Antiretroviral therapy related adverse effects: Can sub-Saharan Africa cope with the new “test and treat” policy of the World Health Organization?
© The Author(s). 2017
Received: 6 September 2016
Accepted: 10 January 2017
Published: 15 February 2017
Recent studies have shown that early antiretroviral therapy (ART) initiation results in significant HIV transmission reduction. This is the rationale behind the “test and treat” policy of the World Health Organization (WHO). Implementation of this policy will lead to an increased incidence of ART-related adverse effects, especially in sub-Saharan Africa (SSA). Is the region yet ready to cope with such a challenging issue?
The introduction and widespread use of ART have drastically changed the natural history of HIV/AIDS, but exposure to ART leads to serious medication-related adverse effects mainly explained by mitochondrial toxicities, and the situation will get worse in the near future. Indeed, ART is associated with an increased risk of developing cardiovascular disease, lipodystrophy, prediabetes and overt diabetes, insulin resistance and hyperlactatemia/lactic acidosis. The prevalence of these disorders is already high in SSA, and the situation will be exacerbated by the implementation of the new WHO recommendations. Most SSA countries are characterized by (extreme) poverty, very weak health systems, inadequate and low quality of health services, inaccessibility to existing health facilities, lack of (qualified) health personnel, lack of adequate equipment, inaccessibility and unaffordability of medicines, and heavy workload in a context of a double burden of disease. Additionally, there is dearth of data on the incidence and predictive factors of ART-related adverse effects in SSA, to anticipate on strategies that should be put in place to prevent the occurrence of these conditions or properly estimate the upcoming burden and prepare an adequate response plan. These are required if we are to anticipate and effectively prevent this upcoming burden.
While SSA would be the first region to experience the huge benefits of implementing the “test and treat” policy of the WHO, the region is not yet prepared to manage the consequential increased burden of ART-related toxic and metabolic complications. Urgent measures should be taken to fill the lacunae if SSA is not to become over-burdened by the consequences of the “test and treat” policy.
KeywordsHIV/AIDS Test and treat 90-90-90 Antiretroviral therapy Sub-Saharan Africa
Please see Additional file 1 for translations of the abstract into the six official working languages of the United Nations.
According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) global estimates, 38.7 million people were living with HIV in 2015, among whom 2.1 million became newly infected (including 150 000 children) and 1.1 million died from AIDS-related illnesses . The HIV pandemic is to-date one of the most serious health threats the world has ever witnessed. Since the beginning of the epidemic, around 78 million people have become infected with HIV, and 35 million people have died from related complications . For the specific case of sub-Saharan Africa (SSA), 6.5 to 19 million people were living with HIV in the region, with 410 000 to 960 000 new infections and 330 000 to 470 000 related deaths in 2015 .
Fortunately, the introduction and widespread use of highly active antiretroviral therapy (ART) have drastically changed the natural history of HIV/AIDS. Indeed, the longevity, prognosis and quality of life of people living with HIV/AIDS (PLWHA) have significantly improved over time. For instance, AIDS-related deaths have decreased by 45% between 2005 and 2015 . Initiation of ART was initially based on the World Health Organization (WHO) clinical stages or CD4 cell count [2, 3]. But, these guidelines have recently been revised, following conclusive reports from randomized controlled trials which have shown a substantial benefit of early ART initiation with significant reduction in HIV transmission [4–6]. Based on these studies, the UNAIDS has set out an ambitious target for 2020. By this year, they would like 90% of people living with HIV to know their status, 90% of all people with diagnosed HIV infection to receive sustained ART, and 90% of all people receiving ART to have viral suppression . In order to achieve this target, the WHO recommendations changed to a “test and treat” policy advocating that ART should be immediately started in all individuals diagnosed with HIV regardless of age or CD4 cell count .
