Hematological Profile in HIV-Positive Patients: A Cross-Sectional Analysis from a Tertiary Care Centre

As the importance of quality in health care provision is increasingly recognised, it is opportune to consider quality care as a key link between clinical and public health approaches to human immunodeficiency virus (HIV) infection in developing countries, especially in sub-Saharan Africa. This region has the lion's share of the global epidemic and the least resources to respond. Looking at health problems using a 'quality lens' may help bridge the gaps between clinical care and public health, the current and desired standard of care, and prevention and treatment. Quality care, with prompt diagnosis and effective treatment, of people with HIV infection is crucial for good individual health outcomes, public health outcomes (in terms of decreased HIV transmission) and societal outcomes (increased productivity and decreased costs of health provision for HIV-related care). A spotlight on quality care can bring clinicians and public health practitioners together in working towards universal access to quality HIV care and prevention - one of the greatest health challenges faced in developing countries in Africa today.

To achieve epidemic control of human immunodeficiency virus (HIV) infection, sub-Saharan African countries are striving to diagnose 90% of HIV infections, initiate and retain 90% of HIV-diagnosed persons on antiretroviral therapy (ART), and achieve viral load suppression* for 90% of ART recipients (90-90-90) (1). In Eswatini (formerly Swaziland), the country with the world's highest estimated HIV prevalence (27.2%), achieving 90-90-90 depends upon improving access to early ART for men and young adults with HIV infection, two groups with low ART coverage (1-3). Although community-based strategies test many men and young adults with HIV infection in Eswatini, fewer than one third of all persons who test positive in community settings enroll in HIV care within 6 months of diagnosis after receiving standard referral services (4,5). To evaluate the effectiveness of peer-delivered linkage case management† in improving early ART initiation for persons with HIV infection diagnosed in community settings in Eswatini, CDC analyzed data on 651 participants in CommLink, a community-based, mobile HIV-testing, point-of-diagnosis HIV care, and peer-delivered linkage case management demonstration project, and found that after diagnosis, 635 (98%) enrolled in care within a median of 5 days (interquartile range [IQR] = 2-8 days), and 541 (83%) initiated ART within a median of 6 days (IQR = 2-14 days), including 402 (74%) on the day of their first clinic visit (same-day ART). After expanding ART eligibility to all persons with HIV infection on October 1, 2016, 96% of 225 CommLink clients initiated ART, including 87% at their first clinic visit. Compared with women and adult clients aged ≥30 years, similar high proportions of men and persons aged 15-29 years enrolled in HIV care and received same-day ART. To help achieve 90-90-90 by 2020, the United States President's Emergency Plan for AIDS Relief (PEPFAR) is supporting the national scale-up of CommLink in Eswatini and recommending peer-delivered linkage case management as a potential strategy for countries to achieve >90% early enrollment in care and ART initiation after diagnosis of HIV infection (6).

Are HIV-infected patients candidates for liver transplantation?

Background: Antiretroviral treatment (ART) has been reported to make changes in the functioning of dopaminergic neurons by altering the expression of dopamine active transporter (DAT). ART containing efavirenz drug has been related to show the adverse reactions on the central nervous system (CNS). Reported literature indicates the correlation of DAT19/10 genotype with the risk of progression of human immunodeficiency virus (HIV) infection. Objective: The aim of this study was to assess the polymorphism in the human gene DAT1, including variable number tandem repeats (VNTR) from individuals having an infection of HIV. Methods: Genotyping was completed by performing a polymerase chain reaction (PCR) in a total of 165 HIV-positive patients on ART treatment (34 were HIV-infected patients with hepatotoxicity, 131 HIV-infected patients) and 160 healthy controls without HIV infection. Results: Incidence of DAT19/9, 8/9 genotypes, and allele with 9 repeats were higher in individuals having hepatotoxicity compared to those who do not have hepatotoxicity (5.9 vs. 0.8%, OR = 7.73; 2.9 vs. 0.8%, OR = 3.86; 20.58% vs. 14.12%, OR = 1.56). DAT19/10 genotype was related to severity of hepatotoxicity (OR = 1.86; P = 0.05). Upon comparison of genotype between individuals who do not have hepatotoxicity but had HIV infection and healthy controls without HIV infection, the dispersion of DAT1 10/11, 6/10 genotypes were greater in individuals with HIV infection (1.5% vs. 0.6%, OR = 2.73; 3.1% vs. 1.3%, OR = 2.73). DAT19/10 genotype was related to the people of advanced stage of HIV infection (OR = 2.05, P = 0.04). A higher incidence of DAT19/10 genotype was found in individuals with early stage of HIV infection than healthy controls (26.3 vs. 15.6%, OR = 1.93). In alcohol and tobacco consuming individuals with HIV infection and hepatotoxicity, