Experiences, challenges, gaps, and strategies for counselling persons presenting with advanced HIV-associated meningitis in Uganda

Abstract

Background

Advanced HIV disease (AHD) is still a significant problem in Uganda despite the test-and-treat strategy and the increased access to antiretroviral therapy (ART). Meningitis remains a major cause of morbidity and mortality in people with AHD. HIV counselling is essential and plays an important role in managing persons with AHD-related meningitis. We sought to describe the experiences and challenges we faced during counselling of these individuals, highlighting the strategies, gaps and how we can fill them.

Methods

First, we describe our experience and major challenges in counselling people with AHD-related meningitis. Second, we describe the strategies we used to overcome each of these challenges. Third, we highlight the health system gaps and recommend solutions.

Results

Major challenges include the presence of altered mental status, unknown HIV status at admission, non-disclosure of HIV status to family, insufficient ART history, caretakers-related challenges, pill burden, multiple drug side effects, invasive clinical procedures, myths about medical procedures, poverty, lack of privacy during counselling in the wards, patients/caretakers seeking alternative non-medical interventions including religious, traditional, and herbal therapies before and after initiating meningitis treatment.

Conclusions

Persons with AHD-related meningitis need daily and special consideration during counselling as part of the package of care to improve treatment outcomes.

Trial registrations

NCT01075152 (23 Feb 2010), NCT01802385 (28 Feb 2013), ISRCTN42218549 (24 April 2018), ISRCTN72509687 (13 July 2017), NCT04031833 (01 January 2019), ISRCTN15668391 (23 May 2019), ISRCTN18437550 (05/11/2021).

Background

Human immunodeficiency virus (HIV) remains a leading cause of morbidity and mortality globally [1]. About 39 million people were estimated to be living with HIV globally with 630,000 HIV-related deaths in 2022. The World Health Organization (WHO) African region remains the most affected, with 3.2% of adults living with HIV, which translates into more than two-thirds of the people living with HIV (PLHIV) globally [2]. In 2022, the prevalence of HIV among adults 15–49 years in Uganda was 5.1%. 1.4 million people were living with HIV in Uganda, with 52,000 new cases and 17,000 AIDS-related deaths [3].

The WHO defines advanced HIV disease (AHD) as having a CD4 cell count less than 200 cells/mm³ or WHO clinical stage 3 or 4 in adults and adolescents. All children younger than five years of age are also considered to have AHD due to their high risk of disease progression and mortality [4]. In Uganda, it is estimated that approximately 22% of the individuals initiated on antiretroviral therapy (ART) have a CD4 cell count less than 200 cells/mm³ and approximately 11% of PLHIV in care experience treatment failure on their ART regimens. Approximately 20% of unsuppressed PLHIV are returning to care with AHD [5]. In Uganda, only 66% of people living with HIV achieve the desired level of adherence to ART [6].

People with AHD are at high risk of death, even after starting ART. The most common causes of severe illness and death are tuberculosis, severe bacterial infections, and cryptococcal meningitis [4]. There are four major types of meningitis commonly encountered in Uganda among AHD patients, e.g., cryptococcal meningitis, tuberculous meningitis, bacterial meningitis, and viral meningitis [7, 8]. Overall, approximately 60% of adults presenting to hospitals in Uganda who receive a diagnostic lumbar puncture have cryptococcal infection, and 15% have definite/probable tuberculous meningitis [8,9,10]. Presenting with altered mental status is common.

Counselling is very essential and plays an important role in the management of these individuals and mostly aims to contribute to behavioral change. This is mostly due to the existence of depression, stigma, and myths surrounding HIV, opportunistic infections, and ART. Counselling is a continuous process from the time of HIV screening, during hospitalization, prior to ART initiation, and throughout the life of the person during care. Counselling has also been found useful in managing HIV-related opportunistic infections and participation in HIV clinical trials. It helps to improve the uptake of testing, treatment, retention in care, and enrollment in clinical trials [11]. Counselling may also be extended to caretakers and/or partners of PLHIV to improve social support and prevent transmission among discordant couples. We have previously used intensive counselling to dismiss myths surrounding lumbar punctures and improved acceptance among patients with AHD-related meningitis in Uganda [11].

