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1.
Immunity ; 56(3): 653-668.e5, 2023 03 14.
Article in English | MEDLINE | ID: mdl-36804957

ABSTRACT

Upon infection, HIV disseminates throughout the human body within 1-2 weeks. However, its early cellular targets remain poorly characterized. We used a single-cell approach to retrieve the phenotype and TCR sequence of infected cells in blood and lymphoid tissue from individuals at the earliest stages of HIV infection. HIV initially targeted a few proliferating memory CD4+ T cells displaying high surface expression of CCR5. The phenotype of productively infected cells differed by Fiebig stage and between blood and lymph nodes. The TCR repertoire of productively infected cells was heavily biased, with preferential infection of previously expanded and disseminated clones, but composed almost exclusively of unique clonotypes, indicating that they were the product of independent infection events. Latent genetically intact proviruses were already archived early in infection. Hence, productive infection is initially established in a pool of phenotypically and clonotypically distinct T cells, and latently infected cells are generated simultaneously.


Subject(s)
HIV Infections , HIV-1 , Latent Infection , Humans , CD4-Positive T-Lymphocytes/metabolism , HIV-1/genetics , Latent Infection/metabolism , Latent Infection/pathology , Receptors, Antigen, T-Cell/metabolism , Virus Latency
2.
J Immunol ; 212(10): 1553-1563, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38558245

ABSTRACT

HIV is associated with NK cell dysfunction and expansion of adaptive-like NK cells that persist despite antiretroviral therapy (ART). We investigated the timing of NK cell perturbations during acute HIV infection and the impact of early ART initiation. PBMCs and plasma were obtained from people with HIV (PWH; all men who have sex with men; median age, 26.0 y) diagnosed during Fiebig stages I, II, III, or IV/V. Participants initiated ART a median of 3 d after diagnosis, and immunophenotyping was performed at diagnosis and longitudinally after ART. Anti-CMV Abs were assessed by ELISA. Samples from matched HIV-uninfected males were also analyzed. Proportions of adaptive NK cells (A-NKs; defined as Fcε-Receptor-1γ-) were expanded at HIV diagnosis at all Fiebig stages (pooled median 66% versus 25% for controls; p < 0.001) and were not altered by early ART initiation. Abs to CMV immediate early protein were elevated in PWH diagnosed in Fiebig stages III and IV/V (p < 0.03 for both). Proportions of A-NKs defined as either Fcε-Receptor-1γ- or NKG2C+/CD57+ were significantly associated with HIV DNA levels at diagnosis (p = 0.046 and 0.029, respectively) and trended toward an association after 48 wk of ART. Proportions of activated HLA-DR+/CD38+ NK cells remained elevated in PWH despite early ART initiation. NK cell activation and A-NK expansion occur very early after HIV transmission, before T cell activation, and are not altered by ART initiation during acute infection. A-NKs may contribute to HIV control and thus be useful for HIV cure.


Subject(s)
HIV Infections , Killer Cells, Natural , Humans , HIV Infections/immunology , HIV Infections/drug therapy , Killer Cells, Natural/immunology , Male , Adult , HIV-1/immunology , Anti-Retroviral Agents/therapeutic use , Adaptive Immunity , Acute Disease , Young Adult
3.
N Engl J Med ; 385(7): 595-608, 2021 08 12.
Article in English | MEDLINE | ID: mdl-34379922

ABSTRACT

BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. RESULTS: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. CONCLUSIONS: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).


Subject(s)
HIV Infections/prevention & control , HIV Integrase Inhibitors/administration & dosage , Pre-Exposure Prophylaxis , Pyridones/administration & dosage , Tenofovir/therapeutic use , Administration, Oral , Adult , Aged , Anti-HIV Agents/therapeutic use , Delayed-Action Preparations/administration & dosage , Double-Blind Method , Drug Administration Schedule , Drug Resistance/genetics , Female , HIV Integrase Inhibitors/adverse effects , Homosexuality, Male , Humans , Injections, Intramuscular/adverse effects , Intention to Treat Analysis , Male , Medication Adherence , Middle Aged , Pyridones/adverse effects , Transgender Persons , Young Adult
4.
AIDS Care ; : 1-9, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38574278

