Erratum to: Risky Sex and HIV Acquisition Among HIV Serodiscordant Couples in Zambia, 2002-2012: What Does Alcohol Have To Do With It?

The article Risky Sex and HIV Acquisition Among HIV Serodiscordant Couples in Zambia, 2002-2012: What Does Alcohol Have To Do With It?, written by Dvora Joseph Davey, William Kilembe, Kristin M. Wall, Naw Htee Khu, Ilene Brill, Bellington Vwalika, Elwyn Chomba, Joseph Mulenga, Amanda Tichacek, Marjan Javanbakht, W. Scott Comulada, Susan Allen, Pamina M. Gorbach, was originally published Online First without open access. After publication in volume 21, issue 7, pages 1892-1903, the author decided to opt for Open Choice and to make the article an open access publication. Therefore, the copyright of the article has been changed to

Sustained effect of couples' HIV counselling and testing on risk reduction among Zambian HIV serodiscordant couples.

BACKGROUND: We present temporal trends in self-reported and biological markers of unprotected sex and sex with concurrent partners in discordant couples receiving couples' voluntary HIV counselling and testing (CVCT). METHODS: Heterosexual Zambian HIV-serodiscordant couples were enrolled into longitudinal follow-up in an open cohort (1994-2012). Multivariable Anderson-Gill models explored predictors of self-report and biological indicators of unprotected sex within (including sperm on a vaginal swab, incident pregnancy or incident linked HIV infection) and outside (including self-report, STI and unlinked HIV infection) the union. Measures of secular trends in baseline measures were also examined. RESULTS: At enrolment of 3049 couples, men were 35 years old on average, women were 29 years, and couples had been together for an average of 7 years. M+F- couples reported an average of 16.6 unprotected sex acts in the 3 months prior to enrolment (pre-CVCT), dropping to 5.3 in the >0-3 month interval, and 2.0 in >6 month intervals (p-trend <0.001). Corresponding values for M-F+ couples were 22.4 unprotected sex acts in the 3 months prior enrolment, dropping to 5.2 in the >0-3 month interval, and 3.1 in >6 month intervals (p-trend <0.001). Significant reductions in self-report and biological markers of outside partners were also noted. Predictors of unprotected sex between study partners after CVCT included prevalent pregnancy (adjusted HR, aHR=1.6-1.9); HIV+ men being circumcised (aHR=1.2); and HIV- women reporting sex with outside partners (aHR=1.3), alcohol (aHR=1.2), injectable (aHR=1.4) or oral (aHR=1.4) contraception use. Fertility intentions were also predictive of unprotected sex (aHR=1.2-1.4). Secular trends indicated steady declines in reported outside partners and STIs. CONCLUSION: Reductions in self-reported unprotected sex after CVCT were substantial and sustained. Reinforced risk-reduction counselling in pregnant couples, couples desiring children and couples with HIV- women having outside partners or using alcohol or injectable or oral contraception are indicated.

Risky Sex and HIV Acquisition Among HIV Serodiscordant Couples in Zambia, 2002-2012: What Does Alcohol Have To Do With It?

