• Comparison of Self-Reported Alcohol Consumption to Phosphatidylethanol Measurement among HIV-Infected Patients Initiating Antiretroviral Treatment in Southwestern Uganda

      Bajunirwe, Francis; Haberer, Jessica E; Boum, Yap; Hunt, Peter; Mocello, Rain; Martin, Jeffrey N; Bangsberg, David R; Hahn, Judith A (Public Library of Science, 2014-12-01)
      Alcohol consumption among HIV-infected patients may accelerate HIV disease progression or reduce antiretroviral therapy adherence. Self-reported alcohol use is frequently under-reported due to social desirability and recall bias. The aim of this study was to compare self-reported alcohol consumption to phosphatidylethanol (PEth), a biomarker of alcohol consumption, and to estimate the correlation between multiple measures of self-reported alcohol consumption with PEth.
    • Diagnostic performance and usability of the VISITECT CD4 semi-quantitative test for advanced HIV disease screening

      Ndlovu, Z; Massaquoi, L; Bangwen, NE; Batumba, JN; Bora, RU; Mbuaya, J; Nzadi, R; Ntabugi, N; Kisaka, P; Manciya, G; et al. (Public Library of Science, 2020-04-03)
      BACKGROUND: In sub-Saharan Africa, a third of people starting antiretroviral therapy and majority of patients returning to HIV-care after disengagement, present with advanced HIV disease (ADH), and are at high risk of mortality. Simplified and more affordable point-of-care (POC) diagnostics are required to increase access to prompt CD4 cell count screening for ambulatory and asymptomatic patients. The Visitect CD4 Lateral Flow Assay (LFA) is a disposable POC test, providing a visually interpreted result of above or below 200 CD4cells/mm3. This study evaluated the diagnostic performance of this index test. METHODS: Consenting patients above 18years of age and eligible for CD4 testing were enrolled in Nsanje district hospital (Malawi), Gutu mission hospital (Zimbabwe) and Centre hopitalier de Kabinda (DRC). A total of 708 venous blood samples were tested in the index test and in the BD FACSCount assay (reference test method) in the laboratories (Phase 1) to determine diagnostic accuracy. A total of 433 finger-prick (FP) samples were tested on the index test at POC by clinicians (Phase 2) and a self-completed questionnaire was administered to all testers to explore usability of the index test. RESULTS: Among 708 patients, 67.2% were female and median CD4 was 297cells/mm3. The sensitivity of the Visitect CD4 LFA using venous blood in the laboratory was 95.0% [95% CI: 91.3-97.5] and specificity was 81.9% [95% CI: 78.2-85.2%]. Using FP samples, the sensitivity of the Visitect CD4 LFA was 98.3% [95% CI: 95.0-99.6] and specificity was 77.2% [95% CI: 71.6-82.2%]. Usability of the Visitect CD4 LFA was high across the study sites with 97% successfully completed tests. Due to the required specific multiple incubation and procedural steps during the Visitect CD4 LFA testing, few health workers (7/26) were not confident to manage testing whilst multi-tasking in their clinical work. CONCLUSIONS: Visitect CD4 LFA is a promising test for decentralized CD4 screening in resource-limited settings, without access to CD4 testing and and it can trigger prompt management of patients with AHD. Lay health cadres should be considered to conduct Visitect CD4 LFA testing in PHCs as well as coordinating all other POC quality assurance.
    • Expanding Access to HIV Viral Load Testing: A Systematic Review of RNA Stability in EDTA Tubes and PPT beyond Current Time and Temperature Thresholds

      Bonner, Kimberly; Siemieniuk, Reed A; Boozary, Andrew; Roberts, Teri; Fajardo, Emmanuel; Cohn, Jennifer (Public Library of Science, 2014-12-01)
      HIV viral load (VL) testing is the gold standard for antiretroviral treatment monitoring, but many barriers exist to VL testing in resource-limited settings, including storage and transport limitations for whole blood and plasma. Data from various studies indicate that HIV RNA is stable beyond current recommendations. We conducted a systematic review to assess stability data of HIV RNA in whole blood and plasma across times and temperatures.
    • Genotyping and outcomes of presumptive second line ART failure cases switched to third line or maintained on second line ART in Mumbai, India

