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Background: Antiretroviral therapy (ART) non-adherence and methamphetamine use are associated with higher HIV drug resistance prevalence. How they affect drug resistance mutations accumulation is less studied. Objective: We assessed factors associated with drug resistance mutations accumulation. Methods: We evaluated HIV chronically-infected patients from a clinic-based research cohort on first-line ART regimens with genotype results within 30 days of baseline. Methamphetamine use and ART adherence were self-reported at each study visit. High ART adherence was defined as 0-5% missed doses in the last 30 days. Results: One-hundred twenty-five patients contributed 496 study visits. At baseline, 81% of patients reported high ART adherence; 90% reported no methamphetamine use in the prior 4 months, 8% used monthly or less and 2% used daily or weekly. Methamphetamine users and non-users had similarly high ART adherence (p=0.93). Adjusted incidence rate ratio (aIRR) of drug resistance mutations accumulation was 2.04 (95% CI 0.64, 6.46) for daily/weekly users and 1.71 (95% CI 0.66, 4.42) for patients with monthly or less users, compared to non-users. aIRR was 0.71 (95% CI 0.44, 1.15) with >5-10% missed ART doses and 1.21 (95% CI 0.80, 1.83) with >10% missed doses compared to 0-5% missed doses. Conclusions: We found no strong evidence for the effect of methamphetamine use and ART adherence on drug resistance mutations accumulation. Research cohort patients may have been more engaged in care and treatment adherent than non-cohort patients. Our findings suggest methamphetamine use might not lead to treatment failure among HIV patients who are otherwise engaged in care.

Youth aged 15–24 years comprise 48% of new HIV infections and 15% of persons living with HIV in Kisumu County, Kenya. We assessed factors associated with HIV infection among youth participating in the Community Health Initiative (CHI) implemented in an urban informal settlement in 2018. Predictors of HIV infection were assessed by multivariable logistic regression. CHI engaged 4,441 youth through community health campaigns and home-based HIV testing. HIV prevalence was 3.5% overall and 7.1% among young women aged 20–24. There were 24 youth newly identified as HIV-positive out of 157 total HIV-positive youth. HIV-positive status was positively associated with being female (aOR = 2.46; 95% CI 1.57, 3.84) and aged 20–24 (aOR = 2.40; 95% CI 1.52, 3.79), and inversely associated with secondary school education or higher (aOR = 0.27; 95% CI 0.16, 0.44). Our findings highlight the need for HIV prevention programs specially tailored for youth to further reduce new HIV infections in this priority population.

BACKGROUND Beliefs regarding responsibility for preventing HIV transmission may differ between individuals and their sexual partners. We assessed HIV prevention responsibility beliefs among men who have sex with men (MSM) participating in the 2017 National HIV Behavioral Surveillance survey. METHODS MSM were recruited using time-location sampling at clubs, bars, and street locations in San Francisco. HIV prevention responsibility beliefs were assessed on a four-point scale (1 = strongly disagree to 4 = strongly agree). Associations were assessed using generalizing estimating equations to adjust for behaviors within multiple partnerships. RESULTS A total of 316 HIV-negative men and 76 HIV-positive men reported on 1336 partnerships. HIV-negative compared with HIV-positive men had higher endorsement of mutual responsibility (mean 3.7 vs. 3.5; P < 0.01). Both groups had similar levels of endorsing responsibility on the HIV-negative or HIV-positive partner. HIV-positive men endorsing equal responsibility were more likely to know their partner's HIV status (P < 0.01) and less likely to have serodiscordant condomless anal intercourse (CAI) (P < 0.01) than men who did not endorse equal responsibility. HIV-negative men in partnerships with pre-exposure prophylaxis (PrEP) use were more likely to know their partner's HIV status (P = 0.02) and have serodiscordant CAI (P = 0.04) than men not in partnerships with PrEP use. CONCLUSIONS HIV-negative and HIV-positive men accept responsibility for preventing HIV. The finding that HIV-negative men in partnerships with PrEP use who engage in serodiscordant CAI is concerning because they are still at risk for other sexually transmitted infections, which are presently at elevated levels in San Francisco and other US cities.

Mixed methods studies of human disease that combine surveillance, biomarker, and qualitative data can help elucidate what drives epidemiological trends. Viral genetic data are rarely coupled with other types of data due to legal and ethical concerns about patient privacy. We developed a novel approach to integrate phylogenetic and qualitative methods in order to better target HIV prevention efforts. The overall aim of our mixed methods study was to characterize HIV transmission clusters. We combined surveillance data with HIV genomic data to identify cases whose viruses share enough similarities to suggest a recent common source of infection or participation in linked transmission chains. Cases were recruited through a multi-phase process to obtain consent for recruitment to semi-structured interviews. Through linkage of viral genetic sequences with epidemiological data, we identified individuals in large transmission clusters, which then served as a sampling frame for the interviews. In this article, we describe the multi-phase process and the limitations and challenges encountered. Our approach contributes to the mixed methods research field by demonstrating that phylogenetic analysis and surveillance data can be harnessed to generate a sampling frame for subsequent qualitative data collection, using an explanatory sequential design. The process we developed also respected protections of patient confidentiality. The novel method we devised may offer an opportunity to implement a sampling frame that allows for the recruitment and interview of individuals in high-transmission clusters to better understand what contributes to spread of other infectious diseases, including COVID-19.

Purpose Intergenerational transactional sex (ITS) occurs in Sub-Saharan Africa within the context of widespread poverty and limited employment opportunities. We examined how adolescents describe these relationships, why their peers engage in ITS, and what repercussions adolescents shoulder as a result. Methods We conducted 14 focus group discussions with boys and girls (N = 120) aged 15–19 years in informal settlement communities in Kisumu, Kenya. We used a framework approach to guide data analysis. Results Adolescents referred to a relatively well-off older partner in ITS relationships as a “sponsor.” Poverty proved the main driver of ITS. Boys and girls noted family and peer pressure to have a “better life” via sponsors who provided for three levels of need: urgent (e.g., food), critical (e.g., school fees), and material (e.g., clothes). Adolescents described multiple risks, including “no power” to negotiate condom use. Repercussions included dropping out of school because of community stigma, “abandonment” in the event of pregnancy, and unsafe abortions. Conclusions Adolescents face the difficult choice between the need for money to contribute to their families' income and the discomfort and health risks of a sponsor relationship. The pressure to have a sponsor was higher among out-of-school adolescents and adolescent mothers because of heightened poverty and vulnerability. Structural interventions, such as eliminating school fees, could help reduce adolescents' perceived need to acquire sponsors. Our findings suggest a need to update guidelines for sexual and reproductive health counseling in schools and community settings to openly discuss why ITS is so commonplace and engage in risk reduction conversations with adolescents.

