Non-communicable diseases in people living with HIV in rural Africa: tackling the double burden

In 2019, there were around 38 million people living with HIV (PLHIV) worldwide. For the past decade, new HIV infections have been reduced by 23% and AIDS-related deaths have been reduced by 39% worldwide. All these achievements were possible mainly due to discovery and global rollout of antiretroviral therapies (ART), reduction in stigma and a global effort for funding to tackle the HIV epidemic. Sub-Saharan Africa is the most affected WHO region with around 20.7 million (54%) PLHIV. Since 2010, in the region, new HIV infections have been reduced by 38% and AIDS-related deaths have been reduced by 49%. This accomplishment was possible mostly due to extensive vertical HIV testing and treatment programs.
Each year, more than 41 million people die from non-communicable diseases (NCDs) worldwide. More than 15 millions of these deaths are premature deaths (people aged between 30-69 years) and 85% occur in lower- and middle-income countries. The most common NCDs that cause deaths are cardiovascular diseases, cancers, respiratory diseases, and diabetes mellitus. The risk factors for most NCDs can be grouped as behaviour or metabolic risk factors. The most common modifiable behaviour risk factors are harmful tobacco use, excessive alcohol consumption, eating unhealthy diet, physical inactivity, overweight and obesity. Other metabolic risk factors are raised blood cholesterol, and raised fasting blood glucose.
In sub-Saharan Africa, with the rapid demographic changes, an epidemiological transition from infectious diseases to non-communicable and chronic diseases can be observed. By 2030, mortality due to NCD is projected to surpass the mortality from combined infectious, neonatal, maternal and nutritional diseases. Therefore, there is an urgent need for innovative ways to tackle this double burden of diseases on the African continent.
The overall goal of this doctoral thesis was to summarise the burden of non-communicable diseases in sub-Saharan Africa. Additionally, data from rural Tanzania was used to estimate the burden of renal impairment, excessive weight gain and different comorbidities among HIV-infected patients receiving antiretroviral treatment.
The first study described the burden of the most relevant etiologies for NCDs in sub-Saharan Africa, which are arterial hypertension, heart diseases, diabetes mellitus and chronic kidney diseases. The review emphasized the importance of using a multifactorial approach, with emphasis on strengthening the existing health care systems to facilitate early diagnosis, treatment and management of NCDs. Furthermore, the review highlighted an urgent need for robust high-
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quality evidence directed at informing national stakeholders on the key drivers of NCDs across Africa.
The second study assessed the prevalence, incidence and predictors of renal impairment among PLHIV receiving ritonavir-boosted protease inhibitors (bPI). Renal impairment was present in 7.6% of participants at the switch from first-line to bPI. Among participants with normal kidney function at the time of switch, 7.4% developed renal impairment after a median time of 3.5 years. The study reported risk associated with renal impairment at switch to be older age, low body mass index (BMI) <18.5 kg/m2 and arterial hypertension. Hence, this study highlighted the high burden of renal impairment among patients who are switched from first-line to bPI in rural sub-Saharan Africa and stress the importance of clinical monitoring of renal function for patients using ART.
The third study evaluated the weight change among newly diagnosed PLHIV starting treatment with either dolutegravir-based or efavirenz-based regimen in rural Tanzania. Additionally, it assessed risk factors associated with increased body weight ≥10% after 12 months of treatment. Initiating a dolutegravir-based ART regimen was associated with more weight gain compared to efavirenz-based regimens during the first 12 months of treatment, confirming observations from industrialized settings. Weight gain of ≥10% was associated with use of dolutegravir, level of immunosuppression, BMI at ART initiation and being female.
The fourth article is a letter to the editor that discussed the rollout of dolutegravir-based antiretroviral therapy in sub-Saharan Africa and its public health implications. The letter highlighted the lack of studies to evaluate long-term side effects of dolutegravir-based regimens among PLHIV living in sub-Saharan Africa. At the time, it was vital since there were studies that demonstrated excessive weight in PLHIV either starting treatment with dolutegravir-based regimens or those who were switched from other regimens to dolutegravir-based regimen. Therefore, this letter set the basis for the third study to evaluate weight gain in patients starting ART in rural Tanzania.
The fifth study investigated the age-related causes of morbidity and mortality of people living with HIV in rural Tanzania. Prevalence and incidence of different comorbidities in patients starting antiretroviral treatment was evaluated. The results showed that anaemia, arterial hypertension and undernutrition are the most relevant comorbidities with different age-associated frequencies and impact on death/LTFU in this population.
The sixth study is a study protocol for an open-label, three-arm, parallel randomized controlled trial conducted at two rural hospitals in Lesotho and Tanzania. The clinical trial compares the
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efficacy and cost-effectiveness of three antihypertensive treatment strategies among HIV-positive and negative participants. The primary endpoint is the proportion of participants reaching the target blood pressure at 12 weeks. The results from this trial will help to identify the most effective and cost-effective treatment strategies for uncomplicated arterial hypertension among people of African descent living in rural sub-Saharan Africa.
The seventh article is an editorial that discussed the challenges for HIV-infected adolescents during transition from paediatric to adult HIV clinics in Africa. The editorial addressed the challenge of high HIV prevalence and incidence among adolescents and young adults in sub-Saharan Africa. The editorial stressed an urgent need to ensure that the transition policy from paediatric to adult-centred clinics is part of health care management for HIV-infected adolescents and young adults in Africa.
In conclusion, the studies included in this thesis highlight the double burden of infectious diseases and non-communicable diseases in sub-Saharan Africa. The lessons learnt will help to inform future guidelines on the importance of clinical monitoring of people living with HIV once they start antiretroviral treatment. The results highlighted the urgent need to improve pharmacovigilance systems in the region to monitor side effects of new drugs. Finally, the results from this thesis stress the importance that future research from local context to tackle the double burden of diseases in the region.