of the potential impact and cost-effectiveness of self-testing for HIV in low-income countries.  

Cambiano V, Ford D, Mabugu T, Napierala Mavedzenge S, Miners A, Mugurungi O, Nakagawa F, Revill P, Phillips A. J Infect Dis. 2015 Aug 15;212(4):570-7. doi: 10.1093/infdis/jiv040. Epub 2015 Mar 12.

Background: Studies have demonstrated that self-testing for human immunodeficiency virus (HIV) is highly acceptable among individuals and could allow cost savings, compared with provider-delivered HIV testing and counseling (PHTC), although the longer-term population-level effects are uncertain. We evaluated the cost-effectiveness of introducing self-testing in 2015 over a 20-year time frame in a country such as Zimbabwe.

Methods: The HIV synthesis model was used. Two scenarios were considered. In the reference scenario, self-testing is not available, and the rate of first-time and repeat PHTC is assumed to increase from 2015 onward, in line with past trends. In the intervention scenario, self-testing is introduced at a unit cost of $3.

Results: We predict that the introduction of self-testing would lead to modest savings in healthcare costs of $75 million, while averting around 7000 disability-adjusted life-years over 20 years. Findings were robust to most variations in assumptions; however, higher cost of self-testing, lower linkage to care for people whose diagnosis is a consequence of a positive self-test result, and lower threshold for antiretroviral therapy eligibility criteria could lead to situations in which self-testing is not cost-effective.

Conclusions: This analysis suggests that introducing self-testing offers some health benefits and may well save costs.

Abstract  Full-text [free] access

Editor’s notes: In low-income countries 50% of people living with HIV are unaware of their HIV-status. Some barriers to diagnosis are associated with provider-based models and could potentially be overcome by introducing self-testing strategies. The cost of self-testing is expected to be lower than that of provider-based testing. However, self-testing may have a lower sensitivity, may necessitate provider-based diagnosis confirmation and may lead to lower linkages to care, among other potential disadvantages. This study assesses the cost-effectiveness of introducing self-testing in Zimbabwe over a 20-year time frame.

Two scenarios are modelled using an individual-based stochastic model of HIV transmission and infection progression and treatment: 1) a reference case where self-testing is not introduced, with continuous reliance on provider-based testing and 2) following self-testing introduction. Cost and health outcomes were compared.

The study suggests that introduction of self-testing would lead to a 7% higher proportion tested for HIV compared to the reference scenario. Also, it would lead to a cost reduction of 2.6% (USD 75 million) and to 7000 DALYs averted in a 20-year period. However, the costs and effects depend on a range of factors and in some scenarios (such as in situations of inadequate links to the care and treatment cascade) self-testing could result in worse outcomes than in the reference case. Sensitivity analyses illustrate that key determinants of the magnitude of health gains include the cost of self-testing, the initial level of HIV diagnosis and ART coverage, and self-testing availability.

This study contains some exciting findings that could lead to the use of resources more effectively. However, associated research needs to be carried out to ensure that the introduction of self-testing yields the greatest benefit. More work needs to be done in determining the cost of distribution and management of self-testing, as well as exploring the community acceptance. Further, given the importance of linkages to care, research on self-testing should be embedded into the larger literature around health system strengthening. 

HIV testing
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Wide variation in national HIV policies associated with HIV testing and treatment across six African countries

A comparative analysis of national HIV policies in six African countries with generalized epidemics.

Church K, Kiweewa F, Dasgupta A, Mwangome M, Mpandaguta E, Gomez-Olive FX, Oti S, Todd J, Wringe A, Geubbels E, Crampin A, Nakiyingi-Miiro J, Hayashi C, Njage M, Wagner RG, Ario AR, Makombe SD, Mugurungi O, Zaba B. Bull World Health Organ. 2015 Jul 1;93(7):457-67. doi: 10.2471/BLT.14.147215. Epub 2015 Apr 28.

