Search

Introduction: The "Migrants' Approached Self-Learning Intervention in HIV/AIDS for Tajiks" (MASLIHAT) recruits and trains Tajik labour migrants who inject drugs as peer educators (PEs) in delivering HIV prevention information and encouragement to adopt risk-reduction norms and practices within their diaspora social networks while reducing their own HIV risk., Methods: The MASLIHAT intervention was tested in Moscow in a cluster-randomized controlled trial with 12 recruitment sites assigned to either the MASLIHAT intervention or an equal-time peer-educator training focused on other health conditions (TANSIHAT). From October 2021 to April 2022, 140 male Tajik migrants who inject drugs were recruited as PEs to attend the 5-session MASLIHAT training or the TANSIHAT non-HIV comparison condition. Each participant in both groups recruited two network members (NMs) who inject drugs with the intent to share with them the information and positive strategies for change they had learned (n = 280). All PEs and NMs (n = 420) participated in baseline and follow-up interviews at 3-month intervals for 1 year. All received HIV counselling and testing. Modified mixed effects Poisson regressions tested for group differences in injection practices, sexual risk behaviours and heavy alcohol use over time., Results: At baseline, across both groups, 75% of participants reported receptive syringe sharing (RSS), 42% reported condomless sex and 20% reported binge drinking at least once a month. In contrast to TANSIHAT where HIV risk behaviours remained the same, significant intervention effects that were sustained over the 12 months were observed for receptive syringe and ancillary equipment sharing among both MASLIHAT PEs and NMs (p < 0.0001). Significant declines in the prevalence of sexual risk behaviours were also associated with the MASLIHAT intervention (p < 0.01), but not the comparison condition. Binge alcohol use was not affected in either condition; the MASLIHAT intervention had a transitory effect on drinking frequency that dissipated after 9 months., Conclusions: The MASLIHAT peer-education intervention proved highly effective in reducing HIV-related injection risk behaviour, and moderately effective in reducing sexual risk behaviour among both PEs and NMs. Network-based peer education is an important tool for HIV prevention among people who inject drugs, especially in environments that are not amenable to community-based harm reduction., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Introduction: Assisted partner notification (APN) safely and effectively increases partner awareness of HIV exposure, testing and case identification in community settings. Nonetheless, it has not been specifically developed or evaluated for use in prison settings where people with HIV often are diagnosed and may have difficulty contacting or otherwise notifying partners. We developed Impart, a prison-based APN model, and evaluated its efficacy in Indonesia to increase partner notification and HIV testing., Methods: From January 2020 to January 2021, 55 incarcerated men with HIV were recruited as index participants from six jail and prison facilities in Jakarta in a two-group randomized trial comparing the outcomes of self-tell notification (treatment as usual) versus Impart APN in increasing partner notification and HIV testing. Participants voluntarily provided names and contact information for sex and drug-injection partners in the community with whom they had shared possible HIV exposure during the year prior to incarceration. Participants randomized to the self-tell only condition were coached in how to notify their partners by phone, mail or during an in-person visit within 6 weeks. Participants randomized to Impart APN could choose between self-tell notification or anonymous APN by a two-person team consisting of a nurse and outreach worker. We compared the proportion of partners in each group who were notified of exposure by the end of 6 weeks, subsequently tested and HIV diagnosed., Results: Index participants (n = 55) selected 117 partners for notification. Compared to self-tell notification, Impart APN resulted in nearly a six-fold increase in the odds of a named partner being notified of HIV exposure. Nearly two thirds of the partners notified through Impart APN (15/24) completed HIV testing within 6 weeks post notification compared to none of those whom participants had self-notified. One-third of the partners (5/15) who completed HIV testing post notification were diagnosed as HIV positive for the first time., Conclusions: Voluntary APN can be successfully implemented with a prison population and within a prison setting despite the many barriers to HIV notification that incarceration presents. Our findings suggest that the Impart model holds considerable promise to increase partner notification, HIV testing and diagnosis among sex and drug-injecting partners of HIV-positive incarcerated men., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

The human immunodeficiency virus (HIV) epidemic in Eastern Europe and Central Asia continues to grow with most infections occurring in high-risk groups including people who inject drugs and their sexual partners. Labor migrants from this region who inject drugs while in Russia are at especially high HIV risk. Male Tajik migrant workers who inject drugs in Moscow (N = 420) were interviewed prior to a randomized trial of the Migrants' Approached Self-Learning Intervention in HIV/AIDS (MASLIHAT) peer-education HIV-prevention intervention. Participants were interviewed about their sex and drug use behavior and tested for HIV and hepatitis C (HCV) prior to the intervention. Only 17% had ever been tested for HIV. Over half of the men reported injecting with a previously used syringe in the past month, and substantial proportions reported risky sexual behavior. Prevalence rates of HIV (6.8%) and HCV (2.9%) were elevated, although lower than expected when compared to estimates of prevalence among people who inject drugs at the national level in Tajikistan. Risk behavior in diaspora varied across the men's regional area of origin in Tajikistan and occupation in Moscow, with HIV prevalence rates highest among those working at the bazaars. Evidence-based prevention approaches and messaging that specifically address the drug- and sex-related risk behavior of migrants with varying backgrounds are needed.

Background: Assisted partner notification (APN) is recommended as a public health strategy to increase HIV testing in people exposed to HIV. Yet its adoption in many countries remains at an early stage. This qualitative study sought the opinions of HIV health service providers regarding the appropriateness and feasibility of implementing APN in Indonesia where such services are on the cusp of adoption., Methods: Four focus group discussions totaling 40 health service providers were held in Jakarta, Indonesia to consider APN as an innovative concept and to share their reactions regarding its potential implementation in Indonesia. Voice-recorded discussions were conducted in Bahasa, transcribed verbatim, and analyzed., Results: Participants recognized APN's potential in contacting and informing the partners of HIV-positive clients of possible viral exposure. They also perceived APN's value as a client-driven service permitting clients to select which of three partner notification methods would work best for them across differing partner relationships and settings. Nonetheless, participants also identified personal and health system challenges that could impede successful APN adoption including medical and human resource limitations, the need for specialized APN training, ethical and equity considerations, and lack of sufficient clarity concerning laws and government policies regulating 3 rd party disclosures. They also pointed to the job-overload, stress, personal discomfort, and the ethical uncertainty that providers might experience in delivering APN., Conclusion: Overall, providers of HIV services embraced the concept of APN but forecast practical difficulties in key service areas where investments in resources and system change appeared necessary to ensure effective and equitable implementation., (© 2023. The Author(s).)

