RESUMEN
INTRODUCTION: antiretroviral therapy (ART) has improved survival of People Living with HIV (PLWH); however, this has resulted in an increasingly high prevalence of non-communicable diseases (NCD) like hypertension. Hypertension is a major risk factor for cardiovascular and cerebral vascular disease, which are both associated with high morbidity and mortality rates. We studied the prevalence and factors associated with hypertension among PLWH on ART. METHODS: we conducted a retrospective data analysis of PLWH on ART enrolled between 2011 and 2014 into a randomized double-blinded placebo-controlled trial investigating the safety of discontinuing cotrimoxazole prophylaxis (COSTOP) among PLWH in Central Uganda. We used the mean blood pressure (BP) measurements of the first four monthly clinic visits to define hypertension. Patients were categorised as: having normal BP (≤120/80mmHg), elevated BP (systolic >120-129, and diastolic ≤80), Stage 1 hypertension (systolic 130-139, or diastolic >80-89) and Stage 2 hypertension (systolic ≥140 or diastolic ≥90). Multiple logistic regression was used to evaluate factors associated with hypertension. RESULTS: data from 2026 COSTOP trial study participants were analysed, 74.1% were women and 77.2% were aged 35 years and above. The overall prevalence of hypertension was 29%, of whom 19.5% had Stage 1 hypertension and 9.5% had Stage 2 hypertension. About 21.4% were overweight or obese. Factors independently associated with hypertension among PLWH on ART included increasing age (p≤0.001) and high body mass index (p≤0.001). Efavirenz (p≤0.001) and lopinavir/ritonavir (p=0.036) based regimen had lower odds of hypertension than Nevirapine based regimens. CONCLUSION: PLWH on ART have a high prevalence of hypertension, which rises with increasing age and body mass index (BMI) and among those on nevirapine-based ART. Implementation of hypertension prevention measures among PLWH on ART and integration of NCD and HIV care to improve patients' management outcomes are required.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Infecciones por VIH/epidemiología , Hipertensión/epidemiología , Adolescente , Adulto , Factores de Edad , Índice de Masa Corporal , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Sobrepeso/epidemiología , Prevalencia , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Factores de Riesgo , Uganda/epidemiología , Adulto JovenRESUMEN
OBJECTIVES: To assess the prevalence and risk factors of overweight and obesity among type 2 diabetes mellitus (T2DM) patients in Uganda. DESIGN: Retrospective chart review. SETTING: This study was conducted in the outpatient's T2DM clinic in St. Francis Hospital-Nsambya, Uganda between March and May 2017. PARTICIPANTS: Type 2 diabetes patients registered in the diabetes clinic between July 2003 and September 2016. OUTCOME MEASURES: Overweight and obesity defined as body mass index (kg/m2) of 25.0-29.9 and obesity as 30.0 or higher. RESULTS: Of 1275 T2DM patients, the median age was 54 (IQR: 44-65) years, 770 (60.40%) were females, 887 (69.6%) had hypertension, 385 (28%) had controlled glycaemia, 349 (27%) were obese, while 455 (36%) were overweight. Overweight/obesity were lower among men (OR: 0.45, 95% CI: 0.340 to 0.593, p≤0.001) and among patients aged ≥65 years (OR: 0.52, 95% CI: 0.350 to 0.770, p=0.001); patients who rarely ate fruits and vegetables (OR: 0.66, 95% CI: 0.475 to 0.921, p=0.014) but higher among patients of middle (OR: 1.83, 95% CI: 1.320 to 2.550, p≤0.001) and upper (OR: 2.10, 95% CI: 1.450 to 2.990, p≤0.001) socioeconomic status; on dual therapy (OR: 2.17, 95% CI: 1.024 to 4.604, p=0.043); with peripheral neuropathy (OR: 1.40, 95% CI: 1.039 to 1.834, p=0.026) and hypertension (OR: 1.70, 95% CI: 1.264 to 2.293, p≤0.001). CONCLUSIONS: Overweight and obesity are high among T2DM patients in this population and may contribute significantly to poor outcomes of T2DM. Therefore, strategies to address this problem are urgently needed.
