Increasing intra- and inter-subtype HIV diversity despite declining HIV incidence in Uganda.

HIV incidence has been declining in Africa with scale-up of HIV interventions. However, there is limited data on HIV evolutionary trends in African populations with waning epidemics. We evaluated changes in HIV viral diversity and genetic divergence in southern Uganda over a twenty-five-year period spanning the introduction and scale-up of HIV prevention and treatment programs using HIV sequence and survey data from the Rakai Community Cohort Study, an open longitudinal population-based HIV surveillance cohort. Gag (p24) and env (gp41) HIV data were generated from persons living with HIV (PLHIV) in 31 inland semi-urban trading and agrarian communities (1994 to 2018) and four hyperendemic Lake Victoria fishing communities (2011 to 2018) under continuous surveillance. HIV subtype was assigned using the Recombination Identification Program with phylogenetic confirmation. Inter-subtype diversity was estimated using the Shannon diversity index and intra-subtype diversity with the nucleotide diversity and pairwise TN93 genetic distance. Genetic divergence was measured using root-to-tip distance and pairwise TN93 genetic distance analyses. Evolutionary dynamics were assessed among demographic and behavioral sub-groups, including by migration status. 9,931 HIV sequences were available from 4,999 PLHIV, including 3,060 and 1,939 persons residing in inland and fishing communities, respectively. In inland communities, subtype A1 viruses proportionately increased from 14.3% in 1995 to 25.9% in 2017 (p<0.001), while those of subtype D declined from 73.2% in 1995 to 28.2% in 2017 (p<0.001). The proportion of viruses classified as recombinants significantly increased by more than four-fold. Inter-subtype HIV diversity has generally increased. While p24 intra-subtype genetic diversity and divergence leveled off after 2014, diversity and divergence of gp41 increased through 2017. Inter- and intra-subtype viral diversity increased across all population sub-groups, including among individuals with no recent migration history or extra-community sexual partners. This study provides insights into population-level HIV evolutionary dynamics in declining African HIV epidemics following the scale-up of HIV prevention and treatment programs. Continued molecular surveillance may provide a better understanding of the dynamics driving population HIV evolution and yield important insights for epidemic control and vaccine development.

Efficacy of assisted partner services for people who inject drugs in Kenya to identify partners living with HIV and hepatitis C virus infection: a prospective cohort study.

BACKGROUND: People who inject drugs are at increased risk of both HIV and hepatitis C virus (HCV) infections but face barriers to testing and engagement in care. Assisted partner services are effective in locating people with HIV but are understudied among people who inject drugs. We assessed whether assisted partner services could be used to find, test for HIV and HCV infections, and link to care the partners of people who inject drugs in Kenya. METHODS: In this prospective study at eight sites offering harm-reduction services in Kenya, we enrolled people aged 18 years or older who inject drugs and were living with HIV (index participants) between Feb 27, 2018, and Nov 1, 2021. Index participants provided information about their sexual and injecting partners (ie, anyone with whom they had had sexual intercourse or injected drugs in the previous 3 years), and then community-embedded peer educators located partners and referred them for enrolment in the study (partner participants). All participants underwent testing for HCV infection, and partner participants also underwent HIV testing. Index and partner participants with HIV but who were not on antiretroviral therapy (ART) were linked with treatment services, and those positive for HCV were linked to treatment with direct-acting antivirals. We calculated the number of index participants whom we needed to interview to identify partner participants with HIV and HCV infection. FINDINGS: We enrolled 989 people living with HIV who inject drugs, who mentioned 4705 sexual or injecting partners. Of these 4705 partners, we enrolled 4597 participants, corresponding to 3323 unique individuals. 597 (18%) partner participants had HIV, of whom 506 (85%) already knew their status. 358 (71%) of those who knew they were HIV positive were virally suppressed. 393 (12%) partner participants were HCV antibody positive, 213 (54%) of whom had viraemia and 104 (26%) of whom knew their antibody status. 1·66 (95% CI 1·53-1·80) index participants had to be interviewed to identify a partner with HIV, and 4·24 (3·75-4·85) had to be interviewed to find a partner living with HIV who was unaware of their HIV status, not on ART, or not virally suppressed. To find a partner seropositive for HCV who did not know their antibody status, 3·47 (3·11-3·91) index participants needed to be interviewed. Among the 331 index and partner participants living with HIV who were not on ART at enrolment, 238 (72%) were taking ART at 6-month follow-up. No adverse events were attributed to study procedures. INTERPRETATION: Use of assisted partner services among people with HIV who inject drugs was safe and identified partners with HIV and HCV infections. Assisted partner services was associated with increased uptake of ART for both index participants and partners. FUNDING: US National Institutes of Health.

