Identification of primary HIV-1C infection in Botswana

Abstract

Methods for identification of primary HIV infections seem increasingly important to understand pathogenesis, and to prevent transmission, which is particularly efficient during acute infection. Most current algorithms for HIV testing are based on detection of HIV antibodies and are unable to identify early infections before seroconversion. The efficiency of prospective cohorts, which is a standard approach for identifying primary HIV-1 infection, depends on a variety of epidemiological and cultural factors including HIV incidence and stigma and, not surprisingly, varies significantly in different geographical areas. We report a voluntary counseling and testing (VCT)-based approach to identifying primary HIV-1C infection that was developed as part of a primary HIV-1 subtype C infection study in Botswana. The referral strategy was based on: (1) collaboration with VCT centers at city clinics operated by the Ministry of Health; (2) partnering with the busiest non-government VCT center; (3) educating healthcare workers and the community about primary HIV infection; and (4) pairing with diverse VCT providers, including NGOs and private-sector organizations. Acute HIV-1 infections were defined by a negative HIV-1 serology combined with a positive HIV-1 RT-PCR test. Recent HIV-1 infections were identified by detuned EIA testing according to the classic STARTH algorithm. The VCT-based referral strategy resulted in the successful identification of 57 cases of acute and early HIV infection. A referral strategy of expanded VCT with viral RNA (Ribonucleic acid) testing to a national program in Botswana may be a promising approach for identification of primary HIV infections on a countrywide level. The program should offer VCT with viral RNA testing to the general public, facilitate proper counseling and risk reduction, and allow initiation of early HAART, and may reduce new viral transmissions.

Sample size considerations in the design of cluster randomized trials of combination HIV prevention

“…Parameter values in the model (see Table 1) were set based on published results as well as information from three sources: (1) the Mochudi study, a pilot study to evaluate the uptake of an HIV prevention program for the northeast sector of Mochudi, a village in Botswana with a population of around 45,000 [20]; (2) the Botswana/Durban cohort, a cohort of newly infected individuals combined from two southern African cohorts: the HIV pathogenesis Programme Acute Infection Study in Durban, KwaZulu-Natal, South Africa [21] and the Tshedimoso Study in Gaborone, Botswana [3,22,23]; and (3) the Likoma Island sexual network, a cross-sectional sociocentric survey of sexual partnerships aiming to investigate the population-level structure of sexual networks connecting the young adult population of several villages on Likoma Island, Malawi [24]. …”

Transmitted/Founder HIV-1 Subtype C Viruses Show Distinctive Signature Patterns in Vif, Vpr, and Vpu That Are Under Subsequent Immune Pressure During Early Infection

“…25,36 Vif and Vpr, but not Vpu, have low entropy in t/f viruses To investigate HIV-1C Vif, Vpr, and Vpr amino acid diversity, we reconstructed each patient's t/f virus, using the consensus sequence from the earliest time point postinfection, and computed Shannon entropy scores across Vif, Vpr, and Vpu t/f alignments. The median number of sequences per patient used for reconstruction was 10 [interquartile range [(IQR): [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. The reconstructed t/f viruses exhibited relatively low interpatient amino acid entropy in Vif (median 0.00; IQR: 0.00-0.22) and Vpr (median 0.00; IQR: 0.00-0.22) (Fig.…”

“…Patients were enrolled in an HIV-1C primary infection cohort in Botswana, 21,22 and a subset of 17 subjects was selected based on the stage of HIV infection: six acutely infected individuals (patient code A to H) and 11 randomly selected early infections (patient code OC to QR) ( Table 1). Acutely infected individuals were identified before seroconversion by a positive HIV-1 reverse transcription polymerase chain reaction test accompanied by negative HIV-1 serology (Fiebig stage II).…”

“…All available subtype C sequences fitting these criteria were included in our analysis. The majority of sequences included (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) South Africa (*50%), followed by Botswana (*25%) and others (Supplementary Table S1; Supplementary Data are available online at www.liebertpub.com/aid). A maximum likelihood phylogeny inferred from our combined early and chronic HIV-1 vif sequences was created to confirm that the acute/early sequences are generally interspersed among the chronic ones ( Supplementary Fig.…”

tatExon 1 Exhibits Functional Diversity during HIV-1 Subtype C Primary Infection

“…Patients were enrolled in an HIV-1C primary infection cohort in Botswana (47,48), and a subset of 20 subjects was selected based on the stage of HIV infection: eight acutely infected individuals (patient code A to H) and 12 randomly selected seroconverters (patient code OC to QU) (Table 1). Acutely infected individuals were identified before seroconversion by a positive HIV-1 reverse transcription-PCR (RT-PCR) test with negative HIV-1 serology (Fiebig stage II) (49).…”