Treatment failure and mortality factors in patients receiving second-line HIV therapy in resource-limited countries.

CONTEXT: Long-term antiretroviral therapy (ART) use in resource-limited countries leads to increasing numbers of patients with HIV taking second-line therapy. Limited access to further therapeutic options makes essential the evaluation of second-line regimen efficacy in these settings. OBJECTIVES: To investigate failure rates in patients receiving second-line therapy and factors associated with failure and death. DESIGN, SETTING, AND PARTICIPANTS: Multicohort study of 632 patients > 14 years old receiving second-line therapy for more than 6 months in 27 ART programs in Africa and Asia between January 2001 and October 2008. MAIN OUTCOME MEASURES: Clinical, immunological, virological, and immunovirological failure (first diagnosed episode of immunological or virological failure) rates, and mortality after 6 months of second-line therapy use. Sensitivity analyses were performed using alternative CD4 cell count thresholds for immunological and immunovirological definitions of failure and for cohort attrition instead of death. RESULTS: The 632 patients provided 740.7 person-years of follow-up; 119 (18.8%) met World Health Organization failure criteria after a median 11.9 months following the start of second-line therapy (interquartile range [IQR], 8.7-17.0 months), and 34 (5.4%) died after a median 15.1 months (IQR, 11.9-25.7 months). Failure rates were lower in those who changed 2 nucleoside reverse transcriptase inhibitors (NRTIs) instead of 1 (179.2 vs 251.6 per 1000 person-years; incidence rate ratio [IRR], 0.64; 95% confidence interval [CI], 0.42-0.96), and higher in those with lowest adherence index (383.5 vs 176.0 per 1000 person-years; IRR, 3.14; 95% CI, 1.67-5.90 for < 80% vs > or = 95% [percentage adherent, as represented by percentage of appointments attended with no delay]). Failure rates increased with lower CD4 cell counts when second-line therapy was started, from 156.3 vs 96.2 per 1000 person-years; IRR, 1.59 (95% CI, 0.78-3.25) for 100 to 199/microL to 336.8 per 1000 person-years; IRR, 3.32 (95% CI, 1.81-6.08) for less than 50/microL vs 200/microL or higher; and decreased with time using second-line therapy, from 250.0 vs 123.2 per 1000 person-years; IRR, 1.90 (95% CI, 1.19-3.02) for 6 to 11 months to 212.0 per 1000 person-years; 1.71 (95% CI, 1.01-2.88) for 12 to 17 months vs 18 or more months. Mortality for those taking second-line therapy was lower in women (32.4 vs 68.3 per 1000 person-years; hazard ratio [HR], 0.45; 95% CI, 0.23-0.91); and higher in patients with treatment failure of any type (91.9 vs 28.1 per 1000 person-years; HR, 2.83; 95% CI, 1.38-5.80). Sensitivity analyses showed similar results. CONCLUSIONS: Among patients in Africa and Asia receiving second-line therapy for HIV, treatment failure was associated with low CD4 cell counts at second-line therapy start, use of suboptimal second-line regimens, and poor adherence. Mortality was associated with diagnosed treatment failure.

Treatment outcomes stratified by baseline immunological status among young children receiving nonnucleoside reverse-transcriptase inhibitor-based antiretroviral therapy in resource-limited settings.

A study of 568 children aged <5 years who commenced nonnucleoside reverse-transcriptase inhibitor-based antiretroviral therapy in resource-limited settings revealed good early outcomes. After 12 months of antiretroviral therapy, survival probability was 0.89 (95% confidence interval, 0.86-0.92), with no significant difference among children stratified on the basis of baseline immunological levels; 62% attained a CD4 cell percentage >25%, and 7% continued to have a CD4 cell percentage <15%.

Risk factors for high early mortality in patients on antiretroviral treatment in a rural district of Malawi.

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

Telemedicine for HIV/AIDS Care in Low Resource Settings.

Telemedicine is a way to support health care delivery in remote areas. With our telemedicine project the Institute of Tropical Medicine, Antwerp, Belgium, intended to facilitate the introduction of antiretroviral therapy (ART) for patients affected by Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS) in developing countries, providing training, distance support and education to healthcare providers working in those settings.

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.

