Journal Article > ResearchFull Text
Antivir Ther. 2009 February 1; Volume 14 (Issue 3); 339-347.; DOI:10.1177/135965350901400317
Soria A, Porten K, Fampou-Toundji JC, Galli L, Mougnutou R, et al.
Antivir Ther. 2009 February 1; Volume 14 (Issue 3); 339-347.; DOI:10.1177/135965350901400317
BACKGROUND
The lack of HIV type-1 (HIV-1) viral load (VL) monitoring in resource-limited settings might favour the accumulation of resistance mutations and thus hamper second-line treatment efficacy. We investigated the factors associated with resistance after the initiation of antiretroviral therapy (ART) in the absence of virological monitoring.
METHODS
Cross-sectional VL sampling of HIV-1-infected patients receiving first-line ART (nevirapine or efavirenz plus stavudine or zidovudine plus lamivudine) was carried out; those with a detectable VL were genotyped.
RESULTS
Of the 573 patients undergoing VL sampling, 84 were genotyped. The mean number of nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) mutations increased with the duration of ART exposure (P=0.02). Multivariable analysis showed that patients with a CD4+ T-cell count < or =50 cells/mm(3) at ART initiation (baseline) had a higher mean number of both NRTI and non-NRTI (NNRTI) mutations than those with a baseline CD4+ T-cell count >50 cells/mm(3) (2.10 versus 0.56; P<0.0001; and 1.65 versus 0.76; P=0.005, respectively). A baseline CD4+ T-cell count < or =50 cells/mm(3) predicted > or =1 NRTI mutation (adjusted odds ratio [AOR] 7.49, 95% confidence interval [CI] 2.20-32.14), > or =1 NNRTI mutation (AOR 4.25, 95% CI 1.36-15.48), > or =1 thymidine analogue mutation (AOR 8.45, 95% CI 2.16-40.16) and resistance to didanosine (AOR 6.36, 95% CI 1.49-32.29) and etravirine (AOR 4.72, 95% CI 1.53-15.70).
CONCLUSIONS
Without VL monitoring, the risk of drug resistance increases with the duration of ART and is associated with lower CD4+ T-cell counts at ART initiation. These data might help define strategies to preserve second-line treatment options in resource-limited settings.
The lack of HIV type-1 (HIV-1) viral load (VL) monitoring in resource-limited settings might favour the accumulation of resistance mutations and thus hamper second-line treatment efficacy. We investigated the factors associated with resistance after the initiation of antiretroviral therapy (ART) in the absence of virological monitoring.
METHODS
Cross-sectional VL sampling of HIV-1-infected patients receiving first-line ART (nevirapine or efavirenz plus stavudine or zidovudine plus lamivudine) was carried out; those with a detectable VL were genotyped.
RESULTS
Of the 573 patients undergoing VL sampling, 84 were genotyped. The mean number of nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) mutations increased with the duration of ART exposure (P=0.02). Multivariable analysis showed that patients with a CD4+ T-cell count < or =50 cells/mm(3) at ART initiation (baseline) had a higher mean number of both NRTI and non-NRTI (NNRTI) mutations than those with a baseline CD4+ T-cell count >50 cells/mm(3) (2.10 versus 0.56; P<0.0001; and 1.65 versus 0.76; P=0.005, respectively). A baseline CD4+ T-cell count < or =50 cells/mm(3) predicted > or =1 NRTI mutation (adjusted odds ratio [AOR] 7.49, 95% confidence interval [CI] 2.20-32.14), > or =1 NNRTI mutation (AOR 4.25, 95% CI 1.36-15.48), > or =1 thymidine analogue mutation (AOR 8.45, 95% CI 2.16-40.16) and resistance to didanosine (AOR 6.36, 95% CI 1.49-32.29) and etravirine (AOR 4.72, 95% CI 1.53-15.70).
CONCLUSIONS
Without VL monitoring, the risk of drug resistance increases with the duration of ART and is associated with lower CD4+ T-cell counts at ART initiation. These data might help define strategies to preserve second-line treatment options in resource-limited settings.
Journal Article > ResearchFull Text
Antivir Ther. 2008 September 11; Volume 13 (Issue 5); 697-703.
Spire B, Carrieri P, Sopha P, Protopopescu C, Prak N, et al.
Antivir Ther. 2008 September 11; Volume 13 (Issue 5); 697-703.
BACKGROUND
The long-term maintenance of antiretroviral therapy (ART) remains an important issue, especially in limited-resource settings where additional barriers exist. A cross-sectional study was performed 24 months after ART initiation for patients treated in Cambodia in order to estimate the prevalence and identify determinants of non-adherence.
METHODS
Adults receiving ART for 24 +/- 2 months were considered eligible for the study. Self-reported non-adherence was defined according to an algorithm based on six items. The questionnaire also assessed ART-related side effects and HIV disclosure. HIV-1 RNA plasma viral load was measured using real-time PCR. Multivariate rare events logistic regression analysis was used to identify independent factors associated with non-adherence.
RESULTS
A total of 346 patients participated in the study. At 24 months, 95% of patients were adherent, 80% had HIV RNA <40 copies/ml and 75% had CD4+ T-cell counts >200 cells/mm3. Virological success was significantly higher in adherent patients than in non-adherent patients (81% versus 56%, P=0.021). Living in a rural area, limited HIV disclosure and perceived lipodystrophy were independently associated with non-adherence.
CONCLUSIONS
At 24 months, adherence to ART was high and explained positive virological outcomes. In order to maintain adherence and long-term virological benefits, special attention should be given to patients living in rural areas, those with lipodystrophy-related symptoms and others who express difficulties disclosing their condition to close family members.