Human immunodeficiency virus (HIV) drug resistance increases mortality and morbidity and antiretroviral therapy (ART) costs. We describe Paraguay's first nationally representative survey on pretreatment drug resistance (PDR) conducted among persons who initiated or reinitiated ART in 2019. ​​​​We conducted a cross-sectional survey of antiretroviral (ARV) drug resistance in Paraguay in 2019. Participants were sampled at four comprehensive care clinics where 90% of patients with HIV in Paraguay initiate ART. Patients included were adults ≥18 years old who initiated first-line ART or reinitiated the same first-line ART regimen after ≥3 months of discontinuation. Of 208 patients, 93.8% had no prior ART exposure, 3.8% reinitiated the same regimen, 2.4% had unknown prior ART exposure; and 31.3% had a CD4 count200 cells/µl. Mutations associated with resistance were present in 15.4% of patients. Mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors (NNRTI) were present in 13.0% of patients, nucleoside reverse transcriptase inhibitors in 4.3%, and integrase inhibitors in 3.4%. Mutations associated with resistance to tenofovir were present in 1.0% of patients and emtricitabine/lamivudine in 1.4%. ​​Nearly one in six patients had PDR in Paraguay's first nationally representative sample. High NNRTI PDR prevalence underscores the need to accelerate the transition to dolutegravir-based first-line ART. The low PDR prevalence of tenofovir and emtricitabine is reassuring as these ARVs are part of the World Health Organization (WHO)-recommended oral pre-exposure prophylaxis regimen. The high proportion of individuals initiating ART at a late disease stage highlights the need to improve treatment linkage strategies and implement WHO rapid ART initiation recommendations.

Travelers may adapt HIV risk-reduction practices based on perceived destination-specific norms. We examined the association between perceived condom norms and condomless anal sex (CAS) during international and domestic travel and in the home environment among men who have sex with men. Men who traveled internationally in the past 12 months were recruited by respondent-driven sampling (N = 501). Not knowing destination-specific condom norms was significantly associated with less CAS during international travel and in the home environment but not during domestic travel. Perceiving home environment condom norms to expect use of condoms was significantly associated with less CAS during domestic but not international travel. Men were less likely to engage in CAS during international travel when destination-specific condom norms were unknown. Unfamiliarity with the environment and culture may influence some men to refrain from higher-risk behaviors. During domestic travel, some men appeared to apply home environment condom norms, which may be erroneous in some situations and pose an HIV risk.

Summary Background Some countries are struggling to reach the UNAIDS target of 90% of all individuals with HIV knowing their HIV status, especially among men and youth. To identify individuals who are unaware of their HIV-positive status and achieve testing saturation, we implemented a hybrid HIV testing approach in an urban informal settlement in western Kenya. In this study, we aimed to describe the uptake of HIV testing and linkage to care and treatment during this programme. Methods The Community Health Initiative involved community mapping, household census, multidisease community health campaigns, and home-based tracking in the informal settlement of Obunga in Kisumu, Kenya. 52 multidisease community health campaigns were held throughout the programme coverage area, at which HIV testing by certified testing service counsellors was one of the health services available. Individuals aged 15 years or older who were not previously identified as HIV-positive, children younger than 15 years who reported being sexually active or for whom testing was requested by a parent or guardian, and individuals who tested HIV-negative within the past 3 months but who reported a recent risk were all eligible for testing. Health and counselling services were tailored for men and youth to encourage their participation. Individuals identified during the census who did not attend a community health campaign were tracked using global positioning system data and offered home-based HIV testing services. We calculated the previously unidentified fraction, defined as the number of individuals who were newly identified as HIV-positive as a proportion of all individuals previously identified and newly identified as HIV-positive. Findings Between Jan 11 and Aug 29, 2018, the Community Health Initiative programme reached 23 584 individuals, of whom 11 526 (48·9%) were men and boys and 5635 (23·9%) were aged 15–24 years. Of 12 769 individuals who were eligible for HIV testing, 12 407 (97·2%) accepted testing, including 3917 (31·6%) first-time testers. 101 individuals were newly identified as HIV-positive out of 1248 total individuals who were HIV-positive, representing an 8·1% previously unidentified fraction. The previously unidentified fraction was highest among men (9·8%) and among people aged 15–24 years (15·3%). Interpretation Community-based hybrid HIV testing was successfully implemented in an urban setting. Innovative approaches that make HIV testing more accessible and acceptable, particularly to men and young people, are crucial for achieving testing and treatment saturation. Focusing on identifying individuals who are unaware of their HIV-positive status in combination with monitoring the previously unidentified fraction has the potential to achieve the UNAIDS Fast Track commitment to end AIDS by 2030. Funding US President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention.

Respondent-driven sampling (RDS) uses long-chain referral whereby members of the target population recruit other members. We describe the use of RDS for a mixed-methods sexual and reproductive health (SRH) study in Kisumu, Kenya.Initial seeds for the cross-sectional surveys were selected from adolescents aged 15-19 residing in urban informal settlements. Participants were provided up to five referral coupons to distribute.Across four communities, 18 seeds were selected, 13,489 coupons distributed, and 3,381 adolescents referred, yielding a 25% coupon return rate. We enrolled 3,061 participants for a 23% survey rate. Median referral lag time was three days (IQR 1, 7). Demographic characteristics reached equilibrium between recruitment waves 5 to 8 in three communities, and waves 7 to 15 in the fourth.Our study demonstrated that RDS is a feasible and efficient approach for recruiting a large sample of adolescents. Though our research focused on SRH, many adolescents residing in the impoverished urban environments where our study was implemented also experience food insecurity, housing instability and violence. RDS can therefore be a valuable recruitment approach for future studies to reach vulnerable adolescents and design interventions that address the variety of health-related challenges that affect this underserved population.

BACKGROUND: Knowledge of HIV status is the entry point for linkage to prevention, care, and treatment, and the first step towards achieving the UNAIDS 90–90-90 targets. Most countries rely on proxies for estimating testing saturation, including periodic population-based sampling and yield (number positive among those tested). We conducted a community-based “Hybrid” HIV testing services (HTS) program to identify persons unaware of their HIV-positive status. SETTING: Homa Bay County, Kenya; July through September 2016 METHODS: We conducted community mapping, household census, multi-disease community health campaigns (CHCs), and home-based tracking. HIV testing eligibility was based on 2015 national guidelines. The previously-unidentified fraction (PUF) was defined as the proportion of newly-identified persons living with HIV (PLWH) out of all previously-identified and newly-identified PLWH. RESULTS: The Hybrid HTS program reached 28,885 persons in total: 25,340 residents and 3,545 non-residents. There were 19,288 persons reached through CHCs and tracking. Of 11,316 individuals eligible for HIV testing, 9,463 (83%) accepted testing, including 1,230 (13%) first-time testers. There were 115 newly-identified PLWH out of 1,589 total HIV-positive persons, representing a 7.2% PUF. Of 93 newly-identified PLWH at the CHCs, 68% initiated same-day antiretroviral therapy. CONCLUSION: The Hybrid HTS program identified persons previously unaware of their HIV-positive status, thereby enabling linkage to care and same-day treatment and reducing onward transmission risk. An approach focused on identifying persons unaware of their HIV-positive status in combination with ascertaining the PUF has the potential to better target testing strategies to identify >90% of PLWH in a community.

