Zambia: HIV deaths on treatment underestimated

People with HIV in Zambia were at least ten times more likely to die in the first two years after starting antiretroviral treatment than European patients, according to findings of a study which traced people lost from HIV care in Zambia.

The findings are published in the journal PLOS Medicine.

The researchers say that the national treatment programme had underestimated death rates by anywhere from threefold to ninefold and that more investigation is needed of differences between facilities in referral of sicker patients for more advanced care.

Glossary

loss to follow up

In a research study, participants who drop out before the end of the study. In routine clinical care, patients who do not attend medical appointments and who cannot be contacted.

sample

Studies aim to give information that will be applicable to a large group of people (e.g. adults with diagnosed HIV in the UK). Because it is impractical to conduct a study with such a large group, only a sub-group (a sample) takes part in a study. This isn’t a problem as long as the characteristics of the sample are similar to those of the wider group (e.g. in terms of age, gender, CD4 count and years since diagnosis).

symptomatic

Having symptoms.

 

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

isoniazid

An antibiotic that works by stopping the growth of bacteria. It is used with other medications to treat active tuberculosis (TB) infections, and on its own to prevent active TB in people who may be infected with the bacteria without showing any symptoms (latent TB). 

Although the aim of antiretroviral treatment is to keep people alive, follow-up of people who drop out of treatment is often limited due to lack of resources and a lack of death registry information. This means that it is difficult to identify where treatment might be having less effect on mortality.

The study looked at 64 clinics in four provinces of Zambia. Patients in care for at least 24 months were eligible for inclusion in the study, including people who started antiretroviral therapy (ART) during that period (August 2013-July 2015). From this cohort, a random sample of patients lost to follow-up proportionate to the total number of people receiving care at each facility was selected for tracing. A loss to follow-up was defined as being more than 90 days late for an appointment.

Tracing was carried out by peer health workers in the community and by mobile phone. Health workers made three attempts to trace missing patients. If the patient had died health workers sought to establish the date of death, location and cause of death from family or close contacts.

The death rate exposed by tracing was compared to the death rate recorded at facilities, and also to the death rate recorded in a population study among people with HIV in Denmark, to provide a comparator from a health system with universal death registration.

The study population comprised 165,464 ART users, of which 64% were women, 56% received care at urban facilities and 32% had symptomatic HIV disease (WHO stage 3 or 4) at the time of antiretroviral treatment initiation. The median CD4 count at treatment initiation was 201 cells/mm3. Among those who had started treatment in the previous two years the median CD4 cell count at treatment initiation was 265 cells/mm3.

Seventeen per cent (28,111) of the study population were lost to follow-up. The random sample from the lost-to-follow-up group comprised 2892 people.

Peer health workers traced three-quarters (75%) of the lost-to-follow-up sample. Of those traced, 19% (412) had died. Among those who had started antiretroviral treatment in the previous two years, 76% were traced and of these, 24% had died.

As a result of tracing, the investigators calculated that the two-year incidence of death among people on antiretroviral treatment was 7%, and 8.3% among people who had started treatment within two years. In contrast, medical records showed that only 1.9-2.1% had died.

The vast majority of deaths (95%) were attributed to illness, suggesting that they were HIV-related.

The study found big variations between facilities in the death rate among new initiators (3.5-7.5 deaths per 100 person-years of follow-up). Furthermore, 57% of the deaths occurred in clinics and hospitals treating 15% of the entire population with HIV.

Among new initiators, men, people with CD4 counts below 200 cells/mm3 and people with more advanced HIV disease were more likely to die after becoming lost to follow-up, but none of these factors predicted death in the sample as a whole.

The investigators warn that shifting patients who appear to be stable on treatment to less frequent clinic appointments, or to medication dispensing in the community, may be over-optimistic.

“Death rates remain unacceptably high even after 1 or more years of therapy, a time period when many might assume patients to be stable,” they write.

“Persistent deaths after 2 years on treatment imply that a subset of patients is poorly adherent or retained […] effective support for adherence that is attuned to mitigating threats to adherence over time remains a crucial issue.”

The authors also warn that ART cannot eliminate the risk of developing tuberculosis, so "rolling out isoniazid preventive therapy is a priority."

References

Holmes C et al. Estimated mortality on HIV treatment among active patients and patients lost to follow-up in 4 provinces of Zambia: Findings from a multistage sampling-based survey. PLOS Med 15 (1): e1002489. https://doi.org/10.1371/journal.pmed.1002489