Articles tagged as "Botswana"

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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Continuous IPT: benefits in TB prevalent settings

Continuous isoniazid for the treatment of latent tuberculosis infection in people living with HIV: a systematic review and meta-analysis.

Boon SD, Matteelli A, Ford N, Getahun H. AIDS. 2016 Jan 4. [Epub ahead of print]

Objective: This systematic review was carried out to determine the effectiveness of continuous isoniazid (given for at least 36 months) for the treatment of latent tuberculosis infection (LTBI) in people living with HIV (PLHIV).

Methods: Six databases and HIV and tuberculosis (TB) conference abstract books were searched for randomized controlled trials that compared the effectiveness of continuous isoniazid treatment with 6 months of isoniazid application. Outcomes of interest were TB incidence, mortality, adverse events and risk of drug resistance. Data were pooled using fixed-effects meta-analysis.

Results: Three studies were included, from Botswana, South Africa and India. The risk of active TB was 38% lower among patients receiving continuous isoniazid compared with isoniazid regimen for 6 months [relative risk (RR) 0.62, 95% confidence interval (CI): 0.42-0.89; I = 0%], and 49% lower for those with a positive tuberculin skin test (TST) (RR 0.51, 95% CI: 0.30-0.86; I = 7%). Similarly, individuals with positive TST had a 50% lower chance of death (RR 0.50, 95% CI: 0.27-0.91; I = 3%). Two studies found no evidence of an increase in adverse events in the continuous isoniazid group, whereas a third study, that used a different definition for adverse events, found strong evidence of increase. There was no evidence of increased drug resistance when continuous isoniazid was given.

Conclusion: For PLHIV in settings with high TB and HIV prevalence and transmission, continuous isoniazid for at least 36 months is beneficial and probably outweighs the risk of increased adverse events compared with isoniazid regimen for 6 months.

Abstract access 

Editor’s notes: Isoniazid preventive therapy (IPT) reduces TB incidence among HIV-positive people. Evidence has accumulated from settings where TB is prevalent that the protective effect of a standard six-month course of isoniazid wanes after treatment stops. This may be because of reinfection with rapid progression to TB disease. However, in high transmission settings, where the bacillary burden of latent infection could be higher, six months of isoniazid may be insufficient to “cure” latent tuberculosis infection, and reactivation of residual latent infection may also contribute to TB disease after IPT is discontinued. 

This meta-analysis puts together data from three studies that compared a longer duration of IPT to the standard six-month course. Continuous versus a six-month course of IPT reduced TB incidence. Consistent with other studies, this benefit was clear in people with a positive tuberculin skin test (TST) at baseline but smaller and not significant in people with a negative TST. This meta-analysis also found a reduction in mortality among people with a positive TST receiving continuous IPT, primarily based on data from the study in Botswana. This is notable because most previous trials of IPT versus control have not demonstrated a mortality benefit. Most trials of short-course IPT were undertaken in the pre-antiretroviral therapy (ART) era, when all-cause mortality was very high. In the Botswana study, ART was available and will have reduced HIV-associated mortality among all participants, which may have allowed a difference in TB-specific mortality to become evident.

Adverse events were very similar between the continuous versus short course IPT groups in the studies from Botswana and India. However, in the South African study, adverse events were more common in the continuous IPT group, as were temporary or permanent discontinuations due to adverse events. Abnormal liver function tests were particularly common, but it is not clear how many of these were symptomatic and thus would be detected in a programme where liver function is not routinely monitored.

These data support WHO recommendations for continuous IPT for HIV-positive people in settings where TB transmission is common. What is not clear is how to define settings where TB transmission is common enough for this recommendation to be applied. 

Africa, Asia
Botswana, India, South Africa
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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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HIV-related cancer risk declines with ART in Botswana and Uganda, but population burden a major concern

Cancer incidence following expansion of HIV treatment in Botswana

Dryden-Peterson S, Medhin H, Kebabonye-Pusoentsi M, Seage GR, 3rd, Suneja G, Kayembe MK, Mmalane M, Rebbeck T, Rider JR, Essex M, Lockman S. PLoS One. 2015 Aug 12;10(8):e0135602. doi: 10.1371/journal.pone.0135602. eCollection 2015.

