Maribel Muñoz

Comprehensive Treatment of Extensively Drug-Resistant Tuberculosis

BACKGROUND Extensively drug-resistant tuberculosis has been reported in 45 countries, including countries with limited resources and a high burden of tuberculosis. We describe the management of extensively drug-resistant tuberculosis and treatment outcomes among patients who were referred for individualized outpatient therapy in Peru. METHODS A total of 810 patients were referred for free individualized therapy, including drug treatment, resective surgery, adverse-event management, and nutritional and psychosocial support. We tested isolates from 651 patients for extensively drug-resistant tuberculosis and developed regimens that included five or more drugs to which the infecting isolate was not resistant. RESULTS Of the 651 patients tested, 48 (7.4%) had extensively drug-resistant tuberculosis; the remaining 603 patients had multidrug-resistant tuberculosis. The patients with extensively drug-resistant tuberculosis had undergone more treatment than the other patients (mean [+/-SD] number of regimens, 4.2+/-1.9 vs. 3.2+/-1.6; P<0.001) and had isolates that were resistant to more drugs (number of drugs, 8.4+/-1.1 vs. 5.3+/-1.5; P<0.001). None of the patients with extensively drug-resistant tuberculosis were coinfected with the human immunodeficiency virus (HIV). Patients with extensively drug-resistant tuberculosis received daily, supervised therapy with an average of 5.3+/-1.3 drugs, including cycloserine, an injectable drug, and a fluoroquinolone. Twenty-nine of these patients (60.4%) completed treatment or were cured, as compared with 400 patients (66.3%) with multidrug-resistant tuberculosis (P=0.36). CONCLUSIONS Extensively drug-resistant tuberculosis can be cured in HIV-negative patients through outpatient treatment, even in those who have received multiple prior courses of therapy for tuberculosis.

Burden of depression among impoverished HIV-positive women in Peru.

Objectives:In resource-poor settings, the mental health burden among HIV-positive women is exacerbated by poverty. We sought to describe the extent, risk factors, and experience of depression among impoverished HIV-positive women living in Lima, Peru. Methods:This is a case series of 78 HIV-positive women in Lima, Peru. We measured depression, stigma, and social support and performed a multivariable analysis to identify factors associated with depression. Results:Among 78 HIV-positive patients, 68% were depressed. Depression and suicidal ideation were rarely diagnosed by providers. In multivariable analysis, HIV-related stigma and food scarcity were associated with depression. Conclusions:In our cohort of HIV-positive women in Lima, Peru, poverty and socioeconomic vulnerability contributed to depression. Findings highlight the heavy burden of depression in this cohort of poor women and the need to incorporate mental health services as an integral component of HIV care.

Aggressive Regimens for Multidrug-Resistant Tuberculosis Decrease All-Cause Mortality

Rationale A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB) is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen. Objectives This study assessed the impact of an aggressive regimen–one containing at least five likely effective drugs, including a fluoroquinolone and injectable–on treatment outcomes in a large MDR-TB patient cohort. Methods This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death. Measurements and Main Results In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7) drugs. Cure or completion was achieved in 66.1% (442) of patients; death occurred in 20.8% (139). Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89), compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93). Conclusions The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB.

Food insufficiency is a risk factor for suboptimal antiretroviral therapy adherence among HIV-infected adults in urban Peru.

We examined the relationship between food insufficiency and antiretroviral therapy (ART) adherence. A cohort of HIV-infected adults in urban Peru was followed for a two-year period after ART initiation. ART adherence was measured using a 30-day self-report tool and classified as suboptimal if <95% adherence was reported. We conducted a repeated measures cohort analysis to examine whether food insufficiency was more common during months of suboptimal adherence relative to months with optimal adherence. 1,264 adherence interviews were conducted for 134 individuals. Participants who reported food insufficiency in the month prior to interview were more likely to experience suboptimal adherence than those who did not (odds ratio [O.R.]:2.4; 95% confidence interval [C.I.]:1.4, 4.1), even after adjusting for baseline social support score (O.R. per 5 point increase:0.91; C.I.:[0.85, 0.98]) and good baseline adherence self-efficacy (O.R.:0.25; C.I.:[0.09, 0.69]). Interventions that ensure food security for HIV-infected individuals may help sustain high levels of adherence.

Drug-Resistant Tuberculosis and Pregnancy: Treatment Outcomes of 38 Cases in Lima, Peru

BACKGROUND Multidrug-resistant tuberculosis (MDR-TB) disproportionately affects young adults, including women of childbearing age; however, treatment of MDR-TB during pregnancy is still controversial. This study looks at the treatment and pregnancy outcomes in a cohort of women who were treated for MDR-TB during pregnancy during a period of 10 years. METHODS A retrospective case study was performed using a standardized data collection form and data from 3 ranked sources of patient records. All 38 participants were treated during pregnancy with individualized regimens that included second-line TB medications. We examined the frequency of favorable and adverse outcomes with regard to disease and pregnancy. RESULTS After completion of MDR-TB treatment, 61% of the women were cured, 13% had died, 13% had defaulted, 5% remained in treatment, and 5% had experienced treatment failure. Four of the women experienced clinical deterioration of TB during pregnancy. Five of the pregnancies terminated in spontaneous abortions, and 1 child was stillborn. Among the living newborns, 3 were born with low birth weight, 1 was born prematurely, and 1 had fetal distress. CONCLUSIONS The rates of success in treating MDR-TB in our cohort are comparable to those of other MDR-TB treatment programs in Peru. The birth outcomes of our cohort are similar to those among the general Peru population. Therefore, we advocate that a woman should be given the option to continue treatment of MDR-TB rather than terminating pregnancy or discontinuing MDR-TB treatment.