OBJECTIVE: We explored potential HIV transmission typologies that involve transgender women to obtain insights on sexual and needle-sharing networks as sources of HIV infection. DESIGN: San Francisco residents diagnosed with HIV in care at public facilities who had available viral pol sequences from June 2001 through January 2016 were included in the analysis. METHODS: Viral sequence data were matched to the San Francisco HIV/AIDS Case Registry to obtain demographic and risk classification information. Transmission clusters with ≥2 cases were identified by bootstrap values ≥90% and mean pairwise genetic distances ≤0.025 substitutions per site. RESULTS: Transgender women represented 275 of 5,200 patients; 86 were present in 70 clusters. Four typologies were hypothesized: 1) transgender women in clusters with men who have sex with men (MSM), 2) transgender women who inject drugs in clusters with cisgender women and men who inject drugs, 3) multiple transgender women in clusters with one man, and 4) multiple transgender women who do not inject drugs in clusters with men and cisgender women who inject drugs. CONCLUSIONS: Transmission patterns of transgender women may stand apart from MSM epidemics. Transgender women clustered with people who inject drugs, and with men who have sex with transgender women and cisgender women. Aggregation of transgender women into the category of MSM may obscure understanding of how they acquire HIV and to whom they may transmit infection. Phylogenetic insights strengthen the case that HIV prevention programs for MSM may not be applicable to transgender women or their partners.

In Kenya, adolescent pregnancy rates are high, contraception utilization is low, and adolescent sexuality is stigmatized. We describe how perceptions of sexuality and pregnancy stigma influence decision-making among adolescents in the informal settlements of Kisumu. We used purposive sampling to recruit 120 adolescent boys and girls ages 15-19 for focus group discussions. A semi-structured interview guide was used to elicit social norms and community attitudes about sexual and reproductive health. We analyzed the data using the Framework Approach. The social stigma of adolescent sexuality and the related fear of pregnancy as an unambiguous marker of sexual activity emerged as main themes. This stigma led adolescents to fear social retribution but did not lead to more frequent contraception use due to additional stigma. The intensity of this fear was most acutely expressed by girls, leading some to seek unsafe, sometimes fatal, abortions, and to contemplate suicide. Fear of pregnancy outweighed fear of contracting HIV which was viewed as both treatable and less stigmatized. Our findings illustrate how fear of pregnancy among these adolescents is driven primarily by fears that their community will discover that they are sexually active. Interventions are urgently needed to address adolescent sexual stigma and to prevent negative outcomes.

HIV cure studies require patients to enter an analytical treatment interruption (ATI). Here, we describe previously unanalyzed data that sheds light on ATI dynamics in PLHIV (People Living with HIV). We present drug resistance mutation dynamics on the pol gene among individuals with antiretroviral virological failure who underwent ATI. The study involved a 12-week interruption in antiretroviral therapy (ART), monitoring of viral load, CD4+/CD8+ T cell counts, and sequencing of the pol gene from 38 individuals experiencing virological failure and harboring 3-class resistant HIV strains: nucleoside reverse transcriptase inhibitors (NRTI) non-nucleoside inhibitors (NNRTI), and protease inhibitors (PI). Protease and reverse transcriptase regions of the pol gene were sequenced at baseline before ATI and every four weeks thereafter from PBMCs and at baseline and after 12 weeks from plasma HIV RNA using population-based Sanger sequencing. Average viral load increased 0.559 log10 copies per milliliter. CD4+ T cell count decreased as soon as ART was withdrawn, an average loss of 99.0 cells/mL. Forty-three percent of the mutations associated with antiretroviral resistance in PBMCs disappeared and fifty-seven percent of the mutations in plasma reverted to wild type, which was less than the 100% reversion expected. In PBMC, the PI mutations reverted more slowly than reverse transcriptase mutations. The patients were projected to need an average of 33.7 weeks for PI to revert compared with 20.9 weeks for NRTI and 19.8 weeks for NNRTI. Mutations in the pol gene can cause virological failure and difficulty in re-establishing effective virological suppression.

Youth aged 15-24 years comprise 48% of new HIV infections and 15% of persons living with HIV in Kisumu County, Kenya. We assessed factors associated with HIV infection among youth participating in the Community Health Initiative (CHI) implemented in an urban informal settlement in 2018. Predictors of HIV infection were assessed by multivariable logistic regression. CHI engaged 4,441 youth through community health campaigns and home-based HIV testing. HIV prevalence was 3.5% overall and 7.1% among young women aged 20-24. There were 24 youth newly identified as HIV-positive out of 157 total HIV-positive youth. HIV-positive status was positively associated with being female (aOR = 2.46; 95% CI 1.57, 3.84) and aged 20-24 (aOR = 2.40; 95% CI 1.52, 3.79), and inversely associated with secondary school education or higher (aOR = 0.27; 95% CI 0.16, 0.44). Our findings highlight the need for HIV prevention programs specially tailored for youth to further reduce new HIV infections in this priority population.

HIV pre-exposure prophylaxis (PrEP) has been embraced in Australia, making PrEP available with public funding to people at risk of HIV. Here, we consider the associated 'problems' of reduced condom use and sexually transmissible infections (STIs), as seen by HIV professionals. Twenty-one interviews were conducted during May-August 2017. All agreed that PrEP was a valuable addition to HIV prevention, but their views about reduced condom use and STIs were variable. Using poststructural policy analysis, three main stances were identified: (1) Concerned/alarmed. PrEP was seen as causing reduced condom use, STIs and antibiotic resistance, posing threats to the general population; (2) Neutral/normalising. Stakeholders emphasised that condom use was declining and STIs increasing independently of PrEP, and that PrEP was simply a new tool to be accommodated; (3) Optimistic/critical. PrEP was seen as diminishing fear of HIV and engaging users in more frequent testing and treatment that could lead to declining STI rates. What linked all three stances was the selective performance of evidence, deploying a mixture of personal experience, clinical observations, behavioural data and epidemiology. Anticipating possible futures through evidence-making suggested practical, political and moral consequences for what PrEP could become. We encourage others to consider these consequences with care.

The broadening of access to HIV pre-exposure prophylaxis (PrEP) in Australia has rekindled debates about which types of clinicians are best suited to deliver HIV prevention innovations: specialist HIV services or primary care physicians and general practitioners (GPs). We conducted 21 semi-structured qualitative interviews in 2017 with Australian HIV sector experts working across policy, advocacy, clinical service provision, research, and health promotion. These interviews took place before a national policy commitment to subsidising access to PrEP was achieved. We explored how participants conceptualised PrEP, patients and GPs at this key turning point in the history of HIV prevention. Participants expressed varied views regarding GPs' anticipated ability to successfully navigate the potential complexities associated with PrEP roll-out. While participants were supportive of greater patient access to PrEP, they expressed concerns about non-specialist GPs' cultural competence and expertise regarding sexuality and clinical practice, and the potential for patients to experience discrimination and homophobia from non-expert GPs. This study has broad implications for thinking about experts and expertise, the implementation of previously specialised medicine into mainstream settings, and the anticipated challenges of LGBTIQ+ inclusive healthcare.