By the end of 2015, almost 17 million people were already accessing ART globally and as a result of the policy shift to “test and treat”, an exponential increase in the number of people receiving ART can thus be expected in the near future . However, continuous ART may lead to serious adverse effects mainly explained by mitochondrial toxicities. These include: lactic acidosis, pancreatitis, lipodystrophy, dyslipidaemias, insulin resistance and dysglycemias [9–16]. Accordingly, it can be anticipated that the burden of ART-related complications (both toxic and metabolic) will increase in the near future, especially in SSA which is the epicenter of the HIV pandemic globally. This gives rise to the important question of whether the region is sufficiently equipped and prepared to manage this impending burden. The present paper discusses the readiness of SSA countries in implementing the “test and treat/90-90-90” policies with regard to the upcoming increased burden of ART-mediated toxic and metabolic complications.
Snapshot of challenges to implement the “test and treat/90-90-90” policies in Africa
Each “90” target is subjected to difficulties in its implementation in SSA. For the first “90”: 90% of all people living with HIV should know their HIV status, one can include without limitation, lack of HIV testing proposals by healthcare providers and low acceptance for HIV testing by people . Actually, it is recognized that only 20% of PLWHA in SSA know their HIV seropositive status . One of the greatest challenges in Africa would be to implement easily accessible HIV counselling and voluntary HIV testing. This is due to limited financial resources, medical supplies, and weak health systems.
For the second “90”: 90% of people diagnosed with HIV infection should receive sustained ART, difficulties can include low rate of linkage to care, low rate of early ART initiation after HIV seropositive screening, and inadequate/insufficient stocks of ART to provide continuous medication to PLWHA [17, 19]. A study in SSA showed for instance that only 12% of diagnosed-PLWHA were linked to HIV/AIDS care after home-based HIV counselling and testing .
For the third “90”: 90% of all people receiving ART should have viral suppression, absence of proven methods to ensure long time adherence to ART and retention in care for all HIV-infected people, inadequate stocks of ART, and weak early warning indicators for HIV drug resistance can negatively impact this objective in Africa [17, 21–25]. One can also include as transversal impediments, lack of required financial resources for HIV programs and limited supportive health system infrastructures in resource-constrained settings.
Snapshot of the current burden of medication-related adverse effects of continuous ART in SSA
There is growing evidence of a significant rise in cardiovascular disease (CVD) occurrence in PLWHA, more so to those ART-exposed . Studies in SSA signal to an increased incidence of hypertension, diabetes mellitus (DM), renal disease and stroke among ART-naïve PLWHA as well as those on continuous ART [27–34]. Moreover, lipid disorders are very common in this population: the overall prevalence of metabolic syndrome turns around 8.7–58% in Africa [14, 35, 36]. Other studies have specifically identified other known CVD risk factors: higher low-density lipoproteins levels, lower high-density lipoproteins levels, and higher apolipoprotein B/apolipoprotein A ratio [11, 27].
In addition, ART has been implicated as a risk factor for developing prediabetes and overt diabetes mellitus . In some parts of SSA, the prevalence of dysglycemias is almost 40% in ART-exposed PLWHA [12, 15, 38]. More studies are needed to correctly estimate this risk of CVD and metabolic syndrome, and identify factors that can predict their development.
The prevalence of lipodystrophy in Africa reaches 69.9% and the incidence, 41.6% among PLWHA exposed to ART , especially nucleoside analogue reverse transcriptase inhibitors (NRTI)-containing regimen . Lipodystrophy is known to be associated with older age and longer duration on therapy, and has been linked with a decreased quality of life, alterations in lipid, glucose and insulin metabolisms, and an increased risk of DM and CVD [16, 39].
Due to their ability to inhibit polymerase-γ, NRTIs are associated with several mitochondrial toxicities, including life-threatening lactic acidosis. The prevalence of hyperlactatemia is very high in SSA, varying between 17.1 and 83.2% among PLWHA on ART. Once symptomatic, hyperlactatemia is associated with weakness, skin rashes, tachypnea, and can lead to death [9, 13, 40–42]. However, we recognize that this prevalence could be lower, considering that the new first line ART recommended by the WHO does include ART with a lower toxicity profile than previous regimen (removing stavudine for example).
