Characterization of rare spontaneous human immunodeficiency virus viral controllers attending a national United Kingdom clinical service using a combination of serology and molecular diagnostic assays

BACKGROUND: We report outcomes and novel characterization of a unique cohort of 42 individuals with persistently indeterminate human immunodeficiency virus (HIV) status, the majority of whom are HIV viral controllers. METHODS: Eligible individuals had indeterminate or positive HIV serology, but persistently undetectable HIV ribonucleic acid (RNA) by commercial assays and were not taking antiretroviral therapy (ART). Routine investigations included HIV Western blot, HIV viral load, qualitative HIV-1 deoxyribonucleic acid (DNA), coinfection screen, and T-cell quantification. Research assays included T-cell activation, ART measurement, single-copy assays detecting HIV-1 RNA and DNA, and plasma cytokine quantification. Human immunodeficiency virus seropositivity was defined as ≥3 bands on Western blot; molecular positivity was defined as detection of HIV RNA or DNA. RESULTS: Human immunodeficiency virus infection was excluded in 10 of 42 referrals, remained unconfirmed in 2 of 42, and was confirmed in 30 of 42, who were identified as HIV elite controllers (ECs), normal CD4 T-cell counts (median 820/mL, range 805-1336), and normal CD4/CD8 ratio (median 1.8, range 1.2-1.9). Elite controllers had a median duration of elite control of 6 years (interquartile range = 4-14). Antiretroviral therapy was undetected in all 23 subjects tested. Two distinct categories of ECs were identified: molecular positive (n = 20) and molecular negative (n = 10). CONCLUSIONS: Human immunodeficiency virus status was resolved for 95% of referrals with the majority diagnosed as EC. The clinical significance of the 2 molecular categories among ECs requires further investigation

Enhanced surveillance of HIV-1 drug resistance in recently infected MSM in the UK

OBJECTIVES: To determine the prevalence of inferred low-frequency HIV-1 transmitted drug resistance (TDR) in MSM in the UK and its predicted effect on first-line therapy. METHODS: The HIV-1 pol gene was amplified from 442 newly diagnosed MSM identified as likely recently infected by serological avidity testing in 2011-13. The PCR products were sequenced by next-generation sequencing with a mutation frequency threshold of >2% and TDR mutations defined according to the 2009 WHO surveillance drug resistance mutations list. RESULTS: The majority (75.6%) were infected with subtype B and 6.6% with rare complex or unique recombinant forms. At a mutation frequency threshold of >20%, 7.2% (95% CI 5.0%-10.1%) of the sequences had TDR and this doubled to 15.8% (95% CI 12.6%-19.6%) at >2% mutation frequency (P 20% and 2%-20% mutation frequency differed for each drug class, these respectively being: L90M (n = 7) and M46IL (n = 10) for PIs; T215rev (n = 9) and D67GN (n = 4) for NRTIs; and K103N (n = 5) and G190E (n = 2) for NNRTIs. Combined TDR was more frequent in subtype B than non-B (OR = 0.38; 95% CI = 0.17-0.88; P = 0.024) and had minimal predicted effect on recommended first-line therapies. CONCLUSIONS: The data suggest differences in the types of low-frequency compared with majority TDR variants that require a better understanding of the origins and clinical significance of low-frequency variants. This will better inform diagnostic and treatment strategies

Field evaluation of a new antibody-based diagnostic for Schistosoma haematobium and S. mansoni at the point-of-care in northeast Zimbabwe

BACKGROUND: Rapid diagnostic tests (RDTs) for use at the point-of-care (POC) are likely to become increasingly useful as large-scale control programmes for schistosomiasis get underway. Given the low sensitivity of the reference standard egg count methods in detecting light infections, more sensitive tests will be required to monitor efforts aimed at eliminating schistosomiasis as advocated by the World Health Assembly Resolution 65.21 passed in 2012. METHODS: A recently developed RDT incorporating Schistosoma mansoni cercarial transformation fluid (SmCTF) for detection of anti-schistosome antibodies in human blood was here evaluated in children (mean age: 7.65 years; age range: 1-12 years) carrying light S. mansoni and S. haematobium infections in a schistosome-endemic area of Zimbabwe by comparison to standard parasitological techniques (i.e. the Kato-Katz faecal smear and urine filtration). Enzyme-linked immunosorbent assays (ELISAs) incorporating S. haematobium antigen preparations were also employed for additional comparison. RESULTS: The sensitivity of the SmCTF-RDT compared to standard parasitological methods was 100% while the specificity was 39.5%. It was found that the sera from RDT “false-positive” children showed significantly higher antibody titres in IgM-cercarial antigen preparation (CAP) and IgM-soluble egg antigen (SEA) ELISA assays than children identified by parasitology as “true-negatives”. CONCLUSIONS: Although further evaluations are necessary using more accurate reference standard tests, these results indicate that the RDT could be a useful tool for the rapid prevalence-mapping of both S. mansoni and S. haematobium in schistosome-endemic areas. It is affordable, user-friendly and allows for diagnosis of both schistosome species at the POC