Cohort Profile: IAVI’s HIV epidemiology and early infection cohort studies in Africa to support vaccine discovery

Price, Matt A.; Kilembe, William; Ruzagira, Eugene; Karita, Etienne; Inambao, Mubiana; Sanders, Eduard J.; Anzala, Omu; Allen, Susan; Edward, Vinodh; Kaleebu, Pontiano; Fast, Patricia E.; Rida, Wasima; Kamali, Anatoli; Hunter, Eric; Tang, Jianming; Lakhi, Shabir; Mutua, Gaudensia; Bekker, Linda‐Gail; Ggayi, Abu-Baker; Tichacek, Amanda; Chetty, Paramesh; Latka, Mary H.; Maenetje, Pholo; Makkan, Heeran; Hare, Jonathan; Kibengo, Freddie; Priddy, Fran; Landais, Elise; Chinyenze, Kundai; Gilmour, Jill

doi:10.1093/ije/dyaa100

Cited by 18 publications

(19 citation statements)

References 44 publications

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“…Volunteers included in this study were selected from a historic acute and early HIV infection prospective cohort drawn from nine clinical research centres in South Africa, Zambia, Uganda, Kenya and Rwanda enrolled from 2006 to 2011 (Figure 1). Details of study characteristics, distributions, recruitment procedures, initial immunological methods and epidemiological profiling data of the Protocol C cohort are described elsewhere (18,22,25,26).…”

Section: Study Population and Selection Approachmentioning

confidence: 99%

“…We applied a unique approach to retrospectively classify HIVinfected individuals in order to aid the delineation of a profile associated with early and persistent in vivo control of HIV-1 replication in the absence of antiretroviral treatment. Using this approach, we defined three groups of HIV infected volunteers from Protocol C; a multisite early infection prospective cohort consisting of 613 participants recruited from nine clinical research centres in five African countries (25,26) (Figure 1, also on https://dataspace.iavi.org/). These groups comprised volunteers with low (n = 10), medium (n = 10) and high (n = 10) set point viral load who were identified within days of their estimated date of HIV infection and followed over time for up to 7 years.…”

Section: Introductionmentioning

confidence: 99%

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A Novel Sample Selection Approach to Aid the Identification of Factors That Correlate With the Control of HIV-1 Infection

et al. 2021

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Individuals infected with HIV display varying rates of viral control and disease progression, with a small percentage of individuals being able to spontaneously control infection in the absence of treatment. In attempting to define the correlates associated with natural protection against HIV, extreme heterogeneity in the datasets generated from systems methodologies can be further complicated by the inherent variability encountered at the population, individual, cellular and molecular levels. Furthermore, such studies have been limited by the paucity of well-characterised samples and linked epidemiological data, including duration of infection and clinical outcomes. To address this, we selected 10 volunteers who rapidly and persistently controlled HIV, and 10 volunteers each, from two control groups who failed to control (based on set point viral loads) from an acute and early HIV prospective cohort from East and Southern Africa. A propensity score matching approach was applied to control for the influence of five factors (age, risk group, virus subtype, gender, and country) known to influence disease progression on causal observations. Fifty-two plasma proteins were assessed at two timepoints in the 1st year of infection. We independently confirmed factors known to influence disease progression such as the B*57 HLA Class I allele, and infecting virus Subtype. We demonstrated associations between circulating levels of MIP-1α and IL-17C, and the ability to control infection. IL-17C has not been described previously within the context of HIV control, making it an interesting target for future studies to understand HIV infection and transmission. An in-depth systems analysis is now underway to fully characterise host, viral and immunological factors contributing to control.