The HIV-1 epidemic in the US has historically been dominated by subtype B. HIV subtype diversity has not been extensively examined in most US cities to determine whether non-B variants have become established, as has been observed in many other global regions. We describe the diversity of non-B variants and present evidence of local transmission of non-B HIV in San Francisco. Viral sequences collected from patients between 2000 and 2016 were matched to the San Francisco HIV/AIDS case registry. HIV subtype was determined using COMET. Phylogenies were reconstructed using the pol region of subtypes A, C, D, G, CRF01_AE, CRF02_AG, and CRF07_BC, with reference sequences from the LANL HIV database. Associations of non-B subtypes and circulating recombinant forms (CRFs) with patient characteristics were assessed using multivariable logistic regression. Out of 11,381 sequences, 10,669 were from 7235 registry cases, of which 141 (2%) had non-B subtypes and CRFs and 72 (1%) had unique recombinant forms. CRF01_AE (0.8%) and subtype C (0.5%) were the most prevalent non-B forms. The frequency of non-B subtypes and CRFs increased in San Francisco during years 2000-2016. Out of 146 transmission events involving non-B study sequences, 18% indicated local transmission within the study population and 74% appeared to be inward migration of the virus. Compared to 7016 cases with only subtype B, 141 cases with non-B sequences were more likely to be of non-US country of birth (aOR = 11.02; p 0.001), of Asian/Pacific-Islander race/ethnicity (aOR = 3.17; p 0.001), and diagnosed after 2009 (aOR = 4.81; p 0.001). Results suggest that most non-B infections were likely acquired outside the US and that local transmission of non-B forms has occurred but so far has not produced extensive transmission networks. Thus, non-B variants were not widely established in San Francisco, an observation that differs from cities worldwide with more diverse epidemics.

BACKGROUND Seroadaptive behaviors refer to a wide range of harm reduction practices to decrease HIV transmission risk. Effective implementation of seroadaptive behaviors is dependent on knowledge of one's own serostatus and that of one's sexual partners. Partner-level and environmental-level attributes may affect seroadaptation practices. We assessed factors associated with seroadaptive behaviors. METHODS Men who have sex with men and transgender women were recruited from an HIV pre-exposure prophylaxis clinical trial (iPrEx) with study sites in the US, Peru, Ecuador, Brazil, Thailand, and South Africa. Partnership-level data were collected at the baseline visit for the 3 most recent partners. Participants were considered to have practiced seroadaptive behaviors if: (1) they believed their partner to be HIV-negative, that is, serosorting; or (2) no condomless receptive sex occurred with an HIV-positive or unknown status partner, that is, seropositioning. RESULTS Of 2331 participants, 41% always practiced seroadaptive behaviors, 36% sometimes did, and 23% never did. Participants enrolled at study sites in the US (P < 0.001) and Peru/Ecuador (P < 0.001) were more likely to practice seroadaptive behaviors, whereas transgender women were less likely to do so (P < 0.001). Seroadaptive behaviors were more likely to occur in relationships with steady partners (P = 0.005) and emotionally close relationships (P = 0.013). CONCLUSIONS Seroadaptive behaviors were more frequently observed among iPrEx participants from the US, Peru, and Ecuador study sites and among participants in relationships with partners who they were more committed to and felt emotionally close to. Our findings suggest that seroadaptive behaviors may be influenced by social norms that vary geographically and culturally.

Introduction To be eligible for government-provided treatment in Brazil, all HCV-infected individuals are required to be genotyped shortly after diagnosis. We describe the HCV genotype (G) profiles by geographic region, gender, age and HIV co-infection. Methods We assessed 29,071 genotypes collected from HCV-infected individuals from March 2016 to March 2018 (Abbott Real-Time HCV Genotype). We randomly selected 12,336 samples for HIV co-infection testing using an EIA rapid test kit (TR DPP HIV 1/2 Bio-Manguinhos). Descriptive statistical analyses were performed using R. Results Overall, HCV genotype distribution was 40.9% G1A, 30.2% G1B, 23.8% G3, 3.8% G2, 0.7% G4, 0.1% G5 and 0.6% with multiples genotypes. G1A prevalence was 44.4% among males and 35.8% among females. G1B and G2 were more prevalent in older individuals than G1A and G3. G3 was more prevalent in the South region. Of samples tested for HIV co-infection, 15% were HIV+. Median age among HCV/HIV co-infected individuals was 50 years old compared to 57 years old among mono-infected individuals. Distinct HCV genotype prevalence between HCV/HIV co-infected and HCV mono-infected individuals were respectively: G1A 60.6% versus 37.8%, G1B 15.2% versus 32.9%, and G3 18.9% versus 24.7%. G4 was detected among co-infected young men (3.5% versus 0.2% among mono-infected). Conclusion The increasing prevalence of G3, as inferred by the younger ages of the HCV-infected individuals, poses an extra challenge with regards to disease progression. Distinct genotypical profiles between HCV mono-infection and HCV/HIV co-infection warrant future research in order to better understand and help mitigate HCV chains of transmission.

As evidence of the safety and effectiveness of HIV pre-exposure prophylaxis (PrEP) has grown, so has attention to the views of prospective users and providers. However, far less attention has been paid to understanding the perspectives of other stakeholders in the rollout of PrEP access programs. We conducted 21 semi-structured qualitative interviews in 2017 with key stakeholders working across the policy, advocacy, research and/or clinical dimensions of the Australian HIV response, before federal support for a subsidised access scheme was achieved. Our analysis explored three areas of shared concern: who is a suitable candidate for PrEP; why are disparities in PrEP access important; and how can disparities be addressed? In examining how this diverse group of professionals grappled with the challenges of promoting 'equitable access' to PrEP in an increasingly resource rationed health system, we can see how the principles believed to underpin the Australian response to HIV were both reaffirmed and challenged through this period of significant change.

Among men who have sex with men traveling internationally, self-reported hepatitis B virus (HBV) vaccination prevalence was 77% and less prevalent among older men and those with HBV infection. The HBV infection prevalence was 25% and was associated with older age and HIV infection. Testing for chronic infection, universal vaccination, and treatment for populations with multiple risks is needed.

HIV pre-exposure prophyalxis (PrEP) might lead individuals to view serodisclosure as unnecessary. We examined the prevalence of non-disclosure and lack of knowledge of partner status in a global cohort of men who have sex with men (MSM) and transgender women (TW) enrolled in the iPrEx Open Label Extension (OLE). We calculated prevalence ratios by fitting a logistic model and estimating predicted probabilities using marginal standardization. Prevalence of non-disclosure and lack of knowledge of partner status were highest in Thailand (73% and 74%, respectively) and lowest in the USA (23% and 37%, respectively). In adjusted analyses, PrEP use was not significantly associated with non-disclosure or lack of knowledge of partner status (p-values>0.05). We found that relationship characteristics were significantly associated with both outcomes. Non-disclosure was higher among casual (adjusted prevalence ratio [aPR] 1.54, [95% confidence interval 1.24-1.84]) and transactional sex partners (aPR 2.03, [1.44-2.62]), and among partners whom participants have known only minutes or hours before their first sexual encounter (aPR 1.62, [1.33-1.92]). Similarly, participants were less likely to know the HIV status of casual partners (aPR 1.50, [1.30-1.71]), transactional sex partners (aPR 1.62, [1.30-1.95]), and those they have known for only days or weeks (aPR 1.13, [0.99-1.27]) or minutes or hours (aPR 1.27, [1.11-1.42]). Our findings underscore the role of dyadic factors in influencing serodisclosure. Comprehensive risk reduction counseling provided in conjunction with PrEP that address relationship characteristics are needed to help patients navigate discussions around HIV status.