ABSTRACT

Young MSM (YMSM), aged 15-24, account for nearly half of new HIV infections in Thailand. Pre-exposure prophylaxis (PrEP) is an effective prevention medicine for populations at substantial HIV risk, yet YMSM frequently have suboptimal uptake of and adherence to PrEP. We conducted 35 in-depth interviews with YMSM to explore barriers and facilitators of both PrEP initiation and adherence. Interviews also elicited the perceptions and experiences of healthcare providers (HCPs) working with YMSM at three clinics in Bangkok. Primary barriers to PrEP initiation were limited accessibility, insufficient knowledge, and efficacy concerns; HCPs identified no-to-low self-perception of HIV risk, pre-existing health problems, fears of side effects, and living in distant provinces as barriers to PrEP initiation. YMSM primarily reported PrEP information and self-perceptions of elevated HIV risk as facilitators to PrEP initiation. Additionally, forgetfulness and low HIV risk awareness were common barriers to PrEP adherence. Reminders were a prominent facilitator of PrEP adherence alongside disclosure to close relationships, the routinization of regimens, and convenient facilities. HCPs regarded counseling as the leading facilitator of PrEP adherence. By understanding the barriers/facilitators of PrEP use, the current study seeks to help develop evidence-informed PrEP intervention programs among YMSM while considering cultural sensitivity.

5.
Proc Natl Acad Sci U S A ; 118(46)2021 11 16.
Article in English | MEDLINE | ID: mdl-34753817

ABSTRACT

Acute HIV-1 infection (AHI) results in the widespread depletion of CD4+ T cells in peripheral blood and gut mucosal tissue. However, the impact on the predominantly CD4+ immunoregulatory invariant natural killer T (iNKT) cells during AHI remains unknown. Here, iNKT cells from peripheral blood and colonic mucosa were investigated during treated and untreated AHI. iNKT cells in blood were activated and rapidly depleted in untreated AHI. At the time of peak HIV-1 viral load, these cells showed the elevated expression of cell death-associated transcripts compared to preinfection. Residual peripheral iNKT cells suffered a diminished responsiveness to in vitro stimulation early into chronic infection. Additionally, HIV-1 DNA, as well as spliced and unspliced viral RNA, were detected in iNKT cells isolated from blood, indicating the active infection of these cells in vivo. The loss of iNKT cells occurred from Fiebig stage III in the colonic mucosa, and these cells were not restored to normal levels after initiation of ART during AHI. CD4+ iNKT cells were depleted faster and more profoundly than conventional CD4+ T cells, and the preferential infection of CD4+ iNKT cells over conventional CD4+ T cells was confirmed by in vitro infection experiments. In vitro data also provided evidence of latent infection in iNKT cells. Strikingly, preinfection levels of peripheral blood CD4+ iNKT cells correlated directly with the peak HIV-1 load. These findings support a model in which iNKT cells are early targets for HIV-1 infection, driving their rapid loss from circulation and colonic mucosa.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Colon/immunology , Colon/virology , HIV Infections/immunology , Intestinal Mucosa/immunology , Intestinal Mucosa/virology , Natural Killer T-Cells/immunology , Adolescent , Adult , Disease Progression , Female , HIV Infections/virology , HIV-1/immunology , Humans , Male , Middle Aged , Persistent Infection/immunology , Persistent Infection/virology , Young Adult
6.
Sex Health ; 212024 Jun.
Article in English | MEDLINE | ID: mdl-38833542

ABSTRACT

Long-acting injectable PrEP, particularly cabotegravir (CAB-LA), has the potential to enhance HIV prevention in Asia, and was the topic of a roundtable held in Singapore in June 2023. Despite proven efficacy, CAB-LA's impact in Asia is hindered by regulatory, manufacturing, and cost barriers. There is an urgent need to address these challenges to expedite CAB-LA's introduction and scale-up, including collaborative research, streamlined regulatory processes, and increased manufacturing capacity. We call for better preparedness in long-acting PrEP in research and implementation science, product licensing and accessibility, and capacity readiness for scale-up, to meet the significant demand among key populations in Asia.