Virologic Nonsuppression and HIV Drug Resistance Among People Who Inject Drugs and Their Sexual and Injecting Partners in Kenya.

We evaluated the prevalence and correlates of HIV viral nonsuppression and HIV drug resistance (HIV-DR) in a cohort of people who inject drugs living with HIV (PWID-LH) and their sexual and injecting partners living with HIV in Kenya. HIV-DR testing was performed on participants with viral nonsuppression. Of 859 PWID-LH and their partners, 623 (72.5%) were on antiretroviral therapy (ART) ≥4 months and 148/623 (23.8%) were not virally suppressed. Viral nonsuppression was more common among younger participants and those on ART for a shorter duration. Among 122/148 (82.4%) successfully sequenced samples, 55 (45.1%) had detectable major HIV-DR mutations, mainly to non-nucleoside and nucleotide reverse transcriptase inhibitors (NNRTI and NRTI). High levels of HIV-DR among those with viral nonsuppression suggests need for viral load monitoring, adherence counseling, and timely switching to alternate ART regimens in this key population.

Prevalence and correlates of violence among sexual and injecting partners of people who inject drugs living with HIV in Kenya: a cross-sectional study.

BACKGROUND: In Kenya, violence is common among people who inject drugs (PWID) living with HIV and their sexual and injecting partners and may lead to decreased uptake of HIV services, increased HIV risk behaviors, and increased HIV transmission. Violence is defined as any physical harm, threatened harm, or forced sexual acts inflicted on a person in the past year. Understanding the nature of violence and its correlates among PWID and their partners will inform population-specific public health interventions and policy recommendations. METHODS: This is a cross-sectional study nested in a prospective cohort study conducted in eight public health centers, methadone clinics, and needle syringe programs in Nairobi, Kilifi, and Mombasa counties in Kenya. 3,302 sexual and/or injecting partners of PWID living with HIV were recruited through assisted partner services and participated in the study. Prevalence and correlates of violence were identified using the Wald test and negative binomial regression. RESULTS: Out of 3302 study participants, 1439 (44%) had experienced violence within the past year. Physical violence was the most common form of violence experienced (35%), followed by being threatened (23%) or subjected to sexual violence (7%). In an adjusted analysis, female participants reported higher experiences of sexual violence (prevalence ratio [PR] = 2.46; 95% confidence interval [CI] 1.62, 3.74; p < 0.001) compared to male participants. In adjusted analysis, coastal residents had a higher experience of overall violence (PR = 1.48; 95% CI 1.27, 1.72; p < 0.001) than those living in Nairobi. This regional effect was relatively stronger among the female respondents (pinteraction = 0.025). Participants' sex modified the association between region and experiencing violence after adjusting potential confounding factors. CONCLUSIONS: The study reveals the prevalence of violence among PWID and identifies high-risk sub-groups, including women, specifically for sexual violence, and coastal residents. Tailored interventions addressing their unique needs are essential. A holistic approach that combines violence prevention and response, comprehensive harm reduction, healthcare access, and community support is crucial to address the complex issue of drug use and HIV burden among PWID in Kenya for improved health outcomes.

Evolution of HIV virulence in response to disease-modifying vaccines: A modeling study.