Asunto(s)
Diabetes Mellitus Tipo 2 , Adulto , Anciano , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/epidemiología , Sobrepeso/epidemiología , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Uganda/epidemiologíaRESUMEN
BACKGROUND: Although the prevalence of type 2 diabetes mellitus is increasing in Uganda, data on loss to follow up (LTFU) of patients in care is scanty. We aimed to estimate proportions of patients LTFU and document associated factors among patients attending a private not for profit urban diabetes clinic in Uganda. METHODS: We conducted a descriptive retrospective study between March and May 2017. We reviewed 1818 out-patient medical records of adults diagnosed with type 2 diabetes mellitus registered between July 2003 and September 2016 at St. Francis Hospital - Nsambya Diabetes clinic in Uganda. Data was extracted on: patients' registration dates, demographics, socioeconomic status, smoking, glycaemic control, type of treatment, diabetes mellitus complications and last follow-up clinic visit. LTFU was defined as missing collecting medication for six months or more from the date of last clinic visit, excluding situations of death or referral to another clinic. We used Kaplan-Meier technique to estimate time to defaulting medical care after initial registration, log-rank test to test the significance of observed differences between groups. Cox proportional hazards regression model was used to determine predictors of patients' LTFU rates in hazard ratios (HRs). RESULTS: Between July 2003 and September 2016, one thousand eight hundred eighteen patients with type 2 diabetes mellitus were followed for 4847.1 person-years. Majority of patients were female 1066/1818 (59%) and 1317/1818 (72%) had poor glycaemic control. Over the 13 years, 1690/1818 (93%) patients were LTFU, giving a LTFU rate of 34.9 patients per 100 person-years (95%CI: 33.2-36.6). LTFU was significantly higher among males, younger patients (< 45 years), smokers, patients on dual therapy, lower socioeconomic status, and those with diabetes complications like neuropathy and nephropathy. CONCLUSION: We found high proportions of patients LTFU in this diabetes clinic which warrants intervention studies targeting the identified risk factors and strengthening follow up of patients.
Asunto(s)
Diabetes Mellitus Tipo 2/terapia , Perdida de Seguimiento , Adulto , Anciano , Atención Ambulatoria/estadística & datos numéricos , Instituciones de Atención Ambulatoria , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Femenino , Estudios de Seguimiento , Hospitales Filantrópicos , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Clase Social , Uganda , Salud Urbana , Adulto JovenRESUMEN
BACKGROUND: Antiretroviral therapy (ART) use by people living with HIV reduces HIV transmission, morbidity, mortality, and improves quality of life. Good ART adherence is required to achieve these benefits. We investigated how the environmental, social, economic and behavioural experiences of people living with HIV with poor viral suppression could explain their non-adherence to long term ART. METHODS: This qualitative cross-sectional study was conducted in Uganda between September 2015 and April 2016. Thirty individuals on ART for 5 years or more (10 on first line and 20 on second line), with poor viral suppression, were randomly selected from a cohort of people living with HIV on ART. In-depth interviews about ART; awareness, adherence counselling, obstacles to daily adherence and regimen switches were conducted. Emerging themes from the interviews transcripts and field notes were identified and thematic content analysis done. Participants' consent, compensation, confidentiality and study ethical approvals were ensured. RESULTS: We found that poor adherence to long term ART was due to: travel for work or social activities, stigma, receiving little or no continuous ART adherence education, alcohol consumption and use of alternative 'HIV cure' medicines. Other reasons included; ART side effects, treatment fatigue, belief that long-term ART or God can 'cure HIV', and food security. CONCLUSIONS: Achieving optimal ART benefits requires continuous provision of ART adherence education to individuals on long term ART. This helps them overcome the challenges related to living with HIV: worries of food insecurity, alcohol misuse, economic hardship, and beliefs in HIV cures and use of unproven alternative HIV treatments. People living with HIV who travel require adherence support and larger quantities of ART refills to cover their time away.
Asunto(s)
Terapia Antirretroviral Altamente Activa/psicología , Infecciones por VIH/tratamiento farmacológico , Cumplimiento de la Medicación/psicología , Adulto , Terapias Complementarias , Consejo , Estudios Transversales , Femenino , Humanos , Estudios Longitudinales , Masculino , Investigación Cualitativa , Calidad de Vida , Estigma Social , Apoyo Social , Respuesta Virológica Sostenida , Viaje , UgandaRESUMEN
BACKGROUND: This study aimed to understand the relevance of treatment supporters in adherence among people living with HIV taking Anti-retroviral therapy (ART) for more than five years in Uganda. METHODS: In-depth interviews were conducted with 50 participants (28 women and 22 men) of the Complications of Long-Term ART (CoLTART) cohort with experience of at least five years on ART in Uganda. Participants were stratified by line of ART regimen and viral loads of less or above 1000â copies/ml. Data were analyzed thematically. RESULTS: Many participants felt that a treatment supporter was most useful at the beginning of therapy before individuals get used to the drugs or when they are still weak. However, this did not reflect treatment outcomes, as many individuals without treatment supporters had failed on first line ART regimens and were switched to second line ART. Those who were still on first line had viral loads of ≥1000â copies/ml. There was a preference for female treatment supporters, many of who were persistent in their supportive role. CONCLUSION: Treatment supporters remain important in adherence to long-term ART. HIV-care providers need to encourage the involvement of a treatment supporter for individuals taking ART long-term.
Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Cumplimiento de la Medicación , Apoyo Social , Adulto , Estudios Transversales , Femenino , Infecciones por VIH/epidemiología , Humanos , Entrevistas como Asunto , Masculino , Investigación Cualitativa , Uganda/epidemiología , Carga ViralRESUMEN
INTRODUCTION: We investigated factors affecting Virological failure (VF) on first line Antiretroviral Therapy (ART) and evaluated a pragmatic approach to switching to second line ART. METHODS: Between 2004 and 2011, we assessed adults taking ART. After 6 months or more on ART, participants with VL >1000 copies/ml or two successive VL > 400 copies/ml (Conventional VF) received intensified adherence counselling and continued on first-line ART for 6 more months, after which participants who still had VL > 1000 copies/ml (Pragmatic VF) were switched to second line ART. VF rates were calculated and predictors of failure were found by fitting logistic regression and Cox proportional hazards models. RESULTS: The 316 participants accrued 1036 person years at risk (pyar), 84 (26.6%) had conventional VF (rate 8.6 per 100 pyar) of whom 28 (33.3%) had pragmatic VF (rate 2.7 per 100 pyar). Independent predictors of conventional VF were; alcohol consumption, (adjusted Hazard Ratio; aHR = 1.71, 95% CI 1.05-2.79, P = 0.03) and ART adherence: per 10% decrease in proportion of adherent visits, (aHR = 1.83, 95% CI 1.50-2.23; P < 0.001). Using reference age group < 30 years, among conventional failures, the adjusted odds ratio (aOR) of pragmatic failure for age group 30-39 years were 0.12, 95% CI 0.03-0.57, P = 0.02 and for age group > 40 years were 0.14, 95%CI 0.03-0.71, P = 0.02. Alcohol consumers had a threefold odds of pragmatic failure than non-alcohol consumers (aOR = 3.14, 95%CI 0.95-10.34, P = 0.06). CONCLUSION: A pragmatic VF approach is essential to guide switching to second line ART. Patient tailored ART adherence counselling among young patients and alcohol users is recommended.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Cumplimiento de la Medicación , Población Rural , Adolescente , Adulto , Anciano , Consumo de Bebidas Alcohólicas/epidemiología , Estudios de Cohortes , Consejo , Femenino , Estudios de Seguimiento , Infecciones por VIH/virología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Insuficiencia del Tratamiento , Uganda , Adulto JovenRESUMEN
This report describes the identification of a genetically confirmed linked heterosexual human immunodeficiency virus (HIV) superinfection (HIV-SI) in a woman with chronic HIV infection who acquired a second strain of the virus from her husband. Serum neutralizing antibody (NAb) responses against their homologous and heterologous viruses, including the superinfecting strain, in the woman and her husband were examined before and after onset of HIV-SI. The woman displayed a moderately potent and broad anti-HIV NAb response prior to superinfection but did not possess NAb activity against the superinfecting strain. This case highlights the unique potential of linked HIV-SI studies to examine natural protection from HIV infection.
Asunto(s)
Anticuerpos Neutralizantes/inmunología , Formación de Anticuerpos/inmunología , Anticuerpos Anti-VIH/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Sobreinfección/inmunología , Anticuerpos Neutralizantes/genética , Formación de Anticuerpos/genética , Femenino , Anticuerpos Anti-VIH/genética , Infecciones por VIH/genética , Heterosexualidad/fisiología , Humanos , Masculino , Pruebas de Neutralización/métodos , Sobreinfección/genética , Sobreinfección/virologíaRESUMEN
INTRODUCTION: We investigated the prevalence, predictors of and effect of Antiretroviral Therapy (ART) regimen on cardiometabolic risk among HIV-positive Ugandan adults at enrolment into a prospective cohort to study the Complications of Long-Term ART (CoLTART). METHODS: We collected data on cardiometabolic risk factors including dyslipidemia, hypertension, hyperglycemia, obesity and calculated the mean atherogenic index for Plasma (AIP) and 10 year Framingham risk score (FHS). Exposures were: ART regimen, duration on ART, demographic, socio-economic, behavioral, and life-style factors including smoking, physical activity and diet (including fruit and vegetables consumption). RESULTS: We enrolled 1024 participants, 65% female, mean age was 44.8 years (SD 8.0) and median duration on ART was 9.4 years (IQR 6.1-9.8). The prevalence of abdominal obesity was 52.6%, BMI≥25 kg/m2 -26.1%, hypertension-22.6%, high AIP-31.3% and FHS above 10% was 16.6%. The prevalence of low High Density Lipoprotein (HDL) was 37.5%, high Total cholesterol (Tc)-30.2%, high Low Density Lipoprotein (LDL) -23.6%, high Triglycerides (TG)-21.2%, low physical activity-46.4% and alcohol consumption-26.4%. In multivariate linear regression analyses, increasing age was associated with higher mean Tc, HDL, LDL, FHS (P<0.001) and hyperglycemia (p<0.005). In multivariate logistic regression analyses, Protease Inhibitor (PI) containing regimens were significantly associated with higher risks of abnormal: Tc, LDL, TG, AIP, abdominal obesity, hypertension, low HDL and lower risk of a FHS >10% compared to the non PI regimen. CONCLUSION: ART increases cardiometabolic risk. Integration of routine assessment for cardiometabolic risk factors and preventive interventions into HIV care programs in resource-limited settings is recommended.
