• Monitoring HIV Viral Load in Resource Limited Settings: Still a Matter of Debate?

      Arnedo, M; Alonso, E; Eisenberg, N; Ibáñez, L; Ferreyra, C; Jaén, A; Flevaud, L; Khamadi, S; Roddy, P; Gatell, JM; Dalmau, D (Public Library of Science, 2012-12-06)
      Consequences of lack of viral monitoring in predicting the effects of development of HIV drug resistance mutations during HAART in resource-limited settings (RLS) is still a matter of debate.
    • Monitoring of antiretroviral therapy and mortality in HIV programmes in Malawi, South Africa and Zambia: mathematical modelling study

      Estill, Janne; Egger, Matthias; Johnson, Leigh F; Gsponer, Thomas; Wandeler, Gilles; Davies, Mary-Ann; Boulle, Andrew; Wood, Robin; Garone, Daniela; Stringer, Jeffrey S A; Hallett, Timothy B; Keiser, Olivia; Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland. jestill@ispm.unibe.ch (Public Library of Science, 2013-02-28)
      Mortality in patients starting antiretroviral therapy (ART) is higher in Malawi and Zambia than in South Africa. We examined whether different monitoring of ART (viral load [VL] in South Africa and CD4 count in Malawi and Zambia) could explain this mortality difference.
    • Monitoring the response to antiretroviral therapy in resource-poor settings: the Malawi model.

      Harries, A D; Gomani, P; Teck, R; de Teck, O; Bakali, E; Zachariah, R; Libamba, E; Mwansambo, A; Salaniponi, F; Mpazanje, R; National Tuberculosis Control Programme, Ministry of Health and Population, P.O. Box 30377, Lilongwe, Malawi. adharries@malawi.net (2004-12)
      With assistance from the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM), Malawi is scaling-up the delivery of antiretroviral (ARV) therapy to HIV-positive eligible patients. The country has developed National ARV Treatment Guidelines, which emphasize a structured and standardized approach for all aspects of ARV delivery, including monitoring and evaluation. Using the successful DOTS model adapted by National TB Control Programmes throughout the world, Malawi has developed a system of quarterly ARV cohort and cumulative ARV quarterly analyses. Thyolo district, in the southern region of Malawi, has been using this system since April 2003. This paper describes the standardized ARV treatment regimens and the treatment outcomes used in Thyolo to assess the impact of treatment, the registration and monitoring systems and how the cohort analyses are carried out. Data are presented for case registration and treatment outcome for the first quarterly cohort (April to June) and the combined cohorts (April to June and July to September). Such quarterly analyses may be useful for districts and Ministries of Health in assessing ARV delivery, although the burden of work involved in calculating the numbers may become large once ARV delivery systems have been established for several years.
    • Monitoring the South African National Antiretroviral Treatment Programme, 2003-2007: the IeDEA Southern Africa collaboration.

      Cornell, Morna; Technau, Karl; Fairall, Lara; Wood, Robin; Moultrie, Harry; van Cutsem, Gilles; Giddy, Janet; Mohapi, Lerato; Eley, Brian; MacPhail, Patrick; Prozesky, Hans; Rabie, Helena; Davies, Mary-Ann; Maxwell, Nicola; Boulle, Andrew; Infectious Disease Epidemiology Unit, School of Public Health and Family Medicine, University of Cape Town. morna@global.co.za (2009-09)
      OBJECTIVES: To introduce the combined South African cohorts of the International epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration as reflecting the South African national antiretroviral treatment (ART) programme; to characterise patients accessing these services; and to describe changes in services and patients from 2003 to 2007. DESIGN AND SETTING: Multi-cohort study of 11 ART programmes in Gauteng, Western Cape, Free State and KwaZulu-Natal. SUBJECTS: Adults and children (<16 years old) who initiated ART with > or =3 antiretroviral drugs before 2008. RESULTS: Most sites were offering free treatment to adults and children in the public sector, ranging from 264 to 17,835 patients per site. Among 45,383 adults and 6,198 children combined, median age (interquartile range) was 35.0 years (29.8-41.4) and 42.5 months (14.7-82.5), respectively. Of adults, 68% were female. The median CD4 cell count was 102 cells/microl (44-164) and was lower among males than females (86, 34-150 v. 110, 50-169, p<0.001). Median CD4% among children was 12% (7-17.7). Between 2003 and 2007, enrolment increased 11-fold in adults and 3-fold in children. Median CD4 count at enrolment increased for all adults (67-111 cells/microl, p<0.001) and for those in stage IV (39-89 cells/microl, p<0.001). Among children <5 years, baseline CD4% increased over time (11.5-16.0%, p<0.001). CONCLUSIONS: IeDEA-SA provides a unique opportunity to report on the national ART programme. The study describes dramatically increased enrolment over time. Late diagnosis and ART initiation, especially of men and children, need attention. Investment in sentinel sites will ensure good individual-level data while freeing most sites to continue with simplified reporting.
    • Mortality and Clinical Outcomes in Children Treated With Antiretroviral Therapy in Four African Vertical Programs During The First Decade of Paediatric HIV Care, 2001-2010