In this paper we evaluate the effects of heavy alcohol consumption on sexual behavior, HIV acquisition, and antiretroviral treatment (ART) initiation in a longitudinal open cohort of 1929 serodiscordant couples in Lusaka, Zambia from 2002 to 2012. We evaluated factors associated with baseline heavy alcohol consumption and its association with condomless sex with the study partner, sex outside of the partnership, and ART initiation using multivariable logistic regression. We estimated the effect of alcohol consumption on HIV acquisition using multivariable Cox models. Baseline factors significantly associated with women's heavy drinking (drunk weekly or more in 12-months before enrollment) included woman's older age (adjusted prevalence odds ratio [aPOR] = 1.04), partner heavy drinking (aPOR = 3.93), and being HIV-infected (aPOR = 2.03). Heavy drinking among men was associated with less age disparity with partner (aPOR per year disparity = 0.97) and partner heavy drinking (aPOR = 1.63). Men's being drunk daily (aOR = 1.18), women's being drunk less than monthly (aOR = 1.39) vs. never drunk and being in a male HIV-negative and female HIV-positive union (aOR = 1.45) were associated with condomless sex. Heavy alcohol use was associated with having 1 or more outside sex partners among men (aOR drunk daily = 1.91, drunk weekly = 1.32, drunk monthly = 2.03 vs. never), and women (aOR drunk monthly = 2.75 vs. never). Being drunk weekly or more increased men's risk of HIV acquisition (adjusted hazard ratio [aHR] = 1.72). Men and women being drunk weekly or more was associated (p < 0.1) with women's seroconversion (aHR = 1.42 and aHR = 3.71 respectively). HIV-positive women who were drunk monthly or more had lower odds of initiating ART (aOR = 0.83; 95% CI = 0.70-0.99) adjusting for age, months since baseline and previous pregnancies. Individuals in HIV-serodiscordant couples who reported heavy drinking had more outside sex partnerships and condomless sex with their study partner and were more likely to acquire HIV. HIV-positive women had lower odds of initiating ART if they were heavy drinkers.

Adaptation of HIV-1 to human leukocyte antigen class I.

The rapid and extensive spread of the human immunodeficiency virus (HIV) epidemic provides a rare opportunity to witness host-pathogen co-evolution involving humans. A focal point is the interaction between genes encoding human leukocyte antigen (HLA) and those encoding HIV proteins. HLA molecules present fragments (epitopes) of HIV proteins on the surface of infected cells to enable immune recognition and killing by CD8(+) T cells; particular HLA molecules, such as HLA-B*57, HLA-B*27 and HLA-B*51, are more likely to mediate successful control of HIV infection. Mutation within these epitopes can allow viral escape from CD8(+) T-cell recognition. Here we analysed viral sequences and HLA alleles from >2,800 subjects, drawn from 9 distinct study cohorts spanning 5 continents. Initial analysis of the HLA-B*51-restricted epitope, TAFTIPSI (reverse transcriptase residues 128-135), showed a strong correlation between the frequency of the escape mutation I135X and HLA-B*51 prevalence in the 9 study cohorts (P = 0.0001). Extending these analyses to incorporate other well-defined CD8(+) T-cell epitopes, including those restricted by HLA-B*57 and HLA-B*27, showed that the frequency of these epitope variants (n = 14) was consistently correlated with the prevalence of the restricting HLA allele in the different cohorts (together, P < 0.0001), demonstrating strong evidence of HIV adaptation to HLA at a population level. This process of viral adaptation may dismantle the well-established HLA associations with control of HIV infection that are linked to the availability of key epitopes, and highlights the challenge for a vaccine to keep pace with the changing immunological landscape presented by HIV.

Role of transmitted Gag CTL polymorphisms in defining replicative capacity and early HIV-1 pathogenesis.

Initial studies of 88 transmission pairs in the Zambia Emory HIV Research Project cohort demonstrated that the number of transmitted HLA-B associated polymorphisms in Gag, but not Nef, was negatively correlated to set point viral load (VL) in the newly infected partners. These results suggested that accumulation of CTL escape mutations in Gag might attenuate viral replication and provide a clinical benefit during early stages of infection. Using a novel approach, we have cloned gag sequences isolated from the earliest seroconversion plasma sample from the acutely infected recipient of 149 epidemiologically linked Zambian transmission pairs into a primary isolate, subtype C proviral vector, MJ4. We determined the replicative capacity (RC) of these Gag-MJ4 chimeras by infecting the GXR25 cell line and quantifying virion production in supernatants via a radiolabeled reverse transcriptase assay. We observed a statistically significant positive correlation between RC conferred by the transmitted Gag sequence and set point VL in newly infected individuals (p = 0.02). Furthermore, the RC of Gag-MJ4 chimeras also correlated with the VL of chronically infected donors near the estimated date of infection (p = 0.01), demonstrating that virus replication contributes to VL in both acute and chronic infection. These studies also allowed for the elucidation of novel sites in Gag associated with changes in RC, where rare mutations had the greatest effect on fitness. Although we observed both advantageous and deleterious rare mutations, the latter could point to vulnerable targets in the HIV-1 genome. Importantly, RC correlated significantly (p = 0.029) with the rate of CD4+ T cell decline over the first 3 years of infection in a manner that is partially independent of VL, suggesting that the replication capacity of HIV-1 during the earliest stages of infection is a determinant of pathogenesis beyond what might be expected based on set point VL alone.