This paper focuses on challenges faced by heterosexual couples of mixed HIV status in Porto Alegre, Brazil, and argues for more conceptual nuance in our understanding of 'serodiscordance'. Couples' stories, collected over 11 months of qualitative research, demonstrate how profoundly serodiscordance involves both partners and suggest that the timing of relationship formation relative to HIV diagnosis influenced the particular challenges they confronted. In recognition of this variation, we propose the distinction of 'sero-discovering' from 'sero-cognisant' couples. Though Brazilian health policy strives to address the needs of individuals diagnosed with HIV, the needs of seronegative partners in this cohort received relatively little attention. In addition, the transformation of HIV from a death sentence to a chronic condition both facilitated the formation of serodiscordant unions and raised special challenges for such couples. Conceiving of any person receiving an HIV diagnosis as 'potentially partnered' may help address some of these lacunae while promoting primary prevention within mixed-status couples, and HIV testing more generally. More research with this population is needed.

Objective To evaluate access to treatment after community-based HPV testing as testing within screen-and-treat programs has the potential to lower mortality from cervical cancer in low-resource settings. Methods A prospective cohort study was conducted in western Kenya in 2018. Women aged 25-65 years underwent HPV self-testing. HPV-positive women were referred for cryotherapy. Participant data were obtained from questionnaires during screening and treatment. The proportion successfully accessing treatment and variables associated with successful treatment was determined. Results Of the 750 women included, 140 (18.6%) tested positive for HPV. Of them, 135 were notified of their results, of whom 77 (59.2%) sought treatment and 73 (52.1%) received cryotherapy. Women who received treatment had a shorter time from screening to result notification (median 92 days, interquartile range [IQR] 84-104) compared to those who did not (97 days, IQR 89-106; P=0.061). In adjusted analyses, women with a history of cervical cancer screening (odds ratio [OR] 11, 95% confidence interval [CI] 1.42-85.20) and those electing result notification through a home visit (OR 4, 95% CI 1.23-14.17) were significantly more likely to acquire treatment at follow-up. Conclusion Linkage to treatment after community-based HPV screening in this population was low, highlighting the need for strategies aimed at strengthening treatment linkage in similar settings.

BackgroundEarly initiation of antiretroviral therapy (eiART) can improve clinical outcomes for persons with HIV and reduce onward transmission risk. Baseline drug resistance testing (bDRT) can inform regimen selection upon subsequent treatment initiation. We examined the uptake of eiART and bDRT within 3 months and 30 days of HIV diagnosis.MethodsWe analyzed a population-based sample from the San Francisco Department of Public Health HIV/AIDS Case Registry of newly-diagnosed HIV/non-AIDS individuals between 2001 and 2015 who received care at publicly-funded facilities (N = 3,124).ResultsUptake of eiART within 3 months of diagnosis increased significantly from 2001 to 2015 (pConclusionsObserved increases in eiART and bDRT uptake from 2010 to 2015 may reflect the adoption of treatment as prevention and a local public health policy statement in 2010 recommending treatment initiation at time of diagnosis irrespective of CD4 count. Concerns about stigma may underlie disparities in eiART, however such concerns would not bear as directly on a provider-initiated laboratory test like bDRT.

We examined associations with HIV recent infection and estimated transmitted drug resistance (TDR) prevalence among 3345 men at sexually transmitted infection clinics in Mumbai (2002–2005). HIV seroincidence was 7.92% by the BED-CEIA and was higher at a clinic located near brothels (12.39%) than at a hospital-based clinic (3.94%). HIV recent infection was associated with a lifetime history of female sex worker (FSW) partners, HSV-2, genital warts, and gonorrhea. TDR prevalence among recent infection cases was 5.7%. HIV testing services near sex venues may enhance case detection among high-risk men who represent a bridging population between FSWs and the men’s other sexual partners.

HIV test-seeking behavior among blood donors has been observed worldwide and may pose a threat to the safety of the blood supply. We evaluated current test-seeking motivations and prior alternative HIV testing experiences among blood donors in São Paulo, Brazil. All candidate or potential blood donors were consecutively approached and recruited to participate in the study upon presentation at Fundação Pró-Sangue Hemocentro, the largest blood bank in Brazil. Participants were recruited between August 2012 and May 2013 after they were screened for donor eligibility. Questionnaires were administered through audio computer-assisted self-interview. Among 11,867 donors, 38 % previously tested for HIV apart from blood donation, of whom 47.7 % tested at public facilities and 2.7 % acknowledged getting tested for HIV as the primary reason for donating. Dissatisfaction with prior alternative testing experience was reported by 2.5 % of donors. Current test-seeking motivation was associated with dissatisfaction with prior alternative testing experience and testing at a public alternative facility. The most common reasons for dissatisfaction were too long of a wait to get tested and for results, counseling was too long, lack of privacy, and low confidence in the equipment and accuracy of the test. Lack of awareness about the availability of free and confidential public HIV testing services as well as dissatisfaction with past HIV testing and counseling experiences motivate some individuals to test at blood banks. Test-seeking behavior among blood donors may be best addressed by improving alternative testing programs, particularly with respect to time delays, privacy and perceptions about test accuracy. Educational campaigns on safe blood donation and HIV testing for diagnosis, risk counseling and referral to care are also needed for the general public and for health care providers.

BACKGROUND In a randomized controlled trial (RCT) in a blood bank in Sao Paulo, we tested the hypotheses that offering client-centered human immunodeficiency virus (HIV) counseling and testing to blood donors would: 1) reduce the risk of HIV contamination in the blood supply by diverting higher-risk, test-seeking donors away from donation and 2) increase return for results and referrals to care. STUDY DESIGN AND METHODS We randomly selected weeks between August 2012 and May 2013 when donors were offered HIV counseling and testing (n = 6298), leaving usual procedure weeks as control (n = 5569). RESULTS Few candidate donors chose HIV testing (n = 81, 1.3%). There was no significant difference in herpes simplex virus Type 2 (HSV-2) prevalence (a marker of sexual risk) among donors during intervention weeks compared to control (10.4% vs. 11.1%, p = 0.245). No donor choosing testing was HIV infected, and there was no difference in HSV-2 prevalence between testers and donors (9.9% vs. 10.4%, p = 0.887). Returning for positive results did not differ between testers and donors (three of three vs. 58 of 80, p = 0.386). A higher proportion of donors acknowledged that HIV testing was a strong motivation to donate during intervention weeks compared to control (2.6% vs. 2.0%, p = 0.032). CONCLUSION The evidence of our RCT is that offering HIV counseling and testing at the time of donation would not change the risk of contamination in the blood supply, nor improve results disclosure and referral to care.

We examined whether beliefs about antiretroviral (ART) efficacy and reinfection prospectively predicted subsequent condomless anal intercourse (CAI). Men who have sex with men in San Francisco (N = 773) were recruited for a longitudinal study using time-location sampling. HIV-negative men were more likely to have sero-discordant receptive CAI and HIV-positive men were more likely to have sero-discordant insertive CAI if they previously reported these behaviors at baseline and reported less concern about HIV transmission due to ART. HIV-positive men were more likely to report sero-concordant CAI at follow-up if they reported this behavior at baseline. Previous sexual behavior was consistently the strongest predictor of future sexual behavior. Previous sexual behavior and optimistic beliefs about ART for treatment and prevention predicted subsequent sexual behavior with sero-discordant partners. Since individual-level and population-level benefits of ART depend on persons maintaining adequate drug concentrations, prevention messages should continue emphasizing treatment adherence and practicing a combination of risk-reduction strategies.