      Gill, N; Van den Bergh, R; Wut Yee Kyaw, K; Laxmeshwar, C; Das, M; Rastogi, S; Mansoor, H; Kalon, S; Isaakidis, P; Arago Galindo, M (2019-11-21)
      BACKGROUND: HIV programs are increasingly confronted with failing antiretroviral therapy (ART), including second-line regimens. WHO has provided guidelines on switching to third-line ART. In a Médecins Sans Frontières clinic in Mumbai, India, receiving referred presumptive second-line ART failure cases, an evidence-based protocol consisting of viral load (VL) testing, enhanced adherence counselling (EAC) and genotype for switching was implemented. OBJECTIVE: To document the outcome and genotype of presumptive second-line ART failure cases switched to third-line or maintained on second-line ART. DESIGN: Retrospective cohort study of patients referred between January 2011 and September 2017. RESULTS: The cases (n = 120) were complex with median 9.2 years of ART exposure, poor adherence at baseline, and exposure to multiple ART regimens other than recommended by WHO. Out of 90 evaluated cases, 39(43%) were maintained on second-line ART. Forty-nine (54%) were ever switched to third-line ART. Twelve months virological suppression was 72% in the second-line and 93% in the third-line ART cohort, while retention in care was 80% and 94% respectively. Genotyping showed 62% resistance for PIs, and 52% triple class resistance to NRTIs, NNRTIs and PIs. Resistance was noted for the new class of integrase inhibitors, and for different drugs without any documented previous exposure to the same drug. CONCLUSION: Adopting WHO guidelines on switching ART regimens and provision of EAC can prevent unnecessary switching/exposure to third-line ART regimens. Genotyping is urgently required in national HIV programs, which currently use only the exposure history of patients for switching to third-line ART regimens.
    • "I take my pills every day, but then it goes up, goes down. I don't know what's going on": Perceptions of HIV virological failure in a rural context in Mozambique. A qualitative research study.

      Pulido Tarquino, IA; Venables, E; de Amaral Fidelis, JM; Giuliani, R; Decroo, T (Public Library of Science, 2019-06-17)
      BACKGROUND: HIV prevalence in Mozambique is estimated to be 13.2%. Routine viral load for HIV monitoring was first implemented in the rural area of Tete in 2014. Programmatic data showed an unexpected high proportion of high viral load results, with up to 40% of patients having a viral load above 1000 copies/ml. OBJECTIVES: This qualitative study aimed to explore perceptions about virological failure and viral load monitoring from the perspective of HIV positive patients on first-line antiretroviral therapy (ART) and health-care workers. METHODS: The study was conducted in seven rural communities in Changara-Marara district, Tete province, Mozambique. A total of 91 participants took part in in-depth interviews (IDIs) and focus group discussions (FGDs), including health-care workers (n = 18), patients on ART in individual care or Community Adherence Groups (CAGs) who experienced virological failure and virological re-suppression (n = 39) and CAG focal points (n = 34). Purposive sampling was used to select participants. Interviews and FGDs were conducted in Nhuengue and Portuguese. IDIs and FGDs were translated and transcribed before being coded and thematically analysed. RESULTS: Emergent themes showed that patients and health-care workers attributed great importance to viral load monitoring. A supressed viral load was viewed by participants as a predictor of good health and good adherence. However, some patients were confused and appeared distressed when confronted with virological failure. Viral load results were often little understood, especially when virological failure was detected despite good adherence. Inadequate explanations of causes of virological failure, delayed follow-up viral load results, repeated blood tests and lack of access to second-line ART resulted in reduced confidence in the effectiveness of ART, challenged the patient-provider relationship and disempowered patients and providers. CONCLUSION: In this rural context undetectable viral load is recognized as a predictor of good health by people living with HIV and health-care workers. However, a lack of knowledge and health system barriers caused different responses in patients and health-care workers. Adapted counselling strategies, accelerated viral load follow-up and second-line ART initiation in patients with virological failure need to be prioritized.
    • Monitoring HIV Viral Load in Resource Limited Settings: Still a Matter of Debate?

      Arnedo, M; Alonso, E; Eisenberg, N; Ibáñez, L; Ferreyra, C; Jaén, A; Flevaud, L; Khamadi, S; Roddy, P; Gatell, JM; et al. (Public Library of Science, 2012-12-06)
      Consequences of lack of viral monitoring in predicting the effects of development of HIV drug resistance mutations during HAART in resource-limited settings (RLS) is still a matter of debate.
    • Navigating the risks of prevention of mother to child transmission (PMTCT) of HIV services in Kibera, Kenya: Barriers to engaging and remaining in care

      Thomson, KA; Telfer, B; Opondo Awiti, P; Munge, J; Ngunga, M; Reid, A (Public Library of Science, 2018-01-24)
      Within the first year of implementation, 43% of women who tested HIV positive at their first antenatal care visit were no longer retained and being followed in the free prevention of mother to child transmission (PMTCT) of HIV program offered by the Kenyan Ministry of Health and Médecins Sans Frontières in the informal settlement of Kibera, Nairobi. This study aimed to explore barriers to enrolling and remaining engaged in PMTCT services throughout the pregnancy and postpartum periods. Qualitative data from 31 focus group discussions and 35 in-depth interviews across six stakeholder groups that included women, men, and PMTCT service providers were analyzed. Using an inductive exploratory approach, four researchers coded the data and identified key themes. Five themes emerged from the data that may influence attrition from PMTCT service in this setting: 1) HIV in the context of Kibera, 2) knowledge of HIV status, 3) knowledge of PMTCT, 4) disclosure of HIV status, and 5) male partner support for PMTCT services. A new HIV diagnosis during pregnancy immediately triggered an ongoing risk assessment of perceived hazards in the home, community, and clinic environments that could occur as a result of female participation in PMTCT services. Male partners were a major influence in this risk assessment, but were generally unaware of PMTCT services. To preserve relationships with male partners, meet community expectations of womanhood, and maintain confidentiality while following recommendations of healthcare providers, women had to continuously weigh the risks and benefits of PMTCT services and interventions. Community-based HIV testing and PMTCT education, male involvement in antenatal care, and counseling customized to assist each woman in her own unique risk assessment, may improve uptake of and retention in care and optimize the HIV prevention benefit of PMTCT interventions.
    • Population-level HIV incidence estimates using a combination of synthetic cohort and recency biomarker approaches in KwaZulu-Natal, South Africa