Objective: To compare national human immunodeficiency virus (HIV) policies influencing access to HIV testing and treatment services in six sub-Saharan African countries.

Methods: We reviewed HIV policies as part of a multi-country study on adult mortality in sub-Saharan Africa. A policy extraction tool was developed and used to review national HIV policy documents and guidelines published in Kenya, Malawi, South Africa, Uganda, the United Republic of Tanzania and Zimbabwe between 2003 and 2013. Key informant interviews helped to fill gaps in findings. National policies were categorized according to whether they explicitly or implicitly adhered to 54 policy indicators, identified through literature and expert reviews. We also compared the national policies with World Health Organization (WHO) guidance.

Findings: There was wide variation in policies between countries; each country was progressive in some areas and not in others. Malawi was particularly advanced in promoting rapid initiation of antiretroviral therapy. However, no country had a consistently enabling policy context expected to increase access to care and prevent attrition. Countries went beyond WHO guidance in certain areas and key informants reported that practice often surpassed policy.

Conclusion: Evaluating the impact of policy differences on access to care and health outcomes among people living with HIV is challenging. Certain policies will exert more influence than others and official policies are not always implemented. Future research should assess the extent of policy implementation and link these findings with HIV outcomes.

Abstract  Full-text [free] access

Editor’s notes: Despite evidence on reduction in HIV attributable mortality, concerns still remain on the high attrition rates across the diagnosis-to-treatment cascade. This paper uses a comparative policy analysis to track differences in national HIV policy responses to the HIV epidemic. The methodology used is notable as it offers a helpful conceptual framework for the HIV policy and service factors influencing specific differences in HIV-associated adult mortality across the diagnosis-to-treatment cascade.

The range of policies between countries was unexpected, given the explanation offered by the authors that African countries tend to adopt standards and guidance from WHO. Furthermore, while countries showed progressive elements, no country had the comprehensive policy context necessary for a decisive impact on service access. Important differences were also noted in the influential weight given to some policies, in the timing of policy implementation in some indicators, and in whether WHO national standards were or were not adopted by countries.

These findings are particularly useful in better understanding the incentives and barriers to accessing antiretroviral therapy in different contexts.

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Single dose nevirapine for PMTCT does not jeopardise future NNRTI-based ART in children

Single-dose nevirapine exposure does not affect response to antiretroviral therapy in HIV-infected African children aged below 3 years.

Musoke P, Szubert AJ, Musiime V, Nathoo K, Nahirya-Ntege P, Mutasa K, Williams DE, Prendergast AJ, Spyer M, Walker AS, Gibb DM, and the ARROW Trial Team. AIDS. 2015 Jul 24. [Epub ahead of print]

Objectives: To assess the impact of exposure to single-dose nevirapine (sdNVP) on virological response in young Ugandan/Zimbabwean children (<3 years) initiating antiretroviral therapy (ART), and to investigate other predictors of response.

Design: Observational analysis within the ARROW randomized trial.

Methods: sdNVP exposure was ascertained by the caregiver's self-report when the child initiated non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART. Viral load was assayed retrospectively over a median 4.1 years of follow-up. Multivariable logistic regression models were used to identify independent predictors of viral load below 80 copies/ml, 48 and 144 weeks after ART initiation (backwards elimination, exit P = 0.1).

Results: Median (IQR) age at ART initiation was 17 (10-23) months in 78 sdNVP-exposed children vs. 21 (14-27) months in 289 non-exposed children (36 vs. 20% <12 months). At week 48, 49 of 73 (67%) sdNVP-exposed and 154 of 272 (57%) non-exposed children had viral load below 80 copies/ml [adjusted odds ratio (aOR) 2.34 (1.26-4.34), P = 0.007]; 79 and 77% had viral load below 400 copies/ml. Suppression was significantly lower in males (P = 0.009), those with higher pre-ART viral load (P = 0.001), taking syrups (P = 0.05) and with lower self-reported adherence (P = 0.04). At week 144, 55 of 73 (75%) exposed and 188 of 272 (69%) non-exposed children had less than 80 copies/ml [aOR 1.75 (0.93-3.29), P = 0.08]. There was no difference between children with and without previous sdNVP exposure in intermediate/high-level resistance to NRTIs (P > 0.3) or NNRTIs (P > 0.1) (n = 88) at week 144.

