In addition to the nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs) and integrase inhibitors (INIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs) have contributed significantly in the treatment of HIV-1 infections. More than 60 structurally different classes of compounds have been identified as NNRTIs, which are specifically inhibiting HIV-1 reverse transcriptase (RT). Five NNRTIs (nevirapine, delavirdine, efavirenz, etravirine and rilpivirine) have been approved by US Food and Drug Administration (FDA) for clinical use. The NNRTIs bind with a specific 'pocket' site of HIV-1 RT (allosteric site) that is closely associated with the NRTI binding site. Due to mutations of the amino acid residues surrounding the NNRTI-binding site, NNRTIs are notorious for rapidly eliciting resistance. Though, the emergence of resistant HIV strains can be circumvented if the NNRTIs are used either alone or in combination with NRTIs (AZT, 3TC, ddI, ddC, TVD or d4T) and PIs (Indinavir, nelfinavir, saquinavir, ritonavir and lopinavir etc.) as shown by both a decrease in plasma HIV-1 RNA levels and increased CD4 T-cells. Here we are going to discuss recent advances in structure activity relationship studies on nevirapine, delavirdine, efavirenz, etravirine, rilpivirine and 4-thiazolidinones (privileged scaffold) HIV-1 NNRTIs.
BackgroundIn India, which has the third largest HIV epidemic in the world, depression and HIV–related stigma may contribute to high rates of poor HIV–related outcomes such as loss to care and lack of virologic suppression.MethodsWe analyzed data from a large HIV treatment center in southern India to estimate the burden of depressive symptoms and internalized stigma among Indian people living with HIV (PLHIV) entering into HIV care and to test the hypothesis that probable depression was associated with internalized stigma. We fitted modified Poisson regression models, adjusted for sociodemographic variables, with probable depression (PHQ–9 score ≥10 or recent suicidal thoughts) as the outcome variable and the Internalized AIDS–Related Stigma Scale (IARSS) score as the explanatory variable.Findings521 persons (304 men and 217 women) entering into HIV care between January 2015 and May 2016 were included in the analyses. The prevalence of probable depression was 10% and the mean IARSS score was 2.4 (out of 6), with 82% of participants endorsing at least one item on the IARSS. There was a nearly two times higher risk of probable depression for every additional point on the IARSS score (Adjusted Risk Ratio: 1.83; 95% confidence interval, 1.56–2.14).ConclusionsDepression and internalized stigma are highly correlated among PLHIV entering into HIV care in southern India and may provide targets for policymakers seeking to improve HIV–related outcomes in India.
Psychosocial conditions such as depression, intimate partner violence (IPV), and history of childhood sexual abuse (CSA) have been associated with poor HIV-related outcomes. In India, which has the third-largest HIV epidemic in the world, little is understood about the impact of psychosocial conditions on people living with HIV (PLHIV). We aimed to understand the prevalence and correlates of psychosocial conditions among PLHIV entering into HIV care at the Y.R. Gaitonde Centre for AIDS Research and Education in Chennai, India. Thirteen questions were added to the standard voluntary counseling and testing questionnaire, including the Patient Health Questionnaire-9 (a depression scale) and questions assessing for childhood sexual abuse (CSA) and intimate partner violence (IPV). We fitted logistic regression models, stratified by gender, with psychosocial condition as the outcome of interest and substance use variables and socio-demographic variables as the correlates of interest. 383 persons were enrolled into the study; of these, 253 (66%) tested positive for HIV, including 149 men and 104 women, and were included in the models. More than one-quarter (28%) of the men and 19% of the women reported at least one psychosocial condition (probable depression, CSA, or IPV). In adjusted analysis, current alcohol use was associated with greater than two times higher odds of a psychosocial condition (AOR=2.24, 95% CI, 1.04-4.85) among men. In conclusion, we estimated the prevalence of probable depression, CSA, and IPV among PLHIV presenting for HIV care in southern India and found that, among male PLHIV, alcohol use was associated with a markedly higher odds of reporting a psychosocial condition. Further study is needed to characterize alcohol use among male PLHIV and the possible deleterious impact of psychosocial conditions and alcohol use on HIV-related outcomes in India.
We used data from 660 people living with HIV in southern India to evaluate the reliability, validity, and factor structure of the Internalized AIDS-Related Stigma Scale. Exploratory factor analysis revealed the presence of 2 factors: a 2-item factor related to disclosure concerns and a 4-item factor related to self-hatred. The self-hatred factor demonstrated acceptable internal consistency (Cronbach α = .80). As evidence of construct validity, both factors were correlated with depression symptom severity as measured by the Patient Health Questionnaire-9. Further study is needed to understand the correlates of these factors and their impact on the Indian HIV care continuum.
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