      Ben-Farhat, J; Schramm, B; Nicolay, N; Wanjala, S; Szumilin, E; Balkan, S; Pujades-Rodríguez, M (Wiley-Blackwell, 2016-12-19)
      To assess mortality and clinical outcomes in children treated with antiretroviral therapy in four African vertical programs between 2001 and 2010.
    • Mortality by baseline CD4 cell count among HIV patients initiating antiretroviral therapy: evidence from a large cohort in Uganda

      Mills, Edward J; Bakanda, Celestin; Birungi, Josephine; Mwesigwa, Robert; Chan, Keith; Ford, Nathan; Hogg, Robert S; Cooper, Curtis; Faculty of Health Sciences, University of Ottawa, Ottawa, Canada; The AIDS Support Organization (TASO), Headquarters, Kampala, Uganda; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada; Médecins Sans Frontiers (MSF), Geneva, Switzerland; Division of Infectious Diseases, The Ottawa Hospital, Ottawa, Canada (Lippincott Williams & Wilkins, 2011-03-27)
      Evaluations of CD4 cell count and other prognostic factors on the survival of HIV patients in sub-Saharan Africa are extremely limited. Funders have been reticent to recommend earlier initiation of treatment. We aimed to examine the effect of baseline CD4 cell count on mortality using data from HIV patients receiving combination antiretroviral therapy (cART) in Uganda.
    • Mortality in Patients with HIV-1 Infection Starting Antiretroviral Therapy in South Africa, Europe, or North America: A Collaborative Analysis of Prospective Studies

      Boulle, Andrew; Schomaker, Michael; May, Margaret T; Hogg, Robert S; Shepherd, Bryan E; Monge, Susana; Keiser, Olivia; Lampe, Fiona C; Giddy, Janet; Ndirangu, James; Garone, Daniela; Fox, Matthew; Ingle, Suzanne M; Reiss, Peter; Dabis, Francois; Costagliola, Dominique; Castagna, Antonella; Ehren, Kathrin; Campbell, Colin; Gill, M John; Saag, Michael; Justice, Amy C; Guest, Jodie; Crane, Heidi M; Egger, Matthias; Sterne, Jonathan A C (2014-09-09)
      High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America.
    • Mortality in the first six months among HIV-positive and HIV-negative patients empirically treated for tuberculosis.

      Huerga, H; Ferlazzo, G; Wanjala, S; Bastard, M; Bevilacqua, P; Ardizzoni, E; Sitienei, J; Bonnet, M (BioMed Central, 2019-02-11)
      Empirical treatment of tuberculosis (TB) may be necessary in patients with negative or no Xpert MTB/RIF results. In a context with access to Xpert, we assessed mortality in the 6 months after the initial TB consultation among HIV-positive and HIV-negative patients who received empirical TB treatment or TB treatment based on bacteriological confirmation and we compared it with the mortality among those who did not receive TB treatment.
    • Mortality of patients lost to follow-up in antiretroviral treatment programmes in resource-limited settings: systematic review and meta-analysis

