Expanding antiretroviral therapy in Malawi: drawing on the country's experience with tuberculosis.
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ABSTRACT:
SUBMITTER: Harries AD
PROVIDER: S-EPMC527699 | biostudies-literature | 2004 Nov
REPOSITORIES: biostudies-literature
Publications
Expanding antiretroviral therapy in Malawi: drawing on the country's experience with tuberculosis.
Harries Anthony D AD Libamba Edwin E Schouten Erik J EJ Mwansambo Andrina A Salaniponi Felix M FM Mpazanje Rex R
BMJ (Clinical research ed.) 20041101 7475
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Project description:We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, the timing for the initiation of ART during tuberculosis treatment remains unresolved.We conducted a three-group, open-label, randomized, controlled trial in South Africa involving 642 ambulatory patients, all with tuberculosis (confirmed by a positive sputum smear for acid-fast bacilli), human immunodeficiency virus infection, and a CD4+ T-cell count of less than 500 per cubic millimeter. Findings in the earlier-ART group (ART initiated within 4 weeks after the start of tuberculosis treatment, 214 patients) and later-ART group (ART initiated during the first 4 weeks of the continuation phase of tuberculosis treatment, 215 patients) are presented here.At baseline, the median CD4+ T-cell count was 150 per cubic millimeter, and the median viral load was 161,000 copies per milliliter, with no significant differences between the two groups. The incidence rate of the acquired immunodeficiency syndrome (AIDS) or death was 6.9 cases per 100 person-years in the earlier-ART group (18 cases) as compared with 7.8 per 100 person-years in the later-ART group (19 cases) (incidence-rate ratio, 0.89; 95% confidence interval [CI], 0.44 to 1.79; P=0.73). However, among patients with CD4+ T-cell counts of less than 50 per cubic millimeter, the incidence rates of AIDS or death were 8.5 and 26.3 cases per 100 person-years, respectively (incidence-rate ratio, 0.32; 95% CI, 0.07 to 1.13; P=0.06). The incidence rates of the immune reconstitution inflammatory syndrome (IRIS) were 20.1 and 7.7 cases per 100 person-years, respectively (incidence-rate ratio, 2.62; 95% CI, 1.48 to 4.82; P<0.001). Adverse events requiring a switching of antiretroviral drugs occurred in 10 patients in the earlier-ART group and 1 patient in the later-ART group (P=0.006).Early initiation of ART in patients with CD4+ T-cell counts of less than 50 per cubic millimeter increased AIDS-free survival. Deferral of the initiation of ART to the first 4 weeks of the continuation phase of tuberculosis therapy in those with higher CD4+ T-cell counts reduced the risks of IRIS and other adverse events related to ART without increasing the risk of AIDS or death. (Funded by the U.S. President's Emergency Plan for AIDS Relief and others; SAPIT ClinicalTrials.gov number, NCT00398996.).
| S-EPMC3233684 | biostudies-literature
Project description:BackgroundMany Africans who are on life-saving ART face challenges from a variety of toxicities. After the introduction of a standardized first-line efavirenz-containing ART regimen, reports of gynecomastia appeared in Malawian popular media, however data on the prevalence and risk factors of gynecomastia from Africa are lacking.MethodsWe conducted a cross-sectional study in males ≥18 years registered on ART at the HIV clinic in Zomba Central Hospital. Men who reported to have ever experienced breast or nipple enlargement received a standard questionnaire and underwent physical examination. Questions included perceptions and concerns about gynecomastia. Clinicians confirmed the presence and severity of gynecomastia. Routinely collected data on current and previous ART regimens, CD4 count, WHO clinical stage, anthropometric measurements and history of tuberculosis were extracted from the electronic database.ResultsWe enrolled 1,027 men with median age 44 years (IQR: 38-52). The median ART duration was 57 months (IQR: 27-85); 46.7% were in WHO stage III/IV at ART initiation, 88.2% had exposure to efavirenz and 9% were overweight or obese. The prevalence of self-reported gynecomastia was 6.0% (62/1027) (95%-CI: 4.7-7.7%). Of men with gynecomastia 83.6% reported nipple enlargement and 98.4% enlarged breasts (85.5% bilateral). One-third said they had not reported gynecomastia to a health care worker. Over three-quarters mentioned that gynecomastia was an important or very important problem for them, while more than half were embarrassed by it. On examination gynecomastia was present in 90% (confirmed gynecomastia prevalence 5.5%; 95%-CI: 4.2-7.0%) and 51.8% had severity grade III or IV. History of tuberculosis treatment was independently associated with self-reported gynecomastia, adjusted OR 2.10 (95%-CI: 1.04-4.25).ConclusionsThe burden of gynecomastia among men on ART in Malawi was higher than previously reported, and was associated with adverse psychological consequences, calling for increased awareness, a proactive diagnostic approach and diligent clinical management.