Asunto(s)
Fármacos Anti-VIH/efectos adversos , Enfermedades Cardiovasculares/etiología , Infecciones por VIH/tratamiento farmacológico , Enfermedades Metabólicas/etiología , Adolescente , Adulto , Factores de Edad , Fármacos Anti-VIH/administración & dosificación , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/fisiopatología , Estudios de Cohortes , Femenino , Humanos , Modelos Lineales , Lípidos/sangre , Masculino , Enfermedades Metabólicas/epidemiología , Enfermedades Metabólicas/fisiopatología , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Uganda/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Antiretroviral therapy (ART) improves the survival and quality of life of HIV-positive individuals, but the effects of long-term ART use do eventually manifest. The Complications of Long-Term Antiretroviral Therapy cohort study in Uganda (CoLTART) was established to investigate the metabolic and renal complications of long-term ART use among Ugandan adults. We describe the CoLTART study set-up, aims, objectives, study methods, and also report some preliminary cross-sectional study enrolment metabolic and renal complications data analysis results. METHODS: HIV-positive ART naïve and experienced adults (18 years and above) in Uganda were enrolled. Data on demographic, dietary, medical, social economic and behaviour was obtained; and biophysical measurements and a clinical examination were undertaken. We measured: fasting glucose and lipid profiles, renal and liver function tests, full blood counts, immunology, virology and HIV drug resistance testing. Plasma samples were stored for future studies. RESULTS: Between July 2013 and October 2014, we enrolled 1095 individuals, of whom 964 (88.0%) were ART experienced (6 months or more), with a median of 9.4 years (IQR 7.0-9.9) on ART. Overall, 968 (88.4%) were aged 35 years and above, 711 (64.9%) were females, 608 (59.6%) were or had ever been on a Tenofovir ART regimen and 236 (23.1%) on a Protease Inhibitor (PI) regimen. There were no differences in renal dysfunction between patients on Tenofovir and Non-Tenofovir containing ART regimens. Patients on PI regimens had higher total cholesterol, lower high density lipoprotein, higher low density lipoprotein, higher triglycerides, and a high atherogenic index for plasma than the non-PI regimen, p = 0.001 or < 0.001. Patients on Non-PI regimens had higher mean diastolic hypertension than patients on PI regimens, p < 0.001. CONCLUSIONS: Our finding of no differences in renal dysfunction between patients on Tenofovir and those on Non-Tenofovir containing ART regimens means that Tenofovir based first line ART can safely be initiated even in settings without routine renal function monitoring. However, integration of cardiovascular risk assessment, preventive and curative measures against cardiovascular disease are required. The CoLTART cohort is a good platform to investigate the complications of long-term ART use in Uganda.
Asunto(s)
Antirretrovirales/efectos adversos , Terapia Antirretroviral Altamente Activa/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Síndrome de Lipodistrofia Asociada a VIH/epidemiología , Enfermedades Renales/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/etiología , Estudios Transversales , Femenino , Síndrome de Lipodistrofia Asociada a VIH/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Uganda/epidemiología , Adulto JovenRESUMEN
BACKGROUND: HIV care programs in resource-limited settings have hitherto concentrated on antiretroviral therapy (ART) access, but HIV drug resistance is emerging. In a cross-sectional study of HIV-positive adults on ART for ≥6 months enrolled into a prospective cohort in Uganda, plasma HIV RNA was measured and genotyped if ≥1000 copies/ml. Identified Drug resistance mutations (DRMs) were interpreted using the Stanford database, 2009 WHO list of DRMs and the IAS 2014 update on DRMs, and examined and tabulated by ART drug classes. FINDINGS: Between July 2013 and August 2014, 953 individuals were enrolled, 119 (12.5%) had HIV-RNA ≥1000 copies/ml and 110 were successfully genotyped; 74 (67.3%) were on first-line and 36 (32.7%) on second-line ART regimens. The predominant HIV-1 subtypes were D (34.5%), A (33.6%) and Recombinant forms (21.8%). The commonest clinically significant major resistance mutations associated with the highest levels of reduced susceptibility or virological response to the relevant Nucleoside Reverse Transcriptase Inhibitor (NRTI) were; the Non-thymidine analogue mutations (Non-TAMS) M184V-20.7% and K65R-8.0%; and the TAMs M41L and K70R (both 8.0%). The major Non-NRTI (NNRTI) mutations were K103N-19.0%, G190A-7.0% and Y181C-6.0%. A relatively nonpolymorphic accessory mutation A98G-12.0% was also common. Seven of the 36 patients on second line ART had major Protease Inhibitor (PI) associated DRMS including; V82A-7.0%, I54V, M46I and L33I (all 5.0%). Also common were the accessory PI mutations L10I-27%, L10V-12.0% and L10F-5.0% that either reduce PI susceptibility or increase the replication of viruses containing PI-resistance mutations. Of the 7 patients with major PI DRMs, five had high level resistance to ritonavir boosted Lopinavir and Atazanavir, with Darunavir as the only susceptible PI tested. CONCLUSIONS: In resource-limited settings, HIV care programs that have previously concentrated on ART access, should now consider availing access to routine HIV viral load monitoring, targeted HIV drug resistance testing and availability of third-line ART regimens.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Mutación , Adolescente , Adulto , Sulfato de Atazanavir/uso terapéutico , Estudios Transversales , Darunavir/uso terapéutico , Femenino , Genotipo , VIH-1/efectos de los fármacos , VIH-1/genética , Humanos , Lopinavir/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Uganda , Adulto JovenRESUMEN