      Brinkhof, M; Pujades-Rodriguez, M; Egger, M; Division of International and Environmental Health, Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland; Epicentre, Médecins Sans Frontières, Paris, France; Department of Social Medicine, University of Bristol, Bristol, United Kingdom (2009-06-04)
      BACKGROUND: The retention of patients in antiretroviral therapy (ART) programmes is an important issue in resource-limited settings. Loss to follow up can be substantial, but it is unclear what the outcomes are in patients who are lost to programmes. METHODS AND FINDINGS: We searched the PubMed, EMBASE, Latin American and Caribbean Health Sciences Literature (LILACS), Indian Medlars Centre (IndMed) and African Index Medicus (AIM) databases and the abstracts of three conferences for studies that traced patients lost to follow up to ascertain their vital status. Main outcomes were the proportion of patients traced, the proportion found to be alive and the proportion that had died. Where available, we also examined the reasons why some patients could not be traced, why patients found to be alive did not return to the clinic, and the causes of death. We combined mortality data from several studies using random-effects meta-analysis. Seventeen studies were eligible. All were from sub-Saharan Africa, except one study from India, and none were conducted in children. A total of 6420 patients (range 44 to 1343 patients) were included. Patients were traced using telephone calls, home visits and through social networks. Overall the vital status of 4021 patients could be ascertained (63%, range across studies: 45% to 86%); 1602 patients had died. The combined mortality was 40% (95% confidence interval 33%-48%), with substantial heterogeneity between studies (P<0.0001). Mortality in African programmes ranged from 12% to 87% of patients lost to follow-up. Mortality was inversely associated with the rate of loss to follow up in the programme: it declined from around 60% to 20% as the percentage of patients lost to the programme increased from 5% to 50%. Among patients not found, telephone numbers and addresses were frequently incorrect or missing. Common reasons for not returning to the clinic were transfer to another programme, financial problems and improving or deteriorating health. Causes of death were available for 47 deaths: 29 (62%) died of an AIDS defining illness. CONCLUSIONS: In ART programmes in resource-limited settings a substantial minority of adults lost to follow up cannot be traced, and among those traced 20% to 60% had died. Our findings have implications both for patient care and the monitoring and evaluation of programmes.
    • Mortality reduction associated with HIV/AIDS care and antiretroviral treatment in rural Malawi: evidence from registers, coffin sales and funerals.

      Mwagomba, Beatrice; Zachariah, Rony; Massaquoi, Moses; Misindi, Dalitso; Manzi, Marcel; Mandere, Bester C; Bemelmans, Marielle; Philips, Mit; Kamoto, Kelita; Schouten, Eric J; Harries, A D; Thyolo District Health Services, Ministry of Health and Population, Thyolo, Malawi. (2010-05)
      BACKGROUND: To report on the trend in all-cause mortality in a rural district of Malawi that has successfully scaled-up HIV/AIDS care including antiretroviral treatment (ART) to its population, through corroborative evidence from a) registered deaths at traditional authorities (TAs), b) coffin sales and c) church funerals. METHODS AND FINDINGS: Retrospective study in 5 of 12 TAs (covering approximately 50% of the population) during the period 2000-2007. A total of 210 villages, 24 coffin workshops and 23 churches were included. There were a total of 18,473 registered deaths at TAs, 15781 coffins sold, and 2762 church funerals. Between 2000 and 2007, there was a highly significant linear downward trend in death rates, sale of coffins and church funerals (X(2) for linear trend: 338.4 P<0.0001, 989 P<0.0001 and 197, P<0.0001 respectively). Using data from TAs as the most reliable source of data on deaths, overall death rate reduction was 37% (95% CI:33-40) for the period. The mean annual incremental death rate reduction was 0.52/1000/year. Death rates decreased over time as the percentage of people living with HIV/AIDS enrolled into care and ART increased. Extrapolating these data to the entire district population, an estimated 10,156 (95% CI: 9786-10259) deaths would have been averted during the 8-year period. CONCLUSIONS: Registered deaths at traditional authorities, the sale of coffins and church funerals showed a significant downward trend over a 8-year period which we believe was associated with the scaling up HIV/AIDS care and ART.
    • Mortality, AIDS-morbidity, and loss to follow-up by current CD4 cell count among HIV-1-infected adults receiving antiretroviral therapy in Africa and Asia: data from the ANRS 12222 collaboration

