• Human resources for control of tuberculosis and HIV-associated tuberculosis.

      Harries, A D; Zachariah, R; Bergström, K; Blanc, L; Salaniponi, F; Elzinga, G; National Tuberculosis Control Programme, Lilongwe, Malawi. adharries@malawi.net (2005-02)
      The global targets for tuberculosis (TB) control were postponed from 2000 to 2005, but on current evidence a further postponement may be necessary. Of the constraints preventing these targets being met, the primary one appears to be the lack of adequately trained and qualified staff. This paper outlines: 1) the human resources and skills for global TB and human immunodeficiency virus (HIV) TB control, including the human resources for implementing the DOTS strategy, the additional human resources for implementing joint HIV-TB control strategies and what is known about human resource gaps at global level; 2) the attempts to quantify human resource gaps by focusing on a small country in sub-Saharan Africa, Malawi; and 3) the main constraints to human resources and their possible solutions, under six main headings: human resource planning; production of human resources; distribution of the work-force; motivation and staff retention; quality of existing staff; and the effect of HIV/AIDS. We recommend an urgent shift in thinking about the human resource paradigm, and exhort international policy makers and the donor community to make a concerted effort to bridge the current gaps by investing for real change.
    • Loss to follow up from isoniazid preventive therapy among adults attending HIV voluntary counseling and testing sites in Uganda.

      Namuwenge, P M; Mukonzo, J K; Kiwanuka, N; Wanyenze, R; Byaruhanga, R; Bissell, K; Zachariah, R; Makerere University School of Public Health P.O. Box 7072 Kampala Uganda; AIDS Information Centre headquarters, P.O. Box 10446 Kampala, Uganda. (2012-02)
      Among HIV-infected adults attending non-governmental organization voluntary counseling and testing (VCT) sites in Uganda that provide a nine-month course of isoniazid preventive treatment (IPT), we report on loss to follow-up (LTFU) and its associated risk factors. The design was a retrospective cohort study of program data spanning a three year period (2006-2008). A total of 586 IPT patients were enrolled of whom 335 (57.1%) were females with a mean age of 34 years. Of those starting IPT, 341 (58.1%) were lost to follow-up, 197 (33.6%) completed IPT, 29 (4.9%) were discontinued and 19 (3.2%) died. The return rates at one, three, five and seven months were 78.0% (457), 62.1% (364), 52.9% (310) and 33.6% (197) respectively. Being less than 30 years of age, widowed, separated, or divorced were found to be associated with a higher risk of loss to follow-up. Sudden improvement in retention on IPT was observed between the years 2006 and 2007, although causes of the improvement are poorly understood hence the need for more research. At non-governmental VCT sites in Uganda, six out of ten individuals enrolled on IPT are lost to follow-up and efforts to reduce this attrition including systems strengthening might play a critical role in the success of IPT programs.
    • 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; et al. (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.
    • 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.
    • 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.
    • Offering Integrated Care for HIV/AIDS, Diabetes and Hypertension within Chronic Disease Clinics in Cambodia.

      Janssens, B; Van Damme, W; Raleigh, B; Gupta, J; Khem, S; Soy Ty, K; Vun, M; Ford, N; Zachariah, R; Médecins Sans Frontières, Phnom Penh, Cambodia. b.janssens@bigfoot.com (WHO, 2007-11)
      PROBLEM: In Cambodia, care for people with HIV/AIDS (prevalence 1.9%) is expanding, but care for people with type II diabetes (prevalence 5-10%), arterial hypertension and other treatable chronic diseases remains very limited. APPROACH: We describe the experience and outcomes of offering integrated care for HIV/AIDS, diabetes and hypertension within the setting of chronic disease clinics. LOCAL SETTING: Chronic disease clinics were set up in the provincial referral hospitals of Siem Reap and Takeo, 2 provincial capitals in Cambodia. RELEVANT CHANGES: At 24 months of care, 87.7% of all HIV/AIDS patients were alive and in active follow-up. For diabetes patients, this proportion was 71%. Of the HIV/AIDS patients, 9.3% had died and 3% were lost to follow-up, while for diabetes this included 3 (0.1%) deaths and 28.9% lost to follow-up. Of all diabetes patients who stayed more than 3 months in the cohort, 90% were still in follow-up at 24 months. LESSONS LEARNED: Over the first three years, the chronic disease clinics have demonstrated the feasibility of integrating care for HIV/AIDS with non-communicable chronic diseases in Cambodia. Adherence support strategies proved to be complementary, resulting in good outcomes. Services were well accepted by patients, and this has had a positive effect on HIV/AIDS-related stigma. This experience shows how care for HIV/AIDS patients can act as an impetus to tackle other common chronic diseases.
    • Outcomes and safety of concomitant nevirapine and rifampicin treatment under programme conditions in Malawi.

