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More than a fifth of people living with HIV in the US President's Emergency Plan for AIDS Relief-supported programmes are older individuals, defined as aged 50 years and older, yet optimal person-centred models of care for older adults with HIV in sub-Saharan Africa, including screening and treatment for geriatric syndromes and common comorbidities associated with ageing, remain undefined. This Position Paper explores the disproportionate burden of comorbidities and geriatric syndromes faced by older adults with HIV, with a special focus on women. We seek to motivate global interest in improving quality of life for older people with HIV by presenting available research and identifying research gaps for common geriatric syndromes, including frailty and cognitive decline, and multimorbidity among older people with HIV in sub-Saharan Africa. We share two successful models of holistic care for older people with HIV that are ongoing in Zimbabwe and Kenya. Lastly, we provide policy, research, and implementation considerations to best serve this growing population.
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Infecções por HIV , Assistência Centrada no Paciente , Qualidade de Vida , Humanos , Infecções por HIV/epidemiologia , Infecções por HIV/terapia , Idoso , África Subsaariana/epidemiologia , Feminino , Pessoa de Meia-Idade , Masculino , Fragilidade/epidemiologia , ComorbidadeRESUMO
BACKGROUND: Tenofovir-lamivudine-dolutegravir (TLD) is the preferred first-line antiretroviral therapy (ART) regimen. An additional 50â mg dose of dolutegravir (TLD + 50) is required with rifampin-containing tuberculosis (TB) co-treatment. There are limited data on the effectiveness of TLD + 50 in individuals with TB/HIV. METHODS: Prospective, observational cohort study at 12 sites in Haiti, Kenya, Malawi, South Africa, Uganda, Zimbabwe. Participants starting TLD and rifampin-containing TB treatment were eligible. Primary outcome was HIV-1 RNA ≤1000â copies/mL at end of TB treatment. FINDINGS: We enrolled 91 participants with TB/HIV: 75 (82%) ART-naïve participants starting TLD after a median 15 days on TB treatment, 10 (11%) ART-naïve participants starting TLD and TB treatment, 5 (5%) starting TB treatment after a median 3.3 years on TLD, and 1 (1%) starting TB treatment and TLD after changing from efavirenz/lamivudine/tenofovir. Median age was 37 years, 35% female, median CD4 count 120â cells/mm3 (IQR 50-295), 87% had HIV-1 RNA >1000â copies/mL. Two participants died during TB treatment. Among 89 surviving participants, 80 were followed to TB treatment completion, including 7 who had no HIV-1 RNA result due to missed visits. Primary virologic outcome was assessed in 73 participants, of whom 69 (95%, 95% CI 89-100%) had HIV-1 RNA ≤1000â copies/mL. No dolutegravir resistance mutations were detected among four participants with HIV-1 RNA >1000â copies/mL. INTERPRETATION: In routine programmatic settings, concurrent rifampin-containing TB treatment and TLD + 50 was feasible, well-tolerated, and achieved high rates of viral suppression in a cohort of predominantly ART-naïve people with TB/HIV.
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Despite tremendous advances in HIV research, women and gender diverse people-particularly women from racial and ethnic groups under-represented in research, transgender women, and young women-remain disproportionately affected by HIV. Women and gender diverse people face unique challenges and have been under-represented in HIV research. The National Institutes of Health (NIH) is tasked to apply fundamental knowledge about the nature and behaviour of living systems to enhance health, lengthen life, and reduce disability. Rigorous exploration of-and interventions for-the individual, social, biological, structural, and environmental factors that influence HIV prevention, transmission, treatment, and cure is crucial to advance research for women, girls, and gender diverse people across the lifespan. In this Position Paper, we introduce a framework for an intersectional, equity-informed, data-driven approach to research on HIV and women and highlight selected issues for women and gender diverse people, including HIV prevention, HIV cure, ageing with HIV, substance use and misuse, violence, pregnancy, and breastfeeding or chestfeeding. This framework underlines a new HIV and Women Signature Programme from the NIH Office of AIDS Research and Office of Research on Women's Health that advances the NIH vision for women's health, in which all women receive evidence-based HIV prevention, treatment, and care across their lifespan tailored to their unique needs, circumstances, and goals. The time is now to centre the health of women, girls, and gender diverse people across the HIV research continuum.
