Ziad El-Khatib

Viremia and drug resistance among HIV-1 patients on antiretroviral treatment: a cross-sectional study in Soweto, South Africa

Background:We assessed risk factors for viremia and drug resistance among long-term recipients of antiretroviral therapy (ART) in South Africa. Methods:In 2008, we conducted a cross-sectional study among patients receiving ART for 12 months or more. Genotypic resistance testing was performed on individuals with a viral load higher than 400 RNA copies/ml. Multiple logistic regression analysis was used to assess associations. Results:Of 998 participants, 75% were women with a median age of 41 years. Most (64%) had been on treatment for more than 3 years. The prevalence of viremia was 14% (n = 139): 12% (102/883) on first-line [i.e. nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen] and 33% (37/115) on second-line (i.e. protease inhibitor (PI)-based regimen) ART. Of viremic patients, 78% had drug resistance mutations. For NRTIs, NNRTIs and PIs, the prevalence of mutations was 64, 81 and 2%, respectively, among first-line failures and 29, 54 and 6%, respectively, among second-line failures. M184V/I, K103N and V106A/M were the most common mutations. Significant risk factors associated with viremia on first-line regimen included concurrent tuberculosis treatment [odds ratio (OR) 6.4, 95% confidence interval (CI) 2.2–18.8, P < 0.01] and a recent history of poor adherence (OR 2.7, 1.3–5.6, P = 0.01). Among second-line failures, attending a public clinic (OR 4.6, 95% CI 1.8–11.3, P < 0.01) and not having a refrigerator at home (OR 6.7, 95% CI 1.2–37.5, P = 0.03) were risk factors for virological failure. Conclusion:Risk factors for viral failure were line regimen dependent. Second-line ART recipients had a higher rate of viremia, albeit with infrequent PI drug resistance mutations. Measures to maintain effective virologic suppression should include increased adherence counseling, attention to concomitant tuberculosis treatment and heat-stable formulations of second-line ART regimens.

Adherence to Drug-Refill Is a Useful Early Warning Indicator of Virologic and Immunologic Failure among HIV Patients on First-Line ART in South Africa

Background Affordable strategies to prevent treatment failure on first-line regimens among HIV patients are essential for the long-term success of antiretroviral therapy (ART) in sub-Saharan Africa. WHO recommends using routinely collected data such as adherence to drug-refill visits as early warning indicators. We examined the association between adherence to drug-refill visits and long-term virologic and immunologic failure among non-nucleoside reverse transcriptase inhibitor (NNRTI) recipients in South Africa. Methods In 2008, 456 patients on NNRTI-based ART for a median of 44 months (range 12–99 months; 1,510 person-years) were enrolled in a retrospective cohort study in Soweto. Charts were reviewed for clinical characteristics before and during ART. Multivariable logistic regression and Kaplan-Meier survival analysis assessed associations with virologic (two repeated VL>50 copies/ml) and immunologic failure (as defined by WHO). Results After a median of 15 months on ART, 19% (n = 88) and 19% (n = 87) had failed virologically and immunologically respectively. A cumulative adherence of <95% to drug-refill visits was significantly associated with both virologic and immunologic failure (p<0.01). In the final multivariable model, risk factors for virologic failure were incomplete adherence (OR 2.8, 95%CI 1.2–6.7), and previous exposure to single-dose nevirapine or any other antiretrovirals (adj. OR 2.1, 95%CI 1.2–3.9), adjusted for age and sex. In Kaplan-Meier analysis, the virologic failure rate by month 48 was 19% vs. 37% among adherent and non-adherent patients respectively (logrank p value = 0.02). Conclusion One in five failed virologically after a median of 15 months on ART. Adherence to drug-refill visits works as an early warning indicator for both virologic and immunologic failure.

Adherence and virologic suppression during the first 24 weeks on antiretroviral therapy among women in Johannesburg, South Africa - a prospective cohort study

BackgroundAdherence is a necessary part of successful antiretroviral treatment (ART). We assessed risk factors for incomplete adherence among a cohort of HIV-infected women initiating ART and examined associations between adherence and virologic response to ART.MethodsA secondary data analysis was conducted on a cohort of 154 women initiating non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART at a single site in Johannesburg, South Africa. Ninety women had been enrolled in a prevention of mother-to-child transmission (pMTCT) program and were exposed to single-dose nevirapine (sdNVP) >18 months earlier. Women were interviewed pre-treatment and clinical, virologic and adherence data were collected during follow-up to 24 weeks. Incomplete adherence to ART was defined as returning >5% of medications, estimated by pill counts at scheduled visits. Multivariable logistic regression analysis and unadjusted odds ratio (95%CI) were performed, using STATA/SE (ver 10.1).ResultsAbout half of the women (53%) were <30 years of age, 63% had <11 years of schooling, 69% were unemployed and 37% lived in a shack. Seven percent of women had a viral load >400 copies/ml at 24 weeks and 37% had incomplete adherence at one or more visits. Incomplete adherence was associated with less education (p = 0.01) and lack of financial support from a partner (p = 0.02) after adjustment for confounders. Only when adherence levels dropped below 80% was there a significant association with viremia in the group overall (p = 0.02) although adherence <95% was associated with viremia in the sdNVP-exposed group (p = 0.03). The main reasons for incomplete adherence were being away from home, busy with other things and forgetting to take their medication.ConclusionVirologic response to NNRTI-treatment in the cohort was excellent. However, women who received sdNVP were at greater risk of virologic failure when adherence was <95%. Women exposed to sdNVP, and those with less education and less social support may benefit from additional adherence counseling to ensure the long-term success of ART. More than 80% adherence may be sufficient to maintain virologic suppression on NNRTI-based regimens in the short-term, however complete adherence should be encouraged.