Readiness of SSA countries to implement the new policies of the WHO and UNAIDS: myth or reality?
Countries of the SSA region are resource-poor settings with very weak health systems and poor quality of health services [43–45], especially in the respect of implementing the ‘test and treat’/90-90-90 policies [17, 19]. Health facilities are not found everywhere, particularly in remote and underserved rural areas. When these health centres do exist, they are not always accessible due to non-existent or unpassable roads. There is a crucial lack of (qualified) health care personnel, with some areas not having seen even a nurse. Under these circumstances, who will test the population for HIV and follow-up those found infected? Where are they going to be followed-up, given the insufficient number of health facilities and personnel? With 60% of the African population living in rural areas and considering the extreme shortage of health facilities and professionals in rural Africa, there is urgent need to address these gaps with the regard of the “test and treat” implementation in SSA. In addition to the current shortfall of personnel and facilities necessary to the full implementation of the 90-90-90 policy, and with the expected increase in metabolic disorders secondary to longer ART durations, there is a great need for equipment, and more importantly, adequate numbers of suitably qualified physicians and nurses to closely monitor PLWHA. But these are not currently available. For instance, CVD and DM remain poorly investigated and managed in SSA [46–49]. Moreover, SSA countries are still beset with infectious diseases which continue to exact a heavy tool of illness and death in the region . What’s worse, non-communicable diseases are becoming common in these countries, leading thus to the double burden of disease . With the projected increase in adverse events following initiation of ART in all PLWHA, the current personnel, facilities, equipment, and funding shortfalls will be greatly exacerbated in SSA if some key measures are not implemented.
To date, there are no clear estimates on the incidence of and risk factors for metabolic complications of ART among HIV-infected people living in SSA, children specifically [37, 39]. Therefore, it is difficult to predict what proportion of PLWHA in SSA will develop ART-related adverse effects and develop adequate action plans to counter them. Since the risk factors for developing these adverse effects are not known, measures to prevent them cannot be formulated. Additionally, there is no clear evidence on measures that might prevent PLWHA on long-term continuous ART from developing ART-related adverse effects, this by acting on identified risk factors. Studies are therefore urgently required to fill these gaps and help in designing effective strategies to curtail the expected increase in ART-related adverse effects in SSA following adoption of the new HIV/AIDS recommendations.
Notwithstanding these fears, evidence suggests that WHO/UNAIDS goals may be achievable in some SSA nations. The SEARCH study was conducted in 32 communities in Uganda and Kenya and a total of 334 540 people were enrolled. Participants were randomized to either receive standard HIV services or an expanded testing and treatment program. Preliminary results show that 90% of adults accepted the offer of testing, 93% of those diagnosed with HIV stayed in medical care for at least 6 months, and 92% of those in care had a fully suppressed viral load . Likewise, preliminary results from the PopART study which involved 21 communities in South Africa and Zambia with a cumulative population of 1.2 million people revealed that an estimated 87% of women and 79% of men with HIV knew their status, but just 65 and 62% of diagnosed men and women respectively went on therapy. These numbers are steadily increasing as the study continues [51, 52]. However, the prevalence and incidence of ART-related adverse effects were not looked into in these studies. Also, the researchers have been silent on strategies to identify and handle these complications. The development of evidence-based policy is urgently needed in this regard.
Although it is unequivocally clear that early ART initiation in the course of HIV infection will be beneficial at both the individual and population levels, SSA appears not yet ready to cope with the requirements and consequences of implementing the “test and treat” strategy in an efficient manner. Lack of organized health systems, health facilities and qualified workforce may jeopardize attainment of the WHO/UNAIDS goals. Furthermore, adequate equipment and medicines will need to be made accessible and affordable for all those PLWHA who will develop ART-related adverse effects. Technical and financial aids will be required for SSA countries to develop systems and capacities to fill their gaps and strengthen their weaknesses. Studies are urgently warranted to study the incidence of and risk factors for ART-related complications. These will enable countries in SSA to draw strategies to tackle them effectively.