Conclusion: Given the limited global availability of lopinavir/ritonavir, its significant formulation challenges in young children, and the significant paediatric treatment gap, tablet fixed-dose-combination NVP-based ART remains a good alternative to syrup lopinavir-based ART for children, particularly those over 1 year and even if exposed to sdNVP.

Abstract access 

Editor’s notes: Universal initiation of antiretroviral therapy (ART) is recommended for all children below the age of five years, regardless of immune or clinical status. World Health Organization recommends initiation with lopinavir/ritonavir-containing ART in children aged below three years. This was prompted by the P1060 trials which showed a poorer virologic response to nevirapine compared to lopinavir-containing regimens among infants exposed and unexposed, to single-dose nevirapine (sd NVP) as prophylaxis against mother-to-child HIV transmission. Previous studies had shown a poorer response to nevirapine-containing combination antiretroviral therapy (ART) subsequently initiated by mothers exposed to sd NVP.

However, lopinavir/ritonavir for young children is only available as a liquid formulation. This has limited availability, is highly unpalatable, has cold chain requirements and is bulky and conspicuous to transport. Where lopinavir-containing ART is not feasible, guidelines suggest non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens as an alternative. The NNRTI of choice is nevirapine, because dosing of efavirenz is problematic in young children. Understanding whether sd NVP is associated with substantially greater risks of virologic failure in children who start nevirapine containing regimens is therefore important.

This study compared the risk of virologic failure in young children (aged between six months and three years) initiating nevirapine-containing ART who had been exposed to single dose NVP, compared to people who had not. The study found no higher risk of virologic failure in people who had been exposed to sd NVP compared to people who had not, either at 48 or at 144 weeks after ART initiation. This remained true regardless of whether viral-load cut-off of 80, 400 or 1000 copies/ml was used to define virologic failure. Furthermore, there was no difference between children with and without sd NVP exposure in the percentage of clinically-significant NRTI or NNRTI resistance mutations.

As expected, a high pre-ART viral load was a strong predictor of poor virologic response. Importantly, receiving ART with syrup compared to tablets also predicted poor virologic response, and was equivalent to initiating ART with a 1 log10 higher viral load. This is a similar magnitude of difference in virologic response as that seen between lopinavir- versus nevirapine- containing regimens in the P1060 trials. As triple-drug nevirapine-based tablets are available for young children, this would imply that a tablet nevirapine-based regimen may have similar virologic response to a syrup lopinavir-based regimen in young children.

The study did not do a randomised comparison and sd NVP exposure was based on self-report. Also, a third of the participants took NNRTI for 36 weeks only, following which they were switched to triple NRTI regimens. However, the results were similar when the analyses were restricted to people who took NNRTI-based regimens throughout the study period.

This study should provide reassurance to healthcare providers in resource-limited settings that nevirapine-based ART is a good alternative to syrup lopinavir-based ART, even when there is prior exposure to sd NVP. 

Health care delivery
Uganda, Zimbabwe
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Switching to second-line ART – we need to do better

Monitoring and switching of first-line antiretroviral therapy in sub-Saharan Africa: collaborative analysis of adult treatment cohorts.

Haas AD, Keiser O, Balestre E, Brown S, Bissagnene E, Chimbetete C, Dabis F, Davies MA, Hoffmann CJ, Oyaro P, Parkes-Ratanshi R, Reynolds SJ, Sikazwe I, Wools-Kaloustian K, Zannou DM, Wandeler G, Egger M, for IeDea Southern Africa EA, West A. Lancet HIV. 2015 Jul 1;2(7):e271-e278.

