Peter Saranchuk

Antiretroviral treatment outcomes from a nurse-driven, community-supported HIV/AIDS treatment programme in rural Lesotho: observational cohort assessment at two years

IntroductionLesotho has the third highest HIV prevalence in the world (an adult prevalence of 23.2%). Despite a lack of resources for health, the country has implemented state-of-the-art antiretroviral treatment guidelines, including early initiation of treatment (<350 cells/mm3), tenofovir in first line, and nurse-initiated and managed HIV care, including antiretroviral therapy (ART), at primary health care level.Programme approachWe describe two-year outcomes of a decentralized HIV/AIDS care programme run by Doctors Without Borders/Médecins Sans Frontières, the Ministry of Health and Social Welfare, and the Christian Health Association of Lesotho in Scott catchment area, a rural health zone covering 14 clinics and one district hospital. Outcome data are described through a retrospective cohort analysis of adults and children initiated on ART between 2006 and 2008.Discussion and EvaluationOverall, 13,243 people have been enrolled in HIV care (5% children), and 5376 initiated on ART (6.5% children), 80% at primary care level. Between 2006 and 2008, annual enrolment more than doubled for adults and children, with no major external increase in human resources. The proportion of adults arriving sick (CD4 <50 cells/mm3) decreased from 22.2% in 2006 to 11.9% in 2008. Twelve-month outcomes are satisfactory in terms of mortality (11% for adults; 9% for children) and loss to follow up (8.8%). At 12 months, 80% of adults and 89% of children were alive and in care, meaning they were still taking their treatment; at 24 months, 77% of adults remained in care.ConclusionDespite major resource constraints, Lesotho is comparing favourably with its better resourced neighbour, using the latest international ART recommendations. The successful two-year outcomes are further evidence that HIV/AIDS care and treatment can be provided effectively at the primary care level. The programme highlights how improving HIV care strengthened the primary health care system, and validates several critical areas for task shifting that are being considered by other countries in the region, including nurse-driven ART for adults and children, and lay counsellor-supported testing and counselling, adherence and case management.

Ambulatory Multi-Drug Resistant Tuberculosis Treatment Outcomes in a Cohort of HIV-Infected Patients in a Slum Setting in Mumbai, India

Background India carries one quarter of the global burden of multi-drug resistant TB (MDR-TB) and has an estimated 2.5 million people living with HIV. Despite this reality, provision of treatment for MDR-TB is extremely limited, particularly for HIV-infected individuals. Médecins Sans Frontières (MSF) has been treating HIV-infected MDR-TB patients in Mumbai since May 2007. This is the first report of treatment outcomes among HIV-infected MDR-TB patients in India. Methods HIV-infected patients with suspected MDR-TB were referred to the MSF-clinic by public Antiretroviral Therapy (ART) Centers or by a network of community non-governmental organizations. Patients were initiated on either empiric or individualized second-line TB-treatment as per WHO recommendations. MDR-TB treatment was given on an ambulatory basis and under directly observed therapy using a decentralized network of providers. Patients not already receiving ART were started on treatment within two months of initiating MDR-TB treatment. Results Between May 2007 and May 2011, 71 HIV-infected patients were suspected to have MDR-TB, and 58 were initiated on treatment. MDR-TB was confirmed in 45 (78%), of which 18 (40%) were resistant to ofloxacin. Final treatment outcomes were available for 23 patients; 11 (48%) were successfully treated, 4 (17%) died, 6 (26%) defaulted, and 2 (9%) failed treatment. Overall, among 58 patients on treatment, 13 (22%) were successfully treated, 13 (22%) died, 7 (12%) defaulted, two (3%) failed treatment, and 23 (40%) were alive and still on treatment at the end of the observation period. Twenty-six patients (45%) experienced moderate to severe adverse events, requiring modification of the regimen in 12 (20%). Overall, 20 (28%) of the 71 patients with MDR-TB died, including 7 not initiated on treatment. Conclusions Despite high fluoroquinolone resistance and extensive prior second-line treatment, encouraging results are being achieved in an ambulatory MDR-T- program in a slum setting in India. Rapid scale-up of both ART and second-line treatment for MDR-TB is needed to ensure survival of co-infected patients and mitigate this growing epidemic.

Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral and Second Line Anti-TB Treatment in Mumbai, India

Background Significant adverse events (AE) have been reported in patients receiving medications for multidrug- and extensively-drug-resistant tuberculosis (MDR-TB & XDR-TB). However, there is little prospective data on AE in MDR- or XDR-TB/HIV co-infected patients on antituberculosis and antiretroviral therapy (ART) in programmatic settings. Methods Médecins Sans Frontières (MSF) is supporting a community-based treatment program for drug-resistant tuberculosis in HIV-infected patients in a slum setting in Mumbai, India since 2007. Patients are being treated for both diseases and the management of AE is done on an outpatient basis whenever possible. Prospective data were analysed to determine the occurrence and nature of AE. Results Between May 2007 and September 2011, 67 HIV/MDR-TB co-infected patients were being treated with anti-TB treatment and ART; 43.3% were female, median age was 35.5 years (Interquartile Range: 30.5–42) and the median duration of anti-TB treatment was 10 months (range 0.5–30). Overall, AE were common in this cohort: 71%, 63% and 40% of patients experienced one or more mild, moderate or severe AE, respectively. However, they were rarely life-threatening or debilitating. AE occurring most frequently included gastrointestinal symptoms (45% of patients), peripheral neuropathy (38%), hypothyroidism (32%), psychiatric symptoms (29%) and hypokalaemia (23%). Eleven patients were hospitalized for AE and one or more suspect drugs had to be permanently discontinued in 27 (40%). No AE led to indefinite suspension of an entire MDR-TB or ART regimen. Conclusions AE occurred frequently in this Mumbai HIV/MDR-TB cohort but not more frequently than in non-HIV patients on similar anti-TB treatment. Most AE can be successfully managed on an outpatient basis through a community-based treatment program, even in a resource-limited setting. Concerns about severe AE in the management of co-infected patients are justified, however, they should not cause delays in the urgently needed rapid scale-up of antiretroviral therapy and second-line anti-TB treatment.

Burden of HIV-Related Cytomegalovirus Retinitis in Resource-Limited Settings: A Systematic Review

BACKGROUND Cytomegalovirus (CMV) is a late-stage opportunistic infection in people living with human immunodeficiency virus (HIV)/AIDS. Lack of ophthalmological diagnostic skills, lack of convenient CMV treatment, and increasing access to antiretroviral therapy have all contributed to an assumption that CMV retinitis is no longer a concern in low- and middle-income settings. METHODS We conducted a systematic review and meta-analysis of published and unpublished studies reporting prevalence of CMV retinitis in low- and middle-income countries. Eligible studies assessed the occurrence of CMV retinitis by funduscopic examination within a cohort of at least 10 HIV-positive adult patients. RESULTS We identified 65 studies from 24 countries, mainly in Asia (39 studies, 12 931 patients) and Africa (18 studies, 4325 patients). By region, the highest prevalence was observed in Asia with a pooled prevalence of 14.0% (11.8%-16.2%). Almost a third (31.6%, 95% confidence interval [CI], 27.6%-35.8%) had vision loss in 1 or both eyes. Few studies reported immune status, but where reported CD4 count at diagnosis of CMV retinitis was <50 cells/µL in 73.4% of cases. There was no clear pattern of prevalence over time, which was similar for the period 1993-2002 (11.8%; 95% CI, 8%-15.7%) and 2009-2013 (17.6%; 95% CI, 12.6%-22.7%). CONCLUSIONS Prevalence of CMV retinitis in resource low- and middle-income countries, notably Asian countries, remains high, and routine retinal screening of late presenting HIV-positive patients should be considered. HIV programs must ensure capacity to manage the needs of patients who present late for care.

Poor Outcomes in a Cohort of HIV-Infected Adolescents Undergoing Treatment for Multidrug-Resistant Tuberculosis in Mumbai, India