BACKGROUND: WHO recommends using Tenofovir containing first line antiretroviral therapy (ART), however, Tenofovir has been reported to be associated with renal impairment and dysfunction. We compared renal function among individuals on Tenofovir and those on non-Tenofovir containing ART. METHODS: In a cross-sectional study of HIV-Positive adults on ART, at enrolment into a prospective cohort to study the long-term complications of ART in Uganda, information on biophysical measurements, medical history, clinical examination and renal function tests (RFTs) was collected. Fractional Tubular phosphate reabsorption and estimated glomerular filtration rate (eGFR) were calculated. Mean values of RFTs and proportions with abnormal RFTs were compared between non-Tenofovir containing (Non-TDF) and Tenofovir containing (TDF-ART) ART regimen groups using a general linear regression model. Durations of TDF exposure were also compared. RESULTS: Between July 2013 and October 2014, we enrolled 953 individuals on ART for 6 or more months, median duration on ART was 9.3 years, 385 (40.4 %) were on non-TDF and 568 (59.6 %) on TDF-ART regimens. The proportion of participants with Proteinuria (>30 mg/dl) was higher among the TDF-ART group than the non-TDF ART group. However, in multivariable analysis, there were no significant differences in the adjusted mean differences of eGFR, serum urea, serum creatinine, fractional tubular reabsorption of phosphate and serum phosphates when patients on TDF-ART were compared with those on non-TDF containing ART. There were no differences in renal function even when different durations on Tenofovir were compared. CONCLUSIONS: We found no differences in renal function among patients on Tenofovir and non-Tenofovir containing ART for almost a decade. Tenofovir based first line ART can therefore safely be initiated even in settings without routine renal function monitoring.
Asunto(s)
Antirretrovirales/administración & dosificación , Antirretrovirales/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Riñón/efectos de los fármacos , Insuficiencia Renal/inducido químicamente , Tenofovir/administración & dosificación , Tenofovir/efectos adversos , Adolescente , Adulto , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Creatinina/sangre , Estudios Transversales , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Infecciones por VIH/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Insuficiencia Renal/virología , Uganda , Adulto JovenRESUMEN
HIV-associated Kaposi's sarcoma (KS) is a public health challenge in sub-Saharan Africa since both the causative agent, Kaposi's sarcoma associated-herpesvirus (KSHV), and the major risk factor, HIV, are prevalent. In a nested case-control study within a long-standing clinical cohort in rural Uganda, we used stored sera to examine the evolution of antibody titres against the KSHV antigens K8.1 and latency-associated nuclear antigen (LANA) among 30 HIV-infected subjects who subsequently developed HIV-related KS (cases) and among 108 matched HIV/KSHV coinfected controls who did not develop KS. Throughout the 6 years prior to diagnosis, antibody titres to K8.1 and LANA were significantly higher among cases than controls (p < 0.0001), and titres increased prior to diagnosis in the cases. K8.1 titres differed more between KS cases and controls, compared to LANA titres. These differences in titre between cases and controls suggest a role for lytic viral replication in the pathogenesis of HIV-related KS in this setting.
Asunto(s)
Anticuerpos Antivirales/inmunología , Infecciones por VIH/inmunología , Herpesvirus Humano 8/inmunología , Sarcoma de Kaposi/inmunología , Adulto , Anticuerpos Antivirales/sangre , Antígenos Virales/inmunología , Estudios de Casos y Controles , Coinfección/sangre , Coinfección/inmunología , Coinfección/virología , Ensayo de Inmunoadsorción Enzimática , Femenino , Glicoproteínas/inmunología , Infecciones por VIH/complicaciones , Humanos , Masculino , Proteínas Nucleares/inmunología , Sarcoma de Kaposi/complicaciones , Sarcoma de Kaposi/diagnóstico , Factores de Tiempo , Uganda , Proteínas Virales/inmunologíaRESUMEN
OBJECTIVES: Antiretroviral therapy (ART) availability in a population may influence risky sexual behaviour. We examine the potential impact of ART on the HIV epidemic, incorporating evidence for the impact that ART may have on risky sexual behaviour. METHODS: A mathematical model, parameterised using site-specific data from Uganda and worldwide literature review, was used to examine the likely impact of ART on HIV epidemiologic trends. We varied assumptions about rates of initiating ART, and changes in sexual partner turnover rates. RESULTS: Modelling suggests that ART will reduce HIV incidence over 20 years, and increase prevalence. Even in the optimistic scenario of ART enrollment beginning after just five months of infection (in HIV stage 2), prevalence is estimated to rise from a baseline of 10.5% and 8.3% among women and men, respectively, to at least 12.1% and 10.2%, respectively. It will rise further if sexual disinhibition occurs or infectiousness while on ART is slightly higher (2% female to male, rather than 0.5%). The conditions required for ART to reduce prevalence over this period are likely too extreme to be achievable. For example, if ART enrolment begins in HIV stage 1 (within the first 5 months of infection), and if risky sexual behaviour does not increase, then 3 of our 11 top fitting results estimate a potential drop in HIV prevalence by 2025. If sexual risk taking rises, it will have a large additional impact on expected HIV prevalence. Prevalence will rise despite incidence falling, because ART extends life expectancy. CONCLUSIONS: HIV prevalence will rise. Even small increases in partner turnover rates will lead to an additional substantial increase in HIV prevalence. Policy makers are urged to continue HIV prevention activities, including promoting sex education, and to be prepared for a higher than previously suggested number of HIV infected people in need of treatment.
