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Sigaloff K.C.E.,University of Amsterdam | Hamers R.L.,University of Amsterdam | Wallis C.L.,University of Witwatersrand | Kityo C.,Joint Clinical Research Center | And 9 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2011

Objectives: This study aimed to investigate the consequences of using clinicoimmunological criteria to detect antiretroviral treatment (ART) failure and guide regimen switches in HIV-infected adults in sub-Saharan Africa. Frequencies of unnecessary switches, patterns of HIV drug resistance, and risk factors for the accumulation of nucleoside reverse transcriptase inhibitor (NRTI)-associated mutations were evaluated. Methods: Cross-sectional analysis of adults switching ART regimens at 13 clinical sites in 6 African countries was performed. Two types of failure identification were compared: diagnosis of clinicoimmunological failure without viral load testing (CIF only) or CIF with local targeted viral load testing (targeted VL). After study enrollment, reference HIV RNA and genotype were determined retrospectively. Logistic regression assessed factors associated with multiple thymidine analogue mutations (TAMs) and NRTI crossresistance (≥2 TAMs or Q151M or K65R/K70E). Results: Of 250 patients with CIF switching to second-line ART, targeted VL was performed in 186. Unnecessary switch at reference HIV RNA <1000 copies per milliliter occurred in 46.9% of CIF only patients versus 12.4% of patients with targeted VL (P < 0.001). NRTI cross-resistance was observed in 48.0% of 183 specimens available for genotypic analysis, comprising ≥2 TAMs (37.7%), K65R (7.1%), K70E (3.3%), or Q151M (3.3%). The presence of NRTI cross-resistance was associated with the duration of ART exposure and zidovudine use. Conclusions: Clinicoimmunological monitoring without viral load testing resulted in frequent unnecessary regimen switches. Prolonged treatment failure was indicated by extensive NRTI cross-resistance. Access to virological monitoring should be expanded to prevent inappropriate switches, enable early failure detection and preserve second-line treatment options in Africa. Copyright © 2011 Lippincott Williams & Wilkins.

Bengtson A.M.,University of North Carolina at Chapel Hill | L'Engle K.,FHI | Mwarogo P.,FHI 360 | King'Ola N.,International Center for Reproductive Health
AIDS Care - Psychological and Socio-Medical Aspects of AIDS/HIV | Year: 2014

HIV testing is a critical first step to accessing HIV care and treatment, particularly for high-risk groups such as female sex workers (FSWs). Alcohol use may be a barrier to accessing HIV services, including HIV testing. We analyzed data from a cross-sectional survey of 818 FSWs in Mombasa, Kenya, and estimated the association between different levels of alcohol use and having never tested for HIV. In multivariable analyses, higher levels of alcohol consumption were associated with having never tested for HIV (PR 1.60; 95% CI: 1.07, 2.40). Future interventions should explore whether reducing harmful drinking improves HIV testing among FSWs. © 2014 Taylor & Francis.

Hamers R.L.,University of Amsterdam | Wallis C.L.,University of Witwatersrand | Kityo C.,Joint Clinical Research Center | Siwale M.,Lusaka Trust Hospital | And 12 more authors.
The Lancet Infectious Diseases | Year: 2011

Background: There are few data on the epidemiology of primary HIV-1 drug resistance after the roll-out of antiretroviral treatment (ART) in sub-Saharan Africa. We aimed to assess the prevalence of primary resistance in six African countries after ART roll-out and if wider use of ART in sub-Saharan Africa is associated with rising prevalence of drug resistance. Methods: We did a cross-sectional study in antiretroviral-naive adults infected with HIV-1 who had not started first-line ART, recruited between 2007 and 2009 from 11 regions in Kenya, Nigeria, South Africa, Uganda, Zambia, and Zimbabwe. We did population-based sequencing of the pol gene on plasma specimens with greater than 1000 copies per mL of HIV RNA. We identified drug-resistance mutations with the WHO list for transmitted resistance. The prevalence of sequences containing at least one drug-resistance mutation was calculated accounting for the sampling weights of the sites. We assessed the risk factors of resistance with multilevel logistic regression with random coefficients. Findings: 2436 (94.1%) of 2590 participants had a pretreatment genotypic resistance result. 1486 participants (57.4%) were women, 1575 (60.8%) had WHO clinical stage 3 or 4 disease, and the median CD4 count was 133 cells per μL (IQR 62-204). Overall sample-weighted drug-resistance prevalence was 5.6% (139 of 2436; 95% CI 4.6-6.7), ranging from 1.1% (two of 176; 0.0-2.7) in Pretoria, South Africa, to 12.3% (22 of 179; 7.5-17.1) in Kampala, Uganda. The pooled prevalence for all three Ugandan sites was 11.6% (66 of 570; 8.9-14.2), compared with 3.5% (73 of 1866; 2.5-4.5) for all other sites. Drug class-specific resistance prevalence was 2.5% (54 of 2436; 1.8-3.2) for nucleoside reverse-transcriptase inhibitors (NRTIs), 3.3% (83 of 2436; 2.5-4.2) for non-NRTIs (NNRTIs), 1.3% (31 of 2436; 0.8-1.8) for protease inhibitors, and 1.2% (25 of 2436; 0.7-1.7) for dual-class resistance to NRTIs and NNRTIs. The most common drug-resistance mutations were K103N (43 [1.8%] of 2436), thymidine analogue mutations (33 [1.6%] of 2436), M184V (25 [1.2%] of 2436), and Y181C/I (19 [0.7%] of 2436). The odds ratio for drug resistance associated with each additional year since the start of the ART roll-out in a region was 1.38 (95% CI 1.13-1.68; p=0.001). Interpretation: The higher prevalence of primary drug resistance in Uganda than in other African countries is probably related to the earlier start of ART roll-out in Uganda. Resistance surveillance and prevention should be prioritised in settings where ART programmes are scaled up. Funding: Ministry of Foreign Affairs of the Netherlands. © 2011 Elsevier Ltd.