Pathogens face a tradeoff with respect to virulence; while more virulent strains often have higher per-contact transmission rates, they are also more likely to kill their hosts earlier. Because virulence is a heritable trait, there is concern that a disease-modifying vaccine, which reduces the disease severity of an infected vaccinee without changing the underlying pathogen genotype, may result in the evolution of higher pathogen virulence. We explored the potential for such virulence evolution with a disease-modifying HIV-1 vaccine in an agent-based stochastic epidemic model of HIV in United States men who have sex with men (MSM). In the model, vaccinated agents received no protection against infection, but experienced lower viral loads and slower disease progression. We compared the genotypic set point viral load (SPVL), a measure of HIV virulence, in populations given vaccines that varied in the degree of SPVL reduction they induce. Sensitivity analyses were conducted under varying vaccine coverage scenarios. With continual vaccination rollout under ideal circumstances of 90 % coverage over thirty years, the genotypic SPVL of vaccinated individuals evolved to become greater than the genotypic SPVL of unvaccinated individuals. This virulence evolution in turn diminished the public health benefit of the vaccine, and in some scenarios resulted in an accelerated epidemic. These findings demonstrate the complexity of viral evolution and have important implications for the design and development of HIV vaccines.

Africa-specific human genetic variation near CHD1L associates with HIV-1 load.

HIV-1 remains a global health crisis1, highlighting the need to identify new targets for therapies. Here, given the disproportionate HIV-1 burden and marked human genome diversity in Africa2, we assessed the genetic determinants of control of set-point viral load in 3,879 people of African ancestries living with HIV-1 participating in the international collaboration for the genomics of HIV3. We identify a previously undescribed association signal on chromosome 1 where the peak variant associates with an approximately 0.3 log10-transformed copies per ml lower set-point viral load per minor allele copy and is specific to populations of African descent. The top associated variant is intergenic and lies between a long intergenic non-coding RNA (LINC00624) and the coding gene CHD1L, which encodes a helicase that is involved in DNA repair4. Infection assays in iPS cell-derived macrophages and other immortalized cell lines showed increased HIV-1 replication in CHD1L-knockdown and CHD1L-knockout cells. We provide evidence from population genetic studies that Africa-specific genetic variation near CHD1L associates with HIV replication in vivo. Although experimental studies suggest that CHD1L is able to limit HIV infection in some cell types in vitro, further investigation is required to understand the mechanisms underlying our observations, including any potential indirect effects of CHD1L on HIV spread in vivo that our cell-based assays cannot recapitulate.

Lessons learned from community engagement regarding phylodynamic research with molecular HIV surveillance data.

INTRODUCTION: The widespread implementation of molecular HIV surveillance (MHS) has resulted in an increased discussion about the ethical, human rights and public health implications of MHS. We narrate our process of pausing our research that uses data collected through MHS in response to these growing concerns and summarize the key lessons we learned through conversations with community members. METHODS: The original study aimed to describe HIV transmission patterns by age and race/ethnicity among men who have sex with men in King County, Washington, by applying probabilistic phylodynamic modelling methods to HIV-1 pol gene sequences collected through MHS. In September 2020, we paused the publication of this research to conduct community engagement: we held two public-facing online presentations, met with a national community coalition that included representatives of networks of people living with HIV, and invited two members of this coalition to provide feedback on our manuscript. During each of these meetings, we shared a brief presentation of our methods and findings and explicitly solicited feedback on the perceived public health benefit and potential harm of our analyses and results. RESULTS: Some community concerns about MHS in public health practice also apply to research using MHS data, namely those related to informed consent, inference of transmission directionality and criminalization. Other critiques were specific to our research study and included feedback about the use of phylogenetic analyses to study assortativity by race/ethnicity and the importance of considering the broader context of stigma and structural racism. We ultimately decided the potential harms of publishing our study-perpetuating racialized stigma about men who have sex with men and eroding the trust between phylogenetics researchers and communities of people living with HIV-outweighed the potential benefits. CONCLUSIONS: HIV phylogenetics research using data collected through MHS data is a powerful scientific technology with the potential to benefit and harm communities of people living with HIV. Addressing criminalization and including people living with HIV in decision-making processes have the potential to meaningfully address community concerns and strengthen the ethical justification for using MHS data in both research and public health practice. We close with specific opportunities for action and advocacy by researchers.

