Rapid antiretroviral therapy in primary HIV-1 infection enhances immune recovery.

OBJECTIVE: We present findings from a large cohort of individuals treated during primary HIV infection (PHI) and examine the impact of time from HIV-1 acquisition to antiretroviral therapy (ART) initiation on clinical outcomes. We also examine the temporal changes in the demographics of individuals presenting with PHI to inform HIV-1 prevention strategies. METHODS: Individuals who fulfilled the criteria of PHI and started ART within 3 months of confirmed HIV-1 diagnosis were enrolled between 2009 and 2020. Baseline demographics of those diagnosed between 2009 and 2015 (before preexposure prophylaxis (PrEP) and universal ART availability) and 2015-2020 (post-PrEP and universal ART availability) were compared. We examined the factors associated with immune recovery and time to viral suppression. RESULTS: Two hundred four individuals enrolled, 144 from 2009 to 2015 and 90 from 2015 to 2020; median follow-up was 33 months. At PHI, the median age was 33 years; 4% were women, 39% were UK-born, and 84% were MSM. The proportion of UK-born individuals was 47% in 2009-2015, compared with 29% in 2015-2020. There was an association between earlier ART initiation after PHI diagnosis and increased immune recovery; each day that ART was delayed was associated with a lower likelihood of achieving a CD4 + cell count more than 900 cells/µl [hazard ratio 0.99 (95% confidence interval, 95% CI 0.98-0.99), P  = 0.02) and CD4/CD8 more than 1.0 (hazard ratio 0.98 (95% CI 0.97-0.99). CONCLUSION: Early initiation of ART at PHI diagnosis is associated with enhanced immune recovery, providing further evidence to support immediate ART in the context of PHI. Non-UK-born MSM accounts for an increasing proportion of those with primary infection; UK HIV-1 prevention strategies should better target this group.

Japanese encephalitis clinical update: Changing diseases under a changing climate.

BACKGROUND: Japanese encephalitis virus (JEV) is a mosquito-borne arbovirus endemic to the Asia-Pacific that causes high morbidity and mortality in those who develop symptomatic disease. Prior to 2021, only five locally acquired cases had been detected in Australia, all in northern Australia. Following a sentinel case in 2021, widespread dissemination of JEV was detected in northern and south-eastern Australia, accompanied by an increase in locally acquired cases, which have been detected as far south as Victoria. This expansion has occurred in the setting of warmer and wetter conditions under the influence of climate change. OBJECTIVE: To provide Australian general practitioners (GPs) an overview of JEV, given its recent expansion, and the potential for sustained endemicity. DISCUSSION: As the distribution of JEV expands under the influence of climate change, Australian GPs need to be familiar with this condition, especially those practicing in rural areas and where detections have occurred.

Virological remission after antiretroviral therapy interruption in female African HIV seroconverters.

INTRODUCTION: There are few data on the frequency of virological remission in African individuals after treatment with antiretroviral therapy (ART) in primary HIV infection (PHI). METHODS: We studied participants (n = 82) from South Africa and Uganda in Short Pulse Antiretroviral Treatment at HIV-1 Seroconversion, the first trial of treatment interruption in African individuals with PHI randomized to deferred ART or 48 weeks of immediate ART. All were female and infected with non-B HIV subtypes, mainly C. We measured HIV DNA in CD4+ T cells, CD4+ cell count, plasma viral load (pVL), cell-associated HIV RNA and T-cell activation and exhaustion. We explored associations with clinical progression and time to pVL rebound after treatment interruption (n = 22). Data were compared with non-African Short Pulse Antiretroviral Treatment at HIV-1 Seroconversion participants. RESULTS: Pretherapy pVL and integrated HIV DNA were lower in Africans compared with non-Africans (median 4.16 vs. 4.72 log10 copies/ml and 3.07 vs. 3.61 log10 copies/million CD4+ T cells, respectively; P < 0.001). Pre-ART HIV DNA in Africans was associated with clinical progression (P = 0.001, HR per log10 copies/million CD4+ T cells increase (95% CI) 5.38 (1.95-14.79)) and time to pVL rebound (P = 0.034, HR per log10 copies/ml increase 4.33 (1.12-16.84)). After treatment interruption, Africans experienced longer duration of viral remission than non-Africans (P < 0.001; HR 3.90 (1.75-8.71). Five of 22 African participants (22.7%) maintained VL less than 400 copies/ml over a median of 188 weeks following treatment interruption. CONCLUSION: We find evidence of greater probability of virological remission following treatment interruption among African participants, although we are unable to differentiate between sex, ethnicity and viral subtype. The finding warrants further investigation.