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Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Humanos , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Saúde da Mulher , Identidade de Gênero , ViolênciaRESUMO
In people living with HIV, Kaposi Sarcoma (KS), a vascular neoplasm caused by KS herpesvirus (KSHV/HHV-8), remains one of the most common malignancies worldwide. Individuals living with HIV, receiving otherwise effective antiretroviral therapy, may present with extensive disease requiring chemotherapy. Hence, new therapeutic approaches are needed. The Wilms' tumor 1 (WT1) protein is overexpressed and associated with poor prognosis in several hematologic and solid malignancies and has shown promise as an immunotherapeutic target. We found that WT1 was overexpressed in >90% of a total 333 KS biopsies, as determined by immunohistochemistry and image analysis. Our largest cohort from ACTG, consisting of 294 cases was further analyzed demonstrating higher WT1 expression was associated with more advanced histopathologic subtypes. There was a positive correlation between the proportion of infected cells within KS tissues, assessed by expression of the KSHV-encoded latency-associated nuclear antigen (LANA), and WT1 positivity. Areas with high WT1 expression showed sparse T-cell infiltrates, consistent with an immune evasive tumor microenvironment. We show that major oncogenic isoforms of WT1 are overexpressed in primary KS tissue and observed WT1 upregulation upon de novo infection of endothelial cells with KSHV. KSHV latent viral FLICE-inhibitory protein (vFLIP) upregulated total and major isoforms of WT1, but upregulation was not seen after expression of mutant vFLIP that is unable to bind IKKÆ´ and induce NFκB. siRNA targeting of WT1 in latent KSHV infection resulted in decreased total cell number and pAKT, BCL2 and LANA protein expression. Finally, we show that ESK-1, a T cell receptor-like monoclonal antibody that recognizes WT1 peptides presented on MHC HLA-A0201, demonstrates increased binding to endothelial cells after KSHV infection or induction of vFLIP expression. We propose that oncogenic isoforms of WT1 are upregulated by KSHV to promote tumorigenesis and immunotherapy directed against WT1 may be an approach for KS treatment.
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Infecções por HIV , Herpesvirus Humano 8 , Sarcoma de Kaposi , Humanos , Herpesvirus Humano 8/fisiologia , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Proteínas WT1/genética , Proteínas WT1/metabolismo , Células Endoteliais/metabolismo , Infecções por HIV/metabolismo , Isoformas de Proteínas/metabolismo , Microambiente TumoralRESUMO
BACKGROUND: Protecting the HIV health workforce is critical for continuity of services for people living with HIV, particularly during a pandemic. Early in the COVID-19 pandemic, the Nigerian Ministry of Defence, in partnership with the US Military HIV Research Program, took steps to improve infection prevention and control (IPC) practices among staff working in select PEPFAR-supported Nigerian military health facilities. METHODS: We identified a set of IPC activities a priori for implementation at four Nigerian military hospitals in HIV and related departments in early 2021, including continuous medical masking, physical distancing, placement of additional hand washing stations and hand sanitizers throughout facilities, and training. We fine-tuned planned intervention activities through a baseline needs assessment conducted in December 2020 that covered eight IPC components: 'IPC program structure, funding and leadership engagement'; 'IPC policies, guidelines and standard operating procedures (SOPs)'; 'infrastructure'; 'triage and screening'; 'training, knowledge and practice'; 'personal protective equipment (PPE) materials, availability and adequacy'; 'biosafety and waste management'; and 'monitoring and remediation' prior to implementation. Baseline results were compared with those of a follow up assessment administered in August 2021, following intervention implementation. RESULTS: IPC readiness remained high at both baseline and follow-up assessments for 'IPC guidelines, policies, and SOPs' (96.7%). The components 'infrastructure' and 'monitoring and remediation', which needed improvement at baseline, saw modest improvements at follow-up, by 2% and 7.5%, respectively. At follow-up, declines from high scoring at baseline were seen in 'IPC program structure, funding and leadership engagement', 'training, knowledge and practice', and 'biosafety and waste management'. 'PPE materials availability and adequacy' improved to 88.9% at follow-up. Although unidirectional client flow was newly implemented, the score for 'triage and screening' did not change from baseline to follow-up (73%). CONCLUSION: Variability in IPC component readiness and across facilities highlights the importance of building resilience and employing a quality improvement approach to IPC that includes regular monitoring, re-assessment and re-training at set intervals. Results can be used to encourage solutions-oriented dialogue between staff and leadership, determine needs and implement action plans to protect staff and people with HIV.
