High rates of drug resistance and virological failure among adults with HIV admitted to hospital in Malawi
Thirty-two per cent of participants at the Malawi site of the STAMP trial had virological failure with high levels of resistance to at least two first-line antiretrovirals – according to data published online 1 September 2020 in The Lancet HIV.
This evaluation was from an observational cohort study nested in the rapid urine-based screening for tuberculosis (TB) to reduce AIDS-related mortality in hospitalised patients in Africa (STAMP) trial. It enrolled unselected adults with HIV, admitted to hospital, and the nested study looked at ART failure, drug resistance, and early mortality.
Exclusion criteria were TB treatment within 12 months, TB preventative therapy within 6 months, or being unable or unwilling to provide informed consent.
Participants were included in the nested cohort study if they were enrolled at the Malawi site (Zomba Central Hospital) and had been taking ART for at least 6 months at admission. Management of HIV was according to Malawian national guidelines.
Participants who met inclusion criteria had frozen plasma samples tested for viral load. Virological failure was defined as viral load 1000 copies/mL and above. Those with virological failure were tested for drug resistance by ultra-deep sequencing (results defined as intermediate or high-level resistance according to the Stanford HIVDR programme).
The investigators calculated mortality risk at 56 days from enrolment. Participants were censored at death, at 56 days, or at last contact if lost to follow-up.
They modelled the causal association between HIV multidrug resistance and mortality, excluding cofactors, most notably: CD4 cell count, advanced HIV, and poor functional and nutritional status.
Of 1316 participants with HIV enrolled in the STAMP trial at the Malawi site between 26 October 2015 and 19 September 2017, 786 had taken ART for at least 6 months. And, 252 (32%) of 786 participants had virological failure.
Mean age was 41·5 years and 528 of 786 (67%) were women; 770 (98%) were on first-line ART, and median time on ART was 4·7 years; 606 (77%) had advanced HIV.
Of 237 patients with HIV drug resistance results available, 195 (82%) had resistance to 3TC, 128 (54%) to tenofovir, and 219 (92%) to efavirenz. Resistance to at least two drugs was common (196, 83%).
Analyses adjusted by STAMP trial arm only revealed that age, sex, time on ART, advanced HIV, BMI, Karnofsky score, CD4 count, haemoglobin, WHO danger signs, TB treatment, and virological failure were all strongly associated with increased mortality.
Multidrug resistance was associated with increased mortality: aHR 1·7 (95% CI 1·2 to 2·4), p=0·0042. Mortality in this cohort was high: 20% by day 56.
Few data exist on people taking ART but admitted to hospital, so these findings and recommendations are very useful. Many people in ART programmes are not accessing viral load testing (particularly now COVID-19 is disrupting HIV care) and these results reinforce the need for this for hospital inpatients – ideally using rapid tests.
Besides rapid viral load testing, the investigators recommend that these patients should be switched to alterative ART. They note that dolutegravir will likely overcome the high levels of NNRTI resistance but there are still questions about dolutegravir-based ART and the effect of high viral load and multidrug resistance.
The results support development of low-cost, point of care resistance tests, (which are in the pipeline).
“Differentiated ART clinic care to support adherence and detect ART failure in advanced HIV, testing and screening for opportunistic infections, and improved care post discharge could improve outcomes, although further evidence for such interventions will be needed” they write.
Gupta-Wright A et al. Virological failure, HIV-1 drug resistance, and early mortality in adults admitted to hospital in Malawi: an observational cohort study. Lancet HIV. DOI: 10.1016/S2352-3018(20)30172-7. (1 September 2020).
This article was first posted on 26 November 2020.