Background: The expansion of combination antiretroviral treatment (ART) in southern Africa has dramatically reduced mortality due to AIDS-related infections, but the impact of ART on cancer incidence in the region is unknown. We sought to describe trends in cancer incidence in Botswana during implementation of the first public ART program in Africa.

Methods: We included 8479 incident cases from the Botswana National Cancer Registry during a period of significant ART expansion in Botswana, 2003-2008, when ART coverage increased from 7.3% to 82.3%. We fit Poisson models of age-adjusted cancer incidence and counts in the total population, and in an inverse probability weighted population with known HIV status, over time and estimated ART coverage.

Findings: During this period 61.6% of cancers were diagnosed in HIV-infected individuals and 45.4% of all cancers in men and 36.4% of all cancers in women were attributable to HIV. Age-adjusted cancer incidence decreased in the HIV infected population by 8.3% per year (95% CI -14.1 to -2.1%). However, with a progressively larger and older HIV population the annual number of cancers diagnosed remained constant (0.0% annually, 95% CI -4.3 to +4.6%). In the overall population, incidence of Kaposi's sarcoma decreased (4.6% annually, 95% CI -6.9 to -2.2), but incidence of non-Hodgkin lymphoma (+11.5% annually, 95% CI +6.3 to +17.0%) and HPV-associated cancers increased (+3.9% annually, 95% CI +1.4 to +6.5%). Age-adjusted cancer incidence among individuals without HIV increased 7.5% per year (95% CI +1.4 to +15.2%).

Interpretation: Expansion of ART in Botswana was associated with decreased age-specific cancer risk. However, an expanding and aging population contributed to continued high numbers of incident cancers in the HIV population. Increased capacity for early detection and treatment of HIV-associated cancer needs to be a new priority for programs in Africa.

Abstract  Full-text [free] access


 

A population-level evaluation of the effect of antiretroviral therapy on cancer incidence in Kyadondo county, Uganda, 1999-2008.

Mutyaba I, Phipps W, Krantz EM, Goldman JD, Nambooze S, Orem J, Wabinga HR, Casper C. J Acquir Immune Defic Syndr. 2015 Aug 1;69(4):481-6. doi: 10.1097/QAI.0000000000000620.

Background: The introduction of antiretroviral therapy (ART) in the United States and Europe has led to changes in the incidence of cancers among HIV-infected persons, including dramatic decreases in Kaposi sarcoma and non-Hodgkin lymphoma, and increases in Hodgkin lymphoma, liver, and anogenital malignancies. We sought to evaluate whether increasing availability of ART is associated with changing cancer incidence in Uganda.

Methods: Incident cases of 10 malignancies were identified from Kampala Cancer Registry from 1999 to 2008. ART coverage rates for Uganda were abstracted from the Joint United Nations Program on HIV/AIDS reports. Negative binomial and Poisson regression modeled the association between ART coverage and age-adjusted cancer incidence.

Results: ART coverage in Uganda increased from 0% to 43% from 1999 to 2008. With each 10% increase in ART coverage, incidence of Kaposi sarcoma decreased by 5% [incidence rate ratio (IRR) = 0.95, 95% confidence interval: 0.91 to 0.99, P = 0.02] and stomach cancer decreased by 13% [IRR = 0.87 (95% CI: 0.80 to 0.95), P = 0.002]. Conversely, incidence of non-Hodgkin lymphoma increased by 6% [IRR = 1.06 (95% CI: 1 to 1.12), P = 0.05], liver cancer by 12% [IRR = 1.12 (95% CI: 1.04 to 1.21), P = 0.002], prostate cancer by 5% [IRR = 1.05 (95% CI: 1 to 1.10), P = 0.05], and breast cancer by 5% [IRR = 1.05 (95% CI: 1 to 1.11), P = 0.05]. ART coverage was not associated with incidence of invasive cervical cancer, lung, colon, and Hodgkin disease. These findings were similar when restricted to histologically confirmed cases.