Between 2010 and 2024, we recruited participants for our study who were hospitalised with HIV-related meningitis and were enrolled in one of nine pre-selected clinical studies. As part of the package of care for AHD-related meningitis, these patients and their attendants were provided counselling. Here we describe the experiences and challenges we faced during counselling of these patients, highlighting the gaps and how we can fill them.

Methods

Study design and inclusion criteria

This was a retrospective qualitative study reviewing our positive and negative practical experiences and challenges while counselling in-patients with AHD-related meningitis in Kampala, Uganda. HIV counselling is an active process of communication and dialogue between a trained medical counsellor and a client who presents with problems related to HIV to assist the client to deal with these problems adequately and appropriately. Phenomenology design was used to conduct in-depth interviews using unstructured open-ended questions. We included one HIV counsellor and six nurses on our team (as key informants) who were routinely involved in counselling in-patients with AHD-related meningitis during nine clinical studies [10, 12,13,14,15,16,17,18]. We excluded medical officers and laboratory personnel. The seven key informants selected were interviewed to identify common challenges encountered in counselling this group of patients and any recommendations or strategies based on their lived experiences. They were also asked about any gaps or missing links to optimize counselling this group of patients highlighting any proposed solutions. HIV counselling in this context consisted of drug adherence, pre-and post-test counselling, study-related procedures, emotional and psychosocial support. For some patients without caretakers, we hired social workers to provide basic daily hygiene care and help them with taking their food and drugs as prescribed. Protocol trainings were conducted at the beginning of each clinical study to standardize the counselling sessions across the counselors and nurses.

All these nine clinical studies enrolled persons living with AHD presenting with signs and symptoms of meningitis. Potential participants were counselled about HIV, ART, meningitis and lumbar punctures. Participants were then offered informed consent for study participation. Lumbar punctures were performed at days 0, 3, 7, 14, and as clinically indicated to control intracranial pressures [19]. Meningitis was diagnosed using cryptococcal antigen lateral flow assay (Immy Inc., Norman, Oklahoma) in blood and CSF [20, 21], Xpert MTB/Rif Ultra (Cepheid) [22], Biofire meningitis/encephalitis FilmArray [7, 23], and culture. Participants with AHD-related meningitis were enrolled and followed up for up to one year [24].

Study setting

The clinical studies were conducted at different time points at the infectious diseases ward of Mulago National Referral Hospital and Kiruddu Hospital in Kampala, Uganda between October 2010 to September 2024.

Study cohorts

COAT

The Cryptococcal Optimal ART Timing (COAT) research study was a randomized multi-center clinical trial conducted in Uganda at Mulago National Hospital, Mbarara regional referral hospital and Cape Town in South Africa between 2010 and 2012 [12]. This trial was a treatment strategy trial focusing on determining the optimal time to initiate ART in persons with HIV-associated cryptococcal meningitis [25].

NOAT

The Neurology Outcomes on Antiretroviral Therapy” (NOAT) study was a prospective observational cohort of HIV-infected persons with clinical meningitis in Uganda. This study showed that the exploration of new TB diagnostics along with diagnostic algorithms for the evaluation of meningitis in resource-limited settings remains critical [10].

ASTRO-CM

The Adjunctive Sertraline for the Treatment of Cryptococcal Meningitis (ASTRO-CM) was a phase III randomized trial to evaluate whether sertraline when added to standard amphotericin-based therapy for cryptococcal meningitis, would lead to improved survival [13].

RIFT

The High dose oral and intravenous rifampicin for improved survival of adult Tuberculous meningitis (RIFT) was a phase II open-label randomized controlled trial evaluating the safety and tolerability of high-dose intravenous and oral rifampicin for TB meningitis [14].