      Moses, M; Zachariah, R; Tayler-Smith, K; Misinde, D; Foncha, C; Manzi, M; Bauerfeind, A; Mwagomba, B; Kwanjana, J; Harries, A D; et al. (2010-02)
      SETTING: Thyolo District Hospital, rural Malawi. OBJECTIVES: To report on 1) clinical, immunological and virological outcomes and 2) safety among human immunodeficiency virus (HIV) infected patients with tuberculosis (TB) who received concurrent nevirapine (NVP) and rifampicin (RMP) based treatment. DESIGN: Retrospective cohort study. METHODS: Analysis of programme data, June-December 2007. RESULTS: Of a total of 156 HIV-infected TB patients who started NVP-based antiretroviral treatment, 136 (87%) completed TB treatment successfully, 16 (10%) died and 5 (4%) were transferred out. Mean body weight and CD4 gain (adults) were respectively 4.4 kg (95%CI 3.3-5.4) and 140 cells/mm(3) (95%CI 117-162). Seventy-four per cent of patients who completed TB treatment and had a viral load performed (n = 74) had undetectable levels (<50 copies/ml), while 17 (22%) had a viral load of 50-1000 copies/ml. Hepatotoxicity was present in 2 (1.3%) patients at baseline. Two patients developed Grade 2 and one developed Grade 3 alanine transaminase enzyme elevations during TB treatment (incidence rate per 10 years of follow-up 4.2, 95%CI 1.4-13.1). There were no reported deaths linked to hepatotoxicity. CONCLUSIONS: In a rural district in Malawi, concomitant NVP and RMP treatment is associated with good TB treatment outcomes and appears safe. Further follow-up of patients would be useful to ascertain the longer-term effects of this concurrent treatment.
    • The Partec CyFlow Counter could provide an option for CD4+ T-cell monitoring in the context of scaling-up antiretroviral treatment at the district level in Malawi.

      Fryland, M; Chaillet, P; Zachariah, R; Barnaba, A; Bonte, L; Andereassen, R; Charrondière, S; Teck, R; Didakus, O; Médecins sans Frontières-Luxembourg, Thyolo District, Malawi. (Elsevier, 2006-10)
      A study was conducted in rural Malawi to verify (a) whether the Partec CyFlow Counter((R)) for CD4+ T-cell lymphocyte counting in HIV-positive individuals could be introduced into a district hospital laboratory and (b) whether it would produce CD4 counts of acceptable quality. CD4+ cell counting was performed using the Partec CyFlow Counter and the results were compared with a reference method (FACsCount). A total of 311 blood samples were analysed and the correlation coefficient for the CyFlow Counter was 0.92 (95% CI 0.89-0.95). Mean CD4 counts using the Partec and the reference methods were 308.2 cells/microl and 316.9 cells/microl, respectively. The mean difference in CD4 count values was -8.68 cells/microl (95% CI -18.8 to 1.4). Mean intra-run variation was -6.84 cells/microl (95% CI -12.9 to 0.79). In the district laboratory setting, the instrument could accommodate up to 75 blood samples per technician per day. After being trained, local laboratory staff found the CyFlow Counter procedures simple to run and the instrument easy to manipulate. The Partec CyFlow Counter produces sufficiently reliable results and the instrument appears robust under field conditions. It could provide a new option for introducing routine CD4+ cell monitoring at the district level in the context of scaling-up antiretroviral therapy in Malawi.
    • Patient retention and attrition on antiretroviral treatment at district level in rural Malawi.