Subject(s)
Anti-HIV Agents , HIV Infections , Pre-Exposure Prophylaxis , Humans , HIV Infections/prevention & control , Pre-Exposure Prophylaxis/methods , Asia , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/therapeutic use , Pyridones/administration & dosage , Diketopiperazines
7.
Sex Health ; 212024 Jan.
Article in English | MEDLINE | ID: mdl-38219741

ABSTRACT

BACKGROUND: Transgender women (TGW) are disproportionately affected by HIV, and HIV prevalence among TGW in Thailand has been increasing. Although oral daily pre-exposure prophylaxis (PrEP) is effective for HIV prevention, PrEP uptake and persistence among TGW have been low. This study aimed to provide a deeper understanding of TGW's experiences with PrEP uptake and adherence, and to identify major barriers to PrEP use to inform intervention adaptation. METHODS: We interviewed 20 young TGW (six non-PrEP users, eight adherent, six non-adherent) and 10 health care providers from two HIV clinics in Bangkok, Thailand, in 2022. We focused on understanding challenges to PrEP use in this population using an interview guide based on a theoretical model of behaviour change and thematic content analysis. RESULTS: Thematic analysis identified major barriers to and facilitators of PrEP uptake and adherence. Barriers to PrEP initiation included low self-perceived HIV risk, concern about potential side-effects, patient burdens such as frequent HIV testing for prescription refills and social stigma against PrEP. Barriers to adherence included side-effects, inconvenient access to health services (especially during COVID-19 lockdowns), forgetfulness resulting from busy schedules and low self-perceived HIV risk. TGW also reported health care providers' stigma against PrEP users deterred them from seeking further PrEP services. TGW identified major facilitators of PrEP initiation, including awareness about the benefits of PrEP, concern about risks of HIV and supportive social networks of PrEP users. As to PrEP regimens, most TGW participants reported a clear preference for long-lasting, injectable PrEP over daily oral PrEP. TGW and health care providers largely agreed on barriers and facilitators of PrEP use, but they differed in perceptions of HIV risk. CONCLUSIONS: The results highlighted challenges and opportunities to improve the delivery of PrEP, as well as other sexually transmissable infection and mental health services, especially among TGW. Thus, there is an urgent need for developing effective intervention programs that could raise PrEP awareness and knowledge, reduce PrEP stigma, and improve PrEP delivery systems among TGW in Thailand.


Subject(s)
Anti-HIV Agents , HIV Infections , Pre-Exposure Prophylaxis , Transgender Persons , Male , Humans , Female , Homosexuality, Male/psychology , HIV Infections/drug therapy , Pre-Exposure Prophylaxis/methods , Transgender Persons/psychology , Thailand , Anti-HIV Agents/therapeutic use
8.
Sex Health ; 21(1): NULL, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37967583

ABSTRACT

BACKGROUND: Females with perinatal HIV (PHIV) infection are at elevated risk for anogenital high-risk human papillomavirus (HR-HPV) infection. Limited data are available around the effect of the HPV vaccination after initiation of sexual activity among PHIV youth. This study aims to assess the impact of a bivalent HPV vaccination on the persistence of anogenital HR-HPV among sexually active female PHIV youth and matched HIV-negative controls aged 12-24years in Thailand and Vietnam. METHODS: During a 3-year study, prevalent, incident, and persistent HR-HPV infection were assessed at annual visits. A subset of participants received a bivalent HPV vaccine. Samples were taken for HPV testing from the vagina, cervix, and anus. HR-HPV persistence was defined as the detection of the same genotype(s) at any anogenital compartment over≥two consecutive visits. RESULTS: Of the 93 PHIV and 99 HIV-negative female youth enrolled in this study, 25 (27%) PHIV and 22 (22%) HIV-negative youth received a HPV vaccine. Persistent infection with any HR-HPV type was significantly lower among PHIV youth who received the vaccine compared to those who did not (33%vs 61%, P =0.02); a difference was not observed among HIV-negative youth (35%vs 50%, P =0.82). PHIV infection (adjusted prevalence ratio [aPR] 2.31, 95% CI 1.45-3.67) and not receiving a HPV vaccine (aPR, 1.19, 95%CI 1.06-1.33) were associated with persistent anogenital HR-HPV infection. CONCLUSIONS: Bivalent HPV vaccination after initiation of sexual activity was associated with reduced persistence of anogenital HR-HPV infection in Southeast Asian PHIV female youth, which may be related to vaccine cross-protection. Primary and catch-up HPV vaccinations should be prioritised for children and youth with HIV.