Age and CD4+ T cell counts are inversely associated with HIV drug resistance mutations in treatment naive female sex workers.

The increasing prevalence of human immunodeficiency virus (HIV) drug resistance mutations (HIVDRM) in untreated seropositive persons has consequences for future treatment options. This is extremely important in key populations such as female sex workers (FSWs), where the prevalence of pretreatment drug resistance (PDR) and associated risk factors are unknown. In this study, we analyzed PDR and associated risk factors in recently diagnosed and treatment-naive FSWs in Nairobi, Kenya. In this cross-sectional study, we used 64 HIV-seropositive plasma samples collected from FSWs between November 2020 and April 2021. To identify HIVDRM, the pol gene was amplified and genotyped using sanger sequencing. The effects of age, tropism, CD4+ T cell count, subtype, and location on HIVDRM counts were examined using Poisson regression. Overall, the prevalence of PDR was 35.9% (95% CI: 24.3-48.9), which was strongly influenced by K103N and M184V mutations, which confer resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTI), respectively. Subtype A1 was predominant followed by subtype D with a notable increase in inter-subtype recombinants. We found statistically significant evidence that age was inversely related to HIVDRM. A FSW who is 1 year older had 12% less HIVDRM (incidence rate ratios [IRR]: 0.88; 95% CI: 0.82-0.95; P < .001), after adjusting for CD4+ T cell count, subtype, location, and tropism. Similarly, an increase in CD4+ T cell count by 1 unit, was associated with 0.4% fewer HIVDRM (IRR: 0.996; 95% CI: 0.994-0.998; P = .001), while controlling for the other variables. HIV-1 tropism was not associated with HIVDRM counts. In conclusion, our findings show a high prevalence of NNRTIs. Lower CD4+ T cell counts and younger age were significant risk factors that influenced HIVDRM loads. This finding underscores the relevance of targeted interventions and the importance of continuing to focus on FSWs as a way of addressing the HIV epidemic.

SARS-CoV-2 antibody prevalence, correlates, and access to harm reduction services among people who inject drugs living with and without HIV and their partners in Kenya.

BACKGROUND: In sub-Saharan Africa many people who inject drugs (PWID) are living with undiagnosed or untreated HIV and experience high levels of poverty and conditions that can contribute to worse outcomes from SARS-CoV-2 infection. Identifying the burden of SARS-CoV-2 infection in marginalized populations like PWID may contribute to controlling the pandemic. METHODS: This is a nested cross-sectional study within an ongoing cohort study that recruits PWID living with HIV and their injecting and/or sexual partners at needle and syringe program sites and methadone clinics in Kenya. Blood samples were collected from consenting participants at enrollment to determine SARS-CoV-2 antibodies using a Platellia BioRad SARS-CoV-2 total antibody enzyme-linked immunosorbent assay. Baseline data were collected on HIV status, antiretroviral therapy and methadone adherence. We used logistic regression to identify factors associated with antibody positivity and descriptive statistics to report SARS-CoV-2 antibody prevalence. RESULTS: One thousand participants were enrolled between April and July 2021, of whom 323 (32.3%) were women and 677 (67.7%) were men. Median age of participants was 36 years (interquartile range: 30, 42). SARS-CoV-2 antibody positivity was found in 309 (30.9%) participants. Disruption in obtaining methadone service was reported by 106 (24.3%) of the participants. Men were significantly less likely than women to have SARS-CoV-2 antibodies (adjusted odds ratio [aOR] = 0.68, 95% confidence interval [CI] 0.51, 0.95; p < 0.01) Participants who reported a sexual or injecting partner diagnosed with SARS-CoV-2 were twofold more likely to have SARS-CoV-2 antibodies detected (aOR = 2.21, 95% CI 1.06, 4.58; p < 0.032). Living with HIV was not associated with presence of SARS-CoV-2 antibodies. CONCLUSION: The seroprevalence of SARS-CoV-2 of 30.9% in this cohort suggests high transmission rates within this population. SARS-CoV-2 seroprevalence was similar for people living with and without HIV. A large portion of this population was noted to have had disruption in access to harm reduction services.