| S-EPMC5695797 | biostudies-literature
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| S-EPMC5088011 | biostudies-literature
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| S-EPMC10852317 | biostudies-literature
Project description:The rates of death are high among patients with coinfection with tuberculosis and the human immunodeficiency virus (HIV). The optimal timing for the initiation of antiretroviral therapy in relation to tuberculosis therapy remains controversial.In an open-label, randomized, controlled trial in Durban, South Africa, we assigned 642 patients with both tuberculosis and HIV infection to start antiretroviral therapy either during tuberculosis therapy (in two integrated-therapy groups) or after the completion of such treatment (in one sequential-therapy group). The diagnosis of tuberculosis was based on a positive sputum smear for acid-fast bacilli. Only patients with HIV infection and a CD4+ cell count of less than 500 per cubic millimeter were included. All patients received standard tuberculosis therapy, prophylaxis with trimethoprim-sulfamethoxazole, and a once-daily antiretroviral regimen of didanosine, lamivudine, and efavirenz. The primary end point was death from any cause.This analysis compares data from the sequential-therapy group and the combined integrated-therapy groups up to September 1, 2008, when the data and safety monitoring committee recommended that all patients receive integrated antiretroviral therapy. There was a reduction in the rate of death among the 429 patients in the combined integrated-therapy groups (5.4 deaths per 100 person-years, or 25 deaths), as compared with the 213 patients in the sequential-therapy group (12.1 per 100 person-years, or 27 deaths); a relative reduction of 56% (hazard ratio in the combined integrated-therapy groups, 0.44; 95% confidence interval, 0.25 to 0.79; P=0.003). Mortality was lower in the combined integrated-therapy groups in all CD4+ count strata. Rates of adverse events during follow-up were similar in the two study groups.The initiation of antiretroviral therapy during tuberculosis therapy significantly improved survival and provides further impetus for the integration of tuberculosis and HIV services. (ClinicalTrials.gov number, NCT00398996.)
| S-EPMC3076221 | biostudies-literature
Project description:HIV has increased the incidence of tuberculosis (TB) by up to sevenfold in African countries, but antiretroviral therapy (ART) reduces the incidence of AIDS-related TB. We use a mathematical model to investigate the short-term and long-term impacts of ART on the incidence of TB, assuming that people are tested for HIV once a year, on average, and start ART at a fixed time after HIV seroconversion or at a fixed CD4(+) cell count. We fit the model to trend data on HIV prevalence and TB incidence in nine countries in sub-Saharan Africa. If HIV-positive people start ART within 5 y of seroconversion, the incidence of AIDS-related TB in 2015 will be reduced by 48% (range: 37-55%). Long-term reductions depend sensitively on the delay to starting ART. If treatment is started 5, 2, or 1 y after HIV seroconversion, or as soon as people test positive, the incidence in 2050 will be reduced by 66% (range: 57-80%), 95% (range: 93-96%), 97.7% (range: 96.9-98.2%) and 98.4% (range: 97.8-98.9%), respectively. In the countries considered here, early ART could avert 0.71 ± 0.36 [95% confidence interval (CI)] million of 3.4 million cases of TB between 2010 and 2015 and 5.8 ± 2.9 (95% CI) million of 15 million cases between 2015 and 2050. As more countries provide ART at higher CD4(+) cell counts, the impact on TB should be investigated to test the predictions of this model.
| S-EPMC2984151 | biostudies-literature
Project description:We develop a broader, more fine-grained taxonomy of forms of transformative experience, inspired by the work of L. A. Paul. Our vulnerability to such experiences arises, we argue, due to the vulnerability, dependence, and affliction intrinsic to the human condition. We use this trio to distinguish a variety of positively, negatively, and ambivalently valenced forms of epistemically and/or personally transformative experiences. Moreover, we argue that many transformative experiences can arise gradually and cumulatively, unfolding over the course of longer periods of time.