Syrian refugees, between rocky crisis in Syria and hard inaccessibility to healthcare services in Lebanon and Jordan

Around 3% of the world’s population (n = 214 million people) has crossed international borders for various reasons. Since March 2011, Syria has been going through state of political crisis and instability resulting in an exodus of Syrians to neighbouring countries. More than 1 million Syrian refugees are residents of Lebanon, Jordan, Turkey, Egypt and North Africa. The international community must step up efforts to support Syrian refugees and their host governments.

Drug Resistance Patterns and Virus Re-Suppression among HIV-1 Subtype C Infected Patients Receiving Non-Nucleoside Reverse Transcriptase Inhibitors in South Africa

BACKGROUND: Emergence of HIV-1 drug resistance is at times an inevitable and anticipated consequence of antiretroviral therapy (ART) failure. We examined drug resistance patterns and virus re-suppression among subtype C-infected South African patients receiving first-line ART. METHODS: Treatment records of 431 patients on NNRTI-containing regimens for a median of 45 months were analyzed. Patients with viral load (VL) >400 copies/mL were followed and drug resistance mutations (DRM) were re-assessed. Associations between clinical/demographic measures and drug resistance/virologic outcomes were examined using Fisher exact and ordinal and logistic regression. RESULTS: Ten percent of patients (43/431) were viremic at enrollment (98% previously suppressed); sequences were obtained from 38/43. Of those, 82% had 1-7 DRM. In bivariate analysis remote exposure to single-dose nevirapine or prior ART; higher CD4 counts; lower VL; and >6 months of virologic failure were significantly associated with number of DRM. Of 25 viremic patients followed for a median of 8 months on a continued first-line regimen, 12 (48%) re-suppressed, six with K103N and three with M184V. Thirteen (52%) had continued virologic failure which was significantly associated with detectable VL>6 months prior to enrollment and number of DRM. CONCLUSION: Among these HIV-1 subtype C-infected patients, DRM numbers and patterns were associated with prior exposure to sub-optimal ART, adherence and duration of virologic failure. Viral re-suppression in the presence of K103N and M184V challenges assumptions about drug resistance. In resource-limited settings, where genotyping and alternative drug options are unavailable, continuing first-line treatment, reinforcing adherence and regular virologic monitoring may be effective even after virologic failure.

Impact of Drug Resistance-Associated Amino Acid Changes in HIV-1 Subtype C on Susceptibility to Newer Nonnucleoside Reverse Transcriptase Inhibitors

ABSTRACT The objective of this study was to assess the phenotypic susceptibility of HIV-1 subtype C isolates, with nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated amino acid changes, to newer NNRTIs. A panel of 52 site-directed mutants and 38 clinically derived HIV-1 subtype C clones was created, and the isolates were assessed for phenotypic susceptibility to etravirine (ETR), rilpivirine (RPV), efavirenz (EFV), and nevirapine (NVP) in an in vitro single-cycle phenotypic assay. The amino acid substitutions E138Q/R, Y181I/V, and M230L conferred high-level resistance to ETR, while K101P and Y181I/V conferred high-level resistance to RPV. Y181C, a major NNRTI resistance-associated amino acid substitution, caused decreased susceptibility to ETR and, to a lesser extent, RPV when combined with other mutations. These included N348I and T369I, amino acid changes in the connection domain that are not generally assessed during resistance testing. However, the prevalence of these genotypes among subtype C sequences was, in most cases, <1%. The more common EFV/NVP resistance-associated substitutions, such as K103N, V106M, and G190A, had no major impact on ETR or RPV susceptibility. The low-level resistance to RPV and ETR conferred by E138K was not significantly enhanced in the presence of M184V/I, unlike for EFV and NVP. Among patient samples, 97% were resistant to EFV and/or NVP, while only 24% and 16% were resistant to ETR and RPV, respectively. Overall, only a few, relatively rare NNRTI resistance-associated amino acid substitutions caused resistance to ETR and/or RPV in an HIV-1 subtype C background, suggesting that these newer NNRTIs would be effective in NVP/EFV-experienced HIV-1 subtype C-infected patients.

