Sensory neuropathy and associated factors among patients living with human immuno-deficiency virus in Africa: a systematic review and meta-analysis

Abstract

Introduction

Despite high prevalence of sensory neuropathy among individuals living with HIV, there is no comprehensive information regarding variables that determine sensory neuropathy onset among the patients who attended health care facilities. In conditions where there is a high number of patients with sensory neuropathy, clinicians confront challenges in managing the problem, and increase the burden of health care expenditures. This study aimed to determine the prevalence of peripheral neuropathy and associated factors among people living with HIV in Africa.

Methods

To ensure the transparency, accuracy, and thoroughness of this systematic review and meta-analysis, we adhered to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Systematic electronic searches were conducted across several databases, including African Journal Online, Google Scholar, PubMed, Scopus, and the Wiley Online Library. Articles found during the searching were imported into EndNote software version X7, where duplicates were removed. The extracted data were then imported to Microsoft Excel and analyzed using STATA version 11 for analysis. The Q statistic and I² test were employed to evaluate heterogeneity between studies.

Results

The initial search identified 1,821 articles, which were organized using citation management software. The current meta-analysis found that 36.46% (95% CI: 26.48–46.44, I² = 87.1%) patients living with HIV/AIDS experience peripheral sensory neuropathy. Factors associated with peripheral neuropathy included being older than 40 years (OR = 2.40; 95% CI: 01.24, 4.64), having viral load greater than 1,000 copies (OR = 2.46; 95% CI: 1.03, 5.88) and having a CD4 count below 200 cells (OR = 4.30; 95% CI: 1.24, 14.98).

Conclusion

This study found that peripheral sensory neuropathy is highly prevalent among HIV-infected individuals in Africa. Advanced age, elevated viral load, and low CD4 count were identified as independent predictors of HIV-related peripheral neuropathy. It is recommended that simple, established neurological screening methods be regularly used to identify early signs of HIV-SN or individuals at risk, across all patients.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12985-025-02789-5.

Introduction

As reported by the World Health Organization (WHO) and UNAIDS, approximately 39 million people worldwide were living with HIV in 2022 [1]. People with HIV who receive Anti-retro viral Therapy (ART) early can now expect to live nearly as long as the general population, particularly in regions with good access to healthcare [2]. Both HIV infection itself and the medications used to treat it can cause side effects [3]. HIV-1 can negatively affect both the peripheral nervous system (PNS) and the central nervous system (CNS) [4]. HIV-associated sensory neuropathy (HIV-SN) remains a significant problem in individuals living with HIV, despite progress in treatment. It can severely affect their quality of life, with consequences that go beyond the nerve pain. The absence of truly effective treatments for HIV-SN presents a major challenge for both patients and healthcare providers [5, 6]. In 2022, approximately 76% of adults and 73% of patients living with HIV worldwide were receiving ART [7]. Even though there's been significant progress in treating HIV, peripheral sensory neuropathies (PSNs) are still a common and persistent challenge [8].

HIV-related peripheral neuropathy is a multifaceted problem with a range of symptoms. Distal sensory polyneuropathy (DSP) is the most common form of peripheral neuropathy in individuals with HIV, often caused by the direct effects of the virus and the neurotoxic side effects of antiretroviral therapy. Distal sensory polyneuropathy typically manifests with symptoms such as distal numbness, tingling, and reduced or absent deep tendon reflexes. Although both HIV and ART can contribute to the development of HIV-associated DSP, the precise cause remains uncertain. It is believed that pro-inflammatory cytokines produced by the immune system, along with chronic activation of macrophages, play a significant role in the inflammation associated with this condition [4]. Peripheral neuropathy is a significant overlooked complication for individuals living with HIV, especially in resource-limited countries [9].

The global estimate for HIV-associated sensory neuropathy shows a significant variation across different populations, ranging from 1.73% to 69.4%. Estimates suggest a significant portion of ambulatory (mobile) HIV-positive individuals experience HIV-SN, ranging from 27% to nearly half (around 50%) [10]. The prevalence of HIV-SN does vary significantly depending on the settings, for example, in Australia (42%) [11], Indonesia (15.2%) [12], and the USA (8.6%) [13]. Evidences indicated high prevalence of HIV-associated sensory neuropathy among people living with HIV on ART in sub-Saharan Africa. This may be attributed to delayed HIV diagnosis, which leads to more advanced nerve damage before initiating ART, as well as nutritional deficiencies that exacerbate nerve health [14].