Optimized phylogenetic clustering of HIV-1 sequence data for public health applications.

Clusters of genetically similar infections suggest rapid transmission and may indicate priorities for public health action or reveal underlying epidemiological processes. However, clusters often require user-defined thresholds and are sensitive to non-epidemiological factors, such as non-random sampling. Consequently the ideal threshold for public health applications varies substantially across settings. Here, we show a method which selects optimal thresholds for phylogenetic (subset tree) clustering based on population. We evaluated this method on HIV-1 pol datasets (n = 14, 221 sequences) from four sites in USA (Tennessee, Washington), Canada (Northern Alberta) and China (Beijing). Clusters were defined by tips descending from an ancestral node (with a minimum bootstrap support of 95%) through a series of branches, each with a length below a given threshold. Next, we used pplacer to graft new cases to the fixed tree by maximum likelihood. We evaluated the effect of varying branch-length thresholds on cluster growth as a count outcome by fitting two Poisson regression models: a null model that predicts growth from cluster size, and an alternative model that includes mean collection date as an additional covariate. The alternative model was favoured by AIC across most thresholds, with optimal (greatest difference in AIC) thresholds ranging 0.007-0.013 across sites. The range of optimal thresholds was more variable when re-sampling 80% of the data by location (IQR 0.008 - 0.016, n = 100 replicates). Our results use prospective phylogenetic cluster growth and suggest that there is more variation in effective thresholds for public health than those typically used in clustering studies.

Why does age at HIV infection correlate with set point viral load? An evolutionary hypothesis.

BACKGROUND: Set-point viral load (SPVL) correlates with the age at which people acquire HIV. Although immunosenescence may seem like a parsimonious explanation for this, it does not easily explain the observation that the relationship between age and SPVL attenuates when accounting for source partner SPVL. Here we propose an alternative explanation that encompasses this latter finding: that decreasing risk of acquisition with older age generates a selection bottleneck that selects for more virulent strains with age. METHODS: We adapted a previously published model of HIV transmission and evolution (EvoNetHIV), parameterized here for men who have sex with men (MSM). We conducted a series of simulation experiments that vary seven behavioral or clinical parameters that affect exposure risk as people age. We conducted regressions to determine the mean increase in SPVL per 10-year increase in seroconversion age, with and without source SPVL in the model. RESULTS: All runs generated significant relationships between seroconversion age and SPVL when not including source SPVL. All saw attenuated relationships, most to near 0, with source SPVL included. Four of our behavioral measures (relational duration, age-related homophily, coital frequency, and mean age at relationship formation) had clear effects on this relationship, all in the hypothesized direction. Combining multiple forms of behavioral heterogeneity yielded an increase of 0.056 log10 copies/mL SPVL per 10-year increase in seroconversion age, nearly as large as that seen in two empirical studies of age-SPVL correlations in MSM. CONCLUSION: The higher virulence of HIV among those infected later in life may be partly explained by a combination of selective bottlenecks and behavioral heterogeneity by age. Variation in the strength of this effect across populations may be in part due to different behavioral, epidemiological and clinical conditions, and not require assumptions about differences in patterns of immunosenescence among populations.

Assisted Partner Services for People Who Inject Drugs: Index Characteristics Associated With Untreated HIV in Partners.