Subject(s)
HIV Infections , Papillomavirus Infections , Papillomavirus Vaccines , Sexually Transmitted Diseases , Child , Pregnancy , Adolescent , Humans , Female , HIV , Papillomavirus Infections/epidemiology , Papillomavirus Infections/prevention & control , Papillomavirus Infections/complications , HIV Infections/complications , Sexually Transmitted Diseases/complications , Vaccination , Prevalence , Papillomavirus Vaccines/therapeutic use , Human Papillomavirus Viruses
9.
Clin Infect Dis ; 76(3): e718-e726, 2023 02 08.
Article in English | MEDLINE | ID: mdl-35687498

ABSTRACT

BACKGROUND: Efavirenz (EFV)- and dolutegravir (DTG)-based antiretroviral therapy (ART) is the former and current recommended regimen for treatment-naive individuals with human immunodeficiency virus type 1 (HIV-1). Whether they impact the immunological and neuropsychiatric profile differentially remains unclear. METHODS: This retrospective analysis included 258 participants enrolled during acute HIV-1 infection (AHI). Participants initiated 1 of 3 ART regimens during AHI: EFV-based (n = 131), DTG-based (n = 92), or DTG intensified with maraviroc (DTG/MVC, n = 35). All regimens included 2 nucleoside reverse-transcriptase inhibitors and were maintained for 96 weeks. CD4+ and CD8+ T-cell counts, mood symptoms, and composite score on a 4-test neuropsychological battery (NPZ-4) were compared. RESULTS: At baseline, the median age was 26 years, 99% were male, and 36% were enrolled during Fiebig stage I-II. Plasma viral suppression at weeks 24 and 96 was similar between the groups. Compared with the EFV group, the DTG group showed greater increments of CD4+ (P < .001) and CD8+ (P = .015) T-cell counts but a similar increment of CD4/CD8 ratio at week 96. NPZ-4 improvement was similar between the 2 groups at week 24 but greater in the DTG group at week 96 (P = .005). Depressive mood and distress symptoms based on the Patient Health Questionnaire and distress thermometer were similar between the 2 groups at follow-up. Findings for the DTG/MVC group were comparable to those for the DTG group vs the EFV group. CONCLUSIONS: Among individuals with AHI, 96 weeks of DTG-based ART was associated with greater increments of CD4+ and CD8+ T-cell counts and improvement in cognitive performance.


Subject(s)
Anti-HIV Agents , HIV Infections , Humans , Male , Adult , Female , Retrospective Studies , Benzoxazines/therapeutic use , Heterocyclic Compounds, 3-Ring/adverse effects , Cognition , Anti-HIV Agents/therapeutic use
10.
Clin Infect Dis ; 76(3): e692-e701, 2023 02 08.
Article in English | MEDLINE | ID: mdl-35869839

ABSTRACT

BACKGROUND: Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized. METHODS: We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants. RESULTS: Human papillomavirus (HPV) 16 had the highest incidence-clearance ratio of the hrHPV types. MSMWH had the highest hrHPV incidence (eg, 15.5% newly HPV-16 infected within 2 years), followed by HIV-negative MSM (7.5%), WWH (6.6%), HIV-negative women (2.9%), MSWWH (1.7%), and HIV-negative MSW (0.7%). Determinants of HPV-16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behavior for MSM only. HPV-16 clearance was lower for people with HIV (PWH) and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV-16 infection. CONCLUSIONS: This robust and unifying analysis of anal hrHPV natural history is essential to designing and predicting the impact of HPV vaccination and HPV-based screening programs on anal cancer prevention, particularly in MSM and PWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection.