Intimate partner violence (IPV) in China is a largely understudied, major health risk among women living with HIV. Using structured face-to-face interviews, this research examined partner and couple relationship characteristics associated with physical and sexual IPV among 219 HIV-positive women living with a male partner in Ruili, China. Twenty-nine women (13%) reported past-year occurrences of physical IPV, and 24 (11%) reported sexual IPV. Physical IPV was more common when the woman's partner was of Jingpo ethnicity, drank weekly, or learned of her HIV status indirectly from a third person. Reduced risk of physical IPV was associated with a woman's perceived confidant support that was available through either her partner or a minimum of 2 non-partner confidants. Sexual IPV was more often reported among women with a partner who drank frequently or was concurrently HIV-positive, or in situations where the woman was employed and the partner was not. Sexual IPV was less likely with a partner of Dai ethnicity than Han, the major ethnicity in China. Identifying determinants of IPV vulnerability among women living with HIV may help future interventions to achieve greater impact in similar settings., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We developed and pilot-tested the Migrants' Approached Self-Learning Intervention in HIV/AIDS for Tajiks (MASLIHAT). We recruited 30 Tajik labor migrants who inject drugs in Moscow as peer educators (PEs) to attend the 5-session intervention, then share what they learned with their peers. Each PE recruited two drug-injecting network members for interviewing about their drug and sexual behavior at baseline, 6 weeks, 3 months, and 6 months post-intervention. GEE and mixed effects regression tested time and participant type effects on each outcome. HIV knowledge and risk perception increased among both PEs and network peers, while use of shared syringes, condomless sex, sex with a sex worker, and alcohol use decreased significantly for both groups at 6 weeks and 3 months with a sustained effect through 6 months. The MASLIHAT intervention proved successful in disseminating HIV prevention information and reducing HIV risk behavior over 6 months among both PEs and network members., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Genetic editing of induced pluripotent stem (iPS) cells represents a promising avenue for an HIV cure. However, certain challenges remain before bringing this approach to the clinic. Among them, in vivo engraftment of cells genetically edited in vitro needs to be achieved. In this study, CD34 + cells derived in vitro from iPS cells genetically modified to carry the CCR5Δ32 mutant alleles did not engraft in humanized immunodeficient mice. However, the CD34 + cells isolated from teratomas generated in vivo from these genetically edited iPS cells engrafted in all experiments. These CD34 + cells also gave rise to peripheral blood mononuclear cells in the mice that, when inoculated with HIV in cell culture, were resistant to HIV R5-tropic isolates. This study indicates that teratomas can provide an environment that can help evaluate the engraftment potential of CD34 + cells derived from the genetically modified iPS cells in vitro. The results further confirm the possibility of using genetically engineered iPS cells to derive engraftable hematopoietic stem cells resistant to HIV as an approach toward an HIV cure., Competing Interests: The authors declare no competing interest.

Objectives: To understand key factors influencing Chilean health care providers' perceived comfort performing oral rapid HIV testing., Design: One hundred and fifty health care providers completed a self-administered questionnaire that included a five-item scale measuring self-perceived comfort in conducting HIV pretest counseling, oral rapid testing, finger-prick testing, and delivering test results., Results: Most participants (60%) envisioned good overall comfort performing oral rapid HIV testing (mean score of 16.21; range 0-20), including doing at least four of the five steps. They perceived least comfort delivering HIV-positive test results during posttest counseling. HIV stigmatizing attitudes reduced self-perceived comfort., Conclusions: Providing training to counter HIV stigmatization while increasing comfort in performing oral rapid testing would help facilitate its successful implementation.

Objective: To assess the in-vitro CCR5---tropic and CXCR4---tropic HIV---1 infectivity of immune cells, particularly macrophages, derived from CCR5 gene---edited induced pluripotent stem cells (iPSCs) obtained from the peripheral blood mononuclear cells (PBMC) of HIV---infected patients on antiretroviral therapy (ART)., Design: PBMC were obtained from six patients who had been HIV---infected for over 20 years and were on ART for 1---12 years prior to this study., Methods: The PBMC were derived into iPSCs and genetically edited with TALENs or CRISPR---cas9 endonucleases combined with PiggyBac technology to introduce the naturally occurring 32---bp deletion to the CCR5 gene. These iPSCs were differentiated into macrophages, and subsequently challenged with CCR5---tropic or CCR5/CXCR4 dual--- tropic HIV---1 strains. iPSC derivation, gene editing and immune cell differentiation were done in feeder---free, xeno---free in-vitro conditions., Results: Multiple unedited (wild---type) and CCR5 gene---edited (mutant) iPSCs were derived from patients' PBMC. When differentiated into immune cells and HIV---1 challenged, mutant iPSC lines were resistant to CCR5---tropic and to some extent to CCR5/CXCR4 dual---tropic HIV---1 infection when compared to wild---type iPSC lines., Conclusion: Our study demonstrates that iPSC---derived, gene---edited immune cells are resistant to distinct HIV---1 strains. These findings have important implications for both in-vitro stem cell development and therapeutic approaches to cure HIV infection.

We examined virological non-suppression (VLN) among youth ages 13-24 years receiving HIV treatment in public health facilities in six southern Malawi districts. We also tested three ART adherence measures to determine how well each identified VLN: pill counts, a Likert scale item, and a visual analogue scale. VLN was defined as HIV RNA > 1000 copies/ml. Of the 209 youth, 81 (39%) were virally non-suppressed. Male gender and stigma were independently associated with VLN; social support and self-efficacy were independently protective. Pill count had the highest positive predictive value (66.3%). Using a pill count cut-off of < 80% nonadherence, 36 (17%) of the youth were non-adherent. Of the adherent, 120 (69%) were viral suppressed. Results indicate the need to address HIV-related stigma and to bolster social support and selfefficacy in order to enhance viral suppression. In the absence of viral load testing, pill count appears the most accurate means to assess VLN.