BACKGROUND: Assisted partner services (APSs) is a feasible, acceptable, and effective strategy that increases uptake of HIV testing; however, it has not been used widely among people who inject drugs (PWID) in Africa to notify sexual and injecting partners of potential exposures to HIV and provide testing services. SETTING: Nairobi, Kilifi, and Mombasa counties in Kenya. METHODS: PWID living with HIV (indexes) were enrolled and asked to provide contact information for sexual and injecting partners who were traced and offered HIV testing. APS efficiency was assessed by the number of indexes needed to interview (NNTI) to find 1 additional partner who was unaware of their HIV status or not on antiretroviral therapy (ART). We defined index participant characteristics associated with greater efficiency, defined as lower NNTIs. RESULTS: Among 783 indexes, the NNTI to identify one partner unaware of their HIV status was 7.1 and to identify one HIV-positive partner not on ART (regardless of status awareness) was 4.1. APS was provided to 977 partners and was more efficient in identifying partners who were not on ART (n = 201) among indexes who were female (NNTI = 2.9 vs. 5.7, P < 0.001), unaware of their HIV status (NNTI = 2.2 vs. 4.2, P = 0.009), not on ART (NNTI = 2.1 vs. 4.9; P < 0.001), not enrolled in a methadone program (NNTI = 3.3 vs. 10.4, P < 0.001), reported injecting <5 years (NNTI = 3.3 vs. 5.0; P = 0.005), or from Nairobi (NNTI = 3.2 vs. 5.6, P < 0.001). CONCLUSION: Scaling up APS among PWID living with HIV with certain characteristics could result in more efficient APS and greater partner engagement in HIV care.

A public health approach to monitoring HIV with resistance to HIV pre-exposure prophylaxis.

BACKGROUND: The risk of HIV pre-exposure prophylaxis (PrEP) failure with sufficient medication adherence is extremely low but has occurred due to transmission of a viral strain with mutations conferring resistance to PrEP components tenofovir (TDF) and emtricitabine (FTC). The extent to which such strains are circulating in the population is unknown. METHODS: We used HIV surveillance data to describe primary and overall TDF/FTC resistance and concurrent viremia among people living with HIV (PLWH). HIV genotypes conducted for clinical purposes are reported as part of HIV surveillance. We examined the prevalence of HIV strains with mutations conferring intermediate to high level resistance to TDF/FTC, defining primary resistance (predominantly K65R and M184I/V mutations) among sequences reported within 3 months of HIV diagnosis and total resistance for sequences reported at any time. We examined trends in primary resistance during 2010-2019 and total resistance among all PLWH in 2019. We also monitored resistance with viremia (≥1,000 copies/mL) at the end of 2019 among PLWH. RESULTS: Between 2010 and 2019, 2,172 King County residents were diagnosed with HIV; 1,557 (72%) had a genotypic resistance test within three months; three (0.2%) had primary TDF/FTC resistance with both K65R and M184I/V mutations. Adding isolated resistance for each drug resulted in 0.3% with primary TDF resistance and 0.8% with primary FTC resistance. Of 7,056 PLWH in 2019, 4,032 (57%) had genotype results, 241 (6%) had TDF/FTC resistance and 15 (0.4% of those with a genotype result) had viremia and TDF/FTC resistance. CONCLUSIONS: Primary resistance and viremia combined with TDF/FTC resistance are uncommon in King County. Monitoring trends in TDF/FTC resistance coupled with interventions to help ensure PLWH achieve and maintain viral suppression may help ensure that PrEP failure remains rare.

Community and Provider Perspectives on Molecular HIV Surveillance and Cluster Detection and Response for HIV Prevention: Qualitative Findings From King County, Washington.

ABSTRACT: Responding quickly to HIV outbreaks is one of four pillars of the U.S. Ending the HIV Epidemic (EHE) initiative. Inclusion of cluster detection and response in the fourth pillar of EHE has led to public discussion concerning bioethical implications of cluster detection and response and molecular HIV surveillance (MHS) among public health authorities, researchers, and community members. This study reports on findings from a qualitative analysis of interviews with community members and providers regarding their knowledge and perspectives of MHS. We identified five key themes: (a) context matters, (b) making sense of MHS, (c) messaging, equity, and resource prioritization, (d) operationalizing confidentiality, and (e) stigma, vulnerability, and power. Inclusion of community perspectives in generating innovative approaches that address bioethical concerns related to the use of MHS data is integral to ensure that widely accessible information about the use of these data is available to a diversity of community members and providers.