Exchange sex and higher education were associated with an increased likelihood of international sexual partnerships (ISPs). Exchange sex and older age were associated with an increased likelihood of condomless sex in ISPs. Educational and socioeconomic factors may create unbalanced power dynamics that influence exchange sex and condomless sex in ISPs.

We evaluated plasma samples HIV-infected individuals with different phenotypic profile among five HIV-infected elite controllers and five rapid progressors after recent HIV infection and one year later and from 10 individuals subjected to antiretroviral therapy, five of whom were immunological non-responders (INR), before and after one year of antiretroviral treatment compared to 175 samples from HIV-negative patients. A targeted quantitative tandem mass spectrometry metabolomics approach was used in order to determine plasma metabolomics biosignature that may relate to HIV infection, pace of HIV disease progression, and immunological response to treatment.Twenty-five unique metabolites were identified, including five metabolites that could distinguish rapid progressors and INRs at baseline. Severe deregulation in acylcarnitine and sphingomyelin metabolism compatible with mitochondrial deficiencies was observed. β-oxidation and sphingosine-1-phosphate-phosphatase-1 activity were down-regulated, whereas acyl-alkyl-containing phosphatidylcholines and alkylglyceronephosphate synthase levels were elevated in INRs. Evidence that elite controllers harbor an inborn error of metabolism (late-onset multiple acyl-coenzyme A dehydrogenase deficiency [MADD]) was detected.Blood-based markers from metabolomics show a very high accuracy of discriminating HIV infection between varieties of controls and have the ability to predict rapid disease progression or poor antiretroviral immunological response. These metabolites can be used as biomarkers of HIV natural evolution or treatment response and provide insight into the mechanisms of the disease.

Background We evaluated plasma samples HIV-infected individuals with different phenotypic profile among five HIV-infected elite controllers and five rapid progressors after recent HIV infection and one year later and from 10 individuals subjected to antiretroviral therapy, five of whom were immunological non-responders (INR), before and after one year of antiretroviral treatment compared to 175 samples from HIV-negative patients. A targeted quantitative tandem mass spectrometry metabolomics approach was used in order to determine plasma metabolomics biosignature that may relate to HIV infection, pace of HIV disease progression, and immunological response to treatment. Results Twenty-five unique metabolites were identified, including five metabolites that could distinguish rapid progressors and INRs at baseline. Severe deregulation in acylcarnitine and sphingomyelin metabolism compatible with mitochondrial deficiencies was observed. β-oxidation and sphingosine‐1‐phosphate-phosphatase-1 activity were down-regulated, whereas acyl-alkyl-containing phosphatidylcholines and alkylglyceronephosphate synthase levels were elevated in INRs. Evidence that elite controllers harbor an inborn error of metabolism (late-onset multiple acyl-coenzyme A dehydrogenase deficiency [MADD]) was detected. Conclusions Blood-based markers from metabolomics show a very high accuracy of discriminating HIV infection between varieties of controls and have the ability to predict rapid disease progression or poor antiretroviral immunological response. These metabolites can be used as biomarkers of HIV natural evolution or treatment response and provide insight into the mechanisms of the disease.

Seroadaptive behaviors have been widely described as preventive strategies among men who have sex with men (MSM) and other populations worldwide. However, causal links between intentions to adopt seroadaptive behaviors and subsequent behavior have not been established. We conducted a longitudinal study of 732 MSM in San Francisco to assess consistency and adherence to multiple seroadaptive behaviors, abstinence and condom use, whether prior intentions predict future seroadaptive behaviors and the likelihood that observed behavioral patterns are the result of chance. Pure serosorting (i.e., having only HIV-negative partners) among HIV-negative MSM and seropositioning (i.e., assuming the receptive position during unprotected anal sex) among HIV-positive MSM were more common, more successfully adhered to and more strongly associated with prior intentions than consistent condom use. Seroconcordant partnerships occurred significantly more often than expected by chance, reducing the prevalence of serodiscordant partnerships. Having no sex was intended by the fewest MSM, yet half of HIV-positive MSM who abstained from sex at baseline also did so at 12 month follow-up. Nonetheless, no preventive strategy was consistently used by more than one-third of MSM overall and none was adhered to by more than half from baseline to follow-up. The effectiveness of seroadaptive strategies should be improved and used as efficacy endpoints in trials of behavioral prevention interventions.

"Seroadaptation" comprises sexual behaviors to reduce the risk of HIV acquisition and transmission based on knowing one's own and one's sexual partners' serostatus. We measured the prevalence of seroadaptive behaviors among men who have sex with men (MSM) recruited through time-location sampling (TLS) across three perspectives: by individuals (N = 1207 MSM), among sexual dyads (N = 3746 partnerships), and for sexual episodes (N = 63,789 episodes) in the preceding six months. Seroadaptation was more common than 100% condom use when considering the consistent behavioral pattern of individuals (adopted by 39.1% vs. 25.0% of men, respectively). Among sexual dyads 100% condom use was more common than seroadaptation (33.1% vs. 26.4%, respectively). Considering episodes of sex, not having anal intercourse (65.0%) and condom use (16.0%) were the most common risk reduction behaviors. Sex of highest acquisition and transmission risks (unprotected anal intercourse with a HIV serodiscordant or unknown status partner in the riskier position) occurred in only 1.6% of sexual episodes. In aggregate, MSM achieve a high level of sexual harm reduction through multiple strategies. Detailed measures of seroadaptive behaviors are needed to effectively target HIV risk and gauge the potential of serosorting and related sexual harm reduction strategies on the HIV epidemic.

Introduction: Advances in laboratory methods capable of detecting recent HIV infection offer the promise of quickly and efficiently measuring HIV incidence in cross-sectional surveys, thereby greatly expanding the capabilities of surveillance programs. We compared HIV-1 incidence estimates derived from 3 different methods: Vironostika-less sensitive, BED capture enzyme immuno assay (BED-CEIA), and repeat testing history. Methods: A cross-sectional analysis was performed using HIV testing data from the population of all men who have sex with men presenting for serological HIV voluntary counseling and testing at the largest testing programs in San Francisco from 2000 to 2004 (n = 15,010). Specimens were evaluated for recent HIV-1 infection using Vironostika-LS and BED-CEIA. Concordance between the 2 assays was assessed using the Kappa statistic. Results: The BED-CEIA and Vironostika-LS concurred in 90% of specimen classifications (Kappa = 0.77; "good" strength of agreement). Predictors of recent HIV-1 infection common to both methods were unprotected receptive anal intercourse (P < 0.001), sex with a known HIV-positive partner (P < 0.001), and amphetamine use (P < 0.01). Temporal trends in HIV-1 incidence were also consistent and stable. Conclusions: There was good concordance in the classification of recent HIV-1 infection between BED-CEIA and Vironostika-LS and in the correlates of acquisition of infection. The findings suggest that these incidence assays can be used for the basic epidemiological purposes of measuring HIV-1 incidence, identifying populations at risk for infection, and tracking the leading edge of the epidemic over time.

