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

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.

Assessment of Level of Compliance with the Use of Condom Among HIV Infected Couples in Kaduna State, Nigeria.

Background: The use of condom is key in the global fight against HIV and AIDS, this helps to reduce the rate of infection and disease burden in the general Population. This underscores the need to intermittently study or assess level of compliance with the use of condom as a preventive measure. Methods: The research was conducted to assess the level of compliance on condom use among HIV- infected discordant couples in Kaduna State Nigeria. The study was conducted in Antiretroviral (ART) treatment centers of 9 LGAs of the 23 LGAs in Kaduna State Nigeria. A total of 158 couples or 317 individuals were recruited for the study. A detailed questionnaire was used to collect data on demographics, the use of condom and practice of unprotected sex. Discussion: The results obtained in the study shows that majority of the respondents 225(71%) were Christians, and majority 224(70.7%) were unemployed. Most of the respondents 230(72.6%) never used condom while 87(27.4%) used condom. The study also revealed that Educational status of respondents had strong association to their perceived attitude towards use of condom during sex (p- value 0.009) while attitude towards practice of unprotected sex was statistically insignificant (p-value 0.404). There is need to improve on educational coverage for the entire population in order to mitigate the scourge of HIV transmission.

MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed Individuals

Despite the high number of individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who develop coronavirus disease 2019 (COVID-19) symptoms worldwide, many exposed individuals remain asymptomatic and/or uninfected and seronegative. This could be explained by a combination of environmental (exposure), immunological (previous infection), epigenetic, and genetic factors. Aiming to identify genetic factors involved in immune response in symptomatic COVID-19 as compared to asymptomatic exposed individuals, we analyzed 83 Brazilian couples where one individual was infected and symptomatic while the partner remained asymptomatic and serum-negative for at least 6 months despite sharing the same bedroom during the infection. We refer to these as “discordant couples”. We performed whole-exome sequencing followed by a state-of-the-art method to call genotypes and haplotypes across the highly polymorphic major histocompatibility complex (MHC) region. The discordant partners had comparable ages and genetic ancestry, but women were overrepresented (65%) in the asymptomatic group. In the antigen-presentation pathway, we observed an association between HLA-DRB1 alleles encoding Lys at residue 71 (mostly DRB1*03:01 and DRB1*04:01) and DOB*01:02 with symptomatic infections and HLA-A alleles encoding 144Q/151R with asymptomatic seronegative women. Among the genes related to immune modulation, we detected variants in MICA and MICB associated with symptomatic infections. These variants are related to higher expression of soluble MICA and low expression of MICB. Thus, quantitative differences in these molecules that modulate natural killer (NK) activity could contribute to susceptibility to COVID-19 by downregulating NK cell cytotoxic activity in infected individuals but not in the asymptomatic partners.

HIV transmission in sero-discordant couples with the HIV-positive partner in Xinjiang: incidence and associated predictors

Introduction: To control the spread of human immunodeficiency virus (HIV) among sero-discordant couples, we explored the HIV seroconversion and its contributing factors. Methodology: We recruited negative partners in HIV sero-discordant couples to established a prospective cohort between January 2010 and June 2015 from areas with severe HIV epidemic in Xinjiang. Follow up once every 3 months, serological tests and risk behavior surveys every 6 months. Variables were screened by LASSO regression and a Cox proportional hazards model was established. Results: A total of 1162 negative partners of sero-discordant couples were recruited. The seroconversion occurred in 42 negative partners during follow-up period, with a seroconversion rate of 2/100 (95% CI = 1.21-2.27), and the median time for seroconversion was 0.92 years. The Cox model showed that frequency of sexual behavior for nearly six months, consistent condom use, knowledge of the transmission route for HIV, a history of sexually transmitted diseases, recent CD4 + T lymphocyte count were all significant contributing factors to the seroconversion in negative partner of HIV sero-discordant couples. In addition, the Cox model was used to evaluate the risk factors of seroconversion for HIV negative partners. Conclusions: The seroconversion rate of HIV negative partners in Xinjiang was lower. The LASSO Cox model may accurately predict the risk of HIV transmission in sero-discordant couples.

Coping Mechanisms of Previously Diagnosed and New HIV-Discordant, Heterosexual Couples Enrolled in a Pilot HIV Self-Testing Intervention Trial in Central Uganda

Introduction: Learning that a couple has HIV-discordant results can create tensions in the relationship including separation. We explored the coping mechanisms of HIV-discordant, heterosexual couples enrolled in an HIV self-testing (HIVST) intervention trial in Central Uganda.Materials and Methods: This qualitative study was nested within a pilot HIVST intervention trial targeting pregnant women and their male partners in central Uganda. In-depth interviews were conducted with 18 individuals from 13 HIV-discordant couples between July and September 2018; 18 months after the end of the main trial. Data were collected on the couples' initial reactions after learning about their HIV-discordant status, mechanisms adopted by couples to cope with HIV-discordance, and suggestions on how couples in similar situations can be supported. Interviews were transcribed verbatim and analysed manually following a thematic framework approach.Findings: Of the 13 HIV-discordant couples, the female partner was HIV-positive (M–F+) in seven, while the male partner was HIV-positive (F–M+) in six. The mean (±SD) age of the participants was 32.6 (±6.4) years and participants had stayed together for an average of 5.5 (±3.6) years. Fourteen participants from nine couples already knew about their HIV-discordant status by the time they participated in the HIVST trial. After learning about their HIV-discordant status, most individuals (15) thought of abandoning their relationship; three (3) thought of committing suicide. To cope with HIV-discordance, some couples reported that they sought professional counselling support from healthcare providers, and this was particularly true for couples that were already aware of their HIV-discordant status by the time they participated in the HIVST trial. However, new couples that learnt about their HIV-discordant status after participating in the trial reported that they sought psycho-social support from friends or relatives. In the majority of cases, couples reported that they reduced the frequency of sex or abstained from sex. Some couples temporarily separated from their partners, while a few others resorted to using condoms to reduce HIV infection risk.Conclusion: Couples used a variety of approaches to cope with HIV-discordance. Study findings underscore the importance of ongoing professional counselling and psycho-social support in helping couples to cope with HIV-discordance.