AMBITION-CM

The AMBIsome Therapy Induction OptimisatioN (AMBITION-cm) trial was a Phase III multinational randomized controlled non-inferiority trial that aimed to determine whether a single 10 mg/kg dose of liposomal amphotericin was as effective as the standard treatment in terms of preventing deaths from HIV-related cryptococcal meningitis [15].

ENACT

The Encochleated Oral Amphotericin for Cryptococcal Meningitis (ENACT) was a phase I and II trials evaluating the safety and tolerability of a novel oral formulation of Amphotericin B [16, 26].

COAST

This is an ongoing observational cohort study enrolling participants with meningitis.

HARVEST

The high-dose oral rifampicin to improve survival from adult tuberculous meningitis (HARVEST) study is an ongoing double-blinded randomized placebo-controlled Phase III trial testing 35 mg/kg of rifampicin [17].

IMPROVE

This is an ongoing open label, two arm, randomized controlled strategy trial to evaluate the safety and feasibility of two TB preventive therapy strategies for adults with HIV-associated cryptococcal meningitis [18].

Data analysis

This was a qualitative study and the responses from the key informants interviewed were summarised to highlight the challenges, strategies, ongoing gaps and solutions.

Ethical consideration

In all these cohorts, all research participants or their surrogates provided written informed consent. Ethical approval was obtained from the Uganda National Council of Science and Technology (UNCST), Mulago Hospital Research and Ethics Committee, and the University of Minnesota.

Results

Challenges faced and strategies used to effectively counsel the patients with AHD-meningitis

Altered mental status

The first challenge we encountered with counselling this group of study participants was their altered mental status and therefore the impaired ability to make individual decisions. About 10–35% of the participants in these cohorts had altered mental status with aggressive behavior resulting in impaired understanding. In addition, some patients were unconscious and so could not be counselled. In this case, we resorted to counselling the caretakers until the patient regained their consciousness before we repeated the whole process of counselling with the participant.

Lack of prior HIV testing history

Some patients were admitted with AIDS-related meningitis with no prior history of HIV testing. Following the routine testing offered in the hospital, they had a diagnosis of AHD and other opportunistic infections. It was difficult to counsel such patients and disclose to them not only their HIV status but the complications of other opportunistic infections. This is because it was psychologically stressful to disclose all this bad news at once. The counselling of such patients tended to be prolonged in a phased manner, starting with disclosure of their HIV diagnosis immediately and later the other opportunistic infections that were being managed. This was also extended after discharge during the outpatient visits.

Lack of disclosure of HIV status

We also encountered a challenge with some patients who had never disclosed their HIV status to their spouses and other family members, yet these family members were the ones taking care of them during hospitalization. It would be complicated or tricky to administer ART and HIV counselling to such patients without disclosure of HIV status to caretakers who were ever present at the bedside. Some patient caretakers read patient files or even consulted other medical personnel about the file content. In such scenarios, we encouraged the patient on how to disclose to the caretakers as early as possible. Sometimes the patient would request the counsellor to be present and help in the disclosure process to make it easier. We have had experiences where a partner with HIV was deceased, and the surviving spouse discovered the deceased partner’s HIV status after their death. Dealing with the complexity of the HIV status of the surviving partner remains a challenge in the context of non-disclosure and maintaining study participant confidentiality.

Insufficient ART history

Related to the above, many of the caretakers had insufficient ART history or totally lacked knowledge about the ART history of the participants; especially those who had altered mental status. So, we encouraged the caretakers to search the home of the patient and look for any ART pills or ART refill cards or any other documents that could help us obtain information about the patient’s ART clinic and regimen. These documents could help us trace back to their ART clinics for more information. In one small study, 4 of 22 (18%) meningitis participants, who reported not receiving ART, had detectable antiretrovirals in their blood with 3 of the 4 having reporting via surrogates [27]. Obtaining correct ART information via surrogates remains challenging.