Objectives: To evaluate trends in the HIV epidemic among men who have sex with men (MSM) in San Francisco and the implications for HIV prevention. Methods: An ecological approach assessed temporal trends in sexual risk behaviour, sexually transmitted infections (STI), HIV incidence and prevalence from multiple data sources between 1998 and 2007. Results: By 2007, there were over 13 000 HIV-infected MSM living in San Francisco. No consistent upward or downward temporal trends were found in HIV incidence, newly reported HIV cases, AIDS deaths, proportion of AIDS cases using antiretroviral therapy, rectal gonorrhoea or primary and secondary syphilis cases among MSM during the study period. Trends in indicators of sexual risk behaviour among MSM were mixed. Overall, unprotected anal intercourse (UAI) increased in community-based surveys. Among HIV-positive MSM, no significant trends were noted for UAI. Among HIV-negative MSM, UAI with unknown serostatus partners decreased but increased with potentially discordant serostatus partners. Among MSM seeking HIV testing, increases were noted in insertive UAI at anonymous testing sites and at the STI clinic, in receptive UAI at anonymous test sites and in receptive UAI with a known HIV-positive partner at the STI clinic. Conclusions: Temporal trends in multiple biological and behavioural indicators over the past decade describe a hyperendemic state of HIV infection among MSM in San Francisco, whereby prevalence has stabilised at a very high level. In the absence of new, effective prevention strategies this state will persist.

Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes.We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05-1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06-1.25), North America (OR = 1.19; 95% CI: 1.12-1.26), Europe (OR = 1.07; 95% CI: 1.01-1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12-1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92-1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions—a proxy for recent infection—yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs—K101E, K103N, Y181C, and G190A—accounted for80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling.Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen.

There were 1311 newly diagnosed HIV cases in San Francisco between 2005 and 2011 that were linked to care at publicly funded facilities and had viral sequences available for analysis. Of the 214 cases characterized as recently infected with HIV at the time of diagnosis, 25% had a recent sexually transmitted infection diagnosis (vs. 10% among longer-standing HIV infections, P < 0.001) and 57% were part of a phylogenetic transmission cluster (vs. 42% among longer-standing HIV infection, P < 0.001). The association observed between recent HIV infection and having a sexually transmitted infection diagnosis during the interval overlapping likely HIV acquisition points to potential opportunities to interrupt HIV transmission.

Background International travel poses potential challenges to HIV prevention. A number of studies have observed an association between travel and behavioural disinhibition. In the present study, we assessed differences in sexual behaviour while travelling internationally and within the USA, compared with being in the home environment. Methods A probability-based sample of men who have sex with men (MSM) from the San Francisco Bay Area who had travelled internationally in the previous 12 months was recruited through an adapted respondent-driven sampling methodology (N=501). Participants completed interviewer-administered, computer-assisted surveys. Results Detailed partner-by-partner behavioural data by destination type were collected on 2925 sexual partnerships: 1028 while travelling internationally, 665 while travelling within the USA and 1232 while staying in the San Francisco Bay Area. The proportion of partnerships during international travel that involved unprotected anal intercourse (UAI) was lower compared with during domestic travel and staying locally. International travel was associated with decreased odds of receptive UAI (AOR=0.65, p=0.02) compared with staying locally and there was a trend towards decreased odds of insertive UAI (AOR=0.70, p=0.07). Conclusions MSM engaged in proportionately fewer sexual activities which present a high HIV transmission risk when travelling internationally, namely unprotected receptive and insertive anal intercourse and particularly with HIV serodiscordant partners. The lower sexual risk-taking during international travel was robust to controlling for many factors, including self-reported HIV serostatus, age, relationship status and type of partnership. These findings suggest that when travelling internationally, MSM may experience behavioural disinhibition to a lesser extent than had been described previously.

Author(s): Christopoulos, Katerina A; Scheer, Susan; Steward, Wayne T; Barnes, Revery; Hartogensis, Wendy; Charlebois, Edwin D; Morin, Stephen F; Truong, Hong-Ha M; Geng, Elvin H | Abstract: IntroductionClinic-based tracing efforts and public health surveillance data can provide different information about HIV care status for the same patients. The relative yield and how best to use these sources to identify and reengage out-of-care patients is unknown.MethodsAt a large public HIV clinic in San Francisco, we selected a 10% random sample of active patients who were at least 210 days "late" for an HIV primary care visit as of April 1, 2013, for clinic-based outreach. Patients were considered out of care if they did not have an HIV primary care visit in the 210 days before April 1, 2013. We then matched the sample with the San Francisco Department of Public Health HIV surveillance registry. Patients with a CD4 or viral load result in the 210-day period were classified as in care. We compared results from both sources and estimated the cumulative incidence of disengagement from care for the full cohort of clinic patients.ResultsOf 940 patients lost to follow-up, 95 were sampled. Clinic tracing found 60 (63%) in care, 23 (24%) not located, 9 (10%) out of care, 2 (2%) incarcerated, and 1 (1%) had died. Of 42 individuals surveillance classified as out of care, tracing found 22 (52%) were in care. Of 52 patients found to be in care by surveillance, 12 (23%) were out of care by clinic tracing or unable to be located. The naive estimate of the cumulative incidence of disengagement from care at 3 years for the active clinic cohort was 41.1% [95% confidence interval (CI): 37.6 to 44.5]. The use of surveillance data reduced this estimate to 12.7% (95% CI: 18.2 to 25.4), and when further corrected using tracing outcomes, the estimate dropped to only 6.4% (95% CI: 3.4 to 9.4).ConclusionsClinic-based tracing and surveillance data together provide a better understanding of care status than either method alone. Using surveillance data to inform clinic-based outreach efforts may be an effective strategy, although tracing efforts are most likely to be successful if conducted in real time.