Acquired immunodeficiency syndrome
Human immunodeficiency virus
Nucleoside analogue reverse transcriptase inhibitors
Person living with HIV/AIDS
Joint United Nations Programme on HIV/AIDS
World Health Organization
This paper received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Availability of data and materials
JRNN conceived and designed the study, and drafted the manuscript. JJRB participated in study conception and design, and critically reviewed and revised the manuscript. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Ethics approval and consent to participate
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- UNAIDS. Fact sheet 2016 Global statistics-2015. Geneva: UNAIDS; 2016. http://www.unaids.org/en/resources/fact-sheet. Accessed 3 Sept 2016.Google Scholar
- World health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection - Recommendations for a public health approach. Geneva: World health Organization; 2013. [http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf]. Accessed 03 Sept 2016.Google Scholar
- World Health Organization. Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach - 2010 revision. Geneva: World Health Organization; 2010. [http://apps.who.int/iris/handle/10665/44379]. Accessed 3 Sept 2016.Google Scholar
- Grinsztejn B, Hosseinipour MC, Ribaudo HJ, Swindells S, Eron J, Chen YQ, Wang L, Ou SS, Anderson M, McCauley M, et al. Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial. Lancet Infect Dis. 2014;14(4):281–90.View ArticlePubMedPubMed CentralGoogle Scholar
- INSIGHT START Study Group, Lundgren JD, Babiker AG, Gordin F, Emery S, Grund B, Sharma S, Avihingsanon A, Cooper DA, Fätkenheuer G, et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;373(9):795–807.View ArticleGoogle Scholar
- TEMPRANO ANRS 12136 Study Group, Danel C, Moh R, Gabillard D, Badje A, Le Carrou J, Ouassa T, Ouattara E, Anzian A, Ntakpé JB, et al. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N Engl J Med. 2015;373(9):808–22.View ArticleGoogle Scholar
- UNAIDS. 90-90-90: An ambitious treatment target to help end the AIDS epidemic. Geneva: UNAIDS; 2016. http://www.unaids.org/sites/default/files/media_asset/90-90-90_en_0.pdf. Accessed 3 Sept 2016.
- World health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection - Recommendations for a public health approach - Second edition. Geneva: World health Organization; 2016. [http://www.who.int/hiv/pub/arv/arv-2016/en/]. Accessed 03 Sept 2016.Google Scholar
- Bolhaar MG, Karstaedt AS. A high incidence of lactic acidosis and symptomatic hyperlactatemia in women receiving highly active antiretroviral therapy in Soweto, South Africa. Clin Infect Dis. 2007;45(2):254–60.View ArticlePubMedGoogle Scholar
- de Waal R, Cohen K, Maartens G. Systematic review of antiretroviral-associated lipodystrophy: lipoatrophy, but not central fat gain, is an antiretroviral adverse drug reaction. PLoS One. 2013;8(5), e63623.View ArticlePubMedPubMed CentralGoogle Scholar
- Dillon DG, Gurdasani D, Riha J, Ekoru K, Asiki G, Mayanja BN, Levitt NS, Crowther NJ, Nyirenda M, Njelekela M, et al. Association of HIV and ART with cardiometabolic traits in sub-Saharan Africa: a systematic review and meta-analysis. Int J Epidemiol. 2013;42(6):1754–71.View ArticlePubMedGoogle Scholar
- Maganga E, Smart LR, Kalluvya S, Kataraihya JB, Saleh AM, Obeid L, Downs JA, Fitzgerald DW, Peck RN. Glucose metabolism disorders, HIV and antiretroviral therapy among Tanzanian adults. PLoS One. 2015;10(8), e0134410.View ArticlePubMedPubMed CentralGoogle Scholar
- Mamiafo CT, Moor VJ, Nansseu JR, Pieme CA, Tayou C, Yonkeu JN. Hyperlactatemia in a group of HIV patients living in Yaounde-Cameroon. AIDS Res Ther. 2014;11(1):2.View ArticlePubMedPubMed CentralGoogle Scholar
- Nguyen KA, Peer N, Mills EJ, Kengne AP. A meta-analysis of the metabolic syndrome prevalence in the global HIV-infected population. PLoS One. 2016;11(3), e0150970.View ArticlePubMedPubMed CentralGoogle Scholar
- Rhee JY, Bahtila TD, Palmer D, Tih PM, Aberg JA, LeRoith D, Jao J. Prevalence of and factors associated with prediabetes and diabetes among HIV-infected adults in Cameroon. Diabetes Metab Res Rev. 2016 [Epub ahead of print].
