Table 4.

Top 10 papers of the Zurich Primary Infection Study (ZPHI).

Paper	Design	Methods	Main Outcome	Reference
Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies	Phase I/II study	Infusion of three neutralizing antibodies (2G12, 2F5 and 4E10) for studying suppression of viral rebound upon stop of antiretroviral treatment	Antibody-treated individuals had delayed rebound to a control group of acutely infected patients without Ab	Trkola et al. Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies. Nature Medicine. 2005:11:615-622 [58].
HIV-1 transmission after cessation of early antiretroviral therapy among men having sex with men	Molecular epidemiological population based study to identify transmissions originating from patients stopping ART	pol sequences from genotypic resistance tests and clonal env C2-V3-C3 sequences	Five new primary infection events originating from ZPHI patients within 16–61 weeks after stopping early ART	Rieder et al. HIV-1 transmission after cessation of early antiretroviral therapy among men having sex with men. AIDS. 2010;24:1177-1183 [32].
Ambiguous Nucleotide Calls From Population-based Sequencing of HIV-1 are a Marker for Viral Diversity and the Age of Infection	HIV sequence analysis of PWH and known infection date	Sequence analysis of partial pol sanger sequences from PWH and known infection date determining the fraction of ambiguous nucleotides	Fraction of ambiguous nucleotides is a useful marker for the age of infection	Kouyos et al. Ambiguous Nucleotide Calls From Population-based Sequencing of HIV-1 are a Marker for Viral Diversity and the Age of Infection. Clinical Infectious Diseases. 2011;52(4):532–539 [15].
Origin of minority drug-resistant HIV-1 variants in primary HIV-1 infection	Phylogenetic analysis	Allele specific polymerase chain reaction for drug resistance mutations in 204 acute or recent seroconverters and phylogenetic linkage to chronically infected PWH	Drug-resistant minority variants can be transmitted	Metzner et al. Origin of minority drug-resistant HIV-1 variants in primary HIV-1 infection. The Journal of Infectious Diseases. 2013;208(7):1102–1112 [55].
Frequency and Spectrum of Unexpected Clinical Manifestations of Primary HIV-1 Infection	Prospective collection of clinical signs and symptoms during HIV acute infection	Characterizing typical and atypical belonging to the acute retroviral syndrom’s symptoms and signs	Unexpected clinical presentations occurred in a large fraction of PWH and a primary HIV infection	Braun et al. Frequency and Spectrum of Unexpected Clinical Manifestations of Primary HIV-1 Infection. Clin Infect Dis. 2015 Sep 15;61(6):1013–1021 [23].
Tracing HIV-1 transmission: envelope traits of HIV-1 transmitter and recipient pairs	Comparison of phenotypic and genotypic viral characteristics of transmission pairs	Identification of probably transmission pairs, retrieving plasma and cellular samples from the biobank and phenotype and genotype HI-Virus of transmitter and recipients	No clear distinction of transmitter/founder virus from their matched transmitter viruses, suggesting stochastic transmission	Oberle et al. Tracing HIV-1 transmission: envelope traits of HIV-1 transmitter and recipient pairs. Retrovirology. 2016;13(1):62 [49].
The interplay between replication capacity of HIV-1 and surrogate markers of disease	Determination of replication capacity of 355 whole-genome primary HIV-1 isolates on primary cells	Correlation analysis between disease parameters and RC	RC correlated with set point viral load and showed significant differences between subtypes studied	Rindler et al. The interplay between replication capacity of HIV-1 and surrogate markers of disease. J Infect Dis. 2022; 226 (6), 1057–1068 [59].
Sustained viral suppression with dolutegravir monotherapy over 192 weeks in patients starting combination antiretroviral therapy during primary HIV infection (EARLY-SIMPLIFIED): a randomized, controlled, multi-site, non-inferiority trial	Randomized, open label, non-inferiority trial	2:1 randomization DTG monotherapy vs. continuation of cART among people starting fist cART during PHI with at least 48 weeks viral load suppression	Non-inferiority of DTG monotherapy vs. cART after 5 years of follow-up	West et al. Sustained viral suppression with dolutegravir monotherapy over 192 weeks in patients starting combination antiretroviral therapy during primary HIV infection (EARLY-SIMPLIFIED): a randomized, controlled, multi-site, non-inferiority trial. Clinical Infectious Diseases. 2023; 77, 1012–1020 [24].
High Rates of Subsequent Asymptomatic Sexually Transmitted Infections and Risky Sexual Behaviour in Patients Initially Presenting With Primary Human Immunodeficiency Virus-1 Infection	Prospective longitudinal data collection for sexually transmitted infections (STI)’s	Systematic screening for STI’s with assessment of prevalence, incidence and clinical presentation and identification of risk factor	Very high point prevalence and incidence of STI’s with the vast majority being asymptomatic	Braun et al. High Rates of Subsequent Asymptomatic Sexually Transmitted Infections and Risky Sexual Behavior in Patients Initially Presenting With Primary Human Immunodeficiency Virus-1 Infection. Clin Infect Dis. 2018 25;217(12):1883–1888 [41].
Dolutegravir monotherapy as maintenance strategy: A meta-analysis of individual participant data from randomized controlled trials	Individual participant meta-analysis	Combining four randomized controlled trials evaluating dolutegravir monotherapy versus combined antiretroviral therapy (cART) among virologically individuals controlled for at least 6 months on cART	Significantly increased risk for viral failure on dolutegravir monotherapy compared to cART with D4 T cells nadir <350 mm3 having the highest adjusted hazard ratio for viral failure.	Fournier et al. Dolutegravir monotherapy as maintenance strategy: A meta-analysis of individual participant data from randomized controlled trials. Open Forum Infectious Diseases. 2022;9(6),ofac107 [60].