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COVID-19 , Infecções por HIV , Estados Unidos , Humanos , COVID-19/epidemiologia , Seguimentos , Pandemias/prevenção & controle , Pessoal de Saúde , Infecções por HIV/prevenção & controle , Controle de InfecçõesRESUMO
Globally, children aged <5 years, including those living with HIV who are not receiving antiretroviral treatment (ART), experience disproportionately high mortality. Global mortality among children living with HIV aged <5 years receiving ART is not well described. This report compares mortality and related clinical measures among infants aged <1 year and children aged 1-4 years living with HIV with those among older persons aged 5-14, 15-49, and ≥50 years living with HIV receiving ART services at all clinical sites supported by the U.S. President's Emergency Plan for AIDS Relief. During October 2020-September 2022, an average of 11,980 infants aged <1 year and 105,510 children aged 1-4 years were receiving ART each quarter; among these infants and children receiving ART, 586 (4.9%) and 2,684 (2.5%), respectively, were reported to have died annually. These proportions of infants and children who died ranged from four to nine times higher in infants aged <1 year, and two to five times higher in children aged 1-4 years, than the proportions of older persons aged ≥5 years receiving ART. Compared with persons aged ≥5 years living with HIV, the proportions of children aged <5 years living with HIV who experienced interruptions in treatment were also higher, and the proportions who had a documented HIV viral load result or a suppressed viral load were lower. Prioritizing and optimizing HIV and general health services for children aged <5 years living with HIV receiving ART, including those recommended in the WHO STOP AIDS Package, might help address these disproportionately poorer outcomes.
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Síndrome da Imunodeficiência Adquirida , Fármacos Anti-HIV , Infecções por HIV , Lactente , Humanos , Criança , Idoso , Idoso de 80 Anos ou mais , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Antirretrovirais/uso terapêutico , Carga Viral , Organização Mundial da Saúde , Fármacos Anti-HIV/uso terapêuticoRESUMO
BACKGROUND: In sub-Saharan Africa, more women than men access HIV testing and treatment and may have better viral load suppression (VLS). We utilized routinely reported aggregated HIV program data from 21 sub-Saharan African countries to examine sex differences in VLS and death rates within antiretroviral therapy (ART) programs supported by the United States President's Emergency Plan for AIDS Relief (PEPFAR). METHODS: We included VLS and reported death data for persons aged 15 + years on ART from October-December 2020 disaggregated by sex and age for each subnational unit (SNU). We used linear mixed-model regression to estimate VLS proportion and negative binomial mixed-model regression to estimate the rates of death and death plus interruptions in treatment (IIT). All models were weighted for SNU-level ART population size and adjusted for sex, age, HIV/tuberculosis coinfection, country, and SNU; models for reported deaths and deaths plus IIT were also adjusted for SNU-level VLS. RESULTS: Mean VLS proportion was higher among women than men (93.0% vs. 92.0%, p-value < 0.0001) and 50 + than 15-49 age group (93.7% vs. 91.2%, p-value < 0.0001). The mean rate of reported deaths was higher among men than women (2.37 vs. 1.51 per 1000 persons, p-value < 0.0001) and 50 + than 15-49 age group (2.39 vs. 1.50 per 1000, p-value < 0.0001); the mean rate of reported deaths plus IIT was higher among men (30.1 in men vs. 26.0 in women per 1000, p-value < 0.0001) and higher among 15-49 than 50 + age group (34.7 vs. 22.6 per 1000, p-value < 0.0001). CONCLUSIONS: The mean rate of reported deaths was higher among men in most models despite adjusting for VLS. Further exploration into differences in care-seeking behaviors; coverage of screening, prophylaxis, and/or treatment of opportunistic infections; and more extensive testing options for men to include CD4 is recommended.
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Infecções por HIV , Caracteres Sexuais , Humanos , Masculino , Feminino , Estados Unidos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Carga Viral , Infecções por HIV/epidemiologia , África Subsaariana/epidemiologia , Teste de HIVRESUMO
BACKGROUND: Post-exposure prophylaxis (PEP) offers protection from HIV after condomless sex, but is not widely available in a timely manner in east, central, southern, and west Africa. To inform the potential pilot implementation of such an approach, we modelled the effect and cost-effectiveness of making PEP consisting of tenofovir, lamivudine, and dolutegravir (TLD) freely and locally available in communities without prescription, with the aim of enabling PEP use within 24 h of condomless sex. Free community availability of TLD (referred to as community TLD) might also result in some use of TLD as pre-exposure prophylaxis (PrEP) and as antiretroviral therapy for people living with HIV. METHODS: Using an existing individual-based model (HIV Synthesis), we explicitly modelled the potential positive and negative effects of community TLD. Through the sampling of parameter values we created 1000 setting-scenarios, reflecting the uncertainty in assumptions and a range of settings similar to those seen in east, central, southern, and west Africa (with a median HIV prevalence of 14·8% in women and 8·1% in men). For each setting scenario, we considered the effects of community TLD. TLD PEP was assumed to have at least 90% efficacy in preventing HIV infection after condomless sex with a person living with HIV. FINDINGS: The modelled effects of community TLD availability based on an assumed high uptake of TLD resulted in a mean reduction in incidence of 31% (90% range over setting scenarios, 6% increase to 57% decrease) over 20 years, with an HIV incidence reduction over 50 years in 91% of the 1000 setting scenarios, deaths averted in 55% of scenarios, reduction in costs in 92% of scenarios, and disability-adjusted life-years averted in 64% of scenarios with community TLD. Community TLD was cost-effective in 90% of setting scenarios and cost-saving (with disability-adjusted life-years averted) in 58% of scenarios. When only examining setting scenarios in which there was lower uptake of community TLD, community TLD is cost-effective in 92% of setting scenarios. INTERPRETATION: The introduction of community TLD, enabling greater PEP access, is a promising approach to consider further in pilot implementation projects. FUNDING: Bill & Melinda Gates Foundation to the HIV Modelling Consortium.