      Gabillard, Delphine; Lewden, Charlotte; Ndoye, Ibra; Moh, Raoul; Segeral, Olivier; Tonwe-Gold, Besigin; Etard, Jean-François; Pagnaroat, Men; Fournier-Nicolle, Isabelle; Eholié, Serge; Konate, Issouf; Minga, Albert; Mpoudi-Ngole, Eitel; Koulla-Shiro, Sinata; Zannou, Djimon Marcel; Anglaret, Xavier; Laurent, Christian (Lippincott Williams and Wilkins, 2013-04-15)
      In resource-limited countries, estimating CD4-specific incidence rates of mortality and morbidity among patients receiving antiretroviral therapy (ART) may help assess the effectiveness of care and treatment programmes, identify program weaknesses, and inform decisions.
    • Mother to Mother (M2M) peer support for women in prevention of mother to child transmission (PMTCT) programmes: a qualitative study

      Shroufi, Amir; Mafara, Emma; Saint-Sauveur, Jean François; Taziwa, Fabian; Viñoles, Mari Carmen; Médecins Sans Frontières, Operational Centre Barcelona-Athens, Belgravia, Harare, Zimbabwe (Public Library of Science, 2013-06-05)
      Introduction Mother-to-Mother (M2M) or “Mentor Mother” programmes utilise HIV positive mothers to provide support and advice to HIV positive pregnant women and mothers of HIV exposed babies. Médecins Sans Frontières (MSF) supported a Mentor Mother programme in Bulawayo, Zimbabwe from 2009 to 2012; with programme beneficiaries observed to have far higher retention at 6–8 weeks (99% vs 50%, p<0.0005) and to have higher adherence to Prevention of Mother to Child Transmission (PMTCT) guidelines, compared to those not opting in. In this study we explore how the M2M progamme may have contributed to these findings. Methods In this qualitative study we used thematic analysis of in-depth interviews (n = 79). This study was conducted in 2 urban districts of Bulawayo, Zimbabwe’s second largest city. Results Interviews were completed by 14 mentor mothers, 10 mentor mother family members, 30 beneficiaries (women enrolled both in PMTCT and M2M), 10 beneficiary family members, 5 women enrolled in PMTCT but who had declined to take part in the M2M programme and 10 health care staff members. All beneficiaries and health care staff reported that the programme had improved retention and provided rich information on how this was achieved. Additionally respondents described how the programme had helped bring about beneficial behaviour change. Conclusions M2M programmes offer great potential to empower communities affected by HIV to catalyse positive behaviour change. Our results illustrate how M2M involvement may increase retention in PMTCT programmes. Non-disclosure to one’s partner, as well as some cultural practices prevalent in Zimbabwe appear to be major barriers to participation in M2M programmes.
    • Motives, sexual behaviour, and risk factors associated with HIV in individuals seeking voluntary counselling and testing in a rural district of Malawi.

      Zachariah, R; Spielmann M P; Harries, A D; Buhendwa, L; Chingi, C; Medecins sans Frontieres, Thyolo, Malawi. zachariah@internet.lu (2003-04)
      A study was conducted among individuals seeking voluntary HIV counselling and testing (VCT) in order to (a) describe their motives and source(s) of information, (b) describe their sexual behaviour; and (c) identify risk factors associated with HIV infection. Of 723 individuals who sought VCT, the most common reason (50%) was recent knowledge of HIV/AIDS and a desire to know their HIV status. The majority (77%) underwent VCT after being encouraged by others who knew their status. Ninety five per cent reported sexual encounters, with 337 (49%) engaging in unprotected sex. HIV prevalence was 31% and an HIV-positive status was associated with being female, being over 25 years of age and/or being a farmer. There is a demand for VCT, and the service provides an opportunity for intensive education about HIV/AIDS prevention on a one-to-one basis. It could also be an entry point to prevention and care for those who are infected.
    • Moxifloxacin for Buruli ulcer/HIV coinfected patients: kill two birds with one stone?

