Consider a Quick Switch to Second-Line ART When Elevated Viral Load Is Observed, Study Suggests

In sub-Saharan Africa, clinicians have observed that an increasing number of patients that are antiretroviral therapy (ART)-experienced are hospitalized with advanced HIV. Additionally, mortality among these patients is extremely high during and after hospitalization.

Currently, the World Health Organization recommends that patients on first-line ART with an elevated viral load (VL) of ≥1000 copies/ml, switch to second-line conditional therapy following a second elevated VL 3 months after the first elevation was noted and that enhanced adherence counseling be implemented, regardless of CD4 level and hospitalization status.

In a new study, investigators aspired to determine if patients could benefit from a faster switch to second-line therapy, by measuring rates of antiretroviral drug resistance among ART-experienced hospitalized patients. The study topic was critically important as there were previously no data available on HIV-drug resistance among these patients.

The results of the study were presented in an oral abstract session at the Annual Conference on Retroviruses and Opportunistic Infections (CROI 2019) on March 7, 2019.

Between September 2017 and April, the investigators implemented a cross-sectional survey in 2 hospitals supported by Doctors Without Borders in Kinshasa, Democratic Republic of Congo, and Homa Bay, Kenya.

Hospitalized individuals who were over the age of 15 years, living with HIV, receiving first-line ART for at least 6 months and with CD4< 350 cells/µL were invited to participate.

In total, 305 participants were included, and accounted for a median time of 5.3 years [Interquartile Range (IQR):2.5-10.3] on ART in Kinshasa (77%-TDF/3TC/EFV, 8%-ABC/3TC/EFV) and 4 years [IQR:1.8-8.9] in Homa Bay (71%-TDF/3TC/EFV,11%-AZT/3TC/NVP).

In total 69% of participants in Kinshasa and 54% in Homa Bay were female, and the median age was 38 [31-48] and 40 [32-48] years, respectively.

CD4 count, viral load, and resistance genotype were completed at the point of inclusion. Resistance was defined as any major nucleoside reverse transcriptase inhibitor or non-nucleoside reverse transcriptase inhibitor drug resistance. Additionally, a regimen-specific genotypic sensitivity score was calculated.

The median CD4 was 69 cells/µL [IQR:29-134] and 135 cells/µL [IQR:46- 255] in Kinshasa and Homa Bay, respectively. It was also reported that 70% in Kinshasa and 37% in Homa Bay had a VL≥1,000 cp/mL.

“Among those with CD4 <50cells/mL, 87% and 84% had a VL≥1,000 cp/ mL in Kinshasa and HB. Of those with VL≥1000cp/mL, 73% had dual-class DR in both sites, with 73% on an ineffective regimen (sGSS <2) in Kinshasa, and 74% in Homa Bay,” the abstract notes.

The study found that age, low CD4 count, and suboptimal self-reported adherence were associated with treatment failure (VL >100 cp/mL and Dual-class DR) in Homa Bay and CD4 (CD4 <50 cells/µL) was also associated with treatment failure in Kinshasa.

The results of the study indicate that a high proportion of individuals with HIV that were hospitalized with advanced disease and on first-line ART were resistant to their antiretroviral treatments in both study sites. Therefore, the investigators conclude that a fast switch to second-line ART after observation of elevated VL or CD4<50 cells/mL should be immediately recommended to accelerate immune reconstruction and improve patient outcomes.

The study, “High Levels of Drug-Resistance Among ART-Experienced Hospitalized Patients,” was presented on March 7, 2019, at CROI 2019 in Seattle, Washington.