Molecular Epidemiology of Individuals Experiencing Unstable Housing or Living Homeless at HIV Diagnosis: Analysis of HIV Surveillance Data in King County, Washington.

We examined patterns of genetic clustering among individuals diagnosed with HIV between 2010 and 2018 using data from King County, Washington's National HIV Surveillance System. Among 2,371 individuals newly diagnosed with HIV, 231 (10%) experienced unstable housing or were living homeless at the time of diagnosis. Among the 1,658 (70%) people with an available HIV-1 pol gene sequence, 1,071 (65%) were identified to be part of 296 genetic clusters. In our analysis, housing status was not associated with genetic clustering (OR 1.02; 95%CI:0.75,1.39). After adjusting for demographic and behavioral factors, people who were living homeless at HIV diagnosis had 35% lower odds of being identified as part of a genetic cluster (AOR 0.65; 95%CI:0.44,0.95) compared to people with stable housing. Our findings highlight that people experiencing unstable housing are disproportionately burdened by HIV, and that within this population in King County, being in a genetic cluster is predominantly associated with substance use.

Evolution during primary HIV infection does not require adaptive immune selection.

Modern HIV research depends crucially on both viral sequencing and population measurements. To directly link mechanistic biological processes and evolutionary dynamics during HIV infection, we developed multiple within-host phylodynamic models of HIV primary infection for comparative validation against viral load and evolutionary dynamics data. The optimal model of primary infection required no positive selection, suggesting that the host adaptive immune system reduces viral load but surprisingly does not drive observed viral evolution. Rather, the fitness (infectivity) of mutant variants is drawn from an exponential distribution in which most variants are slightly less infectious than their parents (nearly neutral evolution). This distribution was not largely different from either in vivo fitness distributions recorded beyond primary infection or in vitro distributions that are observed without adaptive immunity, suggesting the intrinsic viral fitness distribution may drive evolution. Simulated phylogenetic trees also agree with independent data and illuminate how phylogenetic inference must consider viral and immune-cell population dynamics to gain accurate mechanistic insights.

HIV transmission patterns among transgender women, their cisgender male partners, and cisgender MSM in Lima, Peru: A molecular epidemiologic and phylodynamic analysis.

BACKGROUND: Transgender women (TW) in Peru are disproportionately affected by HIV. The role that cisgender men who have sex with TW (MSTW) and their sexual networks play in TW's risk of acquiring HIV is not well understood. We used HIV sequences from TW, MSTW, and cisgender men who have sex with men (MSM) to examine transmission dynamics between these groups. METHODS: We used HIV-1 pol sequences and epidemiologic data collected through three Lima-based studies from 2013 to 2018 (n = 139 TW, n = 25 MSTW, n = 303 MSM). We identified molecular clusters based on pairwise genetic distance and used structured coalescent phylodynamic modeling to estimate transmission patterns between groups. FINDINGS: Among 200 participants (43%) found in 62 clusters, the probability of clustering did not differ by group. Both MSM and TW were more likely to cluster with members of their own group than would be expected based on random mixing. Phylodynamic modeling estimated that there was frequent transmission from MSTW to TW (67·9% of transmission from MSTW; 95%CI = 52·8-83·2%) and from TW to MSTW (76·5% of transmissions from TW; 95%CI = 65·5-90·3%). HIV transmission between MSM and TW was estimated to comprise a small proportion of overall transmissions (4·9% of transmissions from MSM, and 11·8% of transmissions from TW), as were transmissions between MSM and MSTW (7·2% of transmissions from MSM, and 32·0% of transmissions from MSTW). INTERPRETATION: These results provide quantitative evidence that MSTW play an important role in TW's HIV vulnerability and that MSTW have an HIV transmission network that is largely distinct from MSM.

Characteristics associated with HIV and hepatitis C seroprevalence among sexual and injecting partners of HIV positive persons who inject drugs in Nairobi and coastal Kenya.