      O'Brien, Daniel P; Comte, Eric; Ford, Nathan; Christinet, Vanessa; du Cros, Philipp; aManson Unit, Médecins Sans Frontières, London, UK bDepartment of Infectious Diseases, Geelong Hospital, Geelong cDepartment of Medicine and Infectious Diseases, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia dMedical Unit, Médecins Sans Frontières, Geneva, Switzerland eCenter for Infectious Diseases Epidemiology Research, University of Cape Town, Cape Town, South Africa fDepartment of HIV, University Hospitals of Geneva, Geneva, Switzerland. (2013-09-10)
    • Multi-Country Validation of SAMBA - A Novel Molecular Point-of- Care Test for HIV-1 Detection in Resource-Limited Setting

      Ondiek, J; Namukaya, Z; Mtapuri-Zinyowera, S; Balkan, S; Elbireer, A; Ushiro Lumb, I; Kiyaga, C; Goel, N; Ritchie, A; Ncube, P; Omuomu, K; Ndiege, K; Kekitiinwa, A; Mangwanya, D; Fowler, Mary G; Nadala, L; Lee, H (Lippincott Williams & Wilkins, 2017-06-09)
      Early diagnosis of HIV-1 infection and the prompt initiation of antiretroviral therapy are critical to achieving a reduction in the morbidity and mortality of infected infants. The SAMBA HIV-1 Qual Whole Blood Test was developed specifically for early infant diagnosis and prevention of mother-to-child transmission programs implemented at the point-of-care in resource-limited settings.
    • Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration

      Rhee, SY; Varghese, V; Holmes, SP; Van Zyl, GU; Steegen, K; Boyd, MA; Cooper, DA; Nsanzimana, S; Saravanan, S; Charpentier, C; de Oliveira, T; Etiebet, MA; Garcia, F; Goedhals, D; Gomes, P; Günthard, HF; Hamers, RL; Hoffmann, CJ; Hunt, G; Jiamsakul, A; Kaleebu, P; Kanki, P; Kantor, R; Kerschberger, B; Marconi, VC; D'amour Ndahimana, J; Ndembi, N; Ngo-Giang-Huong, N; Rokx, C; Santoro, MM; Schapiro, JM; Schmidt, D; Seu, L; Sigaloff, KCE; Sirivichayakul, S; Skhosana, L; Sunpath, H; Tang, M; Yang, C; Carmona, S; Gupta, RK; Shafer, RW (Elsevier, 2017-03-19)
      Tenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT) mutations selected in individuals with VF on such a regimen is not known. To identify TDF regimen-associated mutations (TRAMs), we compared the proportion of each RT mutation in 2873 individuals with VF on a WHO-recommended first-line TDF-containing regimen to its proportion in a cohort of 50,803 antiretroviral-naïve individuals. To identify TRAMs specifically associated with TDF-selection pressure, we compared the proportion of each TRAM to its proportion in a cohort of 5805 individuals with VF on a first-line thymidine analog-containing regimen. We identified 83 TRAMs including 33 NRTI-associated, 40 NNRTI-associated, and 10 uncommon mutations of uncertain provenance. Of the 33 NRTI-associated TRAMs, 12 - A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and Y115F - were more common among individuals receiving a first-line TDF-containing compared to a first-line thymidine analog-containing regimen. These 12 TDF-selected TRAMs will be important for monitoring TDF-associated transmitted drug-resistance and for determining the extent of reduced TDF susceptibility in individuals with VF on a TDF-containing regimen.
    • A national survey of the impact of rapid scale-up of antiretroviral therapy on health-care workers in Malawi: effects on human resources and survival.