      Massaquoi, M; Zachariah, R; Manzi, M; Pasulani, O; Misindi, D; Mwagomba, B; Bauernfeind, A; Harries, A D; Médecins Sans Frontières, Thyolo District, Thyolo, Malawi. (Published by Elsevier, 2009-06)
      We report on rates of patient retention and attrition in the context of scaling-up antiretroviral treatment (ART) within a district hospital and its primary health centres in rural Malawi. 'Retention' was defined as being alive and on ART or transferred out, whereas 'attrition' was defined as died, lost to follow-up or stopped treatment. A total of 4074 patients were followed-up for 1803 person-years: 2904 were at the hospital and 1170 at health centres. Approximately 85% of patients were retained in care, both at hospital and health centres, with a retention rate per 100 person-years of 185 and 211, respectively [adjusted hazard ratio (HR) 1.18, 95% CI 1.10-1.28, P=0.001). Attrition rates per 100 person-years were similar: 33 and 36, respectively (adjusted HR 1.17, 95% CI 0.97-1.4, P=0.1). At health centres the incidence of loss to follow-up was significantly lower than at the hospital (adjusted HR 0.24, P<0.001, risk reduction 77%), but the rate of reported deaths was higher at health centres (adjusted HR 2.2, 95% CI 1.76-2.72, P<0.001). As Malawi continues to extend the coverage (and equity) of ART, including in rural areas, attention is needed to reduce losses to follow-up at hospital level and reduce mortality at primary care level.
    • Payment for antiretroviral drugs is associated with a higher rate of patients lost to follow-up than those offered free-of-charge therapy in Nairobi, Kenya.

      Zachariah, R; Van Engelgem, I; Massaquoi, M; Kocholla, L; Manzi, M; Suleh, A; Philips, M; Borgdorff, M; Médecins Sans Frontières - Brussels, Medical Department (Operational Research), 68 Rue de Gasperich, L-1617, Luxembourg. (Elsevier, 2008-03)
      This retrospective analysis of routine programme data from Mbagathi District Hospital, Nairobi, Kenya shows the difference in rates of loss to follow-up between a cohort that paid 500 shillings/month (approximately US$7) for antiretroviral drugs (ART) and one that received medication free of charge. A total of 435 individuals (mean age 31.5 years, 65% female) was followed-up for 146 person-years: 265 were in the 'payment' cohort and 170 in the 'free' cohort. The incidence rate for loss to follow-up per 100 person-years was 47.2 and 20.5, respectively (adjusted hazard ratio 2.27, 95% CI 1.21-4.24, P=0.01). Overall risk reduction attributed to offering ART free of charge was 56.6% (95% CI 20.0-76.5). Five patients diluted their ART regimen to one tablet (instead of two tablets) twice daily in order to reduce the monthly cost of medication by half. All these patients were from the payment cohort. Payment for ART is associated with a significantly higher rate of loss to follow-up, as some patients might be unable to sustain payment over time. In resource-limited settings, ART should be offered free of charge in order to promote treatment compliance and prevent the emergence of drug resistance.
    • Predictive value of C-reactive protein for tuberculosis, bloodstream infection or death among HIV-infected individuals with chronic, non-specific symptoms and negative sputum smear microscopy.