Role of donor genital tract HIV-1 diversity in the transmission bottleneck.

The predominant mode of HIV-1 infection is heterosexual transmission, where a genetic bottleneck is imposed on the virus quasispecies. To probe whether limited genetic diversity in the genital tract (GT) of the transmitting partner drives this bottleneck, viral envelope sequences from the blood and genital fluids of eight transmission pairs from Rwanda and Zambia were analyzed. The chronically infected transmitting partner's virus population was heterogeneous with distinct genital subpopulations, and the virus populations within the GT of two of four women sampled longitudinally exhibited evidence of stability over time intervals on the order of weeks to months. Surprisingly, the transmitted founder variant was not derived from the predominant GT subpopulations. Rather, in each case, the transmitting variant was phylogenetically distinct from the sampled locally replicating population. Although the exact distribution of the virus population present in the GT at the time of transmission cannot be unambiguously defined in these human studies, it is unlikely, based on these data, that the transmission bottleneck is driven in every case by limited viral diversity in the donor GT or that HIV transmission is solely a stochastic event.

Syphilis treatment response among HIV-discordant couples in Zambia and Rwanda.

BACKGROUND: Syphilis continues to be a common sexually transmitted infection, despite the availability of inexpensive and effective treatment. Infection in human immunodeficiency virus (HIV)-discordant couples is important because syphilis increases the risk of HIV acquisition. Current US treatment guidelines recommend 1 dose of benzathine penicillin for early syphilis, irrespective of HIV status, but data from coinfected patients are limited. METHODS: Retrospective analysis of 1321 individuals in 2 African HIV-discordant couple cohorts was performed. Cox proportional hazards analysis and multivariable modeling were used to assess predictors of serologic response to treatment at 180 days and 400 days. Modeling was performed for all episodes of positive rapid plasma reagin (RPR) test results and on a subset with higher RPR titers (≥1:4). RESULTS: A total of 1810 episodes of syphilis among 1321 individuals were treated with penicillin between 2002 and 2008. Although a positive RPR was more common in the HIV-infected partners, HIV infection did not impact the likelihood of serologic response to therapy (odds ratio [OR], 1.001; P = .995). By 400 days, 67% had responded to therapy, 27% were serofast, and 6.5% had documented reinfection. Prevalent infections were more likely to remain serofast than incident infections (33% vs 20% at 400 days). CONCLUSIONS: In 2 HIV-serodiscordant couple cohorts in Africa, incident syphilis had a very good likelihood of response to penicillin therapy, irrespective of HIV infection. This supports current Centers for Disease Control and Prevention treatment guidelines. A high proportion of prevalent RPR-positive infections remain serofast despite treatment.

HLA-B signal peptide polymorphism influences the rate of HIV-1 acquisition but not viral load.

Human leukocyte antigen alleles influence the immune response to HIV-1. Signal peptides cleaved from those alleles bind to HLA-E and mediate natural killer cell function. Signal peptides of HLA-A and HLA-C proteins carry methionine (Met) at anchor position 2 (P2); those of HLA-B carry Met or threonine (Thr). Different P2 residues alter HLA-E binding to its cognate receptors and may impact HIV-1 acquisition. Among Zambian couples (N = 566) serodiscordant for HIV-1, P2-Met accelerated acquisition in the HIV-1-negative partner (relative hazard [RH], 1.79). Among seroconverting Zambian (n = 240) and Rwandan (n = 64) partners, P2-Met also accelerated acquisition (RH, 1.47 and RH, 1.83 respectively). HLA-B alleles displaying the reportedly protective Bw4 epitope carry P2-Thr. Bw4/P2-Thr and Bw6/P2-Thr showed similar protective effects compared with Bw6/P2-Met. Neither motif was associated with viral load. The influence of HLA-B alleles on HIV/AIDS may derive from multiple motifs in and beyond the mature proteins.