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Infecções por HIV , Lamivudina , Masculino , Feminino , Humanos , Lamivudina/uso terapêutico , Tenofovir/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Análise Custo-Benefício , África OcidentalAssuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Saúde Mental , Humanos , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Síndrome da Imunodeficiência Adquirida/psicologia , África/epidemiologia , Países em Desenvolvimento , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/psicologia , África do SulRESUMO
OBJECTIVE: In AIDS Clinical Trials Group study A5375, a pharmacokinetic trial of levonorgestrel emergency contraception, double-dose levonorgestrel (3â mg, versus standard dose 1.5â mg) offset the induction effects of efavirenz or rifampin on plasma levonorgestrel exposure over 8â h post-dose (AUC 0-8h ). We characterized the pharmacogenetics of these interactions. METHODS: Cisgender women receiving efavirenz- or dolutegravir-based HIV therapy, or on isoniazid-rifampin for tuberculosis, were followed after a single oral dose of levonorgestrel. Linear regression models, adjusted for BMI and age, characterized associations of CYP2B6 and NAT2 genotypes (which affect plasma efavirenz and isoniazid exposure, respectively) with levonorgestrel pharmacokinetic parameters. RESULTS: Of 118 evaluable participants, 17 received efavirenz/levonorgestrel 1.5â mg, 35 efavirenz/levonorgestrel 3â mg, 34 isoniazid-rifampin/levonorgestrel 3â mg, and 32 (control group) dolutegravir/levonorgestrel 1.5â mg. There were 73 Black and 33 Asian participants. Regardless of genotype, women on efavirenz and isoniazid-rifampin had higher levonorgestrel clearance. In the efavirenz/levonorgestrel 3â mg group, CYP2B6 normal/intermediate metabolizers had levonorgestrel AUC 0-8h values similar to controls, while CYP2B6 poor metabolizers had AUC 0-8h values of 40% lower than controls. In the isoniazid-rifampin group, NAT2 rapid/intermediate acetylators had levonorgestrel AUC 0-8h values similar to controls, while NAT2 slow acetylators had AUC 0-8h values 36% higher than controls. CONCLUSION: CYP2B6 poor metabolizer genotypes exacerbate the efavirenz-levonorgestrel interaction, likely by increased CYP3A induction with higher efavirenz exposure, making the interaction more difficult to overcome. NAT2 slow acetylator genotypes attenuate the rifampin-levonorgestrel interaction, likely by increased CYP3A inhibition with higher isoniazid exposure.
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Fármacos Anti-HIV , Anticoncepção Pós-Coito , Infecções por HIV , Tuberculose , Feminino , Humanos , Rifampina/efeitos adversos , Isoniazida , Levanogestrel/efeitos adversos , Antituberculosos/efeitos adversos , Citocromo P-450 CYP2B6/genética , Farmacogenética , Citocromo P-450 CYP3A/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Tuberculose/tratamento farmacológico , Tuberculose/genética , Benzoxazinas/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , GenótipoRESUMO
BACKGROUND: Guidelines for limited-stage human immunodeficiency virus-associated Kaposi sarcoma (AIDS/KS) recommend antiretroviral therapy (ART) as initial treatment. However, many such individuals show worsening KS and require additional chemotherapy. Methods to identify such patients are lacking. SETTING: We studied whether serum levels of biomarkers associated with angiogenesis, systemic inflammation, and immune activation, which are elevated in HIV-infected individuals and implicated in the development of KS, could prospectively identify individuals with limited-stage AIDS-KS who would benefit from chemotherapy administered with ART. METHODS: Serum specimens were obtained from participants in a randomized trial evaluating the value of adding oral etoposide chemotherapy to ART in treatment-naïve people with limited-stage AIDS-KS in resource-limited settings. Serum biomarkers of inflammation (C-reactive protein [CRP], interleukin [IL]-6, IL-8, IL-10, granulocyte colony stimulating factor, soluble tumor necrosis factor receptor-2), immune system activation (soluble IL-2 receptor alfa, C-X-C motif chemokine ligand 10/interferon gamma-induced protein 10, C-C motif ligand 2/monocyte chemoattractant protein 1), and angiogenesis (vascular endothelial growth factor, matrix metalloproteinase-2, -9, endoglin, hepatocyte growth factor) were measured at entry to determine whether baseline levels are associated with KS response. On-treatment changes in biomarker levels were determined to assess how etoposide modifies the effects of ART. RESULTS: Pretreatment CRP and IL-10 were higher in those whose KS progressed, and lowest in those who had good clinical responses. Pretreatment CRP, IL-6, and soluble tumor necrosis factor receptor-2 showed significant associations with KS progression at the week-48 primary endpoint. Immediate etoposide led to lower inflammation biomarker levels compared with ART alone. Early KS progression was associated with elevated pretreatment levels of inflammation-associated biomarkers and increasing levels post-treatment. CONCLUSIONS: Quantifying serum biomarkers, especially CRP, may help identify persons with AIDS-KS who would benefit from early introduction of chemotherapy in addition to ART.