Partner services provide a safe and humane way for people living with HIV (PLWH) to alert their sex and/or drug-injecting partners to the possibility of HIV exposure and the need for HIV testing, yet little is known about the ethical challenges of delivering partner services in prisons. In this article, we consider 7 key ethical and methodological questions that should be considered when developing, testing, or implementing partner services in prison settings. These questions relate to the ethics of: (1) mandatory HIV testing, (2) health illiteracy, (3) level of prison staff involvement, (4) protecting confidentiality, (5) minimizing harm, (6) achieving equivalency with community standards of care, and (7) providing HIV prevention and treatment services to index patient and their partners. By assisting PLWH in prison to inform partners with whom they may have shared HIV exposure either before or during incarceration, partner services can help to identify cases of undiagnosed HIV infection for testing and linkage to medical care. The acceptability and effectiveness of a future partner services model for PLWH in prison depends critically on answering these 7 questions to assure the highest ethical standards of research and practice.

Objective: Evidence links depression and stress to more rapid progression of HIV-1 disease. We conducted a randomized controlled trial to test whether an intervention aimed at improving stress management and emotion regulation, mindfulness-based stress reduction (MBSR), would improve immunological (i.e. CD4+ T-cell counts) and psychological outcomes in persons with HIV-1 infection., Methods: We randomly assigned participants with HIV-1 infection and CD4 T-cell counts >350 cells/μl who were not on antiretroviral therapy in a 1:1 ratio to either an MBSR group (n = 89) or an HIV disease self-management skills group (n = 88). The study was conducted at the University of California at San Francisco. We assessed immunologic (CD4, c-reactive protein, IL-6, and d-dimer) and psychological measures (Beck Depression Inventory for depression, modified Differential Emotions Scale for positive and negative affect, Perceived stress-scale, and mindfulness) at 3, 6 and 12 months after initiation of the intervention; we used multiple imputation to address missing values., Results: We observed statistically significant improvements from baseline to 3-months within the MBSR group in depression, positive and negative affect, perceived stress, and mindfulness; between group differences in change were significantly greater in the MBSR group only for positive affect (per item difference on DES-positive 0.25, 95% CI 0.049, 0.44, p = .015). By 12 months the between group difference in positive affect was not statistically significant, although both groups had trends toward improvements compared to baseline in several psychological outcomes that were maintained at 12-months; these improvements were only statistically significant for depression and negative affect in the MBSR group and perceived stress for the control group. The groups did not differ significantly on rates of antiretroviral therapy initiation (MBSR = 39%, control = 29%, p = .22). After 12 months, the mean decrease in CD4+ T-cell count was 49.6 cells/μl in participants in the MBSR arm, compared to 54.2 cells/μl in the control group, a difference of 4.6 cells favoring the MBSR group (95% CI, -44.6, 53.7, p = .85). The between group differences in other immunologic-related outcomes (c-reactive protein, IL-6, HIV-1 viral load, and d-dimer) were not statistically significant at any time point., Conclusions: MBSR improved positive affect more than an active control arm in the 3 months following the start of the intervention. However, this difference was not maintained over the 12-month follow-up and there were no significant differences in immunologic outcomes between intervention groups. These results emphasize the need for further carefully designed research if we are to translate evidence linking psychological states to immunological outcomes into evidence-based clinical practices., (Copyright © 2018. Published by Elsevier Inc.)

Using an ecological model, we describe substance use and sexual risk behaviors of young male laborers at a roadside market in Malawi. Data included observations and interviews with 18 key market leaders and 15 laborers (ages 18-25 years). Alcohol, marijuana, and commercial sex workers (CSWs) were widely available. We identified three patterns of substance use: 6 young men currently used, 6 formerly used, and 3 never used. Substance use was linked to risky sex, including sex with CSWs. The market supported risky behaviors through availability of resources; supportive norms, including beliefs that substance use enhanced strength; and lack of restraints. Community-level poverty, cultural support for alcohol, interpersonal family/peer influences, early substance use, and school dropout also contributed to risky behaviors. Parental guidance was protective but not often reported. Local programs addressing substance use and risky sex simultaneously and better national substance use policies and mental health services are needed., (Copyright © 2015 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.)

Objective: This study identified the personal characteristics that affect Chilean health care providers' readiness to adopt HIV Oral Rapid Testing (ORT) in Chile as a new clinical evidence-based practice (EBP)., Methods: Using a cross-sectional research design, the study sampled 150 nurses, midwives, and physicians employed at four clinics within the Pontifícia Universidad Católica de Chile Health Network in Santiago. Participants completed a self-administered survey asking about their demographic background, EBP attitudes and experience, personal beliefs related to HIV, the importance of HIV testing, and perceived self-comfort in performing a rapid HIV test., Results: Of the participants, 90% believed that incorporating ORT would make a positive difference in their practice and said that they would be willing to adopt the technology for that reason. Nonetheless, the providers reported a mean "readiness to implement ORT" score of 15.1 out of a possible value of 20, suggesting only moderate self-perceived readiness to adopt the EBP. Education, beliefs about evidence-based practice, perceived comfort in performing ORT, and perceived importance of HIV testing explained 43.6% of the variance in readiness to adopt ORT., Conclusion: The findings of this first ORT pre-implementation study in Chile can help guide policy makers and HIV stakeholders to prepare for and increase primary health care providers' readiness to successfully adopt this evidence-based technology. Successful adoption of ORT could increase Chile's capacity to reach HIV-vulnerable Chileans for testing and referral to care if infected, thus helping the country to reduce further transmission of the virus and its medical complications.