HIV-1 subtype C superinfected individuals mount low autologous neutralizing antibody responses prior to intrasubtype superinfection.

BACKGROUND: The potential role of antibodies in protection against intra-subtype HIV-1 superinfection remains to be understood. We compared the early neutralizing antibody (NAb) responses in three individuals, who were superinfected within one year of primary infection, to ten matched non-superinfected controls from a Zambian cohort of subtype C transmission cases. Sequence analysis of single genome amplified full-length envs from a previous study showed limited diversification in the individuals who became superinfected with the same HIV-1 subtype within year one post-seroconversion. We hypothesized that this reflected a blunted NAb response, which may have made these individuals more susceptible to superinfection. RESULTS: Neutralization assays showed that autologous plasma NAb responses to the earliest, and in some cases transmitted/founder, virus were delayed and had low to undetectable titers in all three superinfected individuals prior to superinfection. In contrast, NAbs with a median IC50 titer of 1896 were detected as early as three months post-seroconversion in non-superinfected controls. Early plasma NAbs in all subjects showed limited but variable levels of heterologous neutralization breadth. Superinfected individuals also exhibited a trend toward lower levels of gp120- and V1V2-specific IgG binding antibodies but higher gp120-specific plasma IgA binding antibodies. CONCLUSIONS: These data suggest that the lack of development of IgG antibodies, as reflected in autologous NAbs as well as gp120 and V1V2 binding antibodies to the primary infection virus, combined with potentially competing, non-protective IgA antibodies, may increase susceptibility to superinfection in the context of settings where a single HIV-1 subtype predominates.

Timing and source of subtype-C HIV-1 superinfection in the newly infected partner of Zambian couples with disparate viruses.

BACKGROUND: HIV-1 superinfection occurs at varying frequencies in different at risk populations. Though seroincidence is decreased, in the negative partner of HIV-discordant couples after joint testing and counseling in the Zambia Emory HIV Research Project (ZEHRP) cohort, the annual infection rate remains relatively high at 7-8%. Based on sequencing within the gp41 region of each partner's virus, 24% of new infections between 2004 and 2008 were the result of transmission from a non-spousal partner. Since these seroconvertors and their spouses have disparate epidemiologically-unlinked viruses, there is a risk of superinfection within the marriage. We have, therefore, investigated the incidence and viral origin of superinfection in these couples. RESULTS: Superinfection was detected by heteroduplex mobility assay (HMA), degenerate base counting of the gp41 sequence, or by phylogenetic analysis of the longitudinal sequences. It was confirmed by full-length env single genome amplification and phylogenetic analysis. In 22 couples (44 individuals), followed for up to five years, three of the newly infected (initially HIV uninfected) partners became superinfected. In each case superinfection occurred during the first 12 months following initial infection of the negative partner, and in each case the superinfecting virus was derived from a non-spousal partner. In addition, one probable case of intra-couple HIV-1 superinfection was observed in a chronically infected partner at the time of his seroconverting spouse's initial viremia. Extensive recombination within the env gene was observed following superinfection. CONCLUSIONS: In this subtype-C discordant couple cohort, superinfection, during the first year after HIV-1 infection of the previously negative partner, occurred at a rate similar to primary infection (13.6% [95% CI 5.2-34.8] vs 7.8% [7.1-8.6]). While limited intra-couple superinfection may in part reflect continued condom usage within couples, this and our lack of detecting newly superinfected individuals after one year of primary infection raise the possibility that immunological resistance to intra-subtype superinfection may develop over time in subtype C infected individuals.