Asunto(s)
Terapia Antirretroviral Altamente Activa , Condones/estadística & datos numéricos , Seropositividad para VIH/tratamiento farmacológico , Seropositividad para VIH/epidemiología , Accesibilidad a los Servicios de Salud , Conducta Sexual/estadística & datos numéricos , Parejas Sexuales , Adolescente , Adulto , Femenino , Seropositividad para VIH/psicología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Modelos Teóricos , Formulación de Políticas , Prevalencia , Asunción de Riesgos , Educación Sexual , Conducta Sexual/psicología , Parejas Sexuales/psicología , Uganda/epidemiología , Carga ViralRESUMEN
BACKGROUND: Evidence exists that even at high CD4 counts, mortality among HIV-infected antiretroviral therapy (ART) naïve individuals is higher than that in the general population. However, many developing countries still initiate ART at CD4 ≤350 cells/mm(3). OBJECTIVE: To compare mortality among HIV-infected ART naïve individuals with CD4 counts ≥350 cells/mm(3) with mortality in the general Ugandan population and to investigate risk factors for death. DESIGN: Population-based prospective HIV cohort. METHODS: The study population consisted of HIV-infected people in rural southwest Uganda. Patients were reviewed at the study clinic every 3 months. CD4 cell count was measured every 6 months. Rate ratios were estimated using Poisson regression. Indirect methods were used to calculate standardised mortality ratios (SMRs). RESULTS: A total of 374 participants with CD4 ≥350 cells/mm(3) were followed for 1,328 person-years (PY) over which 27 deaths occurred. Mortality rates (MRs) (per 1,000 PY) were 20.34 (95% CI: 13.95-29.66) among all participants and 16.43 (10.48-25.75) among participants aged 15-49 years. Mortality was higher in periods during which participants had CD4 350-499 cells/mm(3) than during periods of CD4 ≥500 cells/mm(3) although the difference was not statistically significant [adjusted rate ratio (aRR)=1.52; 95% CI: 0.71-3.25]. Compared to the general Ugandan population aged 15-49 years, MRs were 123% higher among participants with CD4 ≥500 cells/mm(3) (SMR: 223%, 95% CI: 127-393%) and 146% higher among participants with CD4 350-499 cells/mm(3) (246%, 117%-516). After adjusting for current age, mortality was associated with increasing WHO clinical stage (aRR comparing stage 3 or 4 and stage 1: 10.18, 95% CI: 3.82-27.15) and decreasing body mass index (BMI) (aRR comparing categories ≤17.4 Kg/m(2) and ≥18.5 Kg/m(2): 6.11, 2.30-16.20). CONCLUSION: HIV-infected ART naïve individuals with CD4 count ≥350 cells/mm(3) had a higher mortality than the general population. After adjusting for age, the main predictors of mortality were WHO clinical stage and BMI.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4/estadística & datos numéricos , Infecciones por VIH/mortalidad , Mortalidad , Adolescente , Adulto , Factores de Edad , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Uganda/epidemiología , Adulto JovenRESUMEN
BACKGROUND: The basic reproduction number, [Formula: see text], is one of the many measures of the epidemic potential of an infection in a population. We estimate HIV [Formula: see text] over 18 years in a rural population in Uganda, examine method-specific differences in estimated [Formula: see text], and estimate behavioural changes that would reduce [Formula: see text] below one. METHODS: Data on HIV natural history and infectiousness were collated from literature. Data on new sexual partner count were available from a rural clinical cohort in Uganda over 1991-2008. [Formula: see text] was estimated using six methods. Behavioural changes required to reduce [Formula: see text] below one were calculated. RESULTS: Reported number of new partners per year was 0 to 16 (women) and 0 to 80 (men). When proportionate sexual mixing was assumed, the different methods yielded comparable [Formula: see text] estimates. Assuming totally assortative mixing led to increased [Formula: see text] estimates in the high sexual activity class while all estimates in the low-activity class were below one. Using the "effective" partner change rate introduced by Anderson and colleagues resulted in [Formula: see text] estimates all above one except in the lowest sexual activity class. [Formula: see text] could be reduced below one if: (a) medium risk individuals reduce their partner acquisition rate by 70% and higher risk individuals reduce their partner acquisition rate by 93%, or (b) higher risk individuals reduce the partner acquisition rate by 95%. CONCLUSIONS: The estimated [Formula: see text] depended strongly on the method used. Ignoring variation in sexual activity leads to an underestimation of [Formula: see text]. Relying on behaviour change alone to eradicate HIV may require unrealistically large reductions in risk behaviour, even though for a small proportion of the population. To control HIV, complementary prevention strategies such as male circumcision and HIV treatment services need rapid scale up.