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Section: Study Population and Selection Approachmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Novel Sample Selection Approach to Aid the Identification of Factors That Correlate With the Control of HIV-1 Infection

et al. 2021

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“…In this study, we have studied HIV-1 Early infection subjects from two distinct time periods during last 15 years in Kigali Rwanda. During the first period from 2005 to 2011, plasma samples were collected under IAVI Protocol C (Price et al, 2020) from 26/97 (27%) seroconvertors from a heterosexual transmission cohort in Kigali. Individuals enrolled in this cohort were from HIV-1 discordant couples who underwent couples counseling and testing and who were followed, with additional counseling and testing, every 1-3 months to reduce the incidence of transmission.…”

Section: Study Subjectsmentioning

confidence: 99%

“…Couples voluntary counseling and testing (CVCT) in high prevalence areas has been shown to reduce transmission incidence of HIV in cohabiting couples by more than two-thirds (Wall et al, 2019). When infection of the seronegative partner was identified as described in methods, they were enrolled in IAVI Protocol C, an acute infection, long-term follow-up study, and samples were obtained from both partners (Price et al, 2020). Originally, 94 volunteers with incident HIV infection were enrolled into Protocol C from Kigali; in the current study, we analyzed plasma viruses from the 26 seroconverters with the shortest estimated time from the date of infection (median time from EDI = 23 days) calculated as described in methods; with 16 out of 26 plasma collected less than 30 days post-EDI (Table 2).…”

Section: Study Volunteersmentioning

confidence: 99%

Increased Frequency of Inter-Subtype HIV-1 Recombinants Identified by Near Full-Length Virus Sequencing in Rwandan Acute Transmission Cohorts

Umviligihozo¹,

Muok²,

Gisa³

et al. 2021

Front. Microbiol.

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Most studies of HIV-1 transmission have focused on subtypes B and C. In this study, we determined the genomic sequences of the transmitted founder (TF) viruses from acutely infected individuals enrolled between 2005 and 2011 into IAVI protocol C in Rwanda and have compared these isolates to viruses from more recent (2016–2019) acute/early infections in three at risk populations – MSM, high risk women (HRW), and discordant couples (DC). For the Protocol C samples, we utilized near full-length single genome (NFLG) amplification to generate 288 HIV-1 amplicons from 26 acutely infected seroconverters (SC), while for the 21 recent seroconverter samples (13 from HRW, two from DC, and six from MSM), we PCR amplified overlapping half-genomes. Using PacBio SMRT technology combined with the MDPseq workflow, we performed multiplex sequencing to obtain high accuracy sequences for each amplicon. Phylogenetic analyses indicated that the majority of recent transmitted viruses from DC and HRW clustered within those of the earlier Protocol C cohort. However, five of six sequences from the MSM cohort branched together and were greater than 97% identical. Recombination analyses revealed a high frequency (6/26; 23%) of unique inter-subtype recombination in Protocol C with 19% AC and 4% CD recombinant viruses, which contrasted with only 6.5% of recombinants defined by sequencing of the pol gene previously. The frequency of recombinants was significantly higher (12/21; 57%) in the more recent isolates, although, the five related viruses from the MSM cohort had identical recombination break points. While major drug resistance mutations were absent from Protocol C viruses, 4/21 of recent isolates exhibited transmitted nevirapine resistance. These results demonstrate the ongoing evolution and increased prevalence of recombinant and drug resistant transmitted viruses in Rwanda and highlight the importance of defining NFLG sequences to fully understand the nature of TF viruses and in particular the prevalence of unique recombinant forms (URFs) in transmission cohorts.

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“…Subjects were drawn from a large prospective cohort of 613 volunteers living with HIV to evaluate clinical, laboratory, immunologic and viral markers of disease progression (IAVI protocol C) [26]. From this cohort, 13 volunteers from clinics in Uganda, Rwanda, Zambia and South Africa were selected based on being i) apparently healthy in clinical latency, ii) anti-retroviral (ARV) therapy naïve and iii) willing to donate up to 100mL of blood at an additional visit which ranged at between 1203 and 5319 days post estimated date of HIV-1 acquisition (EDA) (Table 1).…”

Section: Subjects and Pbmc Isolationmentioning

confidence: 99%

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Cohort Profile: IAVI’s HIV epidemiology and early infection cohort studies in Africa to support vaccine discovery

Cited by 18 publications

References 44 publications

A Novel Sample Selection Approach to Aid the Identification of Factors That Correlate With the Control of HIV-1 Infection

A Novel Sample Selection Approach to Aid the Identification of Factors That Correlate With the Control of HIV-1 Infection

Increased Frequency of Inter-Subtype HIV-1 Recombinants Identified by Near Full-Length Virus Sequencing in Rwandan Acute Transmission Cohorts

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