The B cell response is redundant and highly focused on V1V2 during early subtype C infection in a Zambian seroconverter.

High-titer autologous neutralizing antibody responses have been demonstrated during early subtype C human immunodeficiency virus type 1 (HIV-1) infection. However, characterization of this response against autologous virus at the monoclonal antibody (MAb) level has only recently begun to be elucidated. Here we describe five monoclonal antibodies derived from a subtype C-infected seroconverter and their neutralizing activities against pseudoviruses that carry envelope glycoproteins from 48 days (0 month), 2 months, and 8 months after the estimated time of infection. Sequence analysis indicated that the MAbs arose from three distinct B cell clones, and their pattern of neutralization compared to that in patient plasma suggested that they circulated between 2 and 8 months after infection. Neutralization by MAbs representative of each B cell clone was mapped to two residues: position 134 in V1 and position 189 in V2. Mutational analysis revealed cooperative effects between glycans and residues at these two positions, arguing that they contribute to a single epitope. Analysis of the cognate gp120 sequence through homology modeling places this potential epitope near the interface between the V1 and V2 loops. Additionally, the escape mutation R189S in V2, which conferred resistance against all three MAbs, had no detrimental effect on virus replication in vitro. Taken together, our data demonstrate that independent B cells repeatedly targeted a single structure in V1V2 during early infection. Despite this assault, a single amino acid change was sufficient to confer complete escape with minimal impact on replication fitness.

Impact of a functional KIR2DS4 allele on heterosexual HIV-1 transmission among discordant Zambian couples.

Killer cell immunoglobulin-like receptors (KIRs) and their HLA ligands interact to regulate natural killer (NK) cell function. KIR gene content and allelic variations are reported to influence human immunodeficiency virus (HIV)-1 infection and pathogenesis. We investigated the impact of KIR genes on heterosexual HIV-1 transmission among 566 discordant couples from Lusaka, Zambia. KIR2DS4*001, the only allele of KIR2DS4 known to encode a functional activating receptor, was associated with relatively high viral load for HIV-1 in index (HIV-1 seroprevalent) partners (ß [standard error (SE)], .17 [.8] log10; P = .04) and with accelerated transmission of HIV-1 to cohabiting seronegative partners (relative hazard [RH], 2.00; P = .004). The latter association was independent of the direction of transmission (male-to-female or female-to-male), genital ulcers, and carriage of the putative ligand (HLA-Cw*04). No KIR-gene variant in the initially seronegative partners was associated with HIV-1 acquisition or early viral load following seroconversion. Further analysis of NK cell function should clarify the role of KIR2DS4*001 in HIV-1 transmission.

Lack of detectable HIV-1-specific CD8(+) T cell responses in Zambian HIV-1-exposed seronegative partners of HIV-1-positive individuals.

Human immunodeficiency virus type 1 (HIV-1)-specific T cell responses were characterized in a blinded study involving infected individuals and their seronegative exposed uninfected (EU) partners from Lusaka, Zambia. HIV-1-specific T cell responses were detected ex vivo in all infected individuals and amplified, on average, 27-fold following in vitro expansion. In contrast, no HIV-1-specific T cell responses were detected in any of the EU partners ex vivo or following in vitro expansion. These data demonstrate that the detection of HIV-1-specific T cell immunity in EU individuals is not universal and that alternative mechanisms may account for protection in these individuals.

Association of chemokine receptor gene (CCR2-CCR5) haplotypes with acquisition and control of HIV-1 infection in Zambians.