Subject(s)
Anus Diseases , Anus Neoplasms , HIV Infections , Papillomavirus Infections , Sexual and Gender Minorities , Male , Humans , Female , Homosexuality, Male , Human Papillomavirus Viruses , HIV Infections/complications , HIV Infections/epidemiology , Incidence , Sexual Behavior , Anal Canal , Anus Diseases/diagnosis , Longitudinal Studies , Anus Neoplasms/complications , Human papillomavirus 16/genetics , HIV , Papillomaviridae/genetics
11.
Sex Transm Infect ; 99(1): 21-29, 2023 02.
Article in English | MEDLINE | ID: mdl-35260436

ABSTRACT

BACKGROUND: Over 50% of HIV infections in Thailand annually occur among men who have sex with men (MSM) and transgender women who use online applications to meet their sexual partners. We conducted a cross-sectional study assessing undetectable=untransmittable (U=U) understanding, pre-exposure prophylaxis (PrEP) awareness, sexual behaviours and factors associated with HIV knowledge among users of Hornet in Thailand. METHODS: From November 2019 to January 2020, a survey was conducted using convenience sampling on Hornet in Thailand. HIV literacy was assessed via 22 questions, and multivariable linear regression was performed. RESULTS: 960 responses were assessed; median age was 34 years, the majority were MSM (80.4%), Thai (83.8%), had at least bachelor's degree (74.9%). Regarding the risk profiles, 39.1% reported inconsistent condom use, 15.0% used amphetamine-type stimulants, 56.9% had not taken PrEP in the last six months and 20.5% never had an HIV test. Only 22.8% thought that U=U was completely accurate. Lower HIV knowledge was associated with being from Africa (ß -8.13, 95% CI -14.39 to -1.87), age of 25 years or younger (ß -2.6, 95% CI -4.37 to -0.82), education less than bachelor's degree (ß -2.58, 95% CI -3.98 to -1.19), having more than one sexual partners (ß -2.41, 95% CI -4.13 to -0.69), paying three or more people to have intercourse (ß -2.5, 95% CI -4.26 to -0.74), not knowing one's HIV status (ß -3.56, 95% CI -5.45 to -1.68) and not answering about previous PrEP use (ß -4.11, 95% CI -7.86 to -0.36). Higher HIV knowledge was associated with being from Europe (ß 2.54, 95% CI 0.46 to 4.61), the Americas (ß 3.37, 95% CI 0.44 to 6.30) and previous PrEP use (ß 2.37, 95% CI 0.94 to 3.81). CONCLUSION: Among Hornet users in Thailand, the U=U message was unclear, and PrEP use was suboptimal. Large HIV knowledge gaps and high-risk behaviours were concerning. Educational campaigns in online spaces are needed to promote awareness and HIV prevention strategies.


Subject(s)
HIV Infections , Pre-Exposure Prophylaxis , Sexual and Gender Minorities , Male , Humans , Female , Adult , HIV Infections/epidemiology , HIV Infections/prevention & control , HIV Infections/drug therapy , Homosexuality, Male , Thailand/epidemiology , Cross-Sectional Studies , Risk-Taking
12.
Trop Med Int Health ; 28(5): 374-383, 2023 05.
Article in English | MEDLINE | ID: mdl-36938836

ABSTRACT

OBJECTIVES: First, to describe the antiretroviral therapy (ART) delivery models available in Thailand to understand differentiated service delivery for further service system optimization and expansion of best practices; second, to determine the client characteristics associated with model uptake. METHODS: Across-sectional assessment using secondary data was conducted to describe ART models implemented as routine services at four public hospitals in three major provinces with a high-HIV burden in Thailand. From April to October 2020, ART clients were screened consecutively according to the inclusion criteria: Thai, aged ≥18 years, and on ART for ≥6 months. HIV treatment models were categorised based on the service type, location, provider, and frequency. Logistic regression was used to identify the associated factors. RESULTS: Seven individual ART delivery models were identified: four were facility-based and three were out-of-facility. No group models were identified. Of 3,366 records of ART clients reviewed, 3,213 (95.5%) met the study criteria and received ART through the following models: conventional (32.6%), nurse-led clinical consultation (10.0%), fast-track refill (29.0%), after-hours clinic (10.6%), pharmacist-led pickup center (3.6%), key population-led community-based organisation (2.7%), and mailing (11.5%). Age, population, duration on ART, and viral load were associated with the uptake of certain alternative service models when compared to the conventional model. CONCLUSIONS: Among the variety of ART delivery approaches available in Thailand, facility-based models remain the most prevalent. Future work should investigate the role of client preference and choice in choosing service models and service utilisation patterns over time, and assess the acceptability and effectiveness of these models.