| S-EPMC7217260 | biostudies-literature
Project description:While the advent of combination antiretroviral therapy (ART) has significantly improved survival, tuberculosis (TB) remains the leading cause of death in the HIV-infected population. We used Mycobacterium tuberculosis/simian immunodeficiency virus-coinfected (M. tuberculosis/SIV-coinfected) macaques to model M. tuberculosis/HIV coinfection and study the impact of ART on TB reactivation due to HIV infection. Although ART significantly reduced viral loads and increased CD4+ T cell counts in blood and bronchoalveolar lavage (BAL) samples, it did not reduce the relative risk of SIV-induced TB reactivation in ART-treated macaques in the early phase of treatment. CD4+ T cells were poorly restored specifically in the lung interstitium, despite their significant restoration in the alveolar compartment of the lung as well as in the periphery. IDO1 induction in myeloid cells in the inducible bronchus-associated lymphoid tissue (iBALT) likely contributed to dysregulated T cell homing and impaired lung immunity. Thus, although ART was indispensable for controlling viral replication, restoring CD4+ T cells, and preventing opportunistic infection, it appeared inadequate in reversing the clinical signs of TB reactivation during the relatively short duration of ART administered in this study. This finding warrants the modeling of concurrent treatment of TB and HIV to potentially reduce the risk of reactivation of TB due to HIV to inform treatment strategies in patients with M. tuberculosis/HIV coinfection.
| S-EPMC7524506 | biostudies-literature
Project description:ObjectivesHighly active antiretroviral therapy (HAART) provision to eligible HIV-infected pregnant and post-partum women is critical for optimizing maternal health. We assessed the impact of maternal HAART on HIV-free survival of breastfed infants in Malawi.MethodsThe post-exposure prophylaxis of infants-Malawi trial (2004-2009) enrolled mothers/infants during labor or immediately post-partum to evaluate 14-week extended infant antiretroviral prophylaxis for preventing HIV transmission through breastfeeding. Mothers meeting national HAART guidelines were referred for therapy. Child HIV-free survival-survival without HIV infection-was compared by maternal HAART status.ResultsOverall, 3022 mother-infant pairs contributed 4214 infant/person-years (PY) at-risk for HIV infection or death, with 532 events (incidence 12.6/100 PY, 95 % confidence interval [CI] 11.6-13.7). During follow-up, 349 mothers were HAART initiated; 581 remained HAART naïve with CD4 cell counts <250 cells/mm(3), and 2092 were never HAART-eligible. By 3 months, 11 % of infants with HAART naïve mothers (CD4 < 250) were infected with HIV or died versus 7 % of infants of HAART-initiated mothers and 4 % of infants of HAART-ineligible mothers. Maternal HAART was associated with a 46 % reduction in infant HIV infection or death as compared to infants with HAART naïve mothers (CD4 < 250) (adjusted hazards ratio 0.54, 95 % CI 0.36-0.81). Among HIV-exposed, uninfected infants, breastfeeding, but not HAART, was significantly associated with decreased child mortality.ConclusionsHIV infection and mortality are high during the first 3 months post-partum in infants of mothers with advanced HIV, and rapid maternal HAART initiation can significantly improve HIV-related infant outcomes. Clinical Trials Registration This study is registered at http://clinicaltrials.gov/ under trial number NCT00115648.
| S-EPMC4754130 | biostudies-literature
Project description:ObjectiveThe risk of transmission of Mycobacterium tuberculosis in antiretroviral therapy (ART) clinics is recognized, particularly, when HIV and tuberculosis services are unified, but the degree of potential exposure to patients with infectious tuberculosis has not been measured. We aimed to quantify this clinic exposure.MethodsOver 1 year, we recorded all visits to a clinic in northern Malawi that offers HIV testing and counselling, HIV care, ART, and TB diagnostic and treatment services. We included patients and guardians, noting timing and reason for the visit, using a palm vein reader to assist recognition of individuals and record times automatically. Screening for tuberculosis was enhanced, including induced sputum if necessary.ResultsInformation was collected on 5011 individuals and 19 426 visits. During the period, 90 individuals with bacteriologically confirmed pulmonary tuberculosis attended the clinic when they were likely to have been infectious (taken as 6 weeks before diagnosis to 2 weeks after the start of treatment), including 76 who attended before tuberculosis was diagnosed or suspected. We estimated that 19% of visits had at least 1 h of potential exposure to patients with infectious tuberculosis, half to patients attending prediagnosis.ConclusionThere was considerable risk of exposure, including of immunosuppressed patients, to patients with infectious tuberculosis, especially as repeated visits are made. Much of this exposure could not be avoided by separation of patients with known tuberculosis. Good ventilation and avoidance of crowding is essential to minimize transmission of M. tuberculosis in this type of setting.
| S-EPMC6200384 | biostudies-literature