      Bedell, RA; van Lettow, M; Meaney, C; Corbett, EL; Chan, AK; Heyderman, RS; Anderson, ST; Akesson, A; Kumwenda, M; Zachariah, R; et al. (Wiley-Blackwell, 2018-01-01)
      BACKGROUND: C-reactive protein (CRP) is an inflammatory biomarker that may identify patients at risk of infections or death. Mortality among HIV-infected persons commencing antiretroviral therapy (ART) is often attributed to tuberculosis (TB) or bloodstream infections (BSI). METHODS: In two district hospitals in southern Malawi, we recruited HIV-infected adults with one or more unexplained symptoms present for at least one month (weight loss, fever or diarrhoea) and negative expectorated sputum microscopy for TB. CRP determination for 452 of 469 (96%) participants at study enrolment was analysed for associations with TB, BSI or death to 120 days post-enrolment. RESULTS: Baseline CRP was significantly elevated among patients with confirmed or probable TB (52), BSI (50) or death (60) compared to those with no identified infection who survived at least 120 days (269). A CRP value of >10 mg/L was associated with confirmed or probable TB (adjusted odds ratio 5.7; 95% CI 2.6, 14.3; 87% sensitivity) or death by 30 days (adjusted odds ratio 9.2; 95% CI 2.2, 55.1; 88% sensitivity). CRP was independently associated with TB, BSI or death, but the prediction of these endpoints was enhanced by including haemoglobin (all outcomes), CD4 count (BSI, death) and whether ART was started (death) in logistic regression models. CONCLUSION: High CRP at the time of ART initiation is associated with TB, BSI and early mortality and so has potential utility for stratifying patients for intensified clinical and laboratory investigation and follow-up. They may also be considered for empirical treatment of opportunistic infections including TB.
    • Providing HIV care for co-infected tuberculosis patients: a perspective from sub-Saharan Africa.

      Harries, A D; Zachariah, R; Lawn, S D; International Union Against Tuberculosis and Lung Disease, Paris, France; Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK. (2009-01)
      Human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS) and tuberculosis (TB) are overlapping epidemics that cause an immense burden of disease in sub-Saharan Africa. This region is home to the majority of the world's co-infected patents, who have higher TB case fatality and recurrence rates than patients with TB alone. A World Health Organization interim policy has been developed to reduce the joint burden of TB-HIV disease, an important component of which is provision of HIV care to co-infected patients. This review focuses on HIV testing of TB patients and, for those who are HIV-positive, the administration of adjunctive cotrimoxazole preventive treatment (CPT) and antiretroviral treatment (ART). HIV testing has moved from a voluntary, client-initiated intervention to one that is provider-initiated and a routine part of the diagnostic work-up. The efficacy and safety of CPT in HIV-infected patients is now well established, and this is an essential part of the package of HIV care. ART scale-up in Africa can substantially improve outcomes in co-infected patients. However, the clinical and programmatic challenges of combining ART with anti-tuberculosis treatment need to be resolved to realise the full potential of this benefit. These include the optimal time to start ART, how best to combine rifampicin-containing regimens with first-line and second-line ART regimens, management of immune reconstitution disease, the role of isoniazid preventive treatment with ART after TB treatment completion, and where and how to provide combined treatment to best suit the patient. Clinical and operational studies in the next few years should help to resolve some of these issues.
    • Reasons for loss to follow-up among mothers registered in a prevention-of-mother-to-child transmission program in rural Malawi

      Bwirire, L; Fitzgerald, M; Zachariah, R; Chikafa, V; Massaquoi, M; Moens, M; Kamoto, K; Schouten, E (Elsevier, 2008-05-16)
    • Reasons for unsatisfactory acceptance of antiretroviral treatment in the urban Kibera slum, Kenya.

      Unge, C; Johansson, A; Zachariah, R; Some, D; Van Engelgem, I; Ekstrom, A M; Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden. christianunge@gmail.com (Taylor & Francis, 2008-02)
      The aim of this study was to explore why patients in the urban Kibera slum, Nairobi, Kenya, offered free antiretroviral treatment (ART) at the Médecins Sans Frontièrs (MSF) clinic, choose not to be treated despite signs of AIDS. Qualitative semi-structured interviews were conducted with 26 patients, 9 men and 17 women. Six main reasons emerged for not accepting ART: a) fear of taking medication on an empty stomach due to lack of food; b) fear that side-effects associated with ART would make one more ill; c) fear of disclosure and its possible negative repercussions; d) concern for continuity of treatment and care; e) conflicting information from religious leaders and community, and seeking alternative care (e.g. traditional medicine); f) illiteracy making patients unable to understand the information given by health workers.
    • Retention and attrition during the preparation phase and after start of antiretroviral treatment in Thyolo, Malawi, and Kibera, Kenya: implications for programmes?

