HIV, multidrug-resistant TB and depressive symptoms: when three conditions collide.

BACKGROUND: Management of multidrug-resistant TB (MDR-TB) patients co-infected with human immunodeficiency virus (HIV) is highly challenging. Such patients are subject to long and potentially toxic treatments and may develop a number of different psychiatric illnesses such as anxiety and depressive disorders. A mental health assessment before MDR-TB treatment initiation may assist in early diagnosis and better management of psychiatric illnesses in patients already having two stigmatising and debilitating diseases. OBJECTIVE: To address limited evidence on the baseline psychiatric conditions of HIV-infected MDR-TB patients, we aimed to document the levels of depressive symptoms at baseline, and any alteration following individualized clinical and psychological support during MDR-TB therapy, using the Patient Health Questionnaire-9 (PHQ-9) tool, among HIV-infected patients. DESIGN: This was a retrospective review of the medical records of an adult (aged >15 years) HIV/MDR-TB cohort registered for care during the period of August 2012 through to March 2014. RESULTS: A total of 45 HIV/MDR-TB patients underwent baseline assessment using the PHQ-9 tool, and seven (16%) were found to have depressive symptoms. Of these, four patients had moderate to severe depressive symptoms. Individualized psychological and clinical support was administered to these patients. Reassessments were carried out for all patients after 3 months of follow-up, except one, who died during the period. Among these 44 patients, three with baseline depressive symptoms still had depressive symptoms. However, improvements were observed in all but one after 3 months of follow-up. CONCLUSION: Psychiatric illnesses, including depressive symptoms, during MDR-TB treatment demand attention. Routine administration of baseline mental health assessments by trained staff has the potential to assist in determining appropriate measures for the management of depressive symptoms during MDR-TB treatment, and help in improving overall treatment outcomes. We recommend regular monitoring of mental health status by trained counsellors or clinical staff, using simple, validated and cost-effective tools.

HPV infection, cervical abnormalities, and cancer in HIV-infected women in Mumbai, India: 12-month follow-up.

BACKGROUND: HIV-infected women are at a higher risk of cervical intraepithelial neoplasia (CIN) and cancer than women in the general population, partly due to a high prevalence of persistent human papillomavirus (HPV) infection. The aim of the study was to assess the burden of HPV infection, cervical abnormalities, and cervical cancer among a cohort of HIV-infected women as part of a routine screening in an urban overpopulated slum setting in Mumbai, India. METHODS: From May 2010 to October 2010, Médecins Sans Frontières and Tata Memorial Hospital Mumbai offered routine annual Pap smears and HPV DNA testing of women attending an antiretroviral therapy (ART) clinic and a 12-month follow-up. Women with abnormal test results were offered cervical biopsy and treatment, including treatment for sexually transmitted infections (STIs). RESULTS: Ninety-five women were screened. Median age was 38 years (IQR: 33-41); median nadir CD4-count 143 cells/µL (IQR: 79-270); and median time on ART 23 months (IQR:10-41). HPV DNA was detected in 30/94 women (32%), and 18/94 (19%) showed either low-grade or high-grade squamous intraepithelial lesions (LSIL/HSIL) on Pap smear. Overall, >50% had cervical inflammatory reactions including STIs. Of the 43 women with a cervical biopsy, eight (8.4%) had CIN-1, five (5.3%) CIN-2, and two (2.1%) carcinoma in situ. All but one had HPV DNA detected (risk ratio: 11, 95% confidence interval: 3.3-34). By October 2011, 56 women had completed the 12-month follow-up and had been rescreened. No new cases of HPV infection/LSIL/HSIL were detected. CONCLUSION: The high prevalence of HPV infection, STIs, and cervical lesions among women attending an ART clinic demonstrates a need for routine screening. Simple, one-stop screening strategies are needed. The optimal screening interval, especially when resources are limited, needs to be determined.

'I cry every day': experiences of patients co-infected with HIV and multidrug-resistant tuberculosis.

OBJECTIVES: To understand patients' challenges in adhering to treatment for MDR-TB/HIV co-infection within the context of their life circumstances and access to care and support. METHODS: Qualitative study using in-depth interviews with 12 HIV/MDR-TB co-infected patients followed in a Médecins Sans Frontières (MSF) clinic in Mumbai, India, five lay caregivers and ten health professionals. The data were thematically analysed along three dimensions of patients' experience of being and staying on treatment: physiological, psycho-social and structural. RESULTS: By the time patients and their families initiate treatment for co-infection, their financial and emotional resources were often depleted. Side effects of the drugs were reported to be severe and debilitating, and patients expressed the burden of care and stigma on the social and financial viability of the household. Family caregivers were crucial to maintaining the mental and physical health of patients, but reported high levels of fatigue and stress. Médecins Sans Frontières providers recognised that the barriers to patient adherence were fundamentally social, rather than medical, yet were limited in their ability to support patients and their families. CONCLUSIONS: The treatment of MDR-TB among HIV-infected patients on antiretroviral therapy is hugely demanding for patients, caregivers and families. Current treatment regimens and case-holding strategies are resource intensive and require high levels of support from family and lay caregivers to encourage patient adherence and retention in care.

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.

Tracing patients on antiretroviral treatment lost-to-follow-up in an urban slum in India.

AIM: This article describes a cooperative initiative between an HIV-clinic and non-government organization network providing lost-to-follow-up tracing and delayed appointment follow-up of patients on antiretroviral treatment. BACKGROUND: Loss-to-follow-up among patients on antiretroviral treatment is a major challenge in resource-constrained settings. A model of cooperation between a Médecins Sans Frontières HIV-clinic and a non-governmental-organization network was piloted in a Mumbai slum. A steady decline in delayed appointments and loss-to-follow-up was observed over 4 years. DESIGN: Mixed method study. METHODS: A study conducted in January 2011 explored potential reasons for declining loss-to-follow-up-rates. A retrospective, quantitative analysis of patient data was undertaken complemented by 22 semi-structured interviews, four focus-group discussions to explore patients' and providers' perceptions of tracing activities. RESULTS/FINDINGS: The clinic loss-to-follow-up-rate has steadily declined from mid-2008-2011. Thirty-eight (4·6%) of 819 patients registered during the period were lost-to-follow-up with most lost during the first year. Rates of loss-to-follow-up between 0·3-2·4% were observed over the last 2 years. Phoning the day before an appointment was perceived as the most useful intervention to avoid missing appointments. The analysis revealed a widespread fear of forced disclosure by patients during home visits. CONCLUSIONS: The low loss-to-follow-up-rate cannot be attributed to the network tracing activities alone. Phoning before appointments may result in fewer delayed appointments and prevent loss-to-follow-up. Home visits should be a last resort method of patient tracing because of the risk of HIV-status disclosure and the opportunity of discrimination from family and neighbours.

Treatment outcomes in a cohort of patients with chronic hepatitis B and human immunodeficiency virus co-infection in Mumbai, India.

Treatment experiences with patients co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in resource-limited settings remain poorly documented. This study aimed to evaluate the treatment outcomes in a cohort of HIV/HBV co-infected individuals receiving tenofovir/lamivudine (TDF/3TC)-based antiretroviral therapy (ART) in a programmatic setting in Mumbai, India. Additionally, a cross-sectional laboratory study was carried out measuring serologic and virologic parameters. A total of 57 patients who received TDF/3TC were included in the study. Of these, 52 (91%) were male and the mean age was 38.7 years. The median follow-up period was 16.8 months (IQR:7.9-37.9). Forty-three patients were included in the cross-sectional laboratory study, of whom 38 (67%) were HBeAg(+) positive. Four patients had serum HBsAg conversion to negative and had developed anti-HBs-antibodies. HBV-DNA became undetectable (<1.3 log10 copies/ml or <20 IU/ml) in 35.5% and 75% of the HBeAg(+) and HBeAg(-) patients, respectively. Overall, 46.5% of patients had undetectable HBV-DNA and 90.7% had adequately suppressed HBV-DNA (<3.3 log10 copies/ml or <2000 IU/ml). The median reduction in serum HBV-DNA was 6 log10 copies/ml. In 29 patients (63%) HIV viral load was undetectable. Outcomes included seven (12%) deaths, four (7%) lost to follow-up, one (2%) transferred out and 45 (79%) alive and on treatment. In conclusion, good treatment outcomes were achieved in a cohort of HIV/HBV co-infected patients in India. In regions with a high HIV/HBV burden, all HIV-infected individuals should be tested for chronic hepatitis B. A TDF/3TC-backbone could be considered as first-line standardized ART regimen in these settings.

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.

Characteristics, immunological response & treatment outcomes of HIV-2 compared with HIV-1 & dual infections (HIV 1/2) in Mumbai.

BACKGROUND AND OBJECTIVES: Information available on HIV-2 and dual infection (HIV-1/2) is limited. This study was carried out among HIV positive individuals in an urban referral clinic in Khar, Mumbai, India, to report on relative proportions of HIV-1, HIV-2 and HIV-1/2 and baseline characteristics, response to and outcomes on antiretroviral treatment (ART). METHODS: Retrospective analysis of programme data (May 2006-May 2009) at Khar HIV/AIDS clinic at Mumbai, India was done. Three test algorithm was used to diagnose HIV-1 and -2 infection. Standard ART was given to infected individuals. Information was collected on standardized forms. RESULTS: A total of 524 individuals (male=51%; median age=37 yr) were included in the analysis over a 3 year period (2006-2009) - 489 (93%) with HIV-1, 28 (6%) with HIV-2 and 7(1%) with dual HIV-1/2 infection. HIV-2 individuals were significantly older than HIV-1 individuals (P<0.001). A significantly higher proportion of HIV-2 patients and those with dual infections had CD4 counts <200 cells/µl compared to HIV-1. HIV-2 individuals were more likely to present in WHO Clinical Stage 4. Of the 443 patients who were started on ART, 358 (81%) were still alive and on ART, 38 (8.5%) died and 3 were transferred out. CD4 count recovery at 6 and 12 months was satisfactory for HIV-1 and HIV-2 patients on protease inhibitor based regimens while this was significantly lower in HIV-2 individuals receiving 3 nucleoside reverse transcriptase inhibitors. INTERPRETATION AND CONCLUSIONS: In an urban HIV clinic in Mumbai, India, HIV-2 and dual infections are not uncommon. Adaptation of the current national diagnostic and management protocols to include discriminatory testing for HIV types and providing access to appropriate and effective ART regimens will prevent the development of viral resistance and preserve future therapeutic options.