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Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Sarcoma de Kaposi , Humanos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/tratamento farmacológico , Interleucina-10/uso terapêutico , Metaloproteinase 2 da Matriz , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Etoposídeo/uso terapêutico , Região de Recursos Limitados , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Ligantes , Biomarcadores , Inflamação/complicações , Receptores do Fator de Necrose Tumoral/uso terapêutico , QuimiorradioterapiaRESUMO
BACKGROUND: Treatment management after repeated failure of antiretroviral therapy (ART) is difficult due to resistance and adherence challenges. For people who have failed non-nucleoside reverse transcriptase inhibitor-(NNRTI-) and protease inhibitor-(PI-) based regimens with no or limited resistance, remaining on PI-based ART is an option. Using data from an ART strategy trial (A5288) in low/middle-income countries which included this option, we explored whether predictors can be identified distinguishing those who experienced further virologic failure from those who achieved and maintained virologic suppression. METHODS: A5288 enrolled people with confirmed HIV-1 RNA ≥ 1000 copies/mL after ≥ 24 weeks of PI-based ART and prior failure on NNRTI-based ART. This analysis focused on the 278 participants with no resistance to the PI being taken and no or limited nucleoside reverse transcriptase inhibitor (NRTI) resistance, who continued their PI with flexibility to change NRTIs. Proportional hazards models were used to evaluate predictors of virologic failure during follow-up (VF: confirmed HIV-1 RNA ≥ 1000 copies/mL at ≥ 24 weeks of follow-up). RESULTS: 56% of participants were female. At study entry, median age was 40 years, time on ART 7.8 years, CD4 count 169 cells/mm3, HIV-1 RNA 20,444 copies/mL; and 37% had NRTI resistance. The estimated proportion experiencing VF increased from 39% at week 24 to 60% at week 96. In multivariable analysis, significant predictors at study entry of VF were higher HIV-1 RNA (adjusted hazard ratio: 2.20 for ≥ 10,000 versus < 10,000 copies/mL), lower age (1.96 for < 30 versus ≥ 30 years), NRTI resistance (1.74 for present versus absent), lower CD4 count (1.73 for < 200 versus ≥ 200 cells/mm3), and shorter ART duration (1.62 for < 10 versus ≥ 10 years). There was a strong trend in proportion with VF at week 96 with the number of these five risk factors that a participant had, varying from 8% for zero, to 31%, 40%, 73%, and 100% for one, two, three, and four/five. Only 13% of participants developed new NRTI or PI resistance mutations. CONCLUSION: A simple count of five predictors might have value for identifying risk of continued VF. Novel antiretroviral and adherence support interventions are needed to improve virologic outcomes for higher risk individuals.