      Zachariah, R; Tayler-Smith, K; Manzi, M; Massaquoi, M; Mwagomba, B; van Griensven, J; van Engelgem, I; Arnould, L; Schouten, E J; Chimbwandira, F M; et al. (2011-08)
      Among adults eligible for antiretroviral therapy (ART) in Thyolo (rural Malawi) and Kibera (Nairobi, Kenya), this study (a) reports on retention and attrition during the preparation phase and after starting ART and (b) identifies risk factors associated with attrition. 'Retention' implies being alive and on follow-up, whilst 'attrition' implies loss to follow-up, death or stopping treatment (if on ART). There were 11,309 ART-eligible patients from Malawi and 3633 from Kenya, of whom 8421 (74%) and 2792 (77%), respectively, went through the preparation phase and started ART. In Malawi, 2649 patients (23%) were lost to attrition in the preparation phase and 2189 (26%) after starting ART. Similarly, in Kenya 546 patients (15%) were lost to attrition in the ART preparation phase and 647 (23%) while on ART. Overall programme attrition was 43% (4838/11,309) for Malawi and 33% (1193/3633) for Kenya. Restricting cohort evaluation to 'on ART' (as is usually done) underestimates overall programme attrition by 38% in Malawi and 36% in Kenya. Risk factors associated with attrition in the preparation phase included male sex, age <35 years, advanced HIV/AIDS disease and increasing malnutrition. Considerable attrition occurs during the preparation phase of ART, and programme evaluations confined to on-treatment analysis significantly underestimate attrition. This has important operational implications, which are discussed here.
    • Risk Factors for High Early Mortality in Patients on Antiretroviral Treatment in a Rural District of Malawi.

      Zachariah, R; Fitzgerald, M; Massaquoi, M; Pasulani, O; Arnould, L; Makombe, S D; Harries, A D; Medecins sans Frontieres, Operational Research, Brussels Operational Center, Belgium. zachariah@internet.lu (2006-11-28)
      OBJECTIVES: Among adults started on antiretroviral treatment (ART) in a rural district hospital (a) to determine the cumulative proportion of deaths that occur within 3 and 6 months of starting ART, and (b) to identify risk factors that may be associated with such mortality. DESIGN AND SETTING: A cross-sectional analytical study set in Thyolo district, Malawi. METHODS: Over a 2-year period (April 2003 to April 2005) mortality within the first 3 and 6 months of starting ART was determined and risk factors were examined. RESULTS: A total of 1507 individuals (517 men and 990 women), whose median age was 35 years were included in the study. There were a total of 190 (12.6%) deaths on ART of which 116 (61%) occurred within the first 3 months (very early mortality) and 150 (79%) during the first 6 months of initiating ART. Significant risk factors associated with such mortality included WHO stage IV disease, a baseline CD4 cell count under 50 cells/mul and increasing grades of malnutrition. A linear trend in mortality was observed with increasing grades of malnutrition (chi for trend = 96.1, P
    • Scaling-up co-trimoxazole prophylaxis in HIV-exposed and HIV-infected children in high HIV-prevalence countries.