Subject(s)
Anti-HIV Agents , HIV Infections , Humans , Adolescent , Adult , Delivery of Health Care , Thailand , Cross-Sectional Studies , HIV Infections/drug therapy , Ambulatory Care Facilities , Anti-HIV Agents/therapeutic use
13.
AIDS Behav ; 27(9): 3098-3108, 2023 Sep.
Article in English | MEDLINE | ID: mdl-36917425

ABSTRACT

Male HIV serodiscordant couples have diverse relationship agreements regarding sex outside the relationship. We examined the relationship agreements as described by 343 male HIV-negative partners in HIV serodiscordant relationships in Australia, Brazil and Thailand participating in a multi-year cohort study. At baseline, 125 (34.1%) HIV-negative partners reported no agreement, 115 (33.5%) had a monogamous agreement, and 103 (37.9%) had an open agreement allowing sex outside the relationship. Relationship agreements were largely stable over time, with 76% of HIV-negative men reporting the same agreement across follow up, while changes were predominantly towards having an open agreement. Behaviour largely matched relationship agreements, and the predictors of breaking an agreement by having condomless anal intercourse (CLAI) with an outside partner were CLAI within the relationship (OR = 3.17, 95%CI: 1.64-6.14, p < 0.001) and PrEP use in the last three months (OR = 3.42, 95%CI: 1.48-7.92, p = 0.004). When considering HIV transmission risk for HIV-negative men in serodiscordant relationships, greater focus needs to be placed on sex that is occurring outside the relationship and the agreements that facilitate this.


Subject(s)
HIV Infections , Homosexuality, Male , Male , Humans , Sexual Partners , Cohort Studies , HIV Infections/epidemiology , HIV Infections/prevention & control , Brazil/epidemiology , Thailand/epidemiology , Sexual Behavior
14.
Sex Health ; 20(3): 250-254, 2023 07.
Article in English | MEDLINE | ID: mdl-37380169

ABSTRACT

BACKGROUND: Thailand National AIDS Committee endorsed Undetectable=Untransmittable (U=U) as a science which needs an urgent translation into actions to address pervasive stigma faced by people living with HIV (PLHIV). We aimed at humanising and demedicalising U=U by exploring a 'people-centered value' of U=U and translate them into efficient U=U communications. METHODS: During August-September 2022, in-depth interviews were conducted with 43 PLHIV and 17 partners from various background in five regions of Thailand. Focus group discussions were made with 28 healthcare providers (HCPs) and 11 PLHIV peers. Thematic analysis was used for data analysis. RESULTS: Among PLHIV, how U=U frees them up to 'live a full life' was valued highest. A great relief from sin, immorality, and irresponsibility was mentioned by all. U=U communications allowed PLHIV and their partners to love/be loved and enjoy intimacy and sex with pleasure again. HCPs and PLHIV peers almost always refer U=U value to 'physical health'. Common concerns were around increasing sexually transmitted infections with condomless sex. The people-centered U=U values, together with dismantling of power imbalance within healthcare system and sexual health skills empowerment among providers, were used to develop a humanised and demedicalised National U=U Training Curriculum. The Curriculum was highlighted in country's planned activities to address multi-level/multi-setting stigma and discrimination. CONCLUSIONS: U=U can be successfully humanised and demedicalised in designing efficient communications. At an individual level, U=U can address one's intersectional stigmatizing attitudes. At a policy level, national endorsement can initiate and sustain tangible actions and interest around U=U across country's leaderships.


Subject(s)
HIV Infections , Sexually Transmitted Diseases , Humans , Thailand , Social Stigma , Focus Groups
15.
J Infect Dis ; 225(12): 2167-2175, 2022 06 15.
Article in English | MEDLINE | ID: mdl-35275599

ABSTRACT

Starting antiretroviral therapy (ART) in Fiebig 1 acute HIV infection limits the size of viral reservoirs in lymphoid tissues, but does not impact time to virus rebound during a treatment interruption. To better understand why the reduced reservoir size did not increase the time to rebound we measured the frequency and location of HIV RNA+ cells in lymph nodes from participants in the RV254 acute infection cohort. HIV RNA+ cells were detected more frequently and in greater numbers when ART was initiated in Fiebig 1 compared to later Fiebig stages and were localized to the T-cell zone compared to the B-cell follicle with treatment in later Fiebig stages. Variability of virus production in people treated during acute infection suggests that the balance between virus-producing cells and the immune response to clear infected cells rapidly evolves during the earliest stages of infection. Clinical Trials Registration: NCT02919306.


