ABSTRACT
INTRODUCTION: Sub-Saharan African countries are introducing integrase strand transfer inhibitors (INSTIs) in their ART programmes as the preferred first-line regimen, and dolutegravir is the INSTI of choice due to its potency, tolerability and high genetic barrier to resistance. Dolutegravir was introduced into the first-line ART regimen in Tanzania in 2019. However, there is a paucity of data on the occurrence of mutations in HIV lineages circulating in Tanzania. This study aimed to determine the prevalence of INSTI primary resistance mutations in Tanzanian patients exposed to ART but not INSTIs. METHODS: Plasma samples from 50 INSTI-naive patients failing first- or second-line ART [median (IQR) age: 40 (21.93-46.41) years; 68% women] were subjected to Sanger sequencing of the HIV integrase gene. Participants had been on ART for a median (IQR) duration of 7.32 (4.73-9.29) years, with 80% and 20% failing first- and second-line ART, respectively. RESULTS: No major INSTI mutations were found, but 2 (4%) participants had the accessory mutation T97A. Using the REGA HIV-1 subtyping tool, HIV subtype A1 (53.1%) was found to be dominant, followed by subtypes C (30.6%) and D (16.3%). CONCLUSIONS: This study found no current evidence for transmitted resistance against INSTIs among unexposed patients failing ART and supports the scale-up of INSTI-based regimens. However, the presence of accessory mutations calls for the surveillance of INSTI resistance mutations to ensure that the anticipated long-term desired outcomes are achieved.
Subject(s)
HIV Infections , HIV Integrase Inhibitors , HIV Integrase , HIV-1 , Humans , Female , Adult , Male , HIV Integrase Inhibitors/pharmacology , HIV Integrase Inhibitors/therapeutic use , Drug Resistance, Viral/genetics , HIV-1/genetics , Tanzania/epidemiology , HIV Infections/drug therapy , HIV Infections/epidemiology , Genotype , HIV Integrase/genetics , Heterocyclic Compounds, 3-Ring/therapeutic use , MutationABSTRACT
BACKGROUND: More than 15 million people in sub-Saharan Africa receive ART. Treatment failure is common, but the role of HIV drug resistance in treatment failure is largely unknown because drug resistance testing is not routinely done. This study determined the prevalence and patterns of HIV drug resistance in patients with suspected virological failure. MATERIALS AND METHODS: A single high viral load of >1000 viral RNA copies/mL of plasma at any point during ART was considered as suspected virological failure. HIV-1 RNA was extracted from plasma samples of these patients using the QIAamp Viral RNA kit. The protease and part of the RT regions of the HIV pol gene were characterized. RESULTS: Viral load was determined in 317 patients; 64 (20.2%) had suspected virological failure. We successfully genotyped 56 samples; 48 (85.7%) had at least one major resistance-associated mutation (RAM). Common mutations in RT were M184V (75%), T215Y (41.1%), K103N (39.3%), M41L (32.1%), D67DN (30.3%), G190A (28.6%) and A98G (26.8%). No RAMs were detected in ART regimens based on a ritonavir-boosted PI. CONCLUSIONS: The Tanzanian national guidelines define 'virological failure' as two consecutive viral load measurement results, at 3 month intervals, above the WHO threshold (1000 copies/mL). Here, we show that a single viral load above the WHO threshold is associated with high rates of RAMs. This suggests that a single high viral load measurement could be used to predict virological failure and avoid delays in switching patients from first-line to higher genetic barrier second-line regimens.
Subject(s)
Anti-HIV Agents , HIV Infections , HIV-1 , Anti-HIV Agents/pharmacology , Anti-HIV Agents/therapeutic use , Drug Resistance, Viral/genetics , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV-1/genetics , Humans , Prevalence , Tanzania/epidemiology , Treatment Failure , Viral LoadABSTRACT
BACKGROUND: Tanzania has a high prevalence (7.17%) of chronic hepatitis B infection. Mother to Child transmission is very common, resulting in high rate of chronic infections. Currently, there is no screening program for HBV in pregnant women. This study investigated the prevalence and risk factors for chronic HBV infection in pregnant women in a tertiary hospital in Mwanza, Tanzania. METHODS: Seven hundred and forty-three women attending antenatal care and/or delivering at the Bugando Medical Centre were enrolled. All answered a questionnaire on sociodemographic and other risk factors and were tested for HBsAg using a rapid test. In HBsAg positive mothers, maternal blood and umbilical cord blood samples collected after delivery were analyzed for serological (HBsAg, HBeAg and anti-HBe) and virologic (HBV-DNA viral load and genotype) markers. All their babies were vaccinated within 24 h of delivery. The children were followed up at 3 years of age. Data was analyzed using the Mann-Whitney U-test, independent sample T-test and logistic regression. RESULTS: Of the 743 participants, 22 (3%) were positive for HBsAg, and 2 (9%) had detectable HBe-antigen. Low condom use was the only statistically significant risk factor for chronic HBV infection (OR = 3.514, 95%CI = 1.4-8.0). Of 14 maternal blood samples genotyped, 10 (71%) were genotype A and 4 (29%) were genotype D. HBV-DNA was detected in 21/22 samples, with a median of 241 IU/ml (range: 27.4-25.9 × 107 IU/ml). Five (33%) of 15 available cord blood samples were positive for HBsAg and 10 (67%) were negative. At follow-up, one child showed chronic HBV infection characteristics, one had anti-HBs level of 7 mIU/ml and 5/7(71%) had protective anti-HBs levels (> 10 mIU/ml). CONCLUSION: This cohort of pregnant women showed a lower-intermediate prevalence of HBV of 3%. In the 3 years follow-up only 1 out of 7 children showed evidence of chronic HBV infection. The child's mother with high viral load (25.9 × 107 IU/ml), was positive for HBeAg with a high degree of sequence similarity suggesting vertical transmission. These results highlight a need for improved diagnosis and treatment of HBV infection in pregnant women in Tanzania, in order to prevent vertical transmission.