Background Little is known about the treatment of multidrug-resistant tuberculosis (MDR-TB) in HIV-co-infected adolescents. This study aimed to present the intermediate outcomes of HIV-infected adolescents aged 10–19 years receiving second-line anti-TB treatment in a Médecins Sans Frontières (MSF) project in Mumbai, India. Methods A retrospective review of medical records of 11 adolescents enrolled between July 2007 and January 2013 was undertaken. Patients were initiated on either empirical or individualized second-line ambulatory anti-TB treatment under direct observation. Results The median age was 16 (IQR 14–18) years and 54% were female. Five (46%) adolescents had pulmonary TB (PTB), two (18%) extrapulmonary disease (EPTB) and four (36%) had both. Median CD4 count at the time of MDR-TB diagnosis was 162.7 cells/µl (IQR: 84.8–250.5). By January 2013, eight patients had final and 3 had interim outcomes. Favourable results were seen in four (36.5%) patients: one was cured and three were still on treatment with negative culture results. Seven patients (64%) had poor outcomes: four (36.5%) died and three (27%) defaulted. Three of the patients who died never started on antiretroviral and/or TB treatment and one died 16 days after treatment initiation. Two of the defaulted died soon after default. All patients (100%) on-treatment experienced adverse events (AEs): two required permanent discontinuation of the culprit drug and two were hospitalized due to AEs. No patient required permanent discontinuation of the entire second-line TB or antiretroviral regimens. Conclusions Early mortality and mortality after default were the most common reasons for poor outcomes in this study. Early mortality suggests the need for rapid diagnosis and prompt treatment initiation, and adolescents might benefit from active contact-tracing and immediate referral. Default occurred at different times, suggesting the need for continuous, intensified and individualized psychosocial support for co-infected adolescents. Operational research among co-infected adolescents will be especially important in designing effective interventions for this vulnerable group.

Alarming Levels of Drug-Resistant Tuberculosis in HIV-Infected Patients in Metropolitan Mumbai, India

Background Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India. Methods A cross-sectional survey was conducted among adults and children ART-center attendees. Smear microscopy, culture and drug-susceptibility-testing (DST) against all first and second-line TB-drugs using phenotypic liquid culture (MGIT) were conducted on all presumptive tuberculosis patients. Analyses were performed to determine DR-TB prevalence and resistance patterns separately for new and previously treated, culture-positive TB-cases. Results Between March 2013 and January 2014, ART-center attendees were screened during 14135 visits, of whom 1724 had presumptive TB. Of 1724 attendees, 72 (4%) were smear-positive and 202 (12%) had a positive culture for Mycobacterium tuberculosis. Overall DR-TB was diagnosed in 68 (34%, 95% CI: 27%–40%) TB-patients. The proportions of DR-TB were 25% (29/114) and 44% (39/88) among new and previously treated cases respectively. The patterns of DR-TB were: 21% mono-resistant, 12% poly-resistant, 38% multidrug-resistant (MDR-TB), 21% pre-extensively-drug-resistant (MDR-TB plus resistance to either a fluoroquinolone or second-line injectable), 6% extensively drug-resistant (XDR-TB) and 2% extremely drug-resistant TB (XDR-TB plus resistance to any group-IV/V drug). Only previous history of TB was significantly associated with the diagnosis of DR-TB in multivariate models. Conclusion The burden of DR-TB among HIV-infected patients attending public ART-centers in Mumbai was alarmingly high, likely representing ongoing transmission in the community and health facilities. These data highlight the need to promptly diagnose drug-resistance among all HIV-infected patients by systematically offering access to first and second-line DST to all patients with ‘presumptive TB’ rather than ‘presumptive DR-TB’ and tailor the treatment regimen based on the resistance patterns.

Resistance Patterns among Multidrug- Resistant Tuberculosis Patients in Greater Metropolitan Mumbai: Trends over Time

Background While the high burden of multidrug-resistant tuberculosis (MDR-TB) itself is a matter of great concern, the emergence and rise of advanced forms of drug-resistance such as extensively drug-resistant TB (XDR-TB) and extremely drug-resistant TB (XXDR-TB) is more troubling. The aim of this study was to investigate the trends over time of patterns of drug resistance in a sample of MDR-TB patients in greater metropolitan Mumbai, India. Methods This was a retrospective, observational study of drug susceptibility testing (DST) results among MDR-TB patients from eight health care facilities in greater Mumbai between 2005 and 2013. We classified resistance patterns into four categories: MDR-TB, pre-XDR-TB, XDR-TB and XXDR-TB. Results A total of 340 MDR-TB patients were included in the study. Pre-XDR-TB was the most common form of drug-resistant TB observed overall in this Mumbai population at 56.8% compared to 29.4% for MDR-TB. The proportion of patients with MDR-TB was 39.4% in the period 2005–2007 and 27.8% in 2011–2013, while the proportion of those with XDR-TB and XXDR-TB was changed from 6.1% and 0% respectively to 10.6% and 5.6% during the same time period. During the same periods, the proportions of patients with ofloxacin, moxifloxacin and ethionamide resistance significantly increased from 57.6% to 75.3%, from 60.0% to 69.5% and from 24.2% to 52.5% respectively (p<0.05). Discussion The observed trends in TB drug-resistance patterns in Mumbai highlight the need for individualized drug regimens, designed on the basis of DST results involving first- and second-line anti-TB drugs and treatment history of the patient. A drug-resistant TB case-finding strategy based on molecular techniques that identify only rifampicin resistance will lead to initiation of suboptimal treatment regimens for a significant number of patients, which may in turn contribute to amplification of resistance and transmission of strains with increasingly advanced resistance within the community.