Since the discovery of HIV over three decades ago, major efforts have been made to control and perhaps eliminate HIV infection worldwide. During these studies, certain myths or misconceptions about this infectious disease have been emphasized and other potentially beneficial concepts have received less attention. A true long-term solution to HIV infection merits an appreciation of alternative ideas and findings that could be beneficial in the ultimate control of HIV/AIDS. Here, I discuss six issues and call for more attention to the science of HIV and well-designed clinical trials., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Cross-reactive peptides on HIV-1 and FIV p24 protein sequences were studied using peripheral blood mononuclear cells (PBMC) from untreated HIV-1-infected long-term survivors (LTS; >10 y of infection without antiretroviral therapy, ART), short-term HIV-1 infected subjects not on ART, and ART-treated HIV-1 infected subjects. IFNγ-ELISpot and CFSE-proliferation analyses were performed with PBMC using overlapping HIV-1 and FIV p24 peptides. Over half of the HIV-1 infected subjects tested (22/31 or 71%) responded to one or more FIV p24 peptide pools by either IFNγ or T-cell proliferation analysis. PBMC and T cells from infected subjects in all 3 HIV(+) groups predominantly recognized one FIV p24 peptide pool (Fp14) by IFNγ production and one additional FIV p24 peptide pool (Fp9) by T-cell proliferation analysis. Furthermore, evaluation of overlapping SIV p24 peptide sequences identified conserved epitope(s) on the Fp14/Hp15-counterpart of SIV, Sp14, but none on Fp9-counterpart of SIV, Sp9. The responses to these FIV peptide pools were highly reproducible and persisted throughout 2-4 y of monitoring. Intracellular staining analysis for cytotoxins and phenotyping for CD107a determined that peptide epitopes from Fp9 and Fp14 pools induced cytotoxic T lymphocyte-associated molecules including perforin, granzyme B, granzyme A, and/or expression of CD107a. Selected FIV and corresponding SIV epitopes recognized by HIV-1 infected patients indicate that these protein sequences are evolutionarily conserved on both SIV and HIV-1 (e.g., Hp15:Fp14:Sp14). These studies demonstrate that comparative immunogenicity analysis of HIV-1, FIV, and SIV can identify evolutionarily-conserved T cell-associated lentiviral epitopes, which could be used as a vaccine for prophylaxis or immunotherapy.

Individuals homozygous for the C-C chemokine receptor type 5 gene with 32-bp deletions (CCR5Δ32) are resistant to HIV-1 infection. In this study, we generated induced pluripotent stem cells (iPSCs) homozygous for the naturally occurring CCR5Δ32 mutation through genome editing of wild-type iPSCs using a combination of transcription activator-like effector nucleases (TALENs) or RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 together with the piggyBac technology. Remarkably, TALENs or CRISPR-Cas9-mediated double-strand DNA breaks resulted in up to 100% targeting of the colonies on one allele of which biallelic targeting occurred at an average of 14% with TALENs and 33% with CRISPR. Excision of the piggyBac using transposase seamlessly reproduced exactly the naturally occurring CCR5Δ32 mutation without detectable exogenous sequences. We differentiated these modified iPSCs into monocytes/macrophages and demonstrated their resistance to HIV-1 challenge. We propose that this strategy may provide an approach toward a functional cure of HIV-1 infection.

Background: This study examines the influence of the double jeopardy of being both a migrant and an injection drug user on the social marginalization of male Tajik labor-migrants working in Moscow and the influence of this dual-marginalization on HIV risk., Methods: Three focus group discussions of 8 participants each were conducted in Moscow with a total of 24 Tajik male migrants who regularly inject drugs (IDUs)., Results: Results suggest that male Tajik IDUs are at double jeopardy for social marginalization from both Russian society and their own Tajik migrant community. In the absence of adequate knowledge about HIV risk through needle-borne infection, such dual social rejection can help to push Tajik migrant IDUs toward forging close social alliances with their drug-using peers based on a sense of community through sharing drugs and injection equipment. Sexual contact with Russian female sex workers, many of whom use drugs, further contributes to HIV vulnerability and forms a potential bridge for the cross-over of the virus between both populations. With little to no access to formal health services, family and friends living in Moscow can form a sole source of social support at a personal level that can over-ride general community censure but which can lessen or disappear as drug dependency increases., Conclusion: Both drug and health services are sorely needed for this highly vulnerable population., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Antiretroviral therapy (ART) significantly reduced the CD8 cell noncytotoxic anti-HIV response in 12 HIV-1-infected subjects (P < 0.0001). In separate experiments, CD8(+) cells from long-term survivors were cocultured with HIV-infected CD4(+) cells using varying concentrations of anti-HIV drugs. The antiviral function of CD8(+) cells from 4 of the 14 LTSs was reduced with exposure to 10 μM of nevirapine (P < 0.05). The antiviral activity of CD8(+) cells from 2 LTSs was inhibited by 5 μM of zidovudine. These studies indicate that nevirapine and probably zidovudine can inhibit the anti-HIV activity of CD8(+) cells and thus could influence the effectiveness of antiretroviral therapy.

In HIV-1 infection, plasmacytoid dendritic cell (PDC) numbers and function are decreased. No detailed comparisons of PDC responses to various stimuli in HIV-1-infected patients are available. Using for the first time purified PDCs, we compared PDC responses [interferon (IFN)-α production/cell] to various stimuli in a large number (n=48) of HIV-1-infected patients and healthy volunteers (n=19). Toll-like receptor (TLR)7- and TLR9-induced expression of PDC surface activation and maturation markers was also compared in the two populations. We have confirmed that PDC number coincides with CD4(+) T cell counts and clinical state. Notably, we have shown that a direct association of PDC function in terms of IFN-α production/cell exists with PDC numbers and CD4(+) cell counts when PDCs are exposed to a TLR9 ligand and HIV-infected cells, but not with a TLR7 ligand. Moreover, in the HIV-infected subjects but not the healthy controls, the magnitude of IFN-α release per PDC in response to the TLR7 ligand is significantly (p<0.01) lower than that to the TLR9 ligand. However, in both study populations, the TLR7 stimulation in comparison to TLR9 stimulation induced higher expression of PDC surface activation and maturation markers and significantly (p<0.05) decreased the expression of BDCA-2, a negative regulator of interferon. Furthermore, the cross-ligation of BDCA-2 significantly (p<0.05) inhibited TLR9- but not TLR7-induced IFN-α production by PDCs from both clinical groups. These findings suggest that differences exist in TLR7- and TLR9-induced IFN-α production by PDCs in HIV-infected individuals that are not directly related to BDCA-2 down-modulation.