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Fármacos Anti-HIV , Infecções por HIV , Humanos , Feminino , Adulto , Masculino , Inibidores da Transcriptase Reversa/uso terapêutico , Inibidores da Transcriptase Reversa/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores de Proteases/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Carga Viral , RNA , Resultado do TratamentoRESUMO
OBJECTIVES: To determine if double-dose levonorgestrel emergency contraception (EC) in combination with efavirenz or rifampicin, 2 drugs known to decrease levonorgestrel exposure, resulted in similar pharmacokinetics compared to standard-dose levonorgestrel EC without drug-drug interactions. STUDY DESIGN: We conducted a phase 2, open-label, multicenter, partially randomized, 4 parallel group trial in pre-menopausal females ≥16 years old without an indication for EC and not on hormonal contraception. Participants on dolutegravir-based antiretroviral therapy (ART) received levonorgestrel 1.5 mg (control group); those on rifampicin-containing tuberculosis therapy received levonorgestrel 3 mg; those on efavirenz-based ART were randomized 1:2 to levonorgestrel 1.5 mg or 3 mg. Plasma was collected through 48 hours post-dose to assess levonorgestrel pharmacokinetics. Area under the concentration-time curve (AUC) over 8 hours was the primary outcome. Levonorgestrel pharmacokinetic parameters were compared between groups using geometric mean ratios (GMR) with 90% confidence intervals. RESULTS: The median (Q1, Q3) age for all participants (n = 118) was 34 (27, 41) years and BMI was 23.2 (20, 26.3) kg/m2. Participants receiving levonorgestrel 1.5mg plus efavirenz (n = 17) had 50% lower AUC0-8h compared to the control group (n = 32) [0.50 (0.40, 0.62)]. Participants receiving levonorgestrel 3 mg had a similar AUC0-8h when receiving either efavirenz (n = 35) [0.99 (0.81, 1.20)] or rifampicin (n = 34) [1.16 (0.99, 1.36)] compared to control. Levonorgestrel 3 mg resulted in similar or higher maximum concentration with either efavirenz [1.17 (0.96, 1.41)] or rifampicin [1.27 (1.09, 1.49)] compared to the control group. CONCLUSIONS: Doubling the dose of levonorgestrel EC successfully increased levonorgestrel exposure over the first 8 hours in participants receiving either efavirenz-based ART or rifampicin-containing tuberculosis therapy. IMPLICATIONS: Adjusting levonorgestrel emergency contraception from 1.5 mg to 3 mg improves levonorgestrel pharmacokinetic exposure in participants receiving either efavirenz-based antiretroviral regimens or rifampicin-containing tuberculosis therapy. These data support guideline recommendations to double the dose of levonorgestrel emergency contraception in persons on medications that decrease levonorgestrel exposure by inducing levonorgestrel metabolism.
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Anticoncepção Pós-Coito , Infecções por HIV , Tuberculose , Feminino , Humanos , Adolescente , Rifampina/farmacocinética , Rifampina/uso terapêutico , Levanogestrel , Tuberculose/tratamento farmacológico , Benzoxazinas , Infecções por HIV/tratamento farmacológicoRESUMO
PURPOSE OF REVIEW: Through December 2020, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) supported more than 25 million voluntary medical male circumcisions (VMMC) as part of the combined HIV prevention strategy in 15 African countries. PEPFAR monitors defined adverse events (AEs) occurring within 30 days of VMMC through its notifiable adverse event reporting system (NAERS). All NAERS reports through December 2020 were reviewed to quantify AE type, severity, and relation to the VMMC procedure. Interventions to improve client safety based on NAERS findings are described. RECENT FINDINGS: Fourteen countries reported 446 clients with notifiable adverse events (NAEs); 394/446 (88%) were determined VMMC-related, representing approximately 18 NAE reports per million circumcisions. Fatalities comprised 56/446 (13%) with 24/56 (43%) of fatalities determined VMMC-related, representing 0.96 VMMC-related fatalities per million circumcisions. The remaining 390 NAEs were non-fatal with 370/390 (95%) VMMC-related. Multiple programmatic changes have been made based on NAERS data to improve client safety. Client safety is paramount in this surgical program designed for individual and population-level benefit. Surveillance of rare but severe complications following circumcision has identified pre-existing or new safety concerns and guided continuous programmatic improvement.
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Síndrome da Imunodeficiência Adquirida , Circuncisão Masculina , Infecções por HIV , Masculino , Humanos , Circuncisão Masculina/efeitos adversos , Infecções por HIV/epidemiologia , Programas Voluntários , ÁfricaRESUMO
INTRODUCTION: Non-communicable diseases (NCDs) are an important driver of morbidity among ageing people living with HIV (PLWH). We examined the composite role of age and HIV status on NCDs in people living with and without HIV. METHODS: The African Cohort Study (AFRICOS) prospectively enrols participants aged ≥15 years with and without HIV at 12 sites in Kenya, Tanzania, Uganda and Nigeria. From 21 January 2013 to 1 September 2021, we assessed participants for renal insufficiency (estimated glomerular filtration rate <60 ml/minute/1.73 m2 ), elevated blood pressure (BP) (any systolic BP >139 mmHg or diastolic BP >89 mmHg), obesity (body mass index >30 kg/m2 ), diabetes mellitus (DM) (fasting glucose ≥126 mg/dl or antidiabetic medication) and dysglycemia (fasting glucose ≥99 mg/dl or non-fasting ≥199 mg/dl). Multivariable logistic regression with generalized estimating equations was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with each NCD. The main exposure of interest was a composite of HIV status and age dichotomized around 50 years. All models were adjusted for study site and sex. The renal insufficiency model was additionally adjusted for elevated BP and dysglycemia. RESULTS AND DISCUSSION: Of 3761 participants with age data, 557 (14.8%) were age ≥50, 2188 (58.2%) were females and 3099 (82.4%) were PLWH. At enrolment, the prevalence of elevated BP, dysglycemia, renal insufficiency and obesity were n = 128 (26.9%), n = 75 (15.8%), n = 8 (1.7%) and n = 40 (8.4%), respectively, for PLWH ≥50. Compared to people without HIV age <50, PLWH age ≥50 had increased adjusted odds of having DM (OR: 2.78, 95% CI: 1.49-5.16), dysglycemia (OR: 1.98, 95% CI: 1.51-2.61) and renal insufficiency (OR: 6.20, 95% CI: 2.31-16.66). There were significant differences by study site, specifically, participants from Nigeria had the highest odds of elevated BP, dysglycemia and renal insufficiency as compared to Uganda. CONCLUSIONS: There was a high burden of NCDs in this African cohort with differences by geographic region. In order to promote healthy ageing with HIV, screening and treatment for common NCDs should be incorporated into routine HIV care with attention paid to geographic heterogeneity to better allocate resources.