Men are the main COVID-19 transmitters: lessons from couples

Background: COVID-19 has affected millions of people worldwide. Clinical manifestations range from severe cases with a lethal outcome to mild or asymptomatic cases. Although there is the same proportion of infected genders, men are more susceptible to severe COVID-19, with a higher risk of death than women. This sex-bias may be explained by biological pathways. Methods: We performed an epidemiological survey from July 2020 to July 2021 including 1744 unvaccinated adult Brazilian couples with at least one infected spouse despite living together during the COVID-19 infection without protective measures. The presence or absence of infection was confirmed by RT-PCR and/or serology results. The couples were divided between groups where both partners were infected (concordant couples) or only one spouse remained asymptomatic despite the close contact with the infected one (discordant couples). Statistical analysis of the collected data was performed aiming to verify a differential transmitter potential between genders in household contact. Results: The combination of our data collected from concordant and discordant couples showed that the man is the first (or the only) affected in the major occurrences when compared to women. Our findings support other published surveys and are in concordance with previous studies of our group. Conclusions: These observations support the hypothesis according to which male individuals are more efficient virus transmitters than females, independently of the use of protective masks. In short, the present study confirmed the existence of gender differences not only for susceptibility to infection and resistance to COVID-19 but also in the transmission rate.

“Immunogenetics of resistance to SARS-CoV-2 infection in discordant couples”

BackgroundDespite the high number of individuals infected by SARS-CoV-2 who develop COVID-19 symptoms worldwide, many exposed individuals remain asymptomatic and/or stay uninfected. This could be explained by a combination of environmental (exposure, previous infection), epigenetic, and genetic factors. Aiming to identify genetic variants involved in SARS-CoV-2 resistance, we analyzed 86 discordant Brazilian couples where one was infected and symptomatic while the partner remained asymptomatic and seronegative despite sharing the same bedroom during the infection. The discordant partners had comparable ages, and genetic ancestry proportions.MethodsWhole-exome sequencing followed by a state-of-the-art method to call genotypes and haplotypes across the highly polymorphic MHC and LRC.ResultsWe observed a minor impact in antigen-presentation genes and KIR genes associated with resistance. Interestingly, genes related to immune modulation, mainly involved in NK cell killing activation/inhibition harbor variants potentially contributing to infection resistance. We hypothesize that individuals prone to produce higher amounts of MICA (possibly soluble), LILRB1, LILRB2, and low amounts of MICB, would be more susceptible to infection.ConclusionAccording to this hypothesis, quantitative differences in these NK activity-related molecules could contribute to resistance to COVID-19 down regulating NK cell cytotoxic activity in infected individuals but not in resistant partners.

A Cross-sectional Study of Female HIV Patient Perspective of Dyadic Adjustment in HIV Sero-concordant and Sero-discordant couples

Background: Dyadic Adjustment is defined as the process with which couples form a steady relationship. This study assessed dyadic adjustment in HIVcouples in Ogun State, Nigeria. Methods: This cross sectional study was carried out among 458 women accessing HIV care in tertiary hospitals in Ogun State, Nigeria. Participants were evaluated using the Revised Dyadic Adjustment Scale and analyzed using the Stata/SE 15.1 statistical Package. Chi-square and t-tests were used to determine the correlates of dyadic adjustment (Distress/Non-distress) while logistic regression was used to determine the predictors of distress. Results: Only 28.82% had relationship distress while the majority (71.18%) had no distress. There was a statistically significant association between marital status and the level of distress. Those who were currently married were less likely to have distress than those who were single or previously married. Conclusion: Those who were not married were more predisposed to distress. More support for these groups is therefore recommended. Keywords: Couple, Distress, Dyadic adjustment, HIV, Sero-concordant, Sero-discordant

Prevalence and predictors of asymptomatic Chlamydia trachomatis and Neisseria gonorrhoeae in a Ugandan population most at risk of HIV transmission

The aim of this study was to establish the prevalence of asymptomatic Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) in key populations at increased risk of transmission of HIV. Additionally, we aimed to identify the associated risk factors for asymptomatic sexually transmitted infections (STIs) and evaluate the acceptability of self-collected samples. Asymptomatic people living with HIV (PLHIV) in the following categories were offered testing: discordant couples, young adults, pregnant patients and those attending the ‘most-at-risk-population’ clinic. Patients provided first-pass urine, self-collected vaginal swabs or both to test for NG and CT by polymerase chain reaction using BD ProbeTec™. Patients also completed an acceptability questionnaire, including the negative partner of an HIV-positive participant. Three hundred and sixty-three PLHIV had an STI screen. Asymptomatic STIs were only diagnosed in women (prevalence 5.7%), overall prevalence 3.9% ( n = 14). Factors independently associated with an STI in women were being under 25 years (OR 9.63 95% CI 1.56–59.5) and having more than one sexual partner (OR 8.06 95% CI 1.07–60.6). Four hundred and seven completed the acceptability questionnaire. More than 95% of patients found self-sampling easy and comfortable and 83.8% would believe the results. Women significantly preferred the option of self-sampling, 56.9% versus 29.3% of men ( p < 0.001). Acceptability of self-sampling was high. Young women with or at risk of HIV are an important target for STI testing regardless of symptoms. There is need for diagnostic tests that are inexpensive, rapid and accurate especially in resource-limited settings.