Subject(s)
HIV Infections , Lymph Nodes , RNA, Viral , Anti-Retroviral Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/pathology , Humans , Lymph Nodes/virology , RNA, Viral/isolation & purification
16.
Clin Infect Dis ; 75(Suppl 4): S549-S556, 2022 11 21.
Article in English | MEDLINE | ID: mdl-36410377

ABSTRACT

Long-acting injectable antiretroviral therapy (LA ART) has been found to be non-inferior to daily oral ART in phase 3 clinical trials and is poised to soon enter routine clinical care. This treatment modality has the potential to address many barriers to daily oral ART adherence among people living with human immunodeficiency virus (HIV) and for HIV Pre-Exposure prevention. Data from the Patient Reported Outcomes (PROs) showed high rates of satisfaction, acceptability, tolerability and preference for the LA regimen, compared with the daily oral treatment. Once LA ART is available, access and uptake will be limited because of current knowledge gaps in the use of these agents and multiple challenges many specific to low-income and middle-income countries, where the epidemic is most concentrated and HIV prevention and treatment options are limited. These gaps will lead to multiple systems-level and individual-level barriers to implementation. Anticipating and addressing these gaps and barriers will help fulfill the promise of these agents against the pandemic.


Subject(s)
Anti-HIV Agents , HIV Infections , Humans , Developing Countries , Anti-HIV Agents/therapeutic use , Anti-Retroviral Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/prevention & control , Poverty
17.
Emerg Infect Dis ; 28(11): 2214-2225, 2022 11.
Article in English | MEDLINE | ID: mdl-36220131

ABSTRACT

Prior immune responses to coronaviruses might affect human SARS-CoV-2 response. We screened 2,565 serum and plasma samples collected from 2013 through early 2020, before the COVID-19 pandemic began, from 2,250 persons in 4 countries in Africa (Kenya, Nigeria, Tanzania, and Uganda) and in Thailand, including persons living with HIV-1. We detected IgG responses to SARS-CoV-2 spike (S) subunit 2 protein in 1.8% of participants. Profiling against 23 coronavirus antigens revealed that responses to S, subunit 2, or subunit 1 proteins were significantly more frequent than responses to the receptor-binding domain, S-Trimer, or nucleocapsid proteins (p<0.0001). We observed similar responses in persons with or without HIV-1. Among all coronavirus antigens tested, SARS-CoV-2, SARS-CoV-1, and Middle East respiratory syndrome coronavirus antibody responses were much higher in participants from Africa than in participants from Thailand (p<0.01). We noted less pronounced differences for endemic coronaviruses. Serosurveys could affect vaccine and monoclonal antibody distribution across global populations.


Subject(s)
COVID-19 , Humans , Antibodies, Monoclonal , Antibodies, Viral , Antibody Formation , COVID-19/epidemiology , Immunoglobulin G , Nigeria , Nucleocapsid Proteins , Pandemics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Thailand/epidemiology , Africa
18.
HIV Med ; 23(3): 227-236, 2022 03.
Article in English | MEDLINE | ID: mdl-34634181

ABSTRACT

OBJECTIVES: The coronavirus disease (COVID-19) pandemic is an unprecedented event with massive global health and socio-economic impacts on vulnerable populations, especially people living with HIV. The epidemic has severely affected Thailand's economy and potentially impacted the financial and psychological wellbeing of Thai HIV-positive men who have sex with men (MSM). METHODS: Between 15 June and 10 December 2020, we conducted qualitative interviews with 26 MSM living with HIV in Thailand who participate in an Adam's Love We Care Study. We intentionally recruited individuals who may have experienced a greater impact of COVID-19. Interviews explored worry, stigma and stress surrounding COVID-19, and multiple domains of potential COVID-19 impact: financial/employment, HIV service delivery and antiretroviral (ART) adherence during the first 10 months of the COVID-19 pandemic. RESULTS: Participants perceived themselves as immunocompromised and susceptible, and feared contracting COVID-19. Participants worried that contracting COVID-19 would lead to HIV status disclosure and stigmatization. Participants had considerable worry about job loss as a result of the economic downturn, and some shared challenges associated with relocation and re-engaging with HIV care. Financial stress and lack of basic necessities caused by job losses were commonly reported. Participants reported optimal ART adherence as a consequence of local HIV service delivery responses, convenient ART refills and Adam's Love online support interventions. CONCLUSIONS: Our study highlights that the COVID-19 pandemic produced high levels of anxiety and concerns about additional stigma among MSM living with HIV. It had a significant negative effect on the daily lives of our participants. These findings indicate a need for the provision of confidential COVID-19 diagnosis and care, relief programmes, vaccination roll-out equity, and addressing employment needs of vulnerable populations.