Implementing the Xpert® MTB/RIF Diagnostic Test for Tuberculosis and Rifampicin Resistance: Outcomes and Lessons Learned in 18 Countries.

Background The Xpert® MTB/RIF (Xpert) is an automated molecular test for simultaneous detection of tuberculosis (TB) and rifampicin resistance, recommended by the World Health Organization as the preferred diagnostic method for individuals presumed to have multi-drug resistant TB (MDR-TB) or HIV-associated TB. We describe the performance of Xpert and key lessons learned during two years of implementation under routine conditions in 33 projects located in 18 countries supported by Médecins Sans Frontières across varied geographic, epidemiological and clinical settings. Methods Xpert was used following three strategies: the first being as the initial test, with microscopy in parallel, for all presumptive TB cases; the second being only for patients at risk of MDR-TB, or with HIV- associated TB, or presumptive paediatric TB; and the third being as the initial test for these high-risk patients plus as an add-on test to microscopy in others. Routine laboratory data were collected, using laboratory registers. Qualitative data such as logistic aspects, human resources, and tool acceptance were collected using a questionnaire. Findings In total, 52,863 samples underwent Xpert testing from April 2011 to December 2012. The average MTB detection rate was 18.5%, 22.3%, and 11.6% for the three different strategies respectively. Analysis of the results on samples tested in parallel showed that using Xpert as add-on test to microscopy would have increased laboratory TB confirmation by 49.7%, versus 42.3% for Xpert replacing microscopy. The main limitation of the test was the high rate of inconclusive results, which correlated with factors such as defective modules, cartridge version (G3 vs. G4) and staff experience. Operational and logistical hurdles included infrastructure renovation, basic computer training, regular instrument troubleshooting and maintenance, all of which required substantial and continuous support. Conclusion The implementation of Xpert was feasible and significantly increased TB detection compared to microscopy, despite the high rate of inconclusive results. Xpert implementation was accompanied by considerable operational and logistical challenges. To further decentralize diagnosis, simpler, low-cost TB technologies well-suited to low-resource settings are still urgently needed.

Ocular inflammatory disease and ocular tuberculosis in a cohort of patients co-infected with HIV and multidrug-resistant tuberculosis in Mumbai, India: a cross-sectional study

BackgroundThe prevalence and the patterns of ocular inflammatory disease and ocular tuberculosis (TB) are largely undocumented among Multidrug Resistant TB (MDR-TB) patients co-infected with Human Immunodeficiency Virus (HIV) and on antituberculosis and antiretroviral therapy (ART).MethodsLilavati Hospital and Research Center and Médecins Sans Frontières (MSF) organized a cross-sectional ophthalmological evaluation of HIV/MDR-TB co-infected patients followed in an MSF-run HIV-clinic in Mumbai, India, which included measuring visual acuity, and slit lamp and dilated fundus examinations.ResultsBetween February and April 2012, 47 HIV/MDR-TB co-infected patients (including three patients with extensively drug-resistant TB) were evaluated. Sixty-four per cent were male, mean age was 39 years (standard deviation: 8.7) and their median (IQR) CD4 count at the time of evaluation was 264 cells/μL (158–361). Thirteen patients (27%) had detectable levels of HIV viremia (>20 copies/ml). Overall, examination of the anterior segments was normal in 45/47 patients (96%). A dilated fundus examination revealed active ocular inflammatory disease in seven eyes of seven patients (15.5%, 95% Confidence Intervals (CI); 5.1-25.8%). ‘These included five eyes of five patients (10%) with choroidal tubercles, one eye of one patient (2%) with presumed tubercular chorioretinitis and one eye of one patient (2%) with evidence of presumed active CMV retinitis. Presumed ocular tuberculosis was thus seen in a total of six patients (12.7%, 95% CI; 3.2-22.2%). Two patients who had completed anti-TB treatment had active ocular inflammatory disease, in the form of choroidal tubercles (two eyes of two patients). Inactive scars were seen in three eyes of three patients (6%). Patients with extrapulmonary TB and patients <39 years old were at significantly higher risk of having ocular TB [Risk Ratio: 13.65 (95% CI: 2.4-78.5) and 6.38 (95% CI: 1.05-38.8) respectively].ConclusionsOcular inflammatory disease, mainly ocular tuberculosis, was common in a cohort of HIV/MDR-TB co-infected patients in Mumbai, India. Ophthalmological examination should be routinely considered in HIV patients diagnosed with or suspected to have MDR-TB, especially in those with extrapulmonary TB.