      Makombe, S D; Jahn, A; Tweya, H; Chuka, S; Yu, J K L; Hochgesang, M; Aberle-Grasse, J; Pasulani, O; Schouten, E J; Kamoto, K; Harries, A D; HIV Unit, Ministry of Health, Lilongwe, Malawi. (WHO, 2007-11)
      OBJECTIVE: To assess the human resources impact of Malawis rapidly growing antiretroviral therapy (ART) programme and balance this against the survival benefit of health-care workers who have accessed ART themselves. METHODS: We conducted a national cross-sectional survey of the human resource allocation in all public-sector health facilities providing ART in mid-2006. We also undertook a survival analysis of health-care workers who had accessed ART in public and private facilities by 30 June 2006, using data from the national ART monitoring and evaluation system. FINDINGS: By 30 June 2006, 59 581 patients had accessed ART from 95 public and 28 private facilities. The public sites provided ART services on 2.4 days per week on average, requiring 7% of the clinician workforce, 3% of the nursing workforce and 24% of the ward clerk workforce available at the facilities. We identified 1024 health-care workers in the national ART-patient cohort (2% of all ART patients). The probabilities for survival on ART at 6 months, 12 months and 18 months were 85%, 81% and 78%, respectively. An estimated 250 health-care workers lives were saved 12 months after ART initiation. Their combined work-time of more than 1000 staff-days per week was equivalent to the human resources required to provide ART at the national level. CONCLUSION: A large number of ART patients in Malawi are managed by a small proportion of the health-care workforce. Many health-care workers have accessed ART with good treatment outcomes. Currently, staffing required for ART balances against health-care workers lives saved through treatment, although this may change in the future.
    • Navigating the risks of prevention of mother to child transmission (PMTCT) of HIV services in Kibera, Kenya: Barriers to engaging and remaining in care

      Thomson, KA; Telfer, B; Opondo Awiti, P; Munge, J; Ngunga, M; Reid, A (Public Library of Science, 2018-01-24)
      Within the first year of implementation, 43% of women who tested HIV positive at their first antenatal care visit were no longer retained and being followed in the free prevention of mother to child transmission (PMTCT) of HIV program offered by the Kenyan Ministry of Health and Médecins Sans Frontières in the informal settlement of Kibera, Nairobi. This study aimed to explore barriers to enrolling and remaining engaged in PMTCT services throughout the pregnancy and postpartum periods. Qualitative data from 31 focus group discussions and 35 in-depth interviews across six stakeholder groups that included women, men, and PMTCT service providers were analyzed. Using an inductive exploratory approach, four researchers coded the data and identified key themes. Five themes emerged from the data that may influence attrition from PMTCT service in this setting: 1) HIV in the context of Kibera, 2) knowledge of HIV status, 3) knowledge of PMTCT, 4) disclosure of HIV status, and 5) male partner support for PMTCT services. A new HIV diagnosis during pregnancy immediately triggered an ongoing risk assessment of perceived hazards in the home, community, and clinic environments that could occur as a result of female participation in PMTCT services. Male partners were a major influence in this risk assessment, but were generally unaware of PMTCT services. To preserve relationships with male partners, meet community expectations of womanhood, and maintain confidentiality while following recommendations of healthcare providers, women had to continuously weigh the risks and benefits of PMTCT services and interventions. Community-based HIV testing and PMTCT education, male involvement in antenatal care, and counseling customized to assist each woman in her own unique risk assessment, may improve uptake of and retention in care and optimize the HIV prevention benefit of PMTCT interventions.
    • Nevirapine versus Efavirenz for patients co-infected with HIV and Tuberculosis: A Randomised Non-Inferiority Trial