Lack of caretakers

Some patients show up in the hospital with AHD and meningitis but without having any caretakers to support them during hospitalization. Most of them stay alone and are brought in by well-wishers or neighbors who volunteer to bring them to the hospital due to their critical condition, oftentimes leaving them in the hospital with no social support. However, some of these patients were homeless and had been neglected by their families due to HIV status/stigma. Their drug adherence is usually sub-optimal. For such patients, we hired social workers to provide basic daily hygiene care and help them with taking their food and drugs as prescribed. Those who were stigmatized could be escorted by a counselor at discharge to help talk to their family about HIV stigma.

Temporary caretakers

Some patients had different caretakers without any specific caretaker being available regularly throughout the participant’s hospitalization. Some caretakers would consent to study procedures while others declined. Thus, every time new caretakers came, we had to repeat the whole counselling process regarding lumbar punctures, ART, concomitant medication, drug adherence, nutrition, infection prevention and control practices and all study-related procedures.

Difficult caretakers

We also encountered cases of difficult caretakers who could not follow the instructions given to them. Such instructions would include sending them to the pharmacy, sending them to imaging, or bathing the patient. We usually requested other patients’ caretakers who were more active to help them with some of these activities.

Unconscious participants

We were conducting the nine clinical studies for HIV-associated meningitis with several patients being admitted while unconscious and surrogate informed consent given by caretakers for study participation. However, some patients would gain consciousness a few days later after hospitalization and were hesitant to continue with some of the study procedures. Although international guidelines do not require re-consenting those consented via surrogate consent upon regaining the capacity to consent, we routinely repeated the informed consent process once participants’ mental status had normalized with the capacity to provide consent.

Pill burden

Since these patients were being managed for AHD, HIV-related opportunistic infections, and sometimes hospital-acquired infections, the problem of pill burden was encountered. Therefore, depending on the patient’s concomitant medications, counselling was crucial in ensuring that participants complied with the plan to spread out the drugs to be taken at different times of the day.

Multiple drug side effects

Related to the above, each drug had its side effects which when combined led to poor adherence. In such cases, we first notified the patients and their caretakers about the possible side effects of the drugs that had been prescribed. We advised them on the medical interventions to reduce some of the side effects. For example, for the rigors and phlebitis caused by intravenous amphotericin B deoxycholate, we asked them to take paracetamol (acetaminophen) at least 30 min before the amphotericin infusion and taught the caretakers how to use a warm compress to reduce the phlebitis inflammation respectively [28].

Lack of space for counselling

The general lack of space to have a conducive environment for patient counselling was problematic, leading to lack of confidentiality and privacy during the daily counselling sessions done at the bedside. We were often interrupted by the neighboring caretakers and medical staff or students who had to give medications. The hospital wards were designed with only 1–2 small side rooms that are meant for staff as changing rooms and to keep their personal belongings. Privacy remains a substantial challenge that needs to be addressed.

Invasive procedures

Additionally, the regular invasive procedures including lumbar punctures, venipunctures, and insertion of intravenous cannulas that participants had to undergo caused emotional stress, which made it difficult to speak to the patient. In such cases, we deferred counselling to the following day when the patient felt better and more relaxed, hence delaying counselling sessions for the next study-specific procedures.

Myths and misconceptions about study procedures

Counselling became more challenging in this patient population in light of the myths and misconceptions about study procedures such as lumbar punctures. Significant amounts of time were spent counselling participants and their attendants to dispel these myths. In some cases, we used peer or expert patients and/or caretakers enrolled in the study to explain to them the benefits of the study procedures and what their experience had been after accepting these procedures.

Use of witchcraft

Most participants believed that meningitis is associated with witchcraft due to its clinical presentation/manifestation. Patients/caretakers resorted to spiritual interventions such as traditional healers, shrines, and churches as they neglected the hospital treatment given to them. We counselled and educated the patients/caretakers about the causes of meningitis and the clinical manifestations of meningitis through other participants and peers who had been treated and discharged following meningitis treatment. Following hospital discharge, we escorted consenting participants to their homes to educate their family members about the clinical care that had been required in order to encourage additional social support for participants to return for outpatient visits and ensure proper follow-up.