Identifying both Human immunodeficiency virus (HIV)-related and co-morbid symptoms experienced by people living with HIV (PLWH) who are receiving antiretroviral therapy (ART) treatment is a major challenge for healthcare providers globally. Yet, little research to date has examined the symptoms of illness experienced by PLWH including patients living in Central and South American. To address this gap, this study was designed to identify symptoms of HIV by socio-demographic and/or clinical characteristics among Chilean patients living with the virus. A convenience sample of 209 Chilean PLWH was recruited from an outpatient clinic in Santiago, Chile. A structured interview was used to elicit socio-demographic information and HIV symptoms status. Additional clinical information was obtained through a review of the participants' medical records. Results show that patients' most commonly reported HIV-related symptoms were fear/worries (66%), anxiety (52%), gas/bloating (50%), and thirst (50%). Multivariate analysis revealed a positive association between the number of reported HIV-related symptoms and number of years living with HIV. Having completed college was negatively associated with number of symptoms. Latent class analysis indicated that PLWH in the sample who had completed college were two times more likely to experience a mild intensity of HIV-related symptoms than their lesser educated counterparts. Similarly, logistic regression revealed that college-educated PLWH were twice as likely to be classified in the subgroup reporting mild intensity of symptoms than those who lacked a college degree. Overall, the study's results reveal that many Chilean PLWH, even those with high CD4 counts and low or undetectable viral loads, are not symptom free. The findings point to the need for clinicians to tailor a plan of care for individuals living with HIV that is based on their symptomatology.

While human immunodeficiency virus (HIV) transmission through the adult oral route is rare, mother-to-child transmission (MTCT) through the neonatal/infant oral and/or gastrointestinal route is common. To study the mechanisms of cell-free and cell-associated HIV transmission across adult oral and neonatal/infant oral/intestinal epithelia, we established ex vivo organ tissue model systems of adult and fetal origin. Given the similarity of neonatal and fetal oral epithelia with respect to epithelial stratification and density of HIV-susceptible immune cells, we used fetal oral the epithelium as a model for neonatal/infant oral epithelium. We found that cell-free HIV traversed fetal oral and intestinal epithelia and infected HIV-susceptible CD4(+) T lymphocytes, Langerhans/dendritic cells, and macrophages. To study the penetration of cell-associated virus into fetal oral and intestinal epithelia, HIV-infected macrophages and lymphocytes were added to the surfaces of fetal oral and intestinal epithelia. HIV-infected macrophages, but not lymphocytes, transmigrated across fetal oral epithelia. HIV-infected macrophages and, to a lesser extent, lymphocytes transmigrated across fetal intestinal epithelia. In contrast to the fetal oral/intestinal epithelia, cell-free HIV transmigration through adult oral epithelia was inefficient and virions did not infect intraepithelial and subepithelial HIV-susceptible cells. In addition, HIV-infected macrophages and lymphocytes did not transmigrate through intact adult oral epithelia. Transmigration of cell-free and cell-associated HIV across the fetal oral/intestinal mucosal epithelium may serve as an initial mechanism for HIV MTCT.

Acquired immune deficiency syndrome (AIDS) was first described 30 years ago in a report from the US Centers for Disease Control. Two years later the causative virus was identified and afterwards named the human immunodeficiency virus (HIV). This article reviews the progress made in the three decades since the recognition of AIDS and the discovery of HIV, with respect to the virus, the infected cell, and the host, as well as directions for future studies., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The challenge of controlling HIV infection involves an understanding of the heterogeneity of the virus, its wide cellular host range, its primary routes of transmission, and the immunologic and intrinsic cellular factors that can prevent its transmission and replication. Identification of HIV-infected individuals who have survived more than 10 years without signs of the infection and without therapy encourages studies examining the natural mechanisms for resistance to infection and disease. Within the immune system, emphasis should be given to the innate or natural response that appears within minutes of the infection and offers the optimal time for controlling HIV. All these parameters in HIV pathogenesis underline the information needed to develop optimal anti-HIV therapies and an effective AIDS vaccine.

HIV replication is suppressed in vitro by a CD8(+) cell noncytotoxic antiviral response (CNAR). This activity directly correlates with an asymptomatic clinical state. The objective of this study was to identify the phenotype of CD8(+) cell subsets having strong CNAR activity. CD8(+) cell subset frequencies and CNAR levels were measured for human immunodeficiency virus (HIV)-uninfected individuals and three groups of HIV type 1 (HIV-1)-infected individuals: asymptomatic individuals with low-level viremia (vHIV), antiretroviral-drug-treated subjects with undetectable virus levels (TxHIV), and therapy-naïve aviremic elite controllers (EC). CD8(+) cells from the vHIV individuals exhibited the highest HIV-suppressing activity and had elevated frequencies of CD45RA(-) CD27(+) and PD-1(+) (CD279(+)) cells. Functional assessments of CD8(+) cells sorted into distinct subsets established that maximal CNAR activity was mediated by CD45RA(-) CCR7(-) CD27(+) and PD-1(+) CD8(+) cells. T cell receptor (TCR) repertoire profiles of CD8(+) cell subsets having strong CNAR activity exhibited increased perturbations in comparison to those of inactive subsets. Together, these studies suggest that CNAR is driven by HIV replication and that this antiviral activity is associated with oligoclonally expanded activated CD8(+) cells expressing PD-1 and having a transitional memory cell phenotype. The findings better describe the identity of CD8(+) cells showing CNAR and should facilitate the evaluation of this important immune response in studies of HIV pathogenesis, resistance to infection, and vaccine development.