Low-income countries face a significant challenge in managing HIV-associated neurological complications due to increased vulnerability of comorbidities, limited access to health care and poor socio-economic status [15]. Although there is no cure for sensory neuropathy, various treatment options are available to help manage the chronic pain it causes. The development of HIV-associated sensory neuropathy in individuals living with HIV can be influenced by multiple factors. Despite the effectiveness of Highly Active Antiretroviral Therapy (HAART) in controlling HIV, HIV-SN can still have a profound negative effect on their quality of life. Painful HIV-associated sensory neuropathy remains a major contributor to both morbidity and mortality [16].

Despite high prevalence of sensory neuropathy among individuals living with HIV, there is no comprehensive information regarding variables that determine sensory neuropathy onset among the patients who attended health care facilities in Africa. In conditions where there is a high number of patients with SN, clinicians confront challenges in managing the problem, and increase the burden of health care expenditures. Because the majority of the world’s HIV1 patients live in Sub-Saharan Africa, a better understanding of neuropathy prevalence and risk factors is critical. In addition, comprehensive studies and a multidisciplinary approach may contribute to a reduction in the morbidity of the neural damage. Therefore, this study aimed to determine the prevalence of peripheral neuropathy and associated factors among people living with HIV in Africa.

Materials and methods

To ensure the transparency, accuracy, and thoroughness of this systematic review and meta-analysis, we adhered to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [17] (Supplementary file 1). The protocol was registered with International Prospective Register of Systematic Reviews (PROSPERO) (CRD420251002919).

Search strategy for articles

Systematic electronic searches were conducted across several databases, including African Journal Online, Google Scholar, PubMed, Scopus, and the Wiley Online Library. We have used the above databases to retrieve relevant articles on the topic. Articles found during searching were imported into EndNote software version X7, where duplicates were removed. The search was conducted from March 20 to April 24, 2024. The search protocol was created using Boolean operators, which combined the following keywords:"Peripheral sensory neuropathy"OR"sensory neuropathy"OR"Distal sensory polyneuropathy"OR"peripheral neuropathy"OR"HIV neuropathy"OR"HIV-associated neuropathy"AND"HIV/AIDS"with each African country (Supplementary file 2). The search results were organized using EndNote X7 software. To identify potentially relevant articles, two authors (WCT and HKN) independently reviewed the titles of the search results. Likewise, the full texts of the selected articles were thoroughly assessed to ensure they met the inclusion criteria.

Eligibility criteria

Inclusion criteria

Study population

People living with HIV/AIDS.

Type of study design

Observational cross-sectional and case–control studies.

Publication status

Only studies published in English were considered for inclusion.

Quality of the studies

The review included only articles of high or moderate quality after assessed by Joanna Briggs Institute (JBI) evaluation checklist.

Exclusion criteria

The final analysis excluded case reports, case series, and studies involving populations other than those affected by HIV/AIDS.

Outcome of interest

The dependent variable in the study is the occurrence of peripheral neuropathy, which was defined as having at least one neuropathy grade greater than 0, along with either abnormal vibratory sensation or altered deep tendon reflexes in both ankles [18].

Article selection and data extraction

Articles identified through the search process were imported into EndNote software version X7 (Thomson Reuters, New York, NY), and duplicates were eliminated. The titles of the remaining articles were reviewed by two independent authors (WCT and HKN), and studies that did not meet the criteria were excluded. Articles that fulfilled the inclusion criteria were then used for data analysis. Data from the included studies were extracted by three authors (YAF, YM and HKN) using standardized data extraction Microsoft Excel template. The extraction form included the following details: name of the corresponding author, publication year, study setting or country, study design, sample size, participant or response rate, sampling method, tools used, prevalence of peripheral sensory neuropathy, and associated factors.

Quality assessment

Two authors (WCT and HKN) assessed the quality of the included studies using the Johanna Briggs Institute's (JBI) quality evaluation checklists [19]. Each question was assigned a score (0 for"not reported or not acceptable"and 1 for"yes"). The scores were then summed across all items to yield an overall quality rating ranging from zero to nine. Based on the total score, studies were categorized as low, medium, or excellent quality, with scores of 0–4, 5–6, and 7–9, respectively.

