Thomas Campbell and colleagues report findings of a randomized trial conducted in multiple countries regarding the efficacy of antiretroviral regimens with simplified dosing.

HIV has now become a manageable chronic disease. However, the treatment outcomes may get hampered by suboptimal adherence to ART. Adherence optimization is a concrete reality in the wake of ‘universal access’ and it is imperative to learn lessons from various studies and programmes. This review examines current literature on ART scale up, treatment outcomes of the large scale programmes and the role of adherence therein. Social, behavioural, biological and programme related factors arise in the context of ART adherence optimization. While emphasis is laid on adherence, retention of patients under the care umbrella emerges as a major challenge. An in-depth understanding of patients’ health seeking behaviour and health care delivery system may be useful in improving adherence and retention of patients in care continuum and programme. A theoretical framework to address the barriers and facilitators has been articulated to identify problematic areas in order to intervene with specific strategies. Empirically tested objective adherence measurement tools and approaches to assess adherence in clinical/ programme settings are required. Strengthening of ART programmes would include appropriate policies for manpower and task sharing, integrating traditional health sector, innovations in counselling and community support. Implications for the use of theoretical model to guide research, clinical practice, community involvement and policy as part of a human rights approach to HIV disease is suggested.

The high risk of experiencing domestic violence (DV) among married women in India who reside in slum communities underscores the need for effective, evidence-based, and culturally-tailored primary prevention. To inform such DV primary prevention strategies for this population, we herein aimed to identify correlates of DV experience in early marriage. Utilizing a cross-sectional design, potential correlates of DV experience were explored among a geographically-clustered random sample of 100 recently-married women residing in slums in Pune, India. In multivariable regression, DV experience was associated with less educational attainment by the participant’s spouse (standardized β = -0.281, p = 0.004), less satisfaction of the spouse’s family with the maanpaan (wedding-related gifts provided by the bride’s family) they received at the time of marriage (standardized β = -0.298, p<0.001), poorer conflict negotiation skills (standardized β = -0.308, p<0.001), and greater acknowledgement of DV occurrence in family and friends (standardized β = 0.436, p<0.001). These correlates suggest strategies that could be incorporated into future DV primary prevention interventions for this vulnerable population (i.e. promoting completion of formal education of boys alongside girls, mitigating causes of familial dowry harassment, improving conflict negotiation skills, and challenging norms surrounding DV).

Background: Immunological non-responders (INR) represent a unique category of HIV-infected patients on antiretroviral therapy. These patients have suppressed viremia but a suboptimal increase in CD4 cell count, which might have opposing effects on functional immune reconstitution. Hence, the extent of immune reconstitution in INR patients was investigated in order to determine their susceptibility to opportunistic infections. Methods: Twenty-three INR patients (CD4 increase <50 cells/mm 3 , viral load <40 copies/ml), 40 age-, sex-, and baseline CD4 count-matched responders (CD4 increase >100 cells/mm 3 , viral load <40 copies/ml), and 18 treatment failures defined as per the national guidelines were enrolled at 1 year of antiretroviral therapy. The following examinations were performed: haemogram, phenotypic characterization by flow cytometry, and assessment of functional immune status by ELISPOT and intracellular cytokine assays. Results: A higher percentage of INR patients had clinically symptomatic infections than the responders. CD8 + activation and innate immune parameters, including the absolute neutrophil count and natural killer (NK) cell frequency and functionality, were restored in the INR patients. They had significantly higher non-HIV antigen-specific T-cell responses and activated CD4 + cells, but significantly compromised T-cell functionality, as assessed after anti-CD3 stimulation, and lower CD31 + and CD62L + CD4 + cells. Conclusions: INR patients showed lower thymic output, incomplete functional T-cell reconstitution, higher responses to HIV co-pathogens, and higher symptomatic events, indicating the need for close monitoring and intervention strategies to overcome their continuing immunocompromised status.