The long-term maintenance of antiretroviral therapy (ART) remains an important issue, especially in limited-resource settings where additional barriers exist. A cross-sectional study was performed 24 months after ART initiation for patients treated in Cambodia in order to estimate the prevalence and identify determinants of non-adherence.
METHODS
Adults receiving ART for 24 +/- 2 months were considered eligible for the study. Self-reported non-adherence was defined according to an algorithm based on six items. The questionnaire also assessed ART-related side effects and HIV disclosure. HIV-1 RNA plasma viral load was measured using real-time PCR. Multivariate rare events logistic regression analysis was used to identify independent factors associated with non-adherence.
RESULTS
A total of 346 patients participated in the study. At 24 months, 95% of patients were adherent, 80% had HIV RNA <40 copies/ml and 75% had CD4+ T-cell counts >200 cells/mm3. Virological success was significantly higher in adherent patients than in non-adherent patients (81% versus 56%, P=0.021). Living in a rural area, limited HIV disclosure and perceived lipodystrophy were independently associated with non-adherence.
CONCLUSIONS
At 24 months, adherence to ART was high and explained positive virological outcomes. In order to maintain adherence and long-term virological benefits, special attention should be given to patients living in rural areas, those with lipodystrophy-related symptoms and others who express difficulties disclosing their condition to close family members.
Journal Article > ReviewFull Text
Antivir Ther. 2014 October 13; Volume 19 (Issue Suppl 3); DOI:10.3851/IMP2905
Bekker LG, Venter F, Cohen K, Goemare E, van Cutsem G, et al.
Antivir Ther. 2014 October 13; Volume 19 (Issue Suppl 3); DOI:10.3851/IMP2905
Public sector antiretroviral provision had a slow start in South Africa despite a raging epidemic and a World AIDS conference that shed significant public light on the disparities of therapy access globally. This was largely due to political prevarication in the midst of AIDS denialism. There has been an unprecedented expansion in the HIV treatment programme since 2008. As a result, South Africa now has the largest number of patients on antiretroviral drugs in the world, and South African life expectancy has increased by more than a decade. However, this has led to a number of fiscal, logistic and operational challenges that the country must face as the treatment programme continues to expand. Challenges include increasing detection within communities, linkage and retention in care, while strengthening operational support functions such as consistent drug supply, health staffing and infrastructure, diagnostic services, programme monitoring and sustainable financing. As a middle-income country, albeit with marked income inequality, and the heaviest HIV burden in the world, South Africa is a test case of whether a large-scale public health programme can boast of success in the face of numerous other health-system challenges.
Journal Article > ResearchFull Text
Antivir Ther. 2008 November 1; Volume 13 (Issue 7); 937-943.
Stead D, Osler M, Boulle AM, Rebe K, Meintjes GA
Antivir Ther. 2008 November 1; Volume 13 (Issue 7); 937-943.
BACKGROUND
In the public sector antiretroviral therapy (ART) programme in South Africa the standardized first-line regimen includes stavudine (d4T). Severe symptomatic hyperlactataemia (SHL) is a potentially life-threatening complication of d4T.
METHODS
GF Jooste Hospital is a referral centre for six ART clinics. We retrospectively reviewed cases referred with lactate levels > or =5 mmol/l that were attributed to nucleoside reverse transcriptase inhibitors from August 2003 to November 2005. We calculated cumulative ART exposure in patients attending these clinics to derive a referral rate.
RESULTS
In total, 75 patients were referred with severe SHL (71 female). All had been on d4T and on ART for a median of 10 months. The referral rate for severe SHL was 17.5 cases per 1,000 patient-years. In 53 patients (71%), lactic acidosis (standard bicarbonate [SHCO3] <20 mmol/l) was confirmed, resulting in a referral rate of 12.3 cases per 1,000 patient-years. Twelve patients (16%) died during acute admission (< or =30 days). SHCO3 <15 mmol/l and pH < 7.2 were the only factors associated with acute mortality (odds ratio [OR] 22.5, 95% confidence interval [CI] 2.8-1,045.7 and OR 13.9, 95% CI 2.7-86.9, respectively). A total of 30 less severe cases were rechallenged with zidovudine without recurrence of SHL.
CONCLUSIONS
This study confirms a high incidence of severe SHL in Africa, which has been shown in previous studies. Rechallenge with zidovudine in less severe cases was found to be safe.
In the public sector antiretroviral therapy (ART) programme in South Africa the standardized first-line regimen includes stavudine (d4T). Severe symptomatic hyperlactataemia (SHL) is a potentially life-threatening complication of d4T.
METHODS
GF Jooste Hospital is a referral centre for six ART clinics. We retrospectively reviewed cases referred with lactate levels > or =5 mmol/l that were attributed to nucleoside reverse transcriptase inhibitors from August 2003 to November 2005. We calculated cumulative ART exposure in patients attending these clinics to derive a referral rate.
RESULTS
In total, 75 patients were referred with severe SHL (71 female). All had been on d4T and on ART for a median of 10 months. The referral rate for severe SHL was 17.5 cases per 1,000 patient-years. In 53 patients (71%), lactic acidosis (standard bicarbonate [SHCO3] <20 mmol/l) was confirmed, resulting in a referral rate of 12.3 cases per 1,000 patient-years. Twelve patients (16%) died during acute admission (< or =30 days). SHCO3 <15 mmol/l and pH < 7.2 were the only factors associated with acute mortality (odds ratio [OR] 22.5, 95% confidence interval [CI] 2.8-1,045.7 and OR 13.9, 95% CI 2.7-86.9, respectively). A total of 30 less severe cases were rechallenged with zidovudine without recurrence of SHL.
CONCLUSIONS
This study confirms a high incidence of severe SHL in Africa, which has been shown in previous studies. Rechallenge with zidovudine in less severe cases was found to be safe.