Background: HIV-1 viral load testing is recommended to monitor antiretroviral therapy (ART) but is not universally available. The aim of our study was to assess monitoring of first-line ART and switching to second-line ART in sub-Saharan Africa.

Methods: We did a collaborative analysis of cohort studies from 16 countries in east Africa, southern Africa, and west Africa that participate in the international epidemiological database to evaluate AIDS (IeDEA). We included adults infected with HIV-1 who started combination ART between January, 2004, and January, 2013. We defined switching of ART as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to one including a protease inhibitor, with adjustment of one or more nucleoside reverse-transcriptase inhibitors (NRTIs). Virological and immunological failures were defined according to WHO criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% CIs comparing routine viral load monitoring, targeted viral load monitoring, CD4 monitoring, and clinical monitoring, adjusting for programme and individual characteristics.

Findings: Of 297 825 eligible patients, 10 352 (3%) switched to second-line ART during 782 412 person-years of follow-up. Compared with CD4 monitoring, hazard ratios for switching were 3·15 (95% CI 2·92–3·40) for routine viral load monitoring, 1·21 (1·13–1·30) for targeted viral load monitoring, and 0·49 (0·43–0·56) for clinical monitoring. Of 6450 patients with confirmed virological failure, 58·0% (95% CI 56·5–59·6) switched by 2 years, and of 15 892 patients with confirmed immunological failure, 19·3% (18·5–20·0) switched by 2 years. Of 10 352 patients who switched, evidence of treatment failure based on one CD4 count or viral load measurement ranged from 86 (32%) of 268 patients with clinical monitoring to 3754 (84%) of 4452 with targeted viral load monitoring. Median CD4 counts at switching were 215 cells per μL (IQR 117–335) with routine viral load monitoring, but were lower with other types of monitoring (range 114–133 cells per μL).

Interpretation: Overall, few patients switched to second-line ART and switching happened late in the absence of routine viral load monitoring. Switching was more common and happened earlier after initiation of ART with targeted or routine viral load testing.

Abstract access 

Editor’s notes: Routine viral load monitoring should allow the early identification of first-line antiretroviral therapy (ART) failure, allowing prompt switch to second-line ART. Prolongation of treatment with a failing regimen compromises future therapeutic options (through the accumulation of drug resistance mutations) and potentially leads to increased morbidity and mortality. Previous reports from Africa have suggested that surprisingly few people switch to second-line therapy, even in programmes with routine viral load monitoring. This raises concerns that there are challenges on the ground with identification and management of ART failure.

This is a comprehensive analysis bringing together data from a number of well-characterised cohorts in Africa. In this analysis, switching to second-line ART was rare (3% over an average of almost three years follow-up). In programmes with routine viral load monitoring, only half of the people with confirmed virologic failure on first-line ART (two viral loads >1000 copies/ml) were recorded as having been switched to second-line ART. Furthermore, half of the people that were switched to a second-line regimen did not have evidence of confirmed virologic failure, suggesting that some may have been switched too early without first attempting adherence programmes which may achieve re-suppression on first-line ART. Unsurprisingly, rates of switching were lower in programmes with CD4+ monitoring (with or without targeted viral load testing) or clinical monitoring alone. 

While guidelines and algorithms around identification and management of first-line ART failure are relatively clear and straightforward, translating this into action on the ground seems to be difficult. At least part of this is likely to be due to the lack of tools to reliably measure adherence and the consequent difficulty that frontline health care workers have in identifying people that truly require a switch to second-line ART. Moreover, most programmes still do not routinely monitor indicators relating to virologic suppression or treatment failure and so this might not be seen as a priority by health care workers and programme managers. There is a need for research to explore how best to maximise virologic suppression in resource-constrained settings, as well as studies to evaluate the impact of programmes such as point-of-care viral load testing.

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