Background Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes. Methods and Findings We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05–1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06–1.25), North America (OR = 1.19; 95% CI: 1.12–1.26), Europe (OR = 1.07; 95% CI: 1.01–1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12–1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92–1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions—a proxy for recent infection—yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs—K101E, K103N, Y181C, and G190A—accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling. Conclusions Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen., In this individual patient and sequence-level meta-analysis, Soo-Yon Rhee and colleagues measure regional trends in HIV-1 transmitted drug resistance prevalence and investigate the specific mutations responsible for TDR in different regions and in different virus subtypes., Editors' Summary Background About 35 million people are currently infected with HIV, the virus that causes AIDS by destroying immune system cells and leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected individuals died within ten years of infection. Then, in 1996, effective antiretroviral (ARV) therapy—drug combinations that suppress HIV replication by inhibiting reverse transcriptase and other essential viral enzymes—became available. For people living in affluent countries, HIV/AIDS became a chronic condition, but because ARV therapy was expensive, HIV/AIDS remained fatal in low- and middle-income countries (LMICs). In 2003, the international community began to work towards achieving universal access to ARV therapy. Now, more than 10 million HIV-positive individuals in LMICs receive ARV therapy, usually as a fixed-dose combination of two nucleoside reverse transcriptase inhibitors (NRTIs), such as tenofovir and lamivudine, plus a non-nucleoside reverse transcriptase inhibitor (NNRTI), such as efavirenz or nevirapine. Why Was This Study Done? The global scale-up of ARV therapy has reduced deaths from HIV/AIDS and the incidence of HIV infection in LMICs, but the development of resistance to ARV therapy is threatening these advances. HIV rapidly accumulates genetic changes (mutations), some of which make HIV resistant to ARV therapy. Up to 30% of patients receiving a fixed-dose NRTI/NNRTI combination develop virological failure, and a high proportion of these patients develop mutations associated with resistance to the ARVs in their regimen. Moreover, the proportion of newly infected, ARV-naïve individuals with transmitted drug resistance (TDR) is also increasing. Organizations involved in HIV/AIDS control need to understand the regional and temporal mutational patterns of TDR to inform the development of guidelines for first-line ARV therapy and of inexpensive resistance mutation assays for use in LMICs. Here, using a statistical approach called meta-analysis to combine information from individual patients about the resistance mutations they carry, the researchers investigate the molecular epidemiology of TDR (the patterns of molecular changes underlying TDR in populations) and identify the HIV drug-resistance mutations most responsible for TDR in different world regions. What Did the Researchers Do and Find? The researchers identified 287 studies published between 2000 and 2013 from 111 countries that included the reverse transcriptase sequences of HIV viruses from 50,870 ARV-naïve, HIV-positive individuals. The researchers analyzed each virus sequence for the presence of 93 surveillance drug-resistance mutations (SDRMs) previously shown to be specific indicators of TDR. Meta-analysis of these data indicated that the average overall prevalence of TDR (the proportion of ARV-naïve, HIV-positive individuals infected with a virus carrying one or more SDRMs) ranged from 2.8% in sub-Saharan Africa to 11.5% in North America. In sub-Saharan Africa, the odds (chance) of TDR increased 1.09-fold per year following national ARV scale-up; this increase was attributable to an increase in NRTI- and NNRTI-associated resistance. By contrast, in LMICs in south/southeast Asia, the odds of TDR remained unchanged following ARV scale-up. In Latin America/Caribbean, North America, Europe, and upper-income Asian countries, the odds of TDR have increased by around 1.10-fold per year since 1995, mainly as a result of increased NNRTI resistance. Four NNRTI-associated and 16 NRTI-associated SDRMs accounted for most NNRTI- and NRTI-associated TDR, respectively, in all regions. Notably, in sub-Saharan Africa and south/southeast Asia, most of the NNRTI-associated SDRMs detected were associated with high-level resistance to nevirapine or efavirenz. Finally, the researchers report that 95% of TDR viruses in sub-Saharan Africa and south/southeast Asia were unrelated and had therefore arisen independently. What Do These Findings Mean? Because many drug-resistance mutations reduce HIV’s fitness and tend to be lost rapidly in individuals not exposed to ARV therapy, differences among the datasets used in this meta-analysis with respect to how long each ARV-naïve patient had been infected with HIV before virus sampling may limit the accuracy of these findings. Nevertheless, the finding that most of the TDR strains detected in sub-Saharan Africa and south/southeast Asia arose independently suggests that improved patient adherence to ARV therapy and the use of ARV regimens that contain drugs to which HIV rarely develops resistance (regimens with a high genetic barrier to resistance) should reduce the generation of new ARV-resistant strains and mitigate TDR increases. In addition, the finding that a few NNRTI-resistance mutations were responsible for most cases of transmitted high-level resistance suggests that an inexpensive assay that detects these specific mutations may be useful for pre-therapy screening in LMICs with high TDR levels. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001810. Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and personal stories about living with HIV/AIDS Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on antiretroviral drugs and on universal access to ARV therapy; Avert also provides personal stories about living with HIV/AIDS The World Health Organization provides information on all aspects of HIV/AIDS (in several languages), including its guidelines on the use of antiretroviral therapy for treating and preventing HIV infection The UNAIDS World AIDS Day Report 2014 provides up-to-date information about the AIDS epidemic and efforts to halt it, including progress towards universal access to antiretroviral therapy The Stanford University HIV Drug Resistance Database includes information about surveillance drug-resistant mutations (SDRMs) and an interactive map displaying HIV drug resistance in ARV-naïve populations

Most HIV-1 transmission studies use self-reported history to define the source contact. To evaluate the reliability of epidemiologic source partner reporting, heteroduplex mobility assays (HMAs) were performed comparing the different viral strains present in the partners. Partners were typed for human leukocyte antigen (HLA) to evaluate the degree of shared alleles. Of 11 couples evaluated, HMA analysis confirmed nine transmissions (including 1 oral-genital transmission), indicated probable transmission in 1 couple, and suggested an alternative source partner in another. Nine source partners transmitted a major variant. Four source partners knew their HIV status. Previous HIV monitoring was reported by 5 of the 6 confirmed source partners who were unaware of their HIV status at the time of transmission. We also evaluated potential "sharing of HLA alleles" as a risk factor for HIV-1 acquisition; partners were not found to have a higher degree of shared HLA alleles. Lack of awareness about infection status as a consequence of infrequent testing plays a major role in the secondary transmission of HIV. These findings re-emphasize the importance of using safe sex practices at all times.

Background The rate of human immunodeficiency virus type 1 (HIV-1) infection in Iran has increased dramatically in the past few years. While the earliest cases were among hemophiliacs, injection drug users (IDUs) fuel the current epidemic. Previous molecular epidemiological analysis found that subtype A was most common among IDUs but more recent studies suggest CRF_35AD may be more prevalent now. To gain a better understanding of the molecular epidemiology of HIV-1 infection in Iran, we analyzed all Iranian HIV sequence data from the Los Alamos National Laboratory. Methods All Iranian HIV sequences from subtyping studies with pol, gag, env and full-length HIV-1 genome sequences registered in the HIV databases (www.hiv.lanl.gov) between 2006 and 2013 were downloaded. Phylogenetic trees of each region were constructed using Neighbor-Joining (NJ) and Maximum Parsimony methods. Results A total of 475 HIV sequences were analyzed. Overall, 78% of sequences were CRF_35AD. By gene region, CRF_35AD comprised 83% of HIV-1 pol, 62% of env, 78% of gag, and 90% of full-length genome sequences analyzed. There were 240 sequences re-categorized as CRF_AD. The proportion of CRF_35AD sequences categorized by the present study is nearly double the proportion of what had been reported. Conclusions Phylogenetic analysis indicates HIV-1 subtype CRF_35AD is the predominant circulating strain in Iran. This result differed from previous studies that reported subtype A as most prevalent in HIV- infected patients but confirmed other studies which reported CRF_35AD as predominant among IDUs. The observed epidemiological connection between HIV strains circulating in Iran and Afghanistan may be due to drug trafficking and/or immigration between the two countries. This finding suggests the possible origins and transmission dynamics of HIV/AIDS within Iran and provides useful information for designing control and intervention strategies.

In 2010, the San Francisco Department of Public Health offered antiretroviral therapy (ART) to all its patients with human immunodeficiency virus (HIV) regardless of CD4 count. We assessed trends in time from diagnosis to ART initiation and factors associated with ART initiation among San Francisco residents living with HIV between 2007 and 2011. Time to ART initiation decreased among those diagnosed with higher CD4 count. ART initiation rate was significantly higher in recent years and lower among African Americans, men who have sex with men who also inject drugs, and persons aged ≥50 years. We found a trend toward early treatment. However, racial and social disparities persist.