Conclusions: Our findings suggest that AIDS-defining malignancies and other malignancies are likely to remain significant public health burdens in sub-Saharan Africa even as ART availability increases.

Abstract access 

Editor’s notes: There is increasing concern about non-communicable diseases, including cancers, in sub-Saharan Africa. The increasing population of people on antiretroviral therapy (ART) may result in increased absolute numbers of people diagnosed with cancer, presenting a major challenge to often under-resourced cancer diagnosis and treatment services. Few African countries have functional cancer registries. This month, we highlight data reported from both Botswanan and Ugandan cancer registries.

The article by Dryden-Petersen et al. presents data from the Botswanan registry from 2003-2008, a time of rapid ART roll-out. Age-adjusted rates of cancer were estimated using population survey denominators which include HIV status. The analysis distinguishes cancers occurring in HIV-positive individuals from those attributable to HIV (includes Kaposi’s sarcoma, non-Hodgkin’s lymphoma and cervical cancer). Kaposi’s sarcoma, cervix and breast cancer were the most commonly-reported cancers. Overall, against a background of increasing age-adjusted incidence of cancers, the age-adjusted incidence in the HIV-positive population decreased compared to an early peak prior to ART implementation. However, given this expanding population of survivors, the absolute numbers of reported cases remained constant. Different cancers had different trends. Cervical cancer, which affects younger women and which increased over the period studied, may be a particular focus as it is common and relatively easy to identify in the early stages.

The article by Mutyaba et al. presents data from the Ugandan cancer registry for Kyadondo county from 1999-2008, similarly a time of rapid ART roll-out. The analysis uses population denominators, and an ecologic analysis to estimate change in cancer incidence by ART coverage for 10 selected cancers, including Kaposi’s sarcoma, invasive cervical cancer and non-Hodgkin’s lymphoma. Although significant differences in the incidence rate of about half of the cancers were observed over this period, the differences per increase of ART coverage (by 10%) were modest.

These data are now somewhat out of date, but despite the limitations of use of routine data (incomplete and biased ascertainment of cancers, HIV status etc) it is clear that the burden of cancers in these two settings is unlikely to decrease and there are major implications for service provision including screening programmes. 

The findings from the two studies are consistent in showing an important decrease in Kaposi’s sarcoma with ART, but an increase in non-Hodgkin’s lymphoma. However the trends for other cancers (cervical, breast, prostate, liver and lung) are in different directions, which may reflect different ascertainment abilities, ART programmatic differences or different methods of data analysis. Overall both studies highlight that cancer is not declining as ART programmes have been rolled out.

Avoid TB deaths
Africa
Botswana, Uganda
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Longer secondary schooling reduces HIV transmission risk

Length of secondary schooling and risk of HIV infection in Botswana: evidence from a natural experiment.

De Neve JW, Fink G, Subramanian SV, Moyo S, Bor J. Lancet Glob Health. 2015 Aug;3(8):e470-7. doi: 10.1016/S2214-109X(15)00087-X. Epub 2015 Jun 28.

Background: An estimated 2.1 million individuals are newly infected with HIV every year. Cross-sectional and longitudinal studies have reported conflicting evidence for the association between education and HIV risk, and no randomised trial has identified a causal effect for education on HIV incidence. We aimed to use a policy reform in secondary schooling in Botswana to identify the causal effect of length of schooling on new HIV infection.

Methods: Data for HIV biomarkers and demographics were obtained from the nationally representative household 2004 and 2008 Botswana AIDS Impact Surveys (N=7018). In 1996, Botswana reformed the grade structure of secondary school, expanding access to grade ten and increasing educational attainment for affected cohorts. Using exposure to the policy reform as an instrumental variable, we used two-stage least squares to estimate the causal effect of years of schooling on the cumulative probability that an individual contracted HIV up to their age at the time of the survey. We also assessed the cost-effectiveness of secondary schooling as an HIV prevention intervention in comparison to other established interventions.