HIV-positive patients treated for multidrug-resistant tuberculosis: clinical outcomes in the HAART era.

SETTING Multidrug-resistant tuberculosis (MDR-TB) and the human immunodeficiency virus (HIV) pose two of the greatest threats to global tuberculosis (TB) control. Given expanding global access to antiretroviral therapy (ART) and second-line TB drugs, more data are needed on experiences treating MDR-TB and HIV co-infection in resource-poor settings. OBJECTIVE To describe the clinical characteristics, management, outcomes, and factors associated with survival among HIV-positive individuals receiving treatment for MDR-TB. DESIGN This was a retrospective case series of 52 HIV-positive individuals receiving treatment for MDR-TB in Lima, Peru. We used Cox proportional hazards regression models to identify risk factors for mortality. RESULTS A total of 31 (57%) of the cohort died on treatment, with the majority of deaths due to MDR-TB. Low baseline weight predicted a three-fold increased rate of death (aHR 3.1, 95%CI 1.5-6.7), while individuals receiving highly active ART experienced a significantly lower rate of death compared to those who were not (aHR 0.4, 95%CI 0.2-0.9). CONCLUSION Early ART is likely a key component of effective MDR-TB management in co-infected individuals.

Microfinance: a General Overview and Implications for Impoverished Individuals Living with HIV/aIDS

Microfinance among people living with HIV/AIDS (PLWHA) faces some opposition and remains understudied. This literature review examines microfinance’s evolution and impact on a variety of social and health indicators and its emerging implementation as a primary prevention tool for HIV and economic intervention for PLWHA. There is an abundance of literature supporting the apparent utility of microfinance. However, our understanding of the subject remains clouded by the heterogeneity and methodological limitations of existing impact studies, and access limitations to microfinance curbs our understanding of microfinance for this population. Existing literature suggests PLWHA could attain economic stability from microfinance and achieve successful repayment rates in some settings. The precarious socioeconomic and health issues of PLWHA pose unique challenges to minimizing loan default risk. Carefully-designed clinical studies are needed to assess whether PLWHA can be as successful with microfinance as healthy individuals.

Time to culture conversion and regimen composition in multidrug-resistant tuberculosis treatment.

Sputum cultures are an important tool in monitoring the response to tuberculosis treatment, especially in multidrug-resistant tuberculosis. There has, however, been little study of the effect of treatment regimen composition on culture conversion. Well-designed clinical trials of new anti-tuberculosis drugs require this information to establish optimized background regimens for comparison. We conducted a retrospective cohort study to assess whether the use of an aggressive multidrug-resistant tuberculosis regimen was associated with more rapid sputum culture conversion. We conducted Cox proportional-hazards analyses to examine the relationship between receipt of an aggressive regimen for the 14 prior consecutive days and sputum culture conversion. Sputum culture conversion was achieved in 519 (87.7%) of the 592 patients studied. Among patients who had sputum culture conversion, the median time to conversion was 59 days (IQR: 31–92). In 480 patients (92.5% of those with conversion), conversion occurred within the first six months of treatment. Exposure to an aggressive regimen was independently associated with sputum culture conversion during the first six months of treatment (HR: 1.36; 95% CI: 1.10, 1.69). Infection with human immunodeficiency virus (HR 3.36; 95% CI: 1.47, 7.72) and receiving less exposure to tuberculosis treatment prior to the individualized multidrug-resistant tuberculosis regimen (HR: 1.58; 95% CI: 1.28, 1.95) were also independently positively associated with conversion. Tachycardia (HR: 0.77; 95% CI: 0.61, 0.98) and respiratory difficulty (HR: 0.78; 95% CI: 0.62, 0.97) were independently associated with a lower rate of conversion. This study is the first demonstrating that the composition of the multidrug-resistant tuberculosis treatment regimen influences the time to culture conversion. These results support the use of an aggressive regimen as the optimized background regimen in trials of new anti-TB drugs.

Scaling up HIV treatment in Peru: applying lessons from DOTS-Plus.

Many countries with financial support for HIV treatment experience delays in scale-up because of bureaucratic, operational, and technical obstacles. The authors describe the Peruvian National HIV Programs response to such challenges. A team of consultants experienced in the scale-up of the Peruvian national program to treat multidrug-resistant tuberculosis worked with the national HIV program to identify and address key factors contributing to slow enrollment of HIV patients into the antiretroviral treatment program. The rate of enrollment into the antiretroviral treatment program increased from 124 patients/month in the first 9 months of the program to 226 patients/month in the last 7 months, an increase of 83%. This strategy achieved 38.5% coverage of the population in need. Effective programmatic expansion of the Peruvian National HIV Program was facilitated by a multidisciplinary collaboration in a systematized effort to overcome barriers to scale-up.

Community-Based Rapid Oral Human Immunodeficiency Virus Testing for Tuberculosis Patients in Lima, Peru

Among tuberculosis patients, timely diagnosis of human immunodeficiency virus (HIV) co-infection and early antiretroviral treatment are crucial, but are hampered by a myriad of individual and structural barriers. Community-based models to provide counseling and rapid HIV testing are few but offer promise. During November 2009-April 2010, community health workers offered and performed HIV counseling and testing by using the OraQuick Rapid HIV-1/2 Antibody Test to new tuberculosis cases in 22 Ministry of Health establishments and their household contacts (n = 130) in Lima, Peru. Refusal of HIV testing or study participation was low (4.7%). Intervention strengths included community-based approach with participant preference for testing site, use of a rapid, non-invasive test, and accompaniment to facilitate HIV care and family disclosure. We will expand the intervention under programmatic auspices for rapid community-based testing for new tuberculosis cases in high incidence establishments. Other potential target populations include contacts of HIV-positive persons and pregnant women.