Statistical analysis

Heterogeneity test

The extracted data were then imported to Microsoft Excel and analyzed using STATA version 11 for analysis. The Q statistic and I² test were employed to evaluate heterogeneity between studies. A P-value of less than 0.05 indicated significant heterogeneity. Heterogeneity was classified as low, moderate, or high based on the Higgs I² values, with thresholds set at less than 25%, between 25 and 75%, and greater than 75%, respectively [19, 20]. Due to the heterogeneity among the studies, a random-effects model was used to determine the pooled estimate of the prevalence across the studies. For the main meta-analysis of the pooled prevalence estimates, we applied the Der-Simonian and Laird (D + L) random effects model [21]. Subgroup analysis was performed to address potential sources of heterogeneity. Additionally, the impact of individual studies on the pooled estimates from the overall studies was assessed through a leave-one-out sensitivity analysis.

Publication bias

The symmetry of the funnel plot was visually inspected, and Egger's test was used to assess publication bias among the included studies. A p-value below 0.05 and an asymmetrical funnel plot were considered indicators of statistically significant publication bias [22].

Results

Study selection

The initial database search retrieved 1,821 articles, which were organized using EndNote citation management software. Of these, 1,760 were from Google Scholar, 2 from PubMed, 6 from Wiley Online Library, 2 from Scopus, and 51 from African Journal Online. After reviewing the titles in EndNote, 1,243 duplicates were removed. From the remaining 578 articles, 348 were removed as they did not focus on patients with HIV/AIDS. The full texts of the remaining 230 articles were further reviewed. Additional articles were excluded if they did not report the outcome variable or were conducted outside of Africa. After a thorough assessment based on predefined criteria and quality evaluation, 12 articles were included in the final analysis (Fig. 1).

Fig. 1.

PRISMA flow diagram for a systematic review and meta-analysis of prevalence and associated factors of peripheral neuropathy among patients with HIV/AIDS in Africa (N = 12)

Study characteristics

The current systematic review and meta-analysis included twelve published articles with a total of 7822 participants. The included articles used institutional based cross-sectional study. Concerning the settings where the included studies were conducted, two were from Ethiopia [23, 24], two from Rwanda [25, 26], two from Tanzania [27, 28], and two from South Africa [29, 30]; the remaining studies were from Ghana, Cameroon, Kenya and Malawi [31–34]. Six studies employed probability sampling, while six used nonprobability sampling methods (Table 1).

Table 1.

Baseline characteristics and outcomes of the included studies in Africa (n = 12)

Author	Pub Year	Country	Study Design	Gender(M/F)	SS	Prevalence (%)
Yitbarek et al. [23]	2022	Ethiopia	IBCS	258/297	555	32.25
Adem et al. [24]	2019	Ethiopia	IBCS	125/234	359	32.9
Luma et al. [34]	2012	Cameroon	IBCS	89/206	295	21
Puplampu et al. [31]	2019	Ghana	IBCS	88/437	525	17.7
Mukoma, J.N et al. [32]	2020	Kenya	IBCS	67/222	289	68.17
Tumusiime et al. [25]	2014	Rwanda	IBCS	138/498	636	59
Biraguma & Rhoda A [26]	2012	Rwanda	IBCS	54/131	185	40.5
Amiji et al. [27]	2021	Tanzania	IBCS	146/237	383	14.1
S. Mullin et al. [28]	2011	Tanzania	IBCS	101/234	335	43.2
Maritz et al. [29]	2009	South Africa	IBCS	167/472	639	60
Beadles et al. [33]	2009	Malawi	IBCS	428/	33,412,913	13
Peters et al. [30]	2013	South Africa	IBCS	88/95	183	24

^*IBCS Institutional-Based Cross-sectional Study, SS Sample Size

Peripheral sensory neuropathy

The current meta-analysis found that 36.46% of HIV/AIDS patients experience peripheral sensory neuropathy (95% CI: 26.48–46.44, I² = 87.1%). The study found significant heterogeneity among the selected articles. Consequently, a random-effects model, specifically the Der-Simonian and Laird (D + L) random-effects model, was used to determine the pooled prevalence of peripheral sensory neuropathy in patients with HIV/AIDS (Fig. 2).

Fig. 2.

Forest plot indicating pooled prevalence of peripheral sensory neuropathy

Publication bias

As shown in Fig. 3, a visual inspection of the funnel plot revealed no evidence of publication bias among the included studies, as indicated by the symmetric distribution of the plot. Similarly, the result of Egger's test was not statistically significant for publication bias (P = 0.727) (Fig. 3).

Fig. 3.