Background: Female sex workers' (FSWs') use of alcohol, a known disinhibitor to risk behaviour, has been largely understudied. Knowledge of how various sex work venues influence FSW's alcohol consumption before engaging in commercial sex is even rarer. Our analysis identifies those factors across three types of sex-work venues that predict alcohol use among FSWs prior to paid sexual intercourse with clients. Our data were collected through structured interviews with FSWs engaging in commercial sex in Senggigi Beach, Lombok Island in the eastern Indonesian province of West Nusa Tenggara., Methods: Employing a cross-sectional and multilevel design, three categories of venues where FSWs meet clients in Senggigi were sampled: (1) discotheques and bars (freelance), (2) brothels, and (3) recreational enterprises such as karaoke establishments and massage parlors. The sample consisted of 115 women "nested" within 16 sex work venues. The FSWs reported on 326 clients interactions., Results: Results show that FSWs consumed alcohol before commercial sex with 157 (48%) of the 326 clients interactions. Alcohol use varied by differences in HIV policies and services offered at the sex work venue, the FSW's educational level and age, and client characteristics., Conclusion: Alcohol use is common prior to sexual intercourse among FSWs and their clients in Senggigi, and the venue where FSWs meet their clients influences the women's alcohol use. Freelancers were likelier to use alcohol than those who work at brothels and recreational enterprises. Given the recognized links between alcohol use prior to sex and high risk behaviour, HIV prevention programmes that discourage alcohol use should be introduced to both women who engage in commercial sex and also sex-work venue managers, owners, and clients., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The number of people ages 50 or older living with HIV in the United States is increasing. Yet, few older adults see themselves at risk of infection. This study examines the heuristic reasoning that low income, minority adults, ages 50 or older use in calculating the likelihood of infection. The data are drawn from face-to-face interviews with a sample of 134 African American and Latino residents, ages 50 to 86, living in low-income housing in Chicago, Illinois, and Hartford, Connecticut. Results show that nearly half of the study's participants thought themselves to be at some level of risk for HIV. In self-assessing their risk, they relied on seven heuristic categories: self-imperilment, social imperilment, fate, incidental contact, situational safety, medical iatrogenesis, and self-protection. These findings extend our understanding of how individuals make sense of their likelihood of experiencing a major health threat and provide insight into more effective HIV prevention programming for older adults., (Copyright © 2011 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.)

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.

Little is known about the manipulation of IL-17 producing CD4+ T cells (T(H)17) on a per-cell basis in humans in vivo. Previous studies on the effects of IL-2 on IL-17 secretion in non-HIV models have shown divergent results. We hypothesized that IL-2 would mediate changes in IL-17 levels among recently HIV-1-infected adults receiving anti-retroviral therapy. We measured cytokine T cell responses to CD3/CD28, HIV-1 Gag, and CMV pp65 stimulation, and changes in multiple CD4+ T cell subsets. Those who received IL-2 showed a robust expansion of naive and total CD4+ T cell counts and T-reg counts. However, after IL-2 treatment, the frequency of T(H)17 cells declined, while counts of T(H)17 cells did not change due to an expansion of the CD4+ naïve T cell population (CD27+CD45RA+). Counts of HIV-1 Gag-specific T cells declined modestly, but CMV pp65 and CD3/CD28 stimulated populations did not change. Hence, in contrast with recent studies, our results suggest IL-2 is not a potent in vivo regulator of T(H)17 cell populations in HIV-1 disease. However, IL-2-mediated T-reg expansions may selectively reduce responses to certain antigen-specific populations, such as HIV-1 Gag.

Most of the HIV-infected long term survivors show strong CD8+ cell noncytotoxic antiviral response (CNAR) that plays as an important factor for maintaining the relative healthy state of infected individuals. HIV infected former blood donors (FBDs) in Anhui, China are the unique population that considered infected by the same or a related HIV strain by the same exposure route, and is better to be studied for viral and host immunological factors associated with disease progression, such as CNAR. We examined CNAR in 63 asymptomatic untreated HIV infected FBDs with different CD4+ cell counts and plasma viral loads. The average CD8+ : CD4+ cell ratio to reach 90% suppression of HIV replication in the groups with CD4+ cell counts of >500, 300-500 and <300 cells/microl were 0.85 : 1, 1.47 : 1 and 1.88 : 1 respectively (P<0.0001). The average CD8+ : CD4+ cell ratio to reach 90% suppression of HIV replication was 1.07 : 1 and 1.66 : 1 in the group with plasma viral load of <30,000 and >30,000 RNA copy/ml respectively (P=0.0002). The results indicated that CNAR activity in long-term HIV-1 infected FBDs correlates directly with CD4+ cell counts, and correlates reversely with plasma viral loads. Our findings in long term infected FBDs confirm the clinical relevancy of CNAR and suggest that CNAR could be an additional marker to help determine the optimal time for starting therapy in HIV infected person.

Introduction: CD8+ lymphocytes can suppress HIV replication without killing the infected cells. This CD8+ cell noncytotoxic anti-HIV response (CNAR) is associated with a beneficial clinical course., Materials and Methods: In this longitudinal study of 16 participants in the Options Project at UCSF, we measured the ability of CD8+ lymphocytes to suppress HIV replication in CD4+ cells during primary HIV infection, early antiretroviral therapy, and after treatment., Results and Discussion: CD8+ lymphocytes from subjects with untreated primary HIV-1 infection strongly suppressed HIV replication. Initiation of antiretroviral therapy during primary HIV-1 infection caused a marked decline in this CNAR. CD8+ cells from these subjects regained anti-HIV activity when early therapy was discontinued. The timing of the appearance of CD8+ cell anti-HIV activity directly correlated with the emergence of detectable virus levels. Maximal CNAR activity coincided with a decay in the kinetics of HIV replication. In addition, peak viral loads during treatment interruption were lower than pre-treatment virus levels (median reduction = 0.8 logs, p = 0.005) and CD4+ T cell counts were maintained for a 24-week period of follow-up., Conclusion: These results suggest that CNAR plays an important role in suppressing HIV replication in the setting of antiretroviral treatment interruption in HIV-infected individuals.

The most up-to-date estimates demonstrate very heterogeneous spread of HIV-1, and more than 30 million people are now living with HIV-1 infection, most of them in sub-Saharan Africa. The efficiency of transmission of HIV-1 depends primarily on the concentration of the virus in the infectious host. Although treatment with antiviral agents has proven a very effective way to improve the health and survival of infected individuals, as we discuss here, the epidemic will continue to grow unless greatly improved prevention strategies can be developed and implemented. No prophylactic vaccine is on the horizon. However, several behavioral and structural strategies have made a difference--male circumcision provides substantial protection from sexually transmitted diseases, including HIV-1, and the application of antiretroviral agents for prevention holds great promise.