Asunto(s)
Número Básico de Reproducción/estadística & datos numéricos , Infecciones por VIH/epidemiología , Población Rural , Femenino , VIH-1 , Humanos , Masculino , Conducta Sexual , Parejas Sexuales , Uganda/epidemiologíaRESUMEN
OBJECTIVE: We examined the association of HIV-1 subtypes with disease progression based on three viral gene regions. DESIGN: A prospective HIV-1 clinical cohort study in rural Uganda. METHODS: Partial gag, env and pol genes were sequenced. Cox proportional hazard regression modelling was used to estimate adjusted hazard ratios (aHRs) of progression to: CD4≤250, AIDS onset and death, adjusted for sex, age and CD4 count at enrolment. RESULTS: Between 1990 and 2010, 292 incident cases were subtyped: 25% had subtype A, 45% had D, 26% had A/D recombinants, 1% had C and 4% were other recombinant forms. Of the 278 incident cases included in the disease progression analysis, 62% progressed to CD4≤250, 32% to AIDS, and 34% died with a higher proportion being among subtype D cases. The proportions of individuals progressing to the three endpoints were significantly higher among individuals infected with subtype D. Throughout the study period, individuals infected with subtype D progressed faster to CD4≤250, adjusted HR (aHR), (95% CI)â=â1.72 (1.16-2.54), but this was mainly due to events in the period before antiretroviral therapy (ART) introduction, when individuals infected with subtype D significantly progressed faster to CD4≤250 than subtype A cases; aHR (95% CI)â=â1.78 (1.01-3.14). CONCLUSIONS: In this population, HIV-1 subtype D was the most prevalent and was associated with faster HIV-1 disease progression than subtype A. Further studies are needed to examine the effect of HIV-1 subtypes on disease progression in the ART period and their effect on the virological and immunological ART outcomes.
Asunto(s)
Genotipo , Infecciones por VIH/epidemiología , VIH-1/genética , Adolescente , Adulto , Anciano , Recuento de Linfocito CD4 , Progresión de la Enfermedad , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/clasificación , Humanos , Masculino , Persona de Mediana Edad , Evaluación del Resultado de la Atención al Paciente , Estudios Prospectivos , Población Rural , Uganda/epidemiología , Carga Viral , Adulto JovenRESUMEN
BACKGROUND: In HIV-infected persons, good adherence to antiretroviral therapy (ART) is essential for successful treatment outcomes. Patients' worries before starting ART may affect their ART adherence and treatment outcomes. METHODS: Between 2004 and 2009, HIV-infected individuals in a prospective cohort study in rural Uganda were assessed for ART eligibility. A counsellor explained the ART eligibility criteria, adherence and side effects, and recorded the patients' worries related to ART. Every quarter, patients who initiated ART had clinical, immunological (CD4 cell counts) and virological (viral loads) assessments, and data were collected on ART adherence using patients' self-reports and pill counts. We describe the patients' worries and examine their association with ART adherence, and immunological and virological outcomes. RESULTS: We assessed 421 patients, 271 (64%) were females, 318 (76%) were aged 30 years and above and 315 (75%) were eligible for ART. 277 (66%) reported any worry, and the proportions were similar by sex, age group and ART eligibility status. The baseline median CD4 counts and viral loads were similar among patients with any worry and those with no worry. The commonest worries were: fear of HIV serostatus disclosure; among 69 (16%) participants, lack of food when appetite improved after starting ART; 50 (12%), concurrent use of other medications; 33 (8%), adherence to ART; 28 (7%) and problems concerning condom use; 27 (6%). After 24 months or more on ART, patients who reported any worry had made more scheduled ART refill visits than patients who reported no worry (p<0.01), but the annual CD4 cell increases were similar (p=0.12). After one year on ART, patients who reported any worry had greater virological suppression than patients who reported no worry (p<0.05). CONCLUSIONS: Despite the lack of significant associations of worries with unfavourable ART outcomes, physicians and counsellors should assist patients in overcoming their worries that can cause stress and discomfort. Food supplements may be desirable for some patients initiating ART.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/psicología , Cooperación del Paciente , Adolescente , Adulto , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Estudios Prospectivos , Resultado del Tratamiento , Uganda , Adulto JovenRESUMEN