Background: Early detection of viremia in HIV infected patients on anti-retroviral therapy (ART) is important to prevent disease progression as well as accumulation of drug resistance mutations. This makes HIV viral load (VL) monitoring indispensable in HIV infected patients on ART. However VL, being an expensive test, results in heavy financial burden on health services. Hence, cheaper surrogate markers of viremia are desired to reduce overall cost of management of HIV infected patients. Methods: We enrolled aviremic (n = 63, M:F = 31:32) and viremic (n = 43, M:F = 21:22) HIV infected patients at 1 year after ART initiation. Viremic individuals were identified as those having a plasma VL of more than 1000 copies/µl and aviremic individuals as less than 40 copies/µl. The study participants also included immuno-virologically discordant patients as they demonstrate differential degrees of immune-reconstitution and are likely to harbour concomitant infections influencing levels of immune-activation markers screened as the surrogate markers. Immune activation markers viz. plasma hs-CRP, soluble-CD14 and Galectin-9 levels were estimated by ELISA, IL-6 by luminex assay and percentages of CD38+ CD8+ cells were determined by flow cytometry. The levels were compared between viremic and aviremic patients and correlated with plasma viral load. Receiver operated curve (ROC) analysis was done for plasma Galectin-9 levels. Results: Viremic patients had significantly higher levels of Galectin-9 and %CD38+ CD8+ cells (p values < 0.0001) than aviremic patients. Levels of the other activation markers did not differ between viremic and aviremic individuals. Galectin-9 levels (r = 0.76) and %CD38+ CD8+ cells (r = 0.39) correlated positively with VL. Area under curve for Galectin-9 levels for distinguishing between viremic and aviremic individuals was 0.98. Youden index, sensitivity, specificity, positive predictive value and negative predictive value for Galectin-9 levels were 0.87, 0.97, 0.90, 0.87 and 0.98, respectively, at the cutoff value of 5.79 ng/ml. Conclusions: Plasma Galectin-9 levels could identify viremic individuals with sensitivity and specificity of more than 90%. Thus, they showed a potential to serve as a surrogate marker of viremia in HIV infected patients on ART and

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Background Empowering female sex workers (FSWs) through women controlled HIV prevention option has been in focus globally. The success of targeted interventions among FSWs indicates that this population could become an important and feasible target for oral PrEP (Pre Exposure Prophylaxis). A qualitative study was conducted to study FSWs’ willingness to use oral PrEP in India.Methods In-depth interviews (n=39) and two focus group discussions (n=14) were conducted at 3 high HIV prevalence urban and rural sites in India among FSWs. Key informant interviews (n=34) were conducted with a bisexual man, 6 brothel keepers and 27 Health Care Providers (HCPs). The study explored issues around willingness to use oral PrEP. The study was approved by the respective institutional ethics committee of the study sites. Thematic analysis using the grounded theory approach was used to analyze the data in N-VIVO version 8.0. Results FSWs were willing to use daily oral PrEP and hoped to use it as an alternative to the male condom. One of the emerging themes showed that the situations of condom-less sex over which FSWs had no control. This made them desire oral PrEP which was easy to use and geared to provide independence, financial gains, and privacy. HCP initiated oral PrEP was not acceptable. However, HCPs pointed out safety monitoring needs. For FSWs, safety concerns pertained to their own physical/ aesthetic attributes and reproductive system in a major way. Adherence emerged as a challenge because of: 1) FSWs’ prevalent habit and need of alcohol use; 2) their notion of daily dosing being too mundane; 3) Stigma because Oral PrEP is ARV based. Alcohol use and dread of repetitive dose bring forth the need for long-acting oral PrEP. Conclusion Oral PrEP is acceptable among FSWs; it should be rolled out alongside strong messages on STI protection given the perceptions of FSWs that oral PrEP might replace condoms. Education about ARV-based oral PrEP needs to be spelled to prevent stigma. Adherence counseling should take cognizance of FSWs’ lifestyle, specifically making oral PrEP less of a mundane task.

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