      Zachariah, R; Harries, A D; Luo, C; Bachman, G; Graham, S M; Médecins Sans Frontières, Medical department (Operational Research), Brussels Operational Center, Brussels, Belgium. zachariah@internet.lu (Elsevier, 2007-10)
      Co-trimoxazole (trimethoprim-sulfamethoxazole) is a widely available antibiotic that substantially reduces HIV-related morbidity and mortality in both adults and children. Prophylaxis with co-trimoxazole is a recommended intervention of proven benefit that could serve not only as an initial step towards improving paediatric care in young children with limited access to antiretroviral treatment, but also as an important complement to antiretroviral therapy in resource-limited settings. Despite co-trimoxazole's known clinical benefits, the potential operational benefits, and favourable recommendations by WHO, UNAIDS, and UNICEF, its routine use in developing countries--particularly sub-Saharan Africa--has remained limited. Out of an estimated 4 million children in need of co-trimoxazole prophylaxis (HIV-exposed and HIV-infected), only 4% are currently receiving this intervention. We discuss some of the major barriers preventing the scale-up of co-trimoxazole prophylaxis for children in countries with a high prevalence of HIV and propose specific actions required to tackle these challenges.
    • Sexually transmitted infections among prison inmates in a rural district of Malawi.

      Zachariah, R; Harries, A D; Chantulo, A; Yadidi, A E; Nkhoma, W; Maganga, O; Mission (Malawi), Medecins sans Frontieres-Luxembourg, 70 rue de Gasperich, L-1617, Luxembourg. zachariah@internet.lu (Elsevier, 2008-02-14)
      As part of a comprehensive human immunodeficiency virus (HIV) prevention strategy targeting high-risk groups, sexually transmitted infection (STI) clinics are offered to all prisoners in Thyolo district, southern Malawi. Prison inmates are not, however, allowed access to condoms as it is felt that such an intervention might encourage homosexuality which is illegal in Malawi. A study was conducted between January 2000 and December 2001 in order to determine the prevalence, incidence, and patterns of STIs among male inmates of 2 prisons in this rural district. A total of 4229 inmates were entered into the study during a 2-year period. Of these, 178 (4.2%) were diagnosed with an STI. This included 83 (46%) inmates with urethral discharge, 60 (34%) with genital ulcer disease (GUD), and 35 (20%) inmates with epididymo-orchitis. Fifty (28%) STIs were considered incident cases acquired within the prisons (incidence risk 12 cases/1000 inmates/year). GUD was the most common STI in this group comprising 52% of all STI. This study shows that a considerable proportion of STIs among inmates are acquired within prison. In a setting of same-sex inmates, this suggests inter-prisoner same-sex sexual activity. The findings have implications for HIV transmission and might help in developing more rational policies on STI control and condom access within Malawi prisons.
    • Stavudine- and nevirapine-related drug toxicity while on generic fixed-dose antiretroviral treatment: incidence, timing and risk factors in a three-year cohort in Kigali, Rwanda.

      van Griensven, J; Zachariah, R; Rasschaert, F; Mugabo, J; Atté, EF; Reid, T; Médecins Sans Frontières, Operational Centre Brussels, Medical Department, Duprestraat 94, 1090 Brussels, Belgium. (2009-09-02)
      This cohort study was conducted to report on the incidence, timing and risk factors for stavudine (d4T)- and nevirapine (NVP)-related severe drug toxicity (requiring substitution) with a generic fixed-dose combination under program conditions in Kigali, Rwanda. Probability of 'time to first toxicity-related drug substitution' was estimated using the Kaplan-Meier method and Cox-proportional hazards modeling was used to identify risk factors. Out of 2190 adults (median follow-up: 1.5 years), d4T was replaced in 175 patients (8.0%) for neuropathy, 69 (3.1%) for lactic acidosis and 157 (7.2%) for lipoatrophy, which was the most frequent toxicity by 3 years of antiretroviral treatment (ART). NVP was substituted in 4.9 and 1.3% of patients for skin rash and hepatotoxicity, respectively. Use of d4T 40mg was associated with increased risk of lipoatrophy and early (<6 months) neuropathy. Significant risk factors associated with lactic acidosis and late neuropathy included higher baseline body weight. Older age and advanced HIV disease increased the risk of neuropathy. Elevated baseline liver tests and older age were identified as risk factors for NVP-related hepatotoxicity. d4T is associated with significant long-term toxicity. d4T-dose reduction, increased access to safer ART in low-income countries and close monitoring for those at risk are all relevant strategies.