BACKGROUND: Polymorphisms in chemokine (C-C motif) receptors 2 and 5 genes (CCR2 and CCR5) have been associated with HIV-1 infection and disease progression. We investigated the impact of CCR2-CCR5 haplotypes on HIV-1 viral load (VL) and heterosexual transmission in an African cohort. Between 1995 and 2006, cohabiting Zambian couples discordant for HIV-1 (index seropositive and HIV-1 exposed seronegative {HESN}) were monitored prospectively to determine the role of host genetic factors in HIV-1 control and heterosexual transmission. Genotyping for eight CCR2 and CCR5 variants resolved nine previously recognized haplotypes. By regression and survival analytic techniques, controlling for non-genetic factors, we estimated the effects of these haplotypic variants on a) index partner VL, b) seroconverter VL, c) HIV-1 transmission by index partners, d) HIV-1 acquisition by HESN partners. RESULTS: Among 567 couples, 240 virologically linked transmission events had occurred through 2006. HHF*2 homozygosity was associated with significantly lower VL in seroconverters (mean beta = -0.58, log10 P = 0.027) and the HHD/HHE diplotype was associated with significantly higher VL in the seroconverters (mean beta = 0.54, log10 P = 0.014) adjusted for age and gender in multivariable model. HHD/HHE was associated with more rapid acquisition of infection by the HESNs (HR = 2.0, 95% CI = 1.20-3.43, P = 0.008), after adjustments for index partner VL and the presence of genital ulcer or inflammation in either partner in Cox multivariable models. The HHD/HHE effect was stronger in exposed females (HR = 2.1, 95% CI = 1.14-3.95, P = 0.018). CONCLUSIONS: Among Zambian discordant couples, HIV-1 coreceptor gene haplotypes and diplotypes appear to modulate HIV-1 VL in seroconverters and alter the rate of HIV-1 acquisition by HESNs. These associations replicate or resemble findings reported in other African and European populations.

Donor and recipient envs from heterosexual human immunodeficiency virus subtype C transmission pairs require high receptor levels for entry.

Compact, glycan-restricted envelope (Env) glycoproteins are selected during heterosexual transmission of subtype C HIV-1. Donor and recipient glycoproteins (Envs) from six transmission pairs were evaluated for entry into HeLa cells expressing different levels of CD4 and CCR5. Donor and recipient Envs demonstrated efficient entry into cells expressing high levels of CD4 and CCR5, and entry declined as CCR5 levels decreased. Infectivity for all Envs was severely impaired in cells expressing low levels of CD4, even at the highest CCR5 levels. In 5/6 pairs, there was no significant difference in efficiency of receptor utilization between the donor and recipient Envs in these HeLa-derived cell lines. Thus, HIV-1 transmission does not appear to select for viruses that can preferentially utilize low levels of entry receptors.

Nonpathogenic simian immunodeficiency virus infection of sooty mangabeys is not associated with high levels of autologous neutralizing antibodies.

Simian immunodeficiency virus (SIV) infection of natural-host species, such as sooty mangabeys (SMs), is characterized by a high level of viral replication and a low level of generalized immune activation, despite evidence of an adaptive immune response. Here the ability of SIV-infected SMs to mount neutralizing antibodies (Nab) against autologous virus was compared to that of human immunodeficiency virus type 1 (HIV-1) subtype C-infected subjects. While high levels of Nab were observed in HIV-1 infection, samples obtained at comparable time points from SM exhibited relatively low titers of autologous Nab. Nevertheless, SM plasma with higher Nab titers also contained elevated peripheral CD4(+) T-cell levels, suggesting a potential immunologic benefit for SMs. These data indicate that AIDS resistance in these primates is not due to high Nab titers and raise the possibility that low levels of Nab might be an inherent feature of natural-host SIV infections.

Escape from autologous neutralizing antibodies in acute/early subtype C HIV-1 infection requires multiple pathways.

One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization.

Inflammatory genital infections mitigate a severe genetic bottleneck in heterosexual transmission of subtype A and C HIV-1.