Subject(s)
COVID-19 , HIV Infections , Sexual and Gender Minorities , COVID-19 Testing , HIV Infections/epidemiology , Homosexuality, Male , Humans , Male , Pandemics , SARS-CoV-2 , Thailand
19.
HIV Med ; 23 Suppl 4: 3-14, 2022 10.
Article in English | MEDLINE | ID: mdl-36254390

ABSTRACT

Human immunodeficiency virus (HIV) continues to be a major public health issue, and the effectiveness of HIV prevention, diagnosis, treatment, and care varies, particularly in the Asia-Pacific region. The rapid initiation of antiretroviral therapy (ART) is important to control the HIV epidemic and to optimize the health of people living with HIV; many guidelines now recommend ART initiation within 7 days of HIV diagnosis, with same-day initiation for people diagnosed with HIV who feel ready. Many countries in the Asia-Pacific region have already implemented or are moving towards implementation of rapid or same-day ART initiation. However, there are many obstacles and challenges to its implementation, which vary substantially across the region. This article summarizes the latest evidence on rapid and same-day ART initiation and discusses lessons learned and barriers to implementation in Asian countries, particularly focusing on Taiwan, Thailand, Singapore, and the Republic of Korea.


Subject(s)
HIV Infections , HIV Infections/diagnosis , Humans , Republic of Korea , Singapore , Thailand
20.
Psychosom Med ; 84(8): 976-983, 2022 10 01.
Article in English | MEDLINE | ID: mdl-36162059

ABSTRACT

OBJECTIVE: We examined individual differences in CD4/CD8 T-cell ratio trajectories and associated risk profiles from acute HIV infection (AHI) through 144 weeks of antiretroviral therapy (ART) using a data-driven approach. METHODS: A total of 483 AHI participants began ART during Fiebig I-V and completed follow-up evaluations for 144 weeks. CD4+, CD8+, and CD4/CD8 T-cell ratio trajectories were defined followed by analyses to identify associated risk variables. RESULTS: Participants had a median viral load (VL) of 5.88 copies/ml and CD4/CD8 T-cell ratio of 0.71 at enrollment. After 144 weeks of ART, the median CD4/CD8 T-cell ratio was 1.3. Longitudinal models revealed five CD4/CD8 T-cell ratio subgroups: group 1 (3%) exhibited a ratio >1.0 at all visits; groups 2 (18%) and 3 (29%) exhibited inversion at enrollment, with normalization 4 and 12 weeks after ART, respectively; and groups 4 (31%) and 5 (18%) experienced CD4/CD8 T-cell ratio inversion due to slow CD4+ T-cell recovery (group 4) or high CD8+ T-cell count (group 5). Persistent inversion corresponded to ART onset after Fiebig II, higher VL, soluble CD27 and TIM-3, and lower eosinophil count. Individuals with slow CD4+ T-cell recovery exhibited higher VL, lower white blood cell count, lower basophil percent, and treatment with standard ART, as well as worse mental health and cognition, compared with individuals with high CD8+ T-cell count. CONCLUSIONS: Early HIV disease dynamics predict unfavorable CD4/CD8 T-cell ratio outcomes after ART. CD4+ and CD8+ T-cell trajectories contribute to inversion risk and correspond to specific viral, immune, and psychological profiles during AHI. Adjunctive strategies to achieve immune normalization merit consideration.


Subject(s)
Anti-HIV Agents , HIV Infections , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , CD8-Positive T-Lymphocytes , HIV Infections/drug therapy , Hepatitis A Virus Cellular Receptor 2/therapeutic use , Humans , Individuality , Viral Load
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