Funnel plot of prevalence of peripheral sensory neuropathy among HIV/AIDS patients

Quality assessment

The quality assessment, using the Joanna Briggs Institute (JBI) critical appraisal checklist, showed that all included studies have good quality, with scores ranging from 7 to 8. A detailed breakdown of the quality assessment for each study is provided in the supplementary file (Supplementary file 3).

Subgroup analysis

Subgroup analysis was conducted based on sampling technique to assess the cause of heterogeneity among the included studies. According to subgroup analysis results, the pooled prevalence of peripheral sensory neuropathy ranged from 24.78% (95% CI: 6.40–43.17) in studies that utilized simple random sampling to 42.01% (95% CI: 25.30–58.72) in studies that used consecutive sampling (Fig. 4).

Fig. 4.

Result of sub-group based on region (N = 12)

Sensitivity analysis

In sensitivity analyses using the leave-one-out method, removing any individual study did not significantly impact the overall burden estimates or measures of heterogeneity across the primary studies. Therefore, the sensitivity analysis with the random-effects model showed that no single study influenced the pooled prevalence (Fig. 5).

Fig. 5.

Result of sensitivity analysis (N = 12)

Associated factors

In the current study, the pooled estimate of two studies revealed that age more than 40 years was significantly associated with peripheral sensory neuropathy in patients with HIV/AIDS (OR = 2.40; 95% CI: 1.24, 4.64). The heterogeneity test (I² = 79.0%) identified significant heterogeneity between studies. The pooled effect of two studies revealed that a viral load of more than 1000 copies was substantially associated with peripheral sensory neuropathy in HIV/AIDS patients (OR = 2.46; 95% CI: 1.03, 5.88). The heterogeneity test (I² = 85%) indicated significant heterogeneity between studies. Furthermore, the pooled effect of two studies revealed that individuals with CD4 + T cells less than 200 were 4.30 times (OR = 4.30; 95% CI: 1.24, 14.98) more likely to develop peripheral sensory neuropathy than those with CD4 + T cells greater than 200. The heterogeneity test (I² = 88.7%) identified significant heterogeneity among studies (Fig. 6).

Fig. 6.

Forest plot showing factors associated with peripheral sensory neuropathy among HIV/AIDS patients in Africa (N = 12)

Discussion

The advent of antiretroviral therapy (ART) has transformed HIV into a manageable chronic illness. While ART has significantly improved the lives of people living with HIV, there are still devastating complications, including sensory neuropathy (SN). Before the introduction of ART or in the early years of the HIV epidemic, many patients went untreated or had limited access to effective medications. During this time, peripheral neuropathy was more common because the virus itself could damage nerves directly, and people lived with uncontrolled HIV for longer periods. But, after the introduction of ART with the widespread use of ART, HIV became more manageable, and immune function improved. This likely reduced the prevalence of neuropathy caused by the virus. However, some older ART drugs (like stavudine and didanosine) were themselves toxic to nerves and could cause peripheral neuropathy as a side effect.

Some studies diagnose PSN based solely on what patients say they are feeling—such as tingling, numbness, burning, or pain in their feet or hands. This approach is more subjective and can lead to higher reported prevalence because symptoms may be caused by other conditions (e.g. diabetes, vitamin deficiencies, or medication side effects). Other studies use tools like nerve conduction studies, monofilament testing, or quantitative sensory testing to detect nerve damage more precisely. These methods are more specific and may result in lower reported prevalence, as they confirm only cases with measurable nerve impairment.

HIV-associated neuropathy is a major contributor to morbidity in people living with HIV (PLHIV) [35]. In the review, the pooled prevalence of peripheral sensory neuropathy among HIV/AIDS patients was found to be 36.46% (95% CI: 26.48–46.44, I² = 87.1%). The amount of PSN in this study is comparable to that found in earlier studies carried out in China (32.1%) [13] and USA (38%) [36].

The results of this study, however, were lower than those of studies performed in Brazil (69.4%) [37], Australia (42%) [11], India (77.8%) [38] and central India (40%) [39]. Moreover, the findings of this study are higher than those of studies conducted in Thailand (28%) [40] and Korea (16%) [41]. The possible justification for this discrepancy might be due to differences in methodologies of primary study, socio-demographic difference, sample size discrepancy, disparities in the inclusion criteria used and other environmental factors.