The HIV-1 epidemic in sub-Saharan Africa is driven largely by heterosexual transmission of non-subtype B viruses, of which subtypes C and A are predominant. Previous studies of subtype B and subtype C transmission pairs have suggested that a single variant from the chronically infected partner can establish infection in their newly infected partner. However, in subtype A infected individuals from a sex worker cohort and subtype B individuals from STD clinics, infection was frequently established by multiple variants. This study examined over 1750 single-genome amplified viral sequences derived from epidemiologically linked subtype C and subtype A transmission pairs very early after infection. In 90% (18/20) of the pairs, HIV-1 infection is initiated by a single viral variant that is derived from the quasispecies of the transmitting partner. In addition, the virus initiating infection in individuals who were infected by someone other than their spouse was characterized to determine if genital infections mitigated the severe genetic bottleneck observed in a majority of epidemiologically linked heterosexual HIV-1 transmission events. In nearly 50% (3/7) of individuals infected by someone other than their spouse, multiple genetic variants from a single individual established infection. A statistically significant association was observed between infection by multiple genetic variants and an inflammatory genital infection in the newly infected individual. Thus, in the vast majority of HIV-1 transmission events in cohabiting heterosexual couples, a single genetic variant establishes infection. Nevertheless, this severe genetic bottleneck can be mitigated by the presence of inflammatory genital infections in the at risk partner, suggesting that this restriction on genetic diversity is imposed in large part by the mucosal barrier.

Diversifying sport-related concussion measures with baseline balance and ocular-motor scores in professional Zambian football athletes.

PURPOSE: Normative values of common sport-related concussion assessment tools may assist clinical diagnosis and management. However, current baseline normative values are not representative of athletic participants across international domains. This study develops healthy baseline norms on the Balance Error Scoring System (BESS), and King-Devick (K-D), providing baseline reference values for professional Zambian football athletes. METHODS: Of the 125 male participants (aged 24.48 ± 5.41 years) screened for this study, 9 (7.2%) reported a previous history of concussion, 98 (78.4%) completed the Balance Error Scoring System and 88 (70.4%) completed the King-Devick. Descriptive statistics calculated for the BESS and the K-D test included mean, standard deviation, median, interquartile range (IQR), and percentiles ranks. MAIN FINDINGS: Participants scored a mean ± standard deviation of 10.15 ± 5.6 and a median [IQR] of 9 [6-12.25] errors on the total BESS and completed the K-D test in a mean ± standard deviation 56.85 ± 10.55 seconds and a median [IQR] 55.28 [48.7-64.8] seconds. CONCLUSIONS: Cross-cultural awareness and management of sport-related concussion are continuously improving the safety and well-being of athletic participants around the world. The diverse representation in these data may aid in interpretation of post-injury performance during sport-related concussion management in Zambia. This study develops baseline reference values currently lacking within African cultures and demonstrates the feasibility and global clinical utility of two sport-related concussion assessment resources.

Cross-cultural exploration of baseline ImPACT Quick Test performance among football athletes in Zambia.

OBJECTIVE: Concussion is a global sport injury; however, this public health issue has yet to be studied across Africa. It is unknown if tests such as the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT) Quick Test (QT) are culturally appropriate for implementation as part of a concussion screening protocol in Zambia or other African nations. Study objectives included: 1) establish that Zambian athletes are able to complete the iPad-based ImPACT QT with respect to language or cultural barriers that may exist, and 2) document baseline neurocognitive percentile ranks among Zambian football athletes on the ImPACT QT. METHODS: This study was completed with adult premiere league football athletes in Zambia (n = 125) aged 24.48 ± 5.41. Participants completed the ImPACT QT neurocognitive assessment prior to a preseason practice. Outcome measures were average performance on 3 factor scores: Motor Speed, Memory, and Attention Tracker, presented as percentile ranks using normative data built-into the ImPACT QT. RESULTS: Zambian athletes scored nearly two standard deviations below the mean on Motor Speed (7th percentile), using North American normative data. However, performance on Attention Tracker (44th percentile) and Memory (56th percentile) was within the average range. CONCLUSION: Results of the current study show that Zambian athletes are able to complete the ImPACT QT, despite any language or cultural differences that may exist. In addition, preliminary percentile ranks suggest Zambian football athletes have average scores on Attention and Memory and below average scores on Motor Speed. These data are the first to explore Zambian athletes' performance on a cognitive concussion measure.