Second-line failure and first experience with third-line antiretroviral therapy in Mumbai, India.

Background There are limited data on the failure of second-line antiretroviral therapy (ART) and the use of third-line ART in people living with HIV in resource-limited settings. Since 2011, the Médecins Sans Frontières (MSF) HIV/tuberculosis programme in Mumbai, India, has been providing third-line ART to patients in care. Objective To describe the experiences and programmatic challenges during management of suspected second-line ART failure and third-line ART therapy for patients living with HIV, including the use of HIV viral load (VL) testing. Design This was a retrospective, observational cohort study of patients with suspected second-line ART treatment failure, who were followed for at least 12 months between January 2011 and March 2014. Results A total of 47 patients with suspected second-line failure met the inclusion criteria during the study period. Twenty-nine of them (62%) responded to enhanced adherence support, had a subsequent undetectable VL after a median duration of 3 months and remained on second-line ART. The other 18 patients had to be initiated on a third-line ART regimen, which consisted of darunavir–ritonavir, raltegravir, and one or more appropriate nucleoside or nucleotide reverse transcriptase inhibitors, based on the results of HIV genotype testing. Of the 13 patients for whom follow-up VL results were available, 11 achieved virological suppression after a median duration of 3 months on third-line ART (interquartile range: 2.5–3.0). No serious treatment-related adverse events were recorded. Conclusions With intensive counselling and adherence support in those suspected of failing second-line ART, unnecessary switching to more expensive third-line ART can be averted in the majority of cases. However, there is an increasing need for access to third-line ART medications such as darunavir and raltegravir, for which national ART programmes should be prepared. The cost of such medications and inadequate access to VL monitoring and HIV genotype testing are currently major barriers to optimal management of patients failing second-line ART.Background There are limited data on the failure of second-line antiretroviral therapy (ART) and the use of third-line ART in people living with HIV in resource-limited settings. Since 2011, the Médecins Sans Frontières (MSF) HIV/tuberculosis programme in Mumbai, India, has been providing third-line ART to patients in care. Objective To describe the experiences and programmatic challenges during management of suspected second-line ART failure and third-line ART therapy for patients living with HIV, including the use of HIV viral load (VL) testing. Design This was a retrospective, observational cohort study of patients with suspected second-line ART treatment failure, who were followed for at least 12 months between January 2011 and March 2014. Results A total of 47 patients with suspected second-line failure met the inclusion criteria during the study period. Twenty-nine of them (62%) responded to enhanced adherence support, had a subsequent undetectable VL after a median duration of 3 months and remained on second-line ART. The other 18 patients had to be initiated on a third-line ART regimen, which consisted of darunavir-ritonavir, raltegravir, and one or more appropriate nucleoside or nucleotide reverse transcriptase inhibitors, based on the results of HIV genotype testing. Of the 13 patients for whom follow-up VL results were available, 11 achieved virological suppression after a median duration of 3 months on third-line ART (interquartile range: 2.5-3.0). No serious treatment-related adverse events were recorded. Conclusions With intensive counselling and adherence support in those suspected of failing second-line ART, unnecessary switching to more expensive third-line ART can be averted in the majority of cases. However, there is an increasing need for access to third-line ART medications such as darunavir and raltegravir, for which national ART programmes should be prepared. The cost of such medications and inadequate access to VL monitoring and HIV genotype testing are currently major barriers to optimal management of patients failing second-line ART.