In the current review, the pooled effect of two studies revealed that individuals older than 40 were more likely to acquire peripheral sensory neuropathy than those younger than 40. This finding is consistent with a previous study from the United States [42]. As one probable explanation research suggests that as age becomes increase, the nervous system becomes more vulnerable to damage from various toxins and insults, including those associated with HIV infection. This also might be due to decline in ability of nerves to repair themselves after damage with age. The pooled effect of two studies revealed that patients with a viral load greater than 1000 copies were more likely to develop peripheral sensory neuropathy than those patients with a viral load less than 1000 copies. Similar observations have been reported in earlier study in the USA [43]. This might be because high levels of viral coat proteins mediate nerve fiber damage and hyper-nociception through direct and indirect mechanisms. The proteins produced by the HIV virus itself can directly interact with and damage the axon, the long fiber that transmits signals away from the cell body [44].

The pooled result of two investigations revealed that patients with CD4 + T cells fewer than 200 were more likely to develop peripheral sensory neuropathy than those with CD4 + T cells higher than 200. These findings are consistent with studies conducted in the USA [13, 45]. Even with effective ART suppressing HIV replication and halting active immune system attacks on nerves, damage that has already occurred to nerve fibers (axons) may not be completely repaired. This residual damage can continue to cause symptoms like pain, numbness, and weakness. Additionally, the association between neuropathic pain and a low CD4 may suggest that a functional immune system may contribute to the stimulation of pain [46].

Limitations

The limitation of this review include there is no consistency in peripheral neuropathy definitions. Furthermore, significant heterogeneity was detected. Moreover, most studies included were cross-sectional, limiting the ability to assess causality or observe longitudinal trends. Finally, there were fewer studies in various nations, making it impossible to use the data as a baseline in some countries.

Conclusion and recommendations

This study found that peripheral sensory neuropathy is highly prevalent among HIV-infected individuals in Africa. Advanced age, elevated viral load, and low CD4 count were identified as independent predictors of HIV-related peripheral neuropathy. It is recommended that simple, established neurological screening methods be regularly used to identify early signs of HIV-SN or individuals at risk, across all patients. This study was conducted designed to provide information on the prevalence of peripheral sensory neuropathy and associated factors in HIV/AIDS patients in order to aid in the development of diagnostic and therapeutic techniques, with a particular emphasis on risk factor prevention. Screening for sensory neuropathy among people living with HIV (PLHIV) is essential due to the high prevalence of HIV-associated sensory neuropathy (HIV-SN), particularly in low- and middle-income countries where older antiretroviral therapies and opportunistic infections are more common. Despite this, routine screening remains inconsistent or entirely absent in many HIV care settings.

Simple and established neurological screening techniques for instance monofilament testing, vibration perception tests, pinprick and temperature sensation testing, as well as ankle reflex assessments, are other straightforward bedside neurological examinations.

These techniques are not only inexpensive but also quick to administer, making them feasible even in resource-limited settings. However, cost-related implications cannot be ignored. While the tools themselves are affordable, the challenge lies in scaling up screening within busy clinics, training healthcare workers, and ensuring ongoing supplies and standardized procedures. Another barrier is staffing inadequacies. Many HIV clinics, especially in low-resource settings, are understaffed or overstretched. Routine screening for complications like neuropathy may be deprioritized in favor of more urgent clinical needs. Furthermore, the lack of trained personnel in neurological assessments contributes to underdiagnoses.

Health practitioners should regularly implement and apply peripheral sensory neuropathy screening protocols to assess peripheral sensory neuropathy in all HIV/AIDS patients, with a special emphasis on those in the late stages of the disease and those with a high plasma viral load and low CD4 count. Researchers should be encouraged to conduct longitudinal studies as this provides more data over time on change and causality.

Abbreviations

ART

Antiretroviral therapy

CNS

Central nervous system

DSP

Distal Sensory Polyneuropathy

HIV-SN

HIV-associated sensory neuropathy

ORs

Odds ratio

IBCS

Institutional-Based Cross-Sectional Study

PN

Peripheral Neuropathy

Authors’ contributions

WCT, AMG, MG, BAM, DAB, ABG, DBA, MMT, MM, NDB, YM and YBB conceived the idea, participated in data extraction, analysis, manuscript preparation, and draft writing. WCT, and HKN participated in analysis, manuscript preparation, and revision. All authors read and approved the final version of the manuscript to be considered for publication.

Funding

The authors received no funding from any specific organization.

Data availability

All relevant data are within the manuscript and its supporting Information files.

Declarations

Ethics approval and consent to participate

Not applicable since the studies used were systematic reviews and meta-analyses.

Competing interests

The authors declare no competing interests.