Use of herbal medicine

Some participants incorporated herbal medicine with study drugs and other concomitant drugs without any consultation, yet they were precautioned against such practices. Among those who developed drug-induced liver injury, herbal medications were a common culprit. We counselled study participants about the potential risks involved in using herbal medicine alongside their other prescribed drugs.

Poverty

Most of our patients were economically disadvantaged and could not afford to buy food during the length of hospitalization. Thus, counselling on proper nutrition required for their recovery was challenging to implement. Some patients left the hospital against medical advice due to a lack of resources. We supported these participants with food during hospitalization and occasionally extended this support to outpatient visits depending on the patient’s needs. Ideally, research studies should make provision for nutritional support to study participants; however, this may be viewed as an enticement to participate in these studies, particularly when it involves critically ill individuals. Table 1 summarizes the common challenges encountered and the recommendations to address them (Table 1).

Table 1 Summary of challenges and recommendations

Discussion

Gaps in counselling patients with AHD-related meningitis and how we can fill them

There remain gaps in counselling and ongoing challenges.

First, crowding on hospital wards leads to a lack of privacy. Rooms should be created for counsellors to enable uninterrupted counselling sessions to support patient care. While research files are carefully controlled to assure confidentiality, routine medical care has no such protections. Often times in routine care, patients’ hospital medical files are left on the beds with unrestricted access. More needs to be done to maintain patient confidentiality and avoid unauthorized access to patient files by attendants or visitors.

Second, in the era of ART test-and-treat, patients are still presenting to medical wards with AHD lacking any history of HIV testing. There remains a need to increase the public sensitization about HIV testing. Activities that occurred 20 years ago are not relevant to the person presenting today. The recent development of HIV self-testing could potentially address this gap as long as there is clear information regarding post-test linkage to care. This sensitization can also be extended to demystify the myths and misconceptions around lumbar punctures, herbal medication, and their benefits or lack thereof.

Third, about 9% of people with HIV currently in care have never disclosed their HIV status to anyone [29]. National HIV programs should encourage patients to bring along treatment buddies preferably from close family who could easily help the healthcare providers during hospitalization with the patient’s ART history or better still, develop an electronic system that would allow patient-level linkage of different healthcare facilities that provide HIV care with access to patient medical records through the patient’s biometrics. This would also help patients who travel and can’t return to their primary ART clinic to receive their ART refills from any ART clinic in the country without necessarily first going back to their primary care provider.

Fourth, many patients were willing to undergo treatment and even participate in clinical studies but lacked social and financial support. More needs to be done within the hospital setting to provide this much-needed psychosocial support to patients who are homeless but are willing to have treatment for their underlying disease(s). In research settings, an ethical dilemma can exist between balancing financial compensation and assistance to participants yet not to the degree that there is coercion. Institutional review boards play a vital role in defining what is appropriate. Table 2 summarizes the outstanding health system gaps and their potential solutions (Table 2).

Table 2 Summary of gaps and potential solutions

Limitations of the study

The experiences, gaps, and recommendations described here originated from experiences at two referral hospitals in Kampala, Uganda involving nine clinical studies on neuro-infections over 15 years. These findings may not be applicable to all settings, but likely are applicable to other conditions where altered mental status is common or to other in-hospital research studies involving AHD conditions.

Conclusions

Advanced HIV Disease remains a significant problem in Uganda despite the test-and-treat strategy and the increased access to ART. Counselling is very essential and plays an important role in the management of these patients. Patients with AHD-related meningitis need daily and special consideration during counselling as part of the package of care. The challenges involved in counselling them are numerous but can be averted by the strategies we proposed here based on our experience. Gaps also still exist in the health system to optimize the counselling in this population. The Ugandan ministry of health should adopt the proposed strategies and solutions highlighted in this manuscript.