BACKGROUND: Persons who inject drugs (PWID) have higher HIV and hepatitis C virus (HCV) seroprevalence than the general population in many parts of sub-Saharan Africa (SSA). The seroprevalences of HIV and HCV are also higher in coastal Kenya than in Nairobi. Understanding drivers of regional HIV and HCV variation among PWID in Kenya may inform population-specific prevention interventions. METHODS: Using a cross-sectional study, we defined HIV and HCV seroprevalence among persons identified as sexual or injecting partners of HIV positive PWID in two regions of Kenya and used logistic regression to identify demographic and behavioral characteristics associated with higher seroprevalence. RESULTS: Among 2386 partners, 469 (19.7%) tested HIV positive and 297(12.4%) tested HCV antibody positive. Partners on the Coast were more likely to live with HIV (seroprevalences: Coast = 23.8%, Nairobi = 17.1%; p < 0.001) and be HCV antibody positive (seroprevalences: Coast = 17.0%, Nairobi = 8.6%; p < 0.001). After adjusting for sex, age, and years injecting and accounting for clustering by site, the higher prevalence of both diseases in the Coast remained significant for HIV (OR 1.68, 95% CI 1.13-2.51) but not for HCV (OR 1.72, 95% CI 0.84-3.74). Compared to those recruited in Nairobi, partners on the Coast were older (Coast = 35 years, Nairobi = 31 years; p < 0.001), more likely to be male (Coast = 77.6%, Nairobi = 61.7%; p < 0.001), to have paid (Coast = 59.2%, Nairobi = 32.8%; p < 0.001) or received (Coast = 44.2%, Nairobi 35.4%; p < 0.001) money for sex, or to have had sex with someone they knew to be HIV positive (Coast 22.0%, Nairobi 10.8%; p < 0.001). Partners who had injected for five or more years had 1.48 times greater odds (95% CI 1.20-1.82) of living with HIV compared to partners who injected less than 5 years and more than twice the odds of HCV (95% CI 1.84-4.11). CONCLUSION: HIV and HCV seroprevalence among sexual and injecting partners of PWID was, respectively, 5 times and > 12 times greater than is reported among the general population in Kenya (4% and < 1%, respectively). Providing resources and education will be crucial to reduce exposure and to maintain the lower needle and equipment sharing that we observed compared to other studies.

Participation in methadone programs improves antiretroviral uptake and HIV viral suppression among people who inject drugs in Kenya.

BACKGROUND: HIV prevalence among people who inject drugs (PWID) in Kenya is estimated to be 18% compared to 4.5% in the general population. Studies from high-income countries have demonstrated that methadone use is associated with increased uptake of antiretroviral therapy (ART) and higher rates of viral suppression among PWID with HIV. However, it is unclear whether methadone use has the same effect among African PWID living with HIV. METHODS: We performed a cross-sectional study to evaluate associations between methadone program participation and ART uptake and viral suppression (HIV RNA viral load <1000 copies/ml) among PWID with HIV in Kenya. Participants were recruited from needle and syringe programs and methadone clinics, interviewed on site, and samples were obtained and assayed for HIV viral loads. Univariate and multiple logistic regression were used to determine associations. RESULTS: Among 679 participants, median age was 37 years, 48% were female, and 24% were in a methadone program. We observed higher proportions of ART use (96% vs. 87%, p = 0.001) and HIV viral suppression (78% vs. 65%, p = 0.012) among PWID on methadone compared to those not on methadone treatment. PWID who were not participating in a methadone program were 3-fold more likely to be off ART and approximately twice as likely to be viremic compared to those in methadone programs (adjusted odds ratio [aOR] = 3.35, 95% confidence interval [CI]: 1.35-8.35 and aOR = 1.90, 95% CI: 1.03-3.52, respectively). CONCLUSIONS: In this study, Kenyan PWID living with HIV participating in a methadone treatment program were more likely to be on ART and to have achieved viral suppression. Scale-up of methadone programs may have a positive impact on HIV epidemic control for this key population.