- Womack J. HIV-related lipodystrophy in Africa and Asia. AIDS Read. 2009;19(4):131–9. 148–152.PubMedGoogle Scholar
- Bigna JJ, Plottel CS, Koulla-Shiro S. Challenges in initiating antiretroviral therapy for all HIV-infected people regardless of CD4 cell count. Infect Dis Poverty. 2016;5:85.View ArticlePubMedPubMed CentralGoogle Scholar
- Towards universal access: scaling up priority HIV/AIDS interventions in the health sector [http://www.who.int/hiv/pub/towards_universal_access_report_2008.pdf]. Accessed 22 Oct 2016.
- Jamieson D, Kellerman SE. The 90 90 90 strategy to end the HIV Pandemic by 2030: Can the supply chain handle it? J Int AIDS Soc. 2016;19(1):20917.View ArticlePubMedPubMed CentralGoogle Scholar
- Doherty T, Tabana H, Jackson D, Naik R, Zembe W, Lombard C, Swanevelder S, Fox MP, Thorson A, Ekstrom AM, et al. Effect of home based HIV counselling and testing intervention in rural South Africa: cluster randomised trial. BMJ. 2013;346:f3481.View ArticlePubMedPubMed CentralGoogle Scholar
- Dube NM, Tint KS, Summers RS. Early warning indicators for HIV drug resistance in adults in South Africa at 2 pilot sites, 2008–2010. Clin Infect Dis. 2014;58(11):1607–14.View ArticlePubMedGoogle Scholar
- Bennett DE, Jordan MR, Bertagnolio S, Hong SY, Ravasi G, McMahon JH, Saadani A, Kelley KF. HIV drug resistance early warning indicators in cohorts of individuals starting antiretroviral therapy between 2004 and 2009: World Health Organization global report from 50 countries. Clin Infect Dis. 2012;54 Suppl 4:S280–9.View ArticlePubMedPubMed CentralGoogle Scholar
- Juma JM, Tiberio JK, Abuya MI, Kilama BK, Somi GR, Sambu V, Banda R, Jullu BS, Ramadhani AA. Monitoring prevention or emergence of HIV drug resistance: results of a population-based foundational survey of early warning indicators in mainland Tanzania. BMC Infect Dis. 2014;14:196.View ArticlePubMedPubMed CentralGoogle Scholar
- Fokam J, Elat JB, Billong SC, Kembou E, Nkwescheu AS, Obam NM, Essiane A, Torimiro JN, Ekanmian GK, Ndjolo A, et al. Monitoring HIV drug resistance early warning indicators in Cameroon: a study following the revised World Health Organization Recommendations. PLoS One. 2015;10(6), e0129210.View ArticlePubMedPubMed CentralGoogle Scholar
- Jonas A, Sumbi V, Mwinga S, DeKlerk M, Tjituka F, Penney S, Jordan MR, Desta T, Tang AM, Hong SY. HIV drug resistance early warning indicators in namibia with updated World Health Organization guidance. PLoS One. 2014;9(7), e100539.View ArticlePubMedPubMed CentralGoogle Scholar
- Friis-Møller N, Thiébaut R, Reiss P, Weber R, Monforte AD, De Wit S, El-Sadr W, Fontas E, Worm S, Kirk O, et al. Predicting the risk of cardiovascular disease in HIV-infected patients: the data collection on adverse effects of anti-HIV drugs study. Eur J Cardiovasc Prev Rehabil. 2010;17(5):491–501.View ArticlePubMedGoogle Scholar