Findings: Each additional year of secondary schooling caused by the policy change led to an absolute reduction in the cumulative risk of HIV infection of 8.1 percentage points (p=0.008), relative to a baseline prevalence of 25.5% in the pre-reform 1980 birth cohort. Effects were particularly large in women (11.6 percentage points, p=0.046). Results were robust to a wide array of sensitivity analyses. Secondary school was cost effective as an HIV prevention intervention by standard metrics (cost per HIV infection averted was US$27 753).

Interpretation: Additional years of secondary schooling had a large protective effect against HIV risk in Botswana, particularly for women. Increasing progression through secondary school could be a cost-effective HIV prevention measure in HIV-endemic settings, in addition to yielding other societal benefits.

Abstract  Full-text [free] access

Editor’s notes: There is conflicting evidence on the association between education and HIV risk, and little causal evidence. Observational studies are limited by strong confounding by factors such as socioeconomic status and psychological traits, while previous randomised trials have been underpowered for HIV incidence. A policy reform in Botswana in 1996 provided a unique opportunity to assess this question. The policy affected specific birth cohorts and meant that the average number of years of schooling increased by nearly one year. The reform was unlikely to have affected HIV risk through mechanisms other than schooling itself. It therefore constitutes a natural experiment to estimate the causal effect of schooling on the risk of HIV infection, through comparison of birth cohorts exposed to the policy reform versus people unexposed. The authors found that, for each additional year of schooling induced by the reform, there was an 8.1 percentage point reduction in the risk of HIV infection. The effect was particularly strong among women, with an 11.6 percentage point reduction. These results translated to a cost of $27 753 per HIV infection averted. Secondary schooling is therefore more expensive than circumcision or treatment as prevention, but of similar cost-effectiveness to the upper range of estimates for pre-exposure prophylaxis. In addition, schooling offers other benefits beyond the reduction of HIV transmission.

Africa
Botswana
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Tenofovir-based regimens improve outcomes in HIV-HBV co-infection

Comparison of HBV-active HAART regimens in an HIV-HBV multinational cohort: outcomes through 144 weeks.

Thio CL, Smeaton L, Hollabaugh K, Saulynas M, Hwang H, Saravanan S, Kulkarni S, Hakim J, Nyirenda M, Iqbal HS, Lalloo UG, Campbell TB, Lockman S, Currier JS. AIDS. 2015 Jun 19;29(10):1173-82. doi: 10.1097/QAD.0000000000000686.

Objectives: To explore factors associated with short and long-term hepatitis B virus (HBV) DNA suppression in a multinational cohort of HIV-HBV co-infected patients receiving HBV-active antiretrovirals.

Methods: One hundred and fifteen HIV-HBV co-infected patients participating in one of the two global randomized clinical trials conducted by the Adult AIDS Clinical Trials Group of different antiretroviral regimens received either HBV monotherapy with either lamivudine or emtricitabine (N = 56), or HBV dual therapy with tenofovir disoproxil fumarate (TDF) + lamivudine or emtricitabine (N = 59). Associations of pretreatment characteristics with the primary (HBV DNA <200 IU/ml at 24 weeks) and longitudinal outcomes through 144 weeks were explored using logistic regression. HBV drug-resistance mutations were determined by pol sequencing in those with viral rebound.

Results: The proportion with HBV DNA below 200 IU/ml was 60% (95% confidence interval 50-69%) at 24 weeks and 79% (95% confidence interval 69-88%) at 144 weeks. Pretreatment factors associated with the primary outcome were HBV DNA, CD4 T-cell count, and aspartate aminotransferase, but only pretreatment HBV DNA remained associated with long-term suppression (P < 0.0001). HBV therapy group was not significantly associated with the primary outcome at 24 weeks; however, longitudinally, a greater proportion in the dual-therapy group achieved HBV DNA below 200 IU/ml (P = 0.007). A higher proportion of hepatitis B e antigen-negative patients (n = 57) achieved HBV DNA below 200 IU/ml at any point, regardless of the therapy group. All 12 patients with emergence of lamivudine-resistant mutants were in the monotherapy group.