Baseline characteristics, response to and outcome of antiretroviral therapy among patients with HIV-1, HIV-2 and dual infection in Burkina Faso.

In an urban district hospital in Burkina Faso we investigated the relative proportions of HIV-1, HIV-2 and HIV-1/2 among those tested, the baseline sociodemographic and clinical characteristics, and the response to and outcome of antiretroviral therapy (ART). A total of 7368 individuals (male=32%; median age=34 years) were included in the analysis over a 6 year period (2002-2008). The proportions of HIV-1, HIV-2 and dual infection were 94%, 2.5% and 3.6%, respectively. HIV-1-infected individuals were younger, whereas HIV-2-infected individuals were more likely to be male, have higher CD4 counts and be asymptomatic on presentation. ART was started in 4255 adult patients who were followed up for a total of 8679 person-years, during which time 469 deaths occurred. Mortality differences by serotype were not statistically significant, but were generally worse for HIV-2 and HIV-1/2 after controlling for age, CD4 count and WHO stage. Among severely immune-deficient patients, mortality was higher for HIV-2 than HIV-1. CD4 count recovery was poorest for HIV-2. HIV-2 and dually infected patients appeared to do less well on ART than HIV-1 patients. Reasons may include differences in age at baseline, lower intrinsic immune recovery in HIV-2, use of ineffective ART regimens (inappropriate prescribing) by clinicians, and poor drug adherence.

An algorithm to optimize viral load testing in HIV-positive patients with suspected first-line antiretroviral therapy failure in Cambodia.

OBJECTIVE: To develop an algorithm for optimal use of viral load testing in patients with suspected first-line antiretroviral treatment (ART) failure. METHODS: Data from a cohort of patients on first-line ART in Cambodia were analyzed in a cross-sectional way to detect markers for treatment failure. Markers with an adjusted likelihood ratio <0.67 or >1.5 were retained to calculate a predictor score. The accuracy of a 2-step algorithm based on this score followed by targeted viral load testing was compared with World Health Organization criteria for suspected treatment failure. RESULTS: One thousand eight hundred three viral load measurements of 764 patients were available for analysis. Prior ART exposure, CD4 count below baseline, 25% and 50% drop from peak CD4 count, hemoglobin drop of > or =1 g/dL, CD4 count <100 cells per microliter after 12 months of treatment, new onset of papular pruritic eruption, and visual analog scale <95% were included in the predictor score. A score >or=2 had the best combination of sensitivity and specificity and required confirmatory viral load testing for only 9% of patients. World Health Organization criteria had a similar sensitivity but a lower specificity and required viral load testing for 24.9% of patients. CONCLUSION: An algorithm combining a predictor score with targeted viral load testing in patients with an intermediate probability of failure optimizes the use of scarce resources.

Evaluation of a systematic substitution of zidovudine for stavudine-based HAART in a program setting in rural Cambodia.

OBJECTIVE: To evaluate a treatment strategy of substituting zidovudine (ZDV) for stavudine (d4T)-based highly active antiretroviral therapy (HAART), aimed at preventing d4T-associated toxicity, in a programmatic setting in rural Cambodia. METHODS: Survival probability, CD4 gain, anemia incidence, and factors associated with severe anemia were analyzed in a cohort of adult patients switched from d4T- to ZDV-containing regimens from March 2006 to March 2007. RESULTS: Among 527 patients systematically switched to ZDV after d4T-based HAART for a median of 18 months, 4 (0.8%) patients died, 2 (0.4%) were lost to follow-up, 18 (3.4%) were transferred out, and 503 (95.4%) remained on HAART. Median CD4 gain was +263.5 cells/microL (interquartile range: 89.25-369.5) at 24 months. Within 1 year after the switch, 21.9% and 7.1% of patients developed anemia (grades 1-4) and severe anemia (grades 3-4), respectively. Low body mass index (< or =18) and low CD4 count (<200 cells/microL) at the time of switch were factors associated with severe anemia. Additional follow-up visits for laboratory monitoring and adherence counseling, increased absenteeism from work, and transportation costs for the patients were noted. CONCLUSIONS: The switch strategy of substituting ZDV for d4T-based HAART led to satisfactory overall clinical outcomes. However, it resulted in a relatively high incidence of mild to severe anemia and increased burden for the program and the patients.