Increasing evidence supports virological remission in a subset of individuals after treatment with antiretroviral therapy (ART) in primary HIV infection (PHI). We present the first analysis of treatment interruption (TI) in individuals with PHI in Africa, to explore the prevalence and predictors of post-treatment control (PTC).
137 individuals within 6 months of seroconversion were recruited to the SPARTAC RCT from South Africa and Uganda. We analysed samples from those randomised to ‘no treatment’ (NT) and 48 weeks of ART (ART48). We measured HIV-1 DNA in CD4 T cells (Total, Integrated), CD4 count, plasma viral load (VL) and markers of T cell activation (CD25, CD38, CD69, HLA-DR) and exhaustion (Lag-3, PD-1, Tim-3). We explored associations with both clinical progression and time to viral load rebound. Data were compared with those for UK SPARTAC participants (n=151) recruited under the same protocol.
Of individuals recruited to SPARTAC in Africa, 91 were randomised to ART48 or NT, and of these, samples were available for 44 and 38, respectively. Of those in the ART48 arm, 22 received the full 48 weeks of ART and had VL < 400 copies/mL at TI. All were female; 19/22 were infected with subtype C. Of UK patients all were MSM infected with subtype B.
Pre-therapy VL was significantly lower in Africans compared with the UK cohort (median 4.16 vs 4.62 log10 copies/mL; p<0.001). CD4 T cell count and Total HIV-DNA were similar in UK and African patients, although Integrated HIV-1 DNA was lower in the latter (median 3.60 vs 3.06 log10 copies/million CD4+ T-cells; p < 0.001).
Measured pre-ART, Total HIV-1 DNA, VL and CD4 count in Africans were associated with clinical progression (p=0.001, HR (CI95) 5.37 (1.95-14.79); p<0.001, 1.99 (1.35-2.94) and p<0.001, 0.34 (0.24-0.48), respectively).
From TI after 48 weeks of ART, 5/22 (22.7%) Africans maintained VL<400 copies/ml over a median 188 weeks follow-up (range 147-203). In multivariable analyses, Africans experienced significantly longer duration of viral remission than UK participants (p<0.001; HR 3.90 (1.75-8.71). Total DNA at TI was a predictor of time to rebound, but the effect was much weaker in African than in UK patients.
We present the first analysis of PTC in Africans with PHI. The difference in virus-free remission post-TI in these individuals compared to the UK patients is striking. Further studies are needed to explore mechanisms and discriminate the distinct effects of sex, ethnicity and HIV subtype.