CD8(+) cells from healthy HIV-1-infected individuals suppress human immunodeficiency virus (HIV) replication in infected cells by a non-cytotoxic mechanism. This activity is associated with the production of a soluble CD8(+) cell antiviral factor (CAF) that inhibits viral replication at the level of transcription. Strong CD8(+) cell non-cytotoxic anti-HIV responses (CNARs) correlate with an asymptomatic state and long-term survival of HIV-infected individuals. This antiviral activity is lost when the infected individual advances to disease. In attempts to define the gene(s) mediating CNAR we have evaluated differential gene expression between CD8(+) cells from infected subjects with high CNAR and CD8(+) cells from uninfected controls that lack this activity. The expression analysis, using the Affymetrix GeneChip Human Genome U133 Set, indicated that 18% of the genes were differentially expressed (DE) of which 9.2% were up-regulated. A total of 568 genes were up-regulated with a >2.0-fold difference in expression levels and a >50% concordance of difference call. Stringent selection criteria narrowed down the list to 52 up-regulated 'high confidence genes' (> or = 75% concordance). These genes function in a wide variety of cellular processes and include 13 associated with immunologic activity.

We have developed a single-step reverse transcriptase kinetic PCR assay (kRT-PCR) to accurately determine the expression of each of the 24 TCRbetaV gene families in CD8(+) cells. We analyzed the long-term effects of highly active antiretroviral therapy (HAART) on the stability of the CD8(+) T cell receptor (TCR) repertoire in a cohort of 15 treated and 10 untreated individuals diagnosed with human immunodeficiency virus (HIV) infection. The CD4(+) TCR repertoire was studied in a second cohort receiving interleukin-2 infusions in addition to HAART. Analysis was based on kinetic (quantitative) reverse-transcription PCR (kRT-PCR) of the TCR variable B gene (TCRbetaV). Expression of each of the 24 Vbeta families was assessed at baseline immediately after infection and following initiation of HAART at 2, 4, 12, 24, and up to 192 weeks in 24-week intervals. Statistically significant family-specific expression changes were observed between treated and untreated individuals for 10 TCRbetaV families. Overall, when compared to untreated patients, a more stable expression of TCR genes was observed for HAART-treated individuals. Interestingly, this difference did not correlate with either CD4 or CD8 counts, which follow the expected curves for treated and untreated patients. When we applied our quantitative analysis to IL-2-treated patients we observed a rapid polyclonal activation of the repertoire. These results suggest that homeostasis in the T cell receptor repertoire is more robust in those patients who stay on HAART for a long time and confirm the polyclonal stimulating capacity of IL-2.

This study explored the association between educational attainment and HIV/AIDS risk among African American active injection drug users (IDUs) in Chicago, US. Using snowball sampling techniques, 813 African American active IDUs were recruited for semi-structured interviewing and HIV counseling, testing and partner notification. Logistic regression examined the relationship between level of education attained (three categories: less than high school; equivalent to high school; and greater than high school) and HIV risk behaviors (12 unsafe sex and drug-related practices) and HIV serostatus (positive or negative). Compared with the reference category (less than high school education), those with education equal to high school were less likely to share water, p = 0.044, OR = 0.70 (95%CI: 0.50-0.99). Compared with the reference category, those with education greater than high school were less likely to receive money for sex, p = 0.048, OR = 0.62 (95%CI: 0.38-0.99); share needles with person having HIV or AIDS, p = 0.015, OR = 0.58 (95%CI: 0.37-0.90); and test positive for HIV, p = 0.027, OR = 0.58 (95%CI: 0.36-0.94). The significant associations found between educational attainment and certain HIV risk behaviors and HIV serostatus have implications for tailoring HIV prevention efforts for less educated African American IDUs.

HIV-specific antibodies become detectable and continue to increase in frequency during primary infection. The effects of early antiretroviral treatment (ART) and its discontinuation on the evolution of this immune response have not been systematically analyzed. To investigate the associations between antibody titer, viral load, and ART, we used a less-sensitive enzyme-linked immunosorbant assay (LS-EIA) to measure changes in HIV-1-specific antibody levels in treated and untreated subjects undergoing primary infection. In this longitudinal study, antibody levels gradually increased in therapy-naive subjects, reaching a plateau approximately 40 weeks postinfection. In contrast, antibody titers remained low among subjects receiving ART. Subjects who discontinued ART exhibited a more rapid rise in antibody titers than therapy-naive subjects, suggesting the presence of an enhanced B cell response. These results demonstrate that early ART prevents the typical evolution of the HIV-1-specific antibody response and can alter the expected kinetics of this response in subjects discontinuing therapy.

Objectives: Reduced dendritic cell (DC) frequencies and functions in individuals with longstanding HIV-1 infection are predictive of opportunistic infections and AIDS. To investigate possible early alterations in DC levels after HIV infection, we prospectively examined plasmacytoid dendritic cell (pDC) and myeloid dendritic cell (mDC) frequencies and plasma IFN-alpha levels in patients undergoing primary HIV-1 infection (PHI)., Methods: Peripheral blood DC frequencies and absolute counts were determined by flow cytometry. Plasma IFN-alpha levels were measured by enzyme-linked immunosorbent assay (ELISA)., Results: In comparison to uninfected subjects, pDC, but not mDC, levels were reduced (P < 0.001) in subjects with PHI, especially in those with high viral loads or low CD4 T-cell counts. During 24-48 weeks of observation, untreated subjects experienced slight declines in pDC and CD4 T-cell levels. In contrast, subjects initiating early antiretroviral therapy (ART) exhibited increases (P < 0.001) in pDC and CD4 T-cell counts. No effect of treatment on mDC counts was observed. Circulating plasma IFN-alpha was undetectable by ELISA regardless of the duration of HIV-1 infection., Conclusion: PHI is characterized by a reduction in pDC and CD4 T-cell counts that correlates with the magnitude of virus replication and is not evidenced by the mDC count or plasma IFN-alpha level. Early ART appears to have similar restorative effects on pDC and CD4 T-cell counts.

