Reference guideline documents

Data from following WHO documents was extracted:

2017: “Guidelines for managing advanced HIV disease and rapid initiation of antiretroviral therapy” published in 2017 (hereinafter called WHO 2017). This guideline provides specific recommendations about management of people presenting with AHD and timing of initiation of ART for all PWH [3].

2021: “Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: recommendations for a public health approach” published in 2021 (hereinafter called WHO 2021). This document includes existing and new clinical and programmatic recommendations and brings together all relevant WHO guidance on HIV produced since 2016. Information about HIV prevention, testing, treatment, service delivery and monitoring is provided across different ages, populations and settings [17].

WHO 2021 was selected as a reference to define the gold standard for guideline comparison. This document was chosen because it is a consolidated guideline including all relevant WHO guidance on HIV produced since 2016 and therefore also incorporated and superseded WHO 2017. “Providing care to people with advanced HIV disease who are seriously ill” [18] was published in 2023 as a policy brief and was not included in this manuscript.

WHO 2021 provides recommendations for all defined items (Tables 1 and 2). Agreement with the national guidelines is shown in Table 3.

National guideline documents

Data was extracted from six national guidelines (Table 4). All countries established country specific guidelines, which were published between 2016 and 2023. Only the guidelines of Nigeria and Uganda include a specific section for AHD. The extracted data from national guidelines is presented in Table 1.

Table 4 Index of national guidlinesDefinition AHD

WHO 2021 defines advanced HIV as CD4 + count < 200 cells/mm3 or WHO clinical stage 3 or 4. Nigeria, Sierra Leone, and Uganda use the same definitions. Botswana uses a CD4 + cut-off of less than 100 cells/mL and Malawi includes additional criteria for the diagnosis, including virological failure, hospitalization status and clinical danger signs. South African guidelines do not provide a definition of AHD.

Screening for opportunistic infections

agreement was found for at least four of the six items for all countries. All national guidelines recommend testing for CD4 + at baseline, if available. However, guidelines differ in their recommendations for screening for cryptococcal antigen and tuberculosis (Tables 1 and 3). Both screening procedures are recommended in every document, but the targeted population groups vary slightly.

Cryptococcal screening

According to WHO 2021, screening for cryptococcal disease is recommended in PWH and a CD4 +  < 100 cells/mm3 and should be considered in PWH with CD4 < 200 cells/mm3. Recommendations of Botswana and South Africa are in line with WHO 2021. Malawi, Nigeria, Sierra Leone, and Uganda screen a wider population group than recommended. Malawi includes all patients with AHD, Nigeria uses a threshold of CD4 + 200 cells/mm3, and Sierra Leone also screens PWH on ART with suspected or confirmed treatment failure. Uganda assesses clinical information, either positive symptom screening or danger signs, or a CD4 + count < 100 cells/mm3.

Tuberculosis screening

WHO 2021 recommends screening for tuberculosis with urine lipoarabinomannan (LAM) for inpatients (CD4 +  < 200 cells/mm3) or outpatients (CD4 +  < 100 cells/mm3), any CD4 count with symptoms, or if seriously ill. Routine tuberculosis symptom screening is recommended in all countries. The use of urine LAM is not addressed in the guideline documents from Botswana. None of the remaining countries uses an approach stratified by CD4 + cell count for in- and outpatient LAM screening. In contrast to WHO 2021, Nigeria and Sierra Leone do not include clinical criteria as an indication for urine LAM testing, both using a CD4 + threshold of 100 cells/mm3 only. Malawi includes all patients with AHD, and South Africa recommends urine LAM screening for patients with CD4 count < 200 cells/mm3 within the last 6 months, AHD or current serious illness.

Prophylaxis of opportunistic infections

Malawi, Nigeria, Sierra Leone (all agreement), South Africa (4 agreement, 2 no agreement), and Uganda (4 agreement, 1 partial agreement, 1 no agreement) addressed all six items. Botswana addressed only 4 items, of which two were described as no agreement.

Cotrimoxazole prophylaxis

In WHO 2021, cotrimoxazole prophylaxis is recommended for PWH with a CD4 + count < 350 cells/mm3, clinical stage 3 or 4, or to any PWH in settings with high prevalence of malaria or severe bacterial infection. All national documents recommend use of cotrimoxazole, but the targeted population group varies. Sierra Leone, Nigeria, and Malawi include all HIV infected adults for cotrimoxazole prophylaxis, which is in line with WHO 2021 because malaria or severe bacterial infection are highly prevalent in those countries. Botswana and South Africa use a lower CD4 + cut off (CD4 +  < 200 cells/mm3). Uganda recommends cotrimoxazole for all people newly initiating ART and for people with ART treatment failure (Table 1).

Malawi and Sierra Leone recommend lifelong prophylaxis with cotrimoxazole. In Nigeria, prophylaxis can be discontinued once clinically stable on ART. Both approaches are in line with WHO 2021. In national recommendations from Uganda five criteria need to be met to discontinue prophylaxis: age, pregnancy status, duration of ART, viral load, and current clinical status (Table 1). In contrast, Botswana and South Africa recommend discontinuing prophylaxis once CD4 + cell count reaches 200 cells/mm3.

Tuberculosis preventive therapy

All national guidelines, except Botswana (not addressed), recommend preventive therapy for tuberculosis for all adults living with HIV.

Supportive care interventions

Intensified treatment adherence support for people with AHD is recommended in all documents. Interventions include adherence counseling in Botswana or home visits—if feasible – in Nigeria.

Antiretroviral therapy (ART)

All national documents addressed items in this domain. All national guidelines include dolutegravir (DTG), emtricitabine (FTC) or lamivudine (3TC), and tenofovir disoproxil fumarate (TDF) as the recommended first line regimen. Guidelines vary in recommendations to defer ART start in patients requiring treatment for tuberculosis.

Start ART in PWH and tuberculosis

In contrast to WHO 2021, which makes recommendations without taking CD4 + levels into account (tuberculosis at non-neurological site, start ART within 2 weeks; tuberculosis meningitis, start at 4–8 weeks), Malawi, Nigeria, and Uganda require a CD4 + count to define when to start ART. South Africa further differentiates according to drug-sensitive or drug-resistant tuberculosis.

Start ART in PWH and cryptococcal meningitis

All national documents agree with WHO 2021 for timing of ART in cryptococcal meningitis, recommending a delayed start of ART for 4–6 weeks after diagnosis.

Overall agreement

Botswana obtained 9 points (9 Agreement, 5 No agreement, 4 Not addressed), Malawi 15.5 points (14 Agreement, 3 Partial agreement, 1 No agreement), Nigeria and Sierra Leone 14.5 points (14 Agreement, 1 Partial agreement, 3 No agreement), South Africa 13.5 points (13 Agreement, 1 Partial agreement, 3 No agreement, 1 Not addressed) and Uganda 13 points (12 Agreement, 2 Partial agreement, 4 No agreement) (Table 2, Fig. 1). Alignment with WHO 2021 recommendations varies over time, but shows an increasing trend (Fig. 2).

Fig. 1

Categories of agreement for national guidelines

Fig. 2

Overall agreement according to year of publication