- Mashinya F, Alberts M, Van Geertruyden JP, Colebunders R. Assessment of cardiovascular risk factors in people with HIV infection treated with ART in rural South Africa: a cross sectional study. AIDS Res Ther. 2015;12:42.View ArticlePubMedPubMed CentralGoogle Scholar
- Benjamin LA, Corbett EL, Connor MD, Mzinganjira H, Kampondeni S, Choko A, Hopkins M, Emsley HC, Bryer A, Faragher B, et al. HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults: a case–control study. Neurology. 2016;86(4):324–33.View ArticlePubMedPubMed CentralGoogle Scholar
- Okello S, Kanyesigye M, Muyindike WR, Annex BH, Hunt PW, Haneuse S, Siedner MJ. Incidence and predictors of hypertension in adults with HIV-initiating antiretroviral therapy in south-western Uganda. J Hypertens. 2015;33(10):2039–45.View ArticlePubMedPubMed CentralGoogle Scholar
- Mandina Ndona M, Longo-Mbenza B, Wumba R, Tandu Umba B, Buassa-Bu-Tsumbu B, Mbula Mambimbi M, Wobin TO, Mbungu Fuele S. Nadir CD4+, religion, antiretroviral therapy, incidence of type 2 diabetes mellitus, and increasing rates of obesity among black Africans with HIV disease. Int J Gen Med. 2012;5:983–90.PubMedPubMed CentralGoogle Scholar
- Naicker S, Fabian J. Risk factors for the development of chronic kidney disease with HIV/AIDS. Clin Nephrol. 2010;74 Suppl 1:S51–6.PubMedGoogle Scholar
- Kengne AP, Echouffo-Tcheugui JB, Sobngwi E, Mbanya JC. New insights on diabetes mellitus and obesity in Africa-Part 1: prevalence, pathogenesis and comorbidities. Heart. 2013;99(14):979–83.View ArticlePubMedGoogle Scholar
- Mallipattu SK, Salem F, Wyatt CM. The changing epidemiology of HIV-related chronic kidney disease in the era of antiretroviral therapy. Kidney Int. 2014;86(2):259–65.View ArticlePubMedGoogle Scholar
- Mallipattu SK, Wyatt CM, He JC. The New epidemiology of HIV-related kidney disease. J AIDS Clin Res. 2012;Suppl 4:001.
- Menanga AP, Ngomseu CK, Jingi AM, Mfangam BM, Noubiap JJ, Gweth MN, Blackett KN, Kingue S. Patterns of cardiovascular disease in a group of HIV-infected adults in Yaoundé, Cameroon. Cardiovasc Diagn Ther. 2015;5(6):420–7.PubMedPubMed CentralGoogle Scholar
- Muyanja D, Muzoora C, Muyingo A, Muyindike W, Siedner MJ. High prevalence of metabolic syndrome and cardiovascular disease risk among people with HIV on stable ART in Southwestern Uganda. AIDS Patient Care STDs. 2016;30(1):4–10.View ArticlePubMedPubMed CentralGoogle Scholar
- Nansseu JR, Bigna JJ, Kaze AD, Noubiap JJ. Rates and drivers of progression to prediabetes and diabetes mellitus among HIV infected adults on antiretroviral therapy: a global systematic review and meta-analysis protocol. BMJ open 2016. [In press].