BACKGROUND: Sub-Saharan Africa (SSA) has the highest burden of HIV in the world and a rising prevalence of cardiometabolic disease; however, the interrelationship between HIV, antiretroviral therapy (ART) and cardiometabolic traits is not well described in SSA populations. METHODS: We conducted a systematic review and meta-analysis through MEDLINE and EMBASE (up to January 2012), as well as direct author contact. Eligible studies provided summary or individual-level data on one or more of the following traits in HIV+ and HIV-, or ART+ and ART- subgroups in SSA: body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs) and fasting blood glucose (FBG) or glycated hemoglobin (HbA1c). Information was synthesized under a random-effects model and the primary outcomes were the standardized mean differences (SMD) of the specified traits between subgroups of participants. RESULTS: Data were obtained from 49 published and 3 unpublished studies which reported on 29 755 individuals. HIV infection was associated with higher TGs [SMD, 0.26; 95% confidence interval (CI), 0.08 to 0.44] and lower HDL (SMD, -0.59; 95% CI, -0.86 to -0.31), BMI (SMD, -0.32; 95% CI, -0.45 to -0.18), SBP (SMD, -0.40; 95% CI, -0.55 to -0.25) and DBP (SMD, -0.34; 95% CI, -0.51 to -0.17). Among HIV+ individuals, ART use was associated with higher LDL (SMD, 0.43; 95% CI, 0.14 to 0.72) and HDL (SMD, 0.39; 95% CI, 0.11 to 0.66), and lower HbA1c (SMD, -0.34; 95% CI, -0.62 to -0.06). Fully adjusted estimates from analyses of individual participant data were consistent with meta-analysis of summary estimates for most traits. CONCLUSIONS: Broadly consistent with results from populations of European descent, these results suggest differences in cardiometabolic traits between HIV-infected and uninfected individuals in SSA, which might be modified by ART use. In a region with the highest burden of HIV, it will be important to clarify these findings to reliably assess the need for monitoring and managing cardiometabolic risk in HIV-infected populations in SSA.
Asunto(s)
Terapia Antirretroviral Altamente Activa/estadística & datos numéricos , Diabetes Mellitus/epidemiología , Dislipidemias/epidemiología , Infecciones por VIH/epidemiología , Hipertensión/epidemiología , África del Sur del Sahara/epidemiología , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Índice de Masa Corporal , Infecciones por VIH/tratamiento farmacológico , HumanosRESUMEN
Non-consensual sex is associated with HIV infection in Africa, but there is little longitudinal data on this association. We describe reported non-consensual sex among women over two decades in southwest Uganda, including associations with incident HIV infection. Between 1990 and 2008, individuals in a population cohort who recently seroconverted to HIV were enrolled into a clinical cohort, along with randomly selected HIV-negative controls. Participants were invited to the study clinic every 3 months, and females asked about recent experiences of sex against their will. Associations of non-consensual sex with HIV status were analyzed prospectively using conditional logistic regression, adjusting for age and year of interview, allowing for within-woman correlation. 476 women aged 14-81 enrolled and attended 10,475 visits over 19 years. The results show high levels of repeated non-consensual sex, often long after HIV infection. There was more reporting among women living with HIV compared to HIV-negative women (22 vs 9 %; OR = 2.29, 95 %CI 1.03-5.09), with the strongest associations among married participants. HIV programmes should address repeated sexual coercion before and subsequent to HIV infection.
Asunto(s)
Coerción , Países en Desarrollo , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Violación/estadística & datos numéricos , Población Rural/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Estudios de Cohortes , Estudios Transversales , Femenino , Infecciones por VIH/psicología , Seropositividad para VIH/epidemiología , Seropositividad para VIH/psicología , Seropositividad para VIH/transmisión , Humanos , Incidencia , Persona de Mediana Edad , Estudios Prospectivos , Violación/psicología , Población Rural/tendencias , Maltrato Conyugal/psicología , Maltrato Conyugal/estadística & datos numéricos , Uganda , Adulto JovenRESUMEN
The high diversity of HIV-1 has been shown to affect disease progression, transmission, and response to antiretroviral therapy and may influence HIV vaccine design. We describe the distribution trends of HIV-1 subtypes over a 7-year period among incident cases in a rural clinical cohort in Southwest Uganda and identify transmission clusters. Viral RNA was extracted from cryopreserved plasma samples from 94 participants who seroconverted and enrolled between 2004 and 2010. Partial gag (p24) and env (gp41) genes were directly sequenced to identify subtypes and transmission clusters with more than 95% bootstrap values. Direct sequencing of the partial pol gene and use of individual participant sexual life histories were also used to confirm these transmission clusters. The overall gag/env subtype distribution was A 28% (n=26), C 1% (n=1), and D 45% (n=42) and 27% (n=25) were intergene unique recombinant forms. The proportions of subtype A, D, or recombinants showed no significant increasing or decreasing trend over this time period (p=0.51). Phylogenetic analysis of the three genes confirmed 13 transmission clusters of which seven clusters were confirmed sexual partners using individual participants' sexual life histories. Subtype D has remained the predominant subtype in this population. From 2004 to 2010, there was no change in the proportions of these subtypes. Phylogenetic analysis and participants' sexual life histories revealed several transmission clusters. The high proportion of transmission clusters observed suggests continued high-risk sexual behavior and mixing in some individuals and possibly super transmitters in this presumed low-risk cohort, but also indicates that many transmissions occur in early HIV infection. This calls for early and targeted effective prevention and treatment intervention in this population.