Great progress has been made in our understanding of HIV since its initial discovery about 20 years ago. The ability of HIV to infect CD4+ lymphocytes and a wide variety of other cells in the body is appreciated, as is its role in immunologic, gastrointestinal, and brain disorders. HIV enters cells via the CD4 molecule, chemokine co-receptors (CXCR4, CCR5), and other cell-surface proteins. Several accessory virus-associated genes (e.g., Rev, Tat, Nef) have uncovered unique pathways that can also be observed in normal cells. Recently, the discovery of natural cellular resistant factors (APOBEC3G and TRIM5a) has provided avenues for novel antiviral therapies. Studies of long-term survivors have given insight into immune responses that control HIV and can prevent infection. Neutralizing antibodies and CD8+ cell cytotoxic responses, as well as plasmacytoid dendritic cells and CD8+ cell non-cytotoxic antiviral responses, are adaptive and innate immune activities mediating this anti-HIV effect. HIV vaccine studies have indicated that conventional approaches do not work against this integrated intracellular parasite. While much has been learned about HIV, more details are needed about its infection cycle and its pathologic effects in the body. The past 20 years have yielded important information on HIV/AIDS that should lead to effective anti-HIV therapies and a vaccine.

Background: We assessed human immunodeficiency virus (HIV) antibody seroreversion among individuals initiating antiretroviral therapy (ART) during acute/early HIV infection and determined whether seroreversion was associated with loss of cytotoxic T lymphocyte responses., Methods: Subjects in a cohort with acute/early HIV infection (<12 months into infection) who initiated ART within 28 days after study entry and maintained HIV type 1 ribonucleic acid levels of < or =500 copies/mL for >24 weeks were selected. Two clinically available second-generation enzyme immunoassays (EIAs) and a confirmatory Western blot were used to screen subjects for antibody reversion. Those with negative screening test results underwent additional antibody testing, including a third-generation EIA, and were assessed for cytotoxic T lymphocyte responses., Results: Of 87 subjects identified, 12 (14%) had negative antibody test results at the start of ART; all 12 had seroconversion, although 1 had seroconversion only on a third-generation EIA. Of the 87 subjects, 6 (7%) had seroreversion on at least 1 EIA antibody assay while receiving ART during a median follow-up of 90 weeks. The only clinical predictor of seroreversion was a low baseline "detuned" (less sensitive) antibody. Cytotoxic T lymphocyte responses to HIV Gag peptides were detected in 4 of 5 subjects with seroreversion who could be tested. All 5 who had seroreversion who stopped ART experienced virologic rebound and antibody evolution., Conclusions: HIV antibody seroconversion on second-generation EIA antibody tests may fail to occur when ART is initiated early. Seroreversion was not uncommon among subjects treated early, although cytotoxic T lymphocyte responses to HIV antigens remained detectable in most subjects. Antibody seroreversion did not indicate viral eradication. A third-generation EIA was the most sensitive test for HIV antibodies.

Plasmacytoid and myeloid dendritic cells are reduced in AIDS patients. The number of these circulating cells was assessed cross-sectionally and longitudinally in 27 uninfected and 72 HIV-infected subjects on and off antiretroviral therapy. The plasmacytoid dendritic cell numbers were significantly reduced in the HIV-infected subjects compared to controls (p < 0.001). This reduction correlated directly with CD4+ cell counts (p < 0.001) and inversely with viral load (p < 0.001). These associations were found to a lesser degree for the myeloid dendritic cells. Intra-assay variability of these dendritic cell counts was < 10%. Antiretroviral therapy significantly increased plasmacytoid dendritic cell (p < 0.001) and CD4+ cell (p = 0.05) counts at 8 months by 76.9% and 19%, respectively. The plasmacytoid dendritic cell levels responded more readily to viral load increases and decreases than CD4+ cells. Circulating plasmacytoid dendritic cells may provide important additional information about immune function in HIV-infected subjects receiving or not receiving antiretroviral therapy.

Plasmacytoid dendritic cells (PDC), natural type-1 interferon (IFN) producing cells, could play a role in the innate anti-HIV immune response. Previous reports indicated that PDC IFN production is induced by HIV. Our results show a more robust IFN induction when purified PDC (>95%) were exposed to HIV-infected cells. This effect was not observed with non-viable cells, DNA, and RNA extracted from infected cells, and viral proteins. The response was blocked by anti-CD4 and neutralizing anti-gp120 antibodies as well as soluble CD4. IFN induction by HIV-infected cells was also prevented by low-dose chloroquine, which inhibits endosomal acidification. PDC IFN release resulted in reduced HIV production by infected CD4+ cells, supporting an anti-HIV activity of PDC. Stimulated CD4+ cells induced PDC activation and maturation; markers for PDC migration (CCR7) were enhanced by HIV-infected CD4+ cells only. This latter finding could explain the decline in circulating PDC in HIV-infected individuals.

Previous studies have shown a positive relationship between religiosity and the practice or adoption of protective health behaviors, including reduction of illicit drug use among hard-core injecting drug users (IDUs). The purpose of this study was to examine the role of religiosity in predicting HIV high-risk drug and sexual practices among a sample of IDUs in Chicago, USA. We hypothesized that high religiosity would be associated with a lower likelihood of IDUs engaging in risky behaviors for HIV transmission. Snowball sampling techniques were used to recruit 1,095 active IDUs for HIV testing, counseling and partner notification. Data were analyzed from 880 subjects who self-identified with one of three religions, Christianity, Islam or Judaism. Logistic regression was used to examine the relationship between religiosity (based on self-reports of personal strength of religious belief: very strong; somewhat strong; not at all), independent of specific religion, and HIV risk behaviors (defined as 12 unsafe sex- and drug-related practices) as well as HIV serostatus. Contrary to our hypothesis, subjects with stronger religiosity were more likely to engage in four risk behaviors related to sharing injection paraphernalia. Compared to those who self-reported having no religiosity, subjects who stated that their lives were strongly influenced by religious beliefs were significantly more likely to share injection outfits, cookers, cotton and water. The association of certain HIV risk behaviors with higher religiosity has implications for HIV prevention and warrants further research to explore IDUs' interpretation of religious teachings and the role of religious education in HIV prevention programs.