- Levitt NS, Peer N, Steyn K, Lombard C, Maartens G, Lambert EV, Dave JA. Increased risk of dysglycaemia in South Africans with HIV; especially those on protease inhibitors. Diabetes Res Clin Pract. 2016;119:41–7.View ArticlePubMedGoogle Scholar
- Musoke PM, Fergusson P. Severe malnutrition and metabolic complications of HIV-infected children in the antiretroviral era: clinical care and management in resource-limited settings. Am J Clin Nutr. 2011;94(6):1716S–20.View ArticlePubMedPubMed CentralGoogle Scholar
- Waiswa M, Byarugaba BB, Ocama P, Mayanja-Kizza H, Seremba E, Ganguli S, Crowther M, Colebunders R. Hyperlactatemia and concurrent use of antiretroviral therapy among HIV infected patients in Uganda. Afr Health Sci. 2012;12(3):268–75.PubMedPubMed CentralGoogle Scholar
- Chagoma N, Mallewa J, Kaunda S, Njalale Y, Kampira E, Mukaka M, Heyderman RS, van Oosterhout JJ. Longitudinal lactate levels from routine point-of-care monitoring in adult Malawian antiretroviral therapy patients: associations with stavudine toxicities. Trans R Soc Trop Med Hyg. 2013;107(10):615–9.View ArticlePubMedPubMed CentralGoogle Scholar
- Wester CW, Eden SK, Shepherd BE, Bussmann H, Novitsky V, Samuels DC, Hendrickson SL, Winkler CA, O’Brien SJ, Essex M, et al. Risk factors for symptomatic hyperlactatemia and lactic acidosis among combination antiretroviral therapy-treated adults in Botswana: results from a clinical trial. AIDS Res Hum Retrovir. 2012;28(8):759–65.View ArticlePubMedPubMed CentralGoogle Scholar
- Peck R, Mghamba J, Vanobberghen F, Kavishe B, Rugarabamu V, Smeeth L, Hayes R, Grosskurth H, Kapiga S. Preparedness of Tanzanian health facilities for outpatient primary care of hypertension and diabetes: a cross-sectional survey. Lancet Global health. 2014;2(5):e285–92.View ArticlePubMedGoogle Scholar
- Ali MK, Rabadán-Diehl C, Flanigan J, Blanchard C, Narayan KM, Engelgau M. Systems and capacity to address noncommunicable diseases in low- and middle-income countries. Sci Transl Med. 2013;5(181):181cm184.View ArticleGoogle Scholar
- Maher D, Sekajugo J, Harries AD, Grosskurth H. Research needs for an improved primary care response to chronic non-communicable diseases in Africa. Trop Med Int Health. 2010;15(2):176–81.View ArticlePubMedGoogle Scholar
- Jingi AM, Noubiap JJ, Ewane Onana A, Nansseu JR, Wang B, Kingue S, Kengne AP. Access to diagnostic tests and essential medicines for cardiovascular diseases and diabetes care: cost, availability and affordability in the West Region of Cameroon. PLoS One. 2014;9(11), e111812.View ArticlePubMedPubMed CentralGoogle Scholar
- Nansseu JR. Primary care physicians and diabetes mellitus care in Sub-Saharan Africa: still very Far behind the goals. Primary Health Care. 2015;5:3.Google Scholar
- Jingi AM, Nansseu JR, Noubiap JJ. Primary care physicians’ practice regarding diabetes mellitus diagnosis, evaluation and management in the West region of Cameroon. BMC Endocr Disord. 2015;15:18.View ArticlePubMedPubMed CentralGoogle Scholar
- Noubiap JJ, Jingi AM, Veigne SW, Onana AE, Yonta EW, Kingue S. Approach to hypertension among primary care physicians in the West Region of Cameroon: substantial room for improvement. Cardiovasc Diagn Ther. 2014;4(5):357–64.PubMedPubMed CentralGoogle Scholar
- Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386(9995):743–800.View ArticlePubMed CentralGoogle Scholar
- UNAIDS Goals of Testing and Treating HIV in Africa Look Achievable. https://www.poz.com/article/90-90-90-27524-9420. Accessed 3 Sept 2016.
- Bond V, Chiti B, Hoddinott G, Reynolds L, Schaap A, Simuyaba M, Ndubani R, Viljoen L, Simwinga M, Fidler S, et al. “The difference that makes a difference”: highlighting the role of variable contexts within an HIV Prevention Community Randomised Trial (HPTN 071/PopART) in 21 study communities in Zambia and South Africa. AIDS Care. 2016;28 Suppl 3:99–107.View ArticlePubMedGoogle Scholar