Two studies presented at the 26th International AIDS Conference (AIDS 2026) last week show that wider access to diagnostic testing and consistent implementation of screening guidance could each improve the diagnosis of opportunistic infections in people with low CD4 counts.
World Health Organization (WHO) guidance recommends that all people with HIV should receive a CD4 cell test at diagnosis or when re-engaging with care after a treatment gap.
People with CD4 counts below 200, anyone with WHO stage 3 or 4 symptoms and children under the age of five years should be screened for tuberculosis using a Gene Xpert assay and urine TB-LAM testing. They should also undergo cryptococcal antigen screening, and anyone who tests positive for cryptococcal antigen should receive pre-emptive antifungal therapy.
WHO recommends that anyone with advanced HIV who does not have active TB should receive TB preventative treatment and cotrimoxazole prophylaxis.
The two studies examined the implementation of diagnostic testing algorithms in Malawi and in eight countries in Latin America and the Caribbean.
Malawi
Malawi’s Ministry of Health estimated that in 2023, around 60,000 people were living with advanced HIV in the country. To improve detection and care of advanced HIV, Malawi has scaled up screening for advanced HIV at facilities providing HIV treatment.
Dr John Fly Phiri of Malawi’s Ministry of Health analysed programme data from the period between July 2024 and September 2025 to assess how many people met advanced HIV criteria, how many underwent CD4 count screening and what proportion were symptomatic. They also evaluated coverage of the recommended diagnostics.
During the evaluation period, 76,415 people were newly diagnosed with HIV or returned to care. Of these, 82% were screened for advanced HIV and 95% of those screened underwent clinical assessment. Through clinical screening, clinics identified 12,517 people (21% of those screened) who had WHO stage 3 or 4 symptoms.
Although the level of screening was high, only half of those who underwent screening (52%) received a CD4 test. Of these, 29% (9846) had a CD4 count below 200. Overall, using criteria of age, clinical symptoms or CD4 count, 29% (18,405) of those screened were diagnosed with advanced HIV.
Few of those identified with advanced HIV received all the recommended diagnostic tests. Nearly a quarter failed to be tested for cryptococcal antigen; similarly just over 25% failed to receive a LAM test for TB. Gene Xpert and chest X-ray were rarely used for TB diagnosis (11% and 12%, respectively) due to lack of availability.
To address the diagnostic gap, Malawi’s Ministry of Health is implementing the use of the Visitect Rapid CD4 test, a lateral flow test that uses a small blood sample to show whether a person has a CD4 count above or below 200. The test provides a result in around 45 minutes and does not require a laboratory or electricity supply.
Latin America and the Caribbean
Ministries of Health in Latin America and the Caribbean collaborated on a similar evaluation of diagnostic testing coverage in people with advanced HIV. Dr Antonio Camiro-Zuñiga of Mexico’s National Cancer Institute presented the results of a pooled analysis of eight national implementation studies that evaluated opportunistic infection screening, the prevalence of opportunistic infections and mortality.
Each country implemented a standard package of serum cryptococcal antigen, urinary TB-LAM and urinary Histoplasma antigen screening using rapid point-of-care tests. Among people with HIV, the fungal infection histoplasmosis is most commonly diagnosed in the Americas.
People with HIV were eligible for screening if they had started antiretroviral therapy in the previous 90 days or had resumed antiretroviral therapy after a gap of at least 90 days, and had a CD4 count below 200 or symptoms suggesting an opportunistic infection.
A total of 2143 people were eligible for opportunistic infection screening and just over half (53%) were previously untreated. Approximately one in three (34%) had CD4 counts below 50. Not all people screened received all three diagnostic tests. Twenty-eight per cent of those tested were positive on at least one test and 18% were positive on at least two tests. Without routine screening, most of these infections would have been missed or remained untreated until they resulted in hospital admission.
Out of 1875 people who underwent TB-LAM screening, 21% tested positive. TB-LAM tripled case finding in this study, Dr Camiro-Zuñiga told the conference. Almost 70% of TB cases were diagnosed using TB-LAM alone, while 54 of 258 cases identified by TB-LAM were confirmed by TB culture and/or Gene XPERT. Fifty-six cases were diagnosed by TB culture and/or Gene XPERT in the absence of a positive TB-LAM result.
A total of 1917 people underwent cryptococcal antigen testing and 8% tested positive. A similar proportion of those tested for histoplasmosis antigen proved to be positive (7.8%). Just under half of those those who tested positive for histoplasmosis antigen also tested positive on the TB-LAM test (49%).
The study also looked at mortality rates 30 days after testing. Sixteen per cent of those who tested positive on at least one test died within 30 days of testing, compared to 7% of those who tested negative on all tests. People who tested positive for histoplasmosis were significantly more likely to die than people who tested positive for TB (p=0.030).
Fly Phiri J et al. Assessing implementation and expansion of advanced HIV disease in Malawi. 26th International AIDS Conference, Rio de Janeiro, abstract OAB2002, 2026.
View the abstract on the conference website.
Camiro-Zuñiga A et al. High prevalence of opportunistic infections detected across all CD4 count strata through the implementation of a point-of-care testing package for opportunistic infections in Latin America and the Caribbean. 26th International AIDS Conference, Rio de Janeiro, abstract OAB4103, 2026.