Assuntos
Diabetes Mellitus , Infecções por HIV , Hipertensão , Doenças não Transmissíveis , Insuficiência Renal , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Feminino , Glucose/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Hipertensão/epidemiologia , Hipoglicemiantes/uso terapêutico , Masculino , Doenças não Transmissíveis/epidemiologia , Obesidade/epidemiologia , Prevalência , Insuficiência Renal/epidemiologia , Uganda/epidemiologiaRESUMO
INTRODUCTION: Differentiated service delivery (DSD) models for HIV are a person-centred approach to providing services across the HIV care cascade; DSD has an increasing policy and implementation support in high-burden HIV countries. The life-course approach to DSD for HIV treatment has focused on earlier life phases, childhood and adolescence, families, and supporting sexual and reproductive health during childbearing years. Older adults, defined as those over the age of 50, represent a growing proportion of HIV treatment cohorts with approximately 20% of those supported by PEPFAR in this age band and have specific health needs that differ from younger populations. Despite this, DSD models have not been designed or implemented to address the health needs of older adults. DISCUSSION: Older adults living with HIV are more likely to have significant co-morbid medical conditions. In addition to the commonly discussed co-morbidities of hypertension and diabetes, they are at increased risk of cognitive impairment, frailty and mental health conditions. Age and HIV-related cognitive impairment may necessitate the development of adapted educational materials. Identifying the optimal package of differentiated services to this population, including the frequency of clinical visits, types and location of services is important as is capacitating the healthcare cadres to adapt to these challenges. Technological advances, which have made remote monitoring of adherence and other aspects of disease management easier for younger populations, may not be as readily available or as familiar to older adults. To date, adaptations to service delivery have not been scaled and are limited to nascent programmes working to integrate treatment of common co-morbidities. CONCLUSIONS: Older individuals living with HIV may benefit from a DSD approach that adapts care to the specific challenges of ageing with HIV. Models could be developed and validated using outcome measures, such as viral suppression and treatment continuity. DSD models for older adults should consider their specific health needs, such as high rates of co-morbidities. This may require educational materials, health worker capacity building and outreach designed specifically to treat this age group.
Assuntos
Atenção à Saúde , Infecções por HIV , Envelhecimento , Atenção à Saúde/métodos , Infecções por HIV/terapia , Humanos , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: ACTG A5288 was a strategy trial conducted in diverse populations from multiple continents of people living with HIV (PLWH) failing second-line protease inhibitor (PI)-based antiretroviral therapy (ART) from 10 low- and middle-income countries (LMICs). Participants resistant to lopinavir (LPV) and/or multiple nucleotide reverse transcriptase inhibitors started on third-line regimens that included raltegravir (RAL), darunavir/ritonavir (DRV/r) and/or etravirine (ETR) according to their resistance profiles. At 48 weeks, 87% of these participants achieved HIV-1 RNA ≤200 copies/ml. We report here long-term outcomes over 144 weeks. METHODS: Study participants were enrolled from 2013 to 2015, prior to the availability of dolutegravir in LMICs. "Extended Follow-up" of the study started after the last participant enrolled had reached 48 weeks and included participants still on antiretroviral (ARV) regimens containing RAL, DRV/r and/or ETR at that time. RAL, DRV/r and ETR were provided for an additional 96 weeks (giving total follow-up of ≥144 weeks), with HIV-1 RNA measured at 48 and 96 weeks and CD4 count at 96 weeks after entry into Extended Follow-up. Proportion of participants with HIV-1 RNA ≤200 copies/ml was estimated every 24 weeks, using imputation if necessary to handle the different measurement schedule in Extended Follow-up; mean CD4 count changes were estimated using loess regression. RESULTS AND DISCUSSION: Of 257 participants (38% females), at study entry, median CD4 count was 179 cells/mm3 , and HIV-1 RNA was 4.6 log10 copies/ml. Median follow-up was 168 weeks (IQR: 156-204); 15 (6%) participants were lost to follow-up and 9 (4%) died. 27/246 (11%), 26/246 (11%) and 13/92 (14%) of participants who started RAL, DRV/r and ETR, respectively, discontinued these drugs; only three due to adverse events. 