Gender Perspective of Risk Factors Associated with Disclosure of HIV Status, a Cross-Sectional Study in Soweto, South Africa

Background Human Immunodeficiency Virus (HIV) status disclosure has been shown to provide several benefits, both at the individual and societal levels. Aim To determine risk factors associated with disclosing HIV status among antiretroviral therapy (ART) recipients in South Africa. Setting A cross-sectional study on risk factors for viremia and drug resistance took place at two outpatient HIV clinics in 2008, at a large hospital located in Soweto, South Africa. Methods We conducted a secondary data analysis on socio-economic characteristics and HIV status disclosure to anyone, focusing on gender differences. Descriptive and multivariable logistic regression analyses were performed to model the associations between risk factors and HIV status disclosure. Additionally, descriptive analysis was conducted to describe gender differences of HIV status disclosure to partner, parents, parents in law, partner, child, family, employer, and other. Patients A total of 883 patients were interviewed. The majority were women (73%) with median age of 39 years. Results Employed patients were less likely to disclose than unemployed (odds ratio (OR) 0.36; 95% confidence interval (CI) 0.1–1.0; p = 0.05)). Women with higher income were more likely to disclose (OR 3.25; 95% CI 0.90–11.7; p = 0.07) than women with lower income, while men with higher income were less likely (OR 0.20; 95% CI 0.02–1.99; p = 0.17) than men with lower income. Men were more likely than women to disclose to their partner (p<0.01), and to partner and family (p<0.01), women were more likely than men to disclose to child and family (p<0.01), to child, family and others (p = 0.01). Conclusion Being employed imposed a risk factor for HIV status disclosure, additionally we found an interaction effect of gender and income on disclosure. Interventions designed to reduce workplace discrimination and gender-sensitive interventions promoting disclosure are strongly recommended.

Correlates of mobile phone use in HIV care: Results from a cross-sectional study in South Africa.

Objective Human Immunodeficiency Virus (HIV) is a major disease burden worldwide. Challenges include retaining patients in care and optimizing adherence to Antiretroviral Therapy (ART). One possible solution is using mobile phones as reminder tools. The main aim of our study was to identify patient demographic groups least likely to use mobile phones as reminder tools in HIV care. Design The data came from a cross-sectional study at the Chris Hani Baragwanath Hospital, Soweto Township, South Africa. Methods A comprehensive questionnaire was used to interview 883 HIV infected patients receiving ART. Logistic regression analysis was performed to identify the influence of age, gender, education level, marital status, number of sexual partners in the last three months, income level, and employment status on the use of mobile phone as reminders for clinic appointments and taking medication. Results Patient groups significantly associated with being less likely to use mobile phones as clinic appointment reminders were: a) patients 45 years or older, b) women, and c) patients with only primary or no schooling level. Patient groups significantly associated with being less likely to use mobile phones as medication reminders were: a) patients 35 years or older and b) patients with a lower monthly income. Conclusions In this setting being a woman, of older age, lower education, and socio-economic level were risk factors for the low usage of mobile phones as reminder aids. Future studies should assimilate reasons for this, such that patient-specific barriers to implementation are identified and interventions can be tailored.

The global burden of child burn injuries in light of country level economic development and income inequality

Child burn mortality differs widely between regions and is closely related to material deprivation, but reports on their global distribution are few. Investigating their country level distribution in light of economic level and income inequality will help assess the potential for macro-level improvements. We extracted data for child burn mortality from the Global Burden of Disease study 2013 and combined data into 1–14 years to calculate rates at country, region and income levels. We also compiled potential lives saved. Then we examined the relationship between country level gross domestic product per capita from the World Bank and income inequality (Gini Index) from the Standardized World Income Inequality Database and child burn mortality using Spearman coefficient correlations. Worldwide, the burden of child burn deaths is 2.5 per 100,000 across 103 countries with the largest burden in Sub-Saharan Africa (4.5 per 100,000). Thirty-four thousand lives could be saved yearly if all countries in the world had the same rates as the best performing group of high-income countries; the majority in low-income countries. There was a negative graded association between economic level and child burns for all countries aggregated and at regional level, but no consistent pattern existed for income inequality at regional level. The burden of child burn mortality varies by region and income level with prevention efforts needed most urgently in middle-income countries and Sub-Saharan Africa. Investment in safe living conditions and access to medical care are paramount to achieving further reductions in the global burden of preventable child burn deaths.

Factors for incomplete adherence to antiretroviral therapy including drug refill and clinic visits among older adults living with human immunodeficiency virus - cross-sectional study in South Africa

To assess adherence outcomes to antiretroviral therapy (ART) of recipients ≥50 years in Soweto, South Africa.