      Grebe, E; Welte, A; Johnson, LF; van Cutsem, G; Puren, A; Ellman, T; Etard, JF; Huerga, H (Public Library of Science, 2018-09-13)
      There is a notable absence of consensus on how to generate estimates of population-level incidence. Incidence is a considerably more sensitive indicator of epidemiological trends than prevalence, but is harder to estimate. We used a novel hybrid method to estimate HIV incidence by age and sex in a rural district of KwaZulu-Natal, South Africa.
    • Surveillance of HIV-1 Pol Transmitted Drug Resistance in Acutely and Recently Infected Antiretroviral Drug-Naïve Persons in Eural Western Kenya

      Onywera, H; Maman, D; Inzaule, S; Auma, E; Were, K; Fredrick, H; Owiti, P; Opollo, V; Etard, JF; Mukui, I; et al. (Public Library of Science, 2017-02-08)
      HIV-1 transmitted drug resistance (TDR) is of increasing public health concern in sub-Saharan Africa with the rollout of antiretroviral (ARV) therapy. Such data are, however, limited in Kenya, where HIV-1 drug resistance testing is not routinely performed. From a population-based household survey conducted between September and November 2012 in rural western Kenya, we retrospectively assessed HIV-1 TDR baseline rates, its determinants, and genetic diversity among drug-naïve persons aged 15-59 years with acute HIV-1 infections (AHI) and recent HIV-1 infections (RHI) as determined by nucleic acid amplification test and both Limiting Antigen and BioRad avidity immunoassays, respectively. HIV-1 pol sequences were scored for drug resistance mutations using Stanford HIVdb and WHO 2009 mutation guidelines. HIV-1 subtyping was computed in MEGA6. Eighty seven (93.5%) of the eligible samples were successfully sequenced. Of these, 8 had at least one TDR mutation, resulting in a TDR prevalence of 9.2% (95% CI 4.7-17.1). No TDR was observed among persons with AHI (n = 7). TDR prevalence was 4.6% (95% CI 1.8-11.2) for nucleoside reverse transcriptase inhibitors (NRTIs), 6.9% (95% CI 3.2-14.2) for non- nucleoside reverse transcriptase inhibitors (NNRTIs), and 1.2% (95% CI 0.2-6.2) for protease inhibitors. Three (3.4% 95% CI 0.8-10.1) persons had dual-class NRTI/NNRTI resistance. Predominant TDR mutations in the reverse transcriptase included K103N/S (4.6%) and M184V (2.3%); only M46I/L (1.1%) occurred in the protease. All the eight persons were predicted to have different grades of resistance to the ARV regimens, ranging from potential low-level to high-level resistance. HIV-1 subtype distribution was heterogeneous: A (57.5%), C (6.9%), D (21.8%), G (2.3%), and circulating recombinant forms (11.5%). Only low CD4 count was associated with TDR (p = 0.0145). Our findings warrant the need for enhanced HIV-1 TDR monitoring in order to inform on population-based therapeutic guidelines and public health interventions.
    • Toxicity associated with stavudine dose reduction from 40 to 30 mg in first-line antiretroviral therapy.

      Pujades-Rodríguez, Mar; Dantony, Emmanuelle; Pinoges, Loretxu; Ecochard, René; Etard, Jean-François; Carrillo-Casas, Esther; Szumilin, Elisabeth; Clinical Research Department, Epicentre, Paris, France. mar.pujades@epicentre.msf.org (2011-11)
      To compare the incidence and timing of toxicity associated with the use of a reduced dose of stavudine from 40 to 30 mg in first-line antiretroviral therapy (ART) for HIV treatment and to investigate associated risk factors.
    • Treatment Response and Mortality among Patients Starting Antiretroviral Therapy with and without Kaposi Sarcoma: A Cohort Study

      Maskew, Mhairi; Fox, Matthew P; van Cutsem, Gilles; Chu, Kathryn; Macphail, Patrick; Boulle, Andrew; Egger, Matthias; for IeDEA Southern Africa; Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. mmaskew@heroza.org (2013-06)
      Improved survival among HIV-infected individuals on antiretroviral therapy (ART) has focused attention on AIDS-related cancers including Kaposi sarcoma (KS). However, the effect of KS on response to ART is not well-described in Southern Africa. We assessed the effect of KS on survival and immunologic and virologic treatment responses at 6- and 12-months after initiation of ART.