87%, 86%, 83% and 80% of the participants had HIV-1 RNA ≤200 copies/ml at weeks 48, 96, 144 and 168 (95% CI at week 168: 74-85%), respectively. Mean increase from study entry in CD4 count at week 168 was 265 cells/mm3 (95% CI 247-283). CONCLUSIONS: Third-line regimens comprising of RAL, DRV/r and/or ETR were very well tolerated and had high rates of durable virologic suppression among PLWH in LMICs who were failing on second-line PI-based ART prior to the availability of dolutegravir.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Inibidores da Protease de HIV , HIV-1 , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Darunavir/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1/genética , Humanos , Masculino , Nitrilas , Pirimidinas , RNA/uso terapêutico , Raltegravir Potássico/efeitos adversos , Ritonavir/uso terapêutico , Carga ViralRESUMO
BACKGROUND: Approaches that allow easy access to pre-exposure prophylaxis (PrEP), such as over-the-counter provision at pharmacies, could facilitate risk-informed PrEP use and lead to lower HIV incidence, but their cost-effectiveness is unknown. We aimed to evaluate conditions under which risk-informed PrEP use is cost-effective. METHODS: We applied a mathematical model of HIV transmission to simulate 3000 setting-scenarios reflecting a range of epidemiological characteristics of communities in sub-Saharan Africa. The prevalence of HIV viral load greater than 1000 copies per mL among all adults (HIV positive and negative) varied from 1·1% to 7·4% (90% range). We hypothesised that if PrEP was made easily available without restriction and with education regarding its use, women and men would use PrEP, with sufficient daily adherence, during so-called seasons of risk (ie, periods in which individuals are at risk of acquiring infection). We refer to this as risk-informed PrEP. For each setting-scenario, we considered the situation in mid-2021 and performed a pairwise comparison of the outcomes of two policies: immediate PrEP scale-up and then continuation for 50 years, and no PrEP. We estimated the relationship between epidemic and programme characteristics and cost-effectiveness of PrEP availability to all during seasons of risk. For our base-case analysis, we assumed a 3-monthly PrEP cost of US$29 (drug $11, HIV test $4, and $14 for additional costs necessary to facilitate education and access), a cost-effectiveness threshold of $500 per disability-adjusted life-year (DALY) averted, an annual discount rate of 3%, and a time horizon of 50 years. In sensitivity analyses, we considered a cost-effectiveness threshold of $100 per DALY averted, a discount rate of 7% per annum, the use of PrEP outside of seasons of risk, and reduced uptake of risk-informed PrEP. FINDINGS: In the context of PrEP scale-up such that 66% (90% range across setting-scenarios 46-81) of HIV-negative people with at least one non-primary condomless sex partner take PrEP in any given period, resulting in 2·6% (0·9-6·0) of all HIV negative adults taking PrEP at any given time, risk-informed PrEP was predicted to reduce HIV incidence by 49% (23-78) over 50 years compared with no PrEP. PrEP was cost-effective in 71% of all setting-scenarios, and cost-effective in 76% of setting-scenarios with prevalence of HIV viral load greater than 1000 copies per mL among all adults higher than 2%. In sensitivity analyses with a $100 per DALY averted cost-effectiveness threshold, a 7% per year discount rate, or with PrEP use that was less well risk-informed than in our base case, PrEP was less likely to be cost-effective, but generally remained cost-effective if the prevalence of HIV viral load greater than 1000 copies per mL among all adults was higher than 3%. In sensitivity analyses based on additional setting-scenarios in which risk-informed PrEP was less extensively used, the HIV incidence reduction was smaller, but the cost-effectiveness of risk-informed PrEP was undiminished. INTERPRETATION: Under the assumption that making PrEP easily accessible for all adults in sub-Saharan Africa in the context of community education leads to risk-informed use, PrEP is likely to be cost-effective in settings with prevalence of HIV viral load greater than 1000 copies per mL among all adults higher than 2%, suggesting the need for implementation of such approaches, with ongoing evaluation. FUNDING: US Agency for International Development, US President's Emergency Plan for AIDS Relief, and Bill & Melinda Gates Foundation.