      Bonnet, Maryline; Bhatt, Nilesh; Baudin, Elisabeth; Silva, Carlota; Michon, Christophe; Taburet, Anne-Marie; Ciaffi, Laura; Sobry, Agnès; Bastos, Rui; Nunes, Elizabete; Rouzioux, Christine; Jani, Ilesh; Calmy, Alexandra; Epicentre, Paris, France. Electronic address: maryline.bonnet@geneva.msf.org. (2013-02-19)
      BACKGROUND: In countries with a high incidence of HIV and tuberculosis co-infection, nevirapine and efavirenz are widely used as antiretroviral therapy but both interact with antituberculosis drugs. We aimed to compare efficacy and safety of a nevirapine-based antiretroviral therapy (started at full dose) with an efavirenz-based regimen in co-infected patients. METHODS: We did a multicentre, open-label, randomised, non-inferiority trial at three health centres in Maputo, Mozambique. We enrolled adults (≥18 years) with tuberculosis and previously untreated HIV infection (CD4 cell counts <250 cells per μL) and alanine aminotransferase and total bilirubin concentrations of less than five times the upper limit of normal. 4-6 weeks after the start of tuberculosis treatment, we randomly allocated patients (1:1) with central randomisation, block sizes of two to six, and stratified by site and CD4 cell count to nevirapine (200 mg twice daily) or efavirenz (600 mg once daily), plus lamivudine and stavudine. The primary endpoint was virological suppression at 48 weeks (HIV-1 RNA <50 copies per mL) in all patients who received at least one dose of study drug (intention-to-treat population); death and loss to follow-up were recorded as treatment failure. The non-inferiority margin for the difference of efficacy was 10%. We assessed efficacy in intention-to-treat and per-protocol populations and safety in all patients who received study drug. This study is registered with ClinicalTrials.gov, number NCT00495326. FINDINGS: Between October, 2007, and March, 2010, we enrolled 285 patients into each group. 242 (85%) patients in the nevirapine group and 233 (82%) patients in the efavirenz group completed follow-up. In the intention-to-treat population, 184 patients (64·6%, 95% CI 58·7-70·1) allocated nevirapine achieved virological suppression at week 48, as did 199 patients (69·8%, 64·1-75·1) allocated efavirenz (one-sided 95% CI of the difference of efficacy 11·7%). In the per-protocol population, 170 (70·0%, 63·8-75·7) of 243 patients allocated nevirapine achieved virological suppression at week 48, as did 194 (78·9%, 73·2-83·8) of 246 patients allocated efavirenz (one-sided 95% CI 15·4%). The median CD4 cell count at randomisation was 89 cells per μL. 15 patients substituted nevirapine with efavirenz and six patients substituted efavirenz with nevirapine. 20 patients allocated nevirapine (7%) had grade 3-4 increase of alanine aminotransferase compared with 17 patients allocated efavirenz (6%). Three patients had severe rash after receipt of nevirapine (1%) but no patients did after receipt of efavirenz. 18 patients in the nevirapine group died, as did 17 patients in the efavirenz group. INTERPRETATION: Although non-inferiority of the nevirapine-regimen was not shown, nevirapine at full dose could be a safe, acceptable alternative for patients unable to tolerate efavirenz. FUNDING: French Research Agency for HIV/AIDS and hepatitis (ANRS).
    • Nevirapine- and efavirenz-associated hepatotoxicity under programmatic conditions in Kenya and Mozambique.

      Chu, K M; Manzi, M; Zuniga, I; Biot, M; Ford, N P; Rasschaert, F; Zachariah, R; South African Medical Unit, Médecins Sans Frontières Johannesburg, PO Box 32117, Braamfontein 2017, South Africa. kathryn.chu@joburg.msf.org (2012-06)
      To describe the frequency, risk factors, and clinical signs and symptoms associated with hepatotoxicity (HT) in patients on nevirapine- or efavirenz-based antiretroviral therapy (ART), we conducted a retrospective cohort analysis of patients attending the ART clinic in Kibera, Kenya, from April 2003 to December 2006 and in Mavalane, Mozambique, from December 2002 to March 2007. Data were collected on 5832 HIV-positive individuals who had initiated nevirapine- or efavirenz-based ART. Median baseline CD4+ count was 125 cells/μL (interquartile range [IQR] 55-196). Over a median follow-up time of 426 (IQR 147-693) days, 124 (2.4%) patients developed HT. Forty-one (54.7%) of 75 patients with grade 3 HT compared with 21 (80.8%) of 26 with grade 4 had associated clinical signs or symptoms (P = 0.018). Four (5.7%) of 124 patients with HT died in the first six months compared with 271 (5.3%) of 5159 patients who did not develop HT (P = 0.315). The proportion of patients developing HT was low and HT was not associated with increased mortality. Clinical signs and symptoms identified 50% of grade 3 HT and most cases of grade 4 HT. This suggests that in settings where alanine aminotransferase measurement is not feasible, nevirapine- and efavirenz-based ART may be given safely without laboratory monitoring.