L'Engle K.L.,Social and Behavioral Health science | Mwarogo P.,FHI 360 | Kingola N.,International Center for Reproductive Health | Sinkele W.,Support for Addiction Prevention and Treatment in Africa SAPTA | Weiner D.H.,Biostatistics
Journal of Acquired Immune Deficiency Syndromes | Year: 2014

Objective: We assessed whether a brief alcohol intervention would lead to reduced alcohol use and sexually transmitted infection (STI)/HIV incidence and related sexual risk behaviors among moderate drinking female sex workers. Methods: A randomized controlled intervention trial was conducted with 818 female sex workers affiliated with the AIDS, Population, Health, and Integrated Assistance II project in Mombasa, Kenya. Eligible women were hazardous or harmful drinkers who scored between 7 and 19 (full range, 1-40) on the Alcohol Use Disorders Identification Test. Intervention participants received 6 counseling sessions approximately monthly. The equal-attention control group received 6 nutrition sessions. Participants were followed for 6 and 12 months after the intervention, with at least 86% retention at both time points. We used general linear models in intention-to-treat analyses, adjusting for recruitment setting and HIV status at enrollment. Results: There was a statistically significant reduction in alcohol use and binge drinking at 6 and 12 months, with intervention participants reporting less than one third of the odds of higher levels of drinking than the control group. The intervention did not impact laboratory-confirmed STI/HIV incidence, self-reported condom use, or sexual violence from nonpaying partners. However, the odds of reporting sexual violence from clients was significantly lower among intervention than control participants at both 6 and 12 months. Conclusions: We found that a brief alcohol intervention can reduce self-reported alcohol consumption among a nondependent and non-treatment-seeking population most at risk for HIV. More attention is needed to understand the pathway from drinking to sexual behavior and STI/HIV acquisition. Copyright © 2014 by Lippincott Williams & Wilkins.

Nichols B.E.,Erasmus Medical Center | Sigaloff K.C.E.,PharmAccess Foundation | Sigaloff K.C.E.,University of Amsterdam | Kityo C.,Joint Clinical Research Center | And 9 more authors.
AIDS | Year: 2014

Background: Earlier antiretroviral therapy initiation can reduce the incidence of HIV-1. This benefit can be offset by increased transmitted drug resistance (TDR). We compared the preventive benefits of reducing incident infections with the potential TDR increase in East Africa. Methods: A mathematical model was constructed to represent Kampala, Uganda, and Mombasa, Kenya. We predicted the effect of initiating treatment at different immunological thresholds (350, 500 CD4+ cells/ml) on infections averted and mutationspecific TDR prevalence over 10 years compared to initiating treatment at CD4+ cell count below 200 cells/ml. Results: When initiating treatment at CD4+ cell count below 350 cells/ml, we predict 18 [interquartile range (IQR) 11-31] and 46 (IQR 30-83) infections averted for each additional case of TDR in Kampala and Mombasa, respectively, and 22 (IQR 17-35) and 32 (IQR 21-57) infections averted when initiating at below 500. TDR is predicted to increase most strongly when initiating treatment at CD4+ cell count below 500 cells/ml, from 8.3% (IQR 7.7-9.0%) and 12.3% (IQR 11.7-13.1%) in 2012 to 19.0% (IQR 16.5-21.8%) and 19.2% (IQR 17.1-21.5%) in 10 years in Kampala and Mombasa, respectively. The TDR epidemic at all immunological thresholds was comprised mainly of resistance to non-nucleoside reverse transcriptase inhibitors. When 80-100% of individuals with virological failure are timely switched to second-line therapy, TDR is predicted to decline irrespective of treatment initiation threshold. Conclusion: Averted HIV infections due to the expansion of antiretroviral treatment eligibility offset the risk of transmitted drug resistance, as defined by more infections averted than TDR gained. The effectiveness of first-line non-nucleoside reverse transcriptase inhibitor-based therapy can be preserved by improving switching practices to second-line therapy. © 2013 Wolters Kluwer Health.

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