Conclusions: TDF-based dual HBV-active antiretroviral therapy is preferred to treat HIV-HBV co-infected patients. In resource-limited settings in which TDF may not be universally available, lamivudine or emtricitabine HBV monotherapy is a reasonable option in patients with low HBV replication.

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Editor’s notes: Hepatitis B virus infection remains a leading cause of preventable morbidity and mortality globally, through cirrhosis and liver cancer. In settings with a high prevalence of HIV-HBV coinfection, there is an opportunity to optimise clinical management within the public health approach to antiretroviral therapy. This study adds to the evidence base suggesting that antiretroviral regimens containing lamivudine/emtricitabine and tenofovir are associated with better virologic outcomes than regimens without tenofovir for people co-infected with HIV and HBV. In this study, a post hoc analysis of two multicentre randomised controlled trials, regimens with two HBV-active agents provided more durable virologic suppression and limited the emergence of lamivudine-resistant HBV strains. Although recommendations about the treatment of HIV-HBV coinfection are incorporated into WHO antiretroviral guidelines, testing for HBV infection within antiretroviral programmes is still uncommon and tenofovir is not universally employed in standard first-line antiretroviral regimens. With an increasing number of people switching to second-line antiretroviral regimens, there is the additional challenge of identifying HBV infection in order to maintain HBV-active agents within the second-line regimen. There is now a need for better evidence around how to operationalise these recommendations within national antiretroviral programmes.        

Comorbidity, HIV Treatment
Africa, Asia, Latin America
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Men who have sex with men in sub-Saharan Africa: a review of the evidence

Emerging themes for sensitivity training modules of African healthcare workers attending to men who have sex with men: a systematic review.

Dijkstra M, van der Elst EM, Micheni M, Gichuru E, Musyoki H, Duby Z, Lange JM, Graham SM, Sanders EJ. Int Health. 2015 May;7(3):151-162. Epub 2015 Jan 16.

Sensitivity training of front-line African health care workers (HCWs) attending to men who have sex with men (MSM) is actively promoted through national HIV prevention programming in Kenya. Over 970 Kenyan-based HCWs have completed an eight-modular online training free of charge (http://www.marps-africa.org) since its creation in 2011. Before updating these modules, we performed a systematic review of published literature of MSM studies conducted in sub-Saharan Africa (sSA) in the period 2011-2014, to investigate if recent studies provided: important new knowledge currently not addressed in existing online modules; contested information of existing module topics; or added depth to topics covered already. We used learning objectives of the eight existing modules to categorise data from the literature. If data could not be categorised, new modules were suggested. Our review identified 142 MSM studies with data from sSA, including 34 studies requiring module updates, one study contesting current content, and 107 studies reinforcing existing module content. ART adherence and community engagement were identified as new modules. Recent MSM studies conducted in sSA provided new knowledge, contested existing information, and identified new areas of MSM service needs currently unaddressed in the online training.

Abstract  Full-text [free] access

Editor’s notes: Same sex practices remain criminalised in sub-Saharan Africa. Gay men and other men who have sex with men face stigma, discrimination, harassment and arrest. Health care workers frequently have no training on issues affecting gay men and other men who have sex with men and are ill-prepared to work sensitively with them. Together these can deter these men from accessing health care and HIV/STI services, increasing their risk of HIV and other poor health outcomes.

This study conducted a systematic review of gay men and other men who have sex with men in sub-Saharan Africa. The findings were used to update an on-line training programme for health care workers in Kenya. This previously comprised modules on i) men who have sex with men and HIV in Africa ii) homophobia: stigma and its effects; iii) sexual identity, coming out and disclosure; iv) anal sex and common sexual practices; v) HIV and STIs; vi) condom and lubricant use; vii) mental health: anxiety, depression and substance use; and viii) risk-reduction counselling. The review updated the training programme with new evidence and two new modules were introduced: ix) ART adherence; and x) community engagement.

Health care workers play a crucial role in reducing stigma and discrimination facing gay men and other men who have sex with men. This systematic review provided a valuable step in updating an important, accessible training programme. Reducing homoprejudice and ensuring health care workers have accurate and up-to-date knowledge are key to improving service uptake by gay men and other men who have sex with men.