Subject(s)
Hepatitis B, Chronic/diagnosis , Adolescent , Adult , Cross-Sectional Studies , DNA, Viral/genetics , DNA, Viral/metabolism , Female , Genotype , Hepatitis B Antibodies/blood , Hepatitis B Surface Antigens/blood , Hepatitis B e Antigens/blood , Hepatitis B virus/genetics , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/virology , Humans , Infant , Infant, Newborn , Male , Pregnancy , Prenatal Care , Prevalence , Tanzania/epidemiology , Tertiary Care Centers , Viral Load , Young AdultABSTRACT
BACKGROUND: Prospective data on the effectiveness of resistance testing in informing treatment decisions and outcomes in with first-line failure in these settings is limited. This study aimed to assess the virological impact of HIV drug-resistance testing in patients with virological failure in Tanzania. METHODS: Participants were randomly assigned to either the control or the experimental group. In addition to the standard of care, patients in the experimental group had access to genotypic drug-resistance testing, information used during treatment change, and were followed up at six-and 12-months to determine virological suppression. RESULTS: A total of 261 patients with a median age of 32 (14.7-44.7) years were enrolled. In the intention-to-treat analysis, at 6-months, suppression was achieved in 58 (42.3%; 95% CI, 34.1-50.1) experimental group patients versus 51 (41.1%; 95% CI, 32.5-49.8) control group patients, with a p-value of 0.4. At-12 months, suppression was achieved in 110 (80.3%; 95% CI, 73.6-87) experimental patients versus 99 (79.8%; 95% CI, 72.8-86.9) control patients, with a p-value of 0.5. In the per-protocol analysis, at 6-months, suppression was observed in 38.46% (95% CI, 27.6-49.3) experimental patients versus 38.6% (95% CI, 26.0-51.2) control patients, with a p-value of 0.5. At 12-months, suppression was observed in 79.49% (95% CI, 70.5-88.5) of experimental patients versus 75.44% (95% CI, 64.3-86.6) of control patients, with a p-value of 0.3. CONCLUSION: Conducting HIV drug-resistance testing, and switch to individualised second-line regimens did not significantly improve virological suppression in patients experiencing first-line ART failure in Tanzania.
ABSTRACT
BACKGROUND: Liver enzymes abnormalities have been found to be common among patients on antiretroviral treatment (ART). Apart from the effects of ART on these changes, other factors that can potentially contribute to the abnormal levels of these enzymes have been found to vary in different geographical locations. This study investigated factors associated with liver enzymes abnormalities among human immunodeficiency virus (HIV) infected individuals on ART from the Lake Victoria zone, Tanzania. METHODS: A cross-sectional study involving a total of 230 sera from HIV seropositive patients from different regions of the Lake Victoria zone was carried out in July 2017. All samples with required variables/parameters such as age, sex, ART regimen, and residence were serially included in the study. Hepatitis B virus (HBV) and Hepatitis C virus (HCV) detection and liver enzymes assays (alanine transaminase (ALAT) and aspartate transaminase (ASAT)) were assessed following the standard procedures. Data were analyzed by using STATA version 13. RESULTS: The median age of the study participants was 38 (interquartile range [IQR]:30-48) years. The overall prevalence of abnormal liver enzymes was 43.04% (99/230, 95% CI: 36.6-49.3). A total of 26.09% (60/230) had elevated ASAT while 23.9% (55/230) patients had elevated ALAT levels. ASAT levels were significantly high among patients with high HIV viral load (P= 0.002) while ALAT levels were significantly high among those coinfected with hepatitis C virus (P=0.017) and hepatitis B virus (P<0.001). CONCLUSION: A significant proportion of HIV seropositive individuals on ART have abnormal levels of liver enzymes, which is significantly associated with high HIV viral load and viral hepatitis. This calls for the need to emphasize screening of viral hepatitis and provision of appropriate management among HIV seropositive individuals in this setting.