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People living with HIV at higher risk of developing disabilities in sub-Saharan Africa

The relationship between HIV and prevalence of disabilities in sub-Saharan Africa: systematic review.

Banks LM, Zuurmond M, Ferrand R, Kuper H. Trop Med Int Health. 2015 Apr;20(4):411-29. doi: 10.1111/tmi.12449. Epub 2015 Jan 14.

Objective: To systematically review evidence on the prevalence and risk of disabilities among children and adults living with HIV in sub-Saharan Africa.

Methods: Articles were identified from 1980 to June 2013 through searching seven electronic databases. Epidemiological studies conducted in sub-Saharan Africa that explored the association between HIV status and general disability or specific impairments, with or without an HIV-uninfected comparison group, were eligible for inclusion.

Results: Of 12 867 records initially identified, 61 papers were deemed eligible for inclusion. The prevalence of disability was high across age groups, impairment types and study locations. Furthermore, 73% of studies using an HIV- comparator found significantly lower levels of functioning in people living with HIV (PLHIV). By disability type, the results were as follows: (i) for studies measuring physical impairments (n = 14), median prevalence of limitations in mobility and motor function among PLHIV was 25.0% (95% CI: 21.8-28.2%). Five of eight comparator studies found significantly reduced functioning among PLHIV; for arthritis, two of three studies which used an HIV- comparison group found significantly increased prevalence among PLHIV; (ii) for sensory impairment studies (n = 17), median prevalence of visual impairment was 11.2% (95%CI: 9.5-13.1%) and hearing impairment was 24.1% (95%CI: 19.2-29.0%) in PLHIV. Significantly increased prevalence among PLHIV was found in one of four (vision) and three of three studies (hearing) with comparators; (iii) for cognitive impairment in adults (n = 30), median prevalence for dementia was 25.3% (95% CI: 22.0-28.6%) and 40.9% (95% CI: 37.7-44.1%) for general cognitive impairment. Across all types of cognitive impairment, twelve of fourteen studies found a significant detrimental effect of HIV infection; (iv) for developmental delay in children with HIV (n = 20), median prevalence of motor delay was 67.7% (95% CI: 62.2-73.2%). All nine studies that included a comparator found a significant difference between PLHIV and controls; for cognitive development and global delay, a significant detrimental effect of HIV was found in five of six and one of two studies, respectively. In the nine cohort studies comparing vertically infected and uninfected children, eight showed a significant gap in development over time in children with HIV. Finally, fifteen of thirty-one (48%) studies found a statistically significant dose-response relationship between indicators of disease progression (CD4 or WHO stage) and disability.

Conclusions: HIV is widespread in sub-Saharan Africa and the evidence suggests that it is linked to disabilities, affecting a range of body structures and functions. More research is needed to better understand the implications of HIV-related disability for individuals, their families as well as those working in the fields of disability and HIV so that appropriate interventions can be developed.

Abstract  Full-text [free] access

Editor’s notes: As ART is scaled-up, and people living with HIV live longer, an increasing number of people will face challenges of HIV-associated disability. Disability may be partly a direct effect of living with HIV, but may also be an indirect effect, for example due to side effects of treatment. There has been relatively little research on this topic, particularly in low and middle-income countries and this is the first systematic review of the prevalence of disability among people living with HIV in sub-Saharan Africa. The review found a high prevalence of all categories of disability. The majority of studies had an HIV-negative comparison group among whom levels of disability were lower than among people living with HIV. Developmental delay was the impairment most strongly linked to HIV, with prevalence as high as 78% in children living with HIV. To minimize the chance that the observed association was due to reverse causality, the review excluded studies which clearly focused on disability as a risk factor for HIV, although it is likely that some studies still included individuals in whom disability preceded HIV infection. There was also relatively little data on ART status and duration in many studies, which may impact on the association of HIV and disability.  Despite these limitations, this study highlights the need to focus on prevention and management of HIV-associated disability in sub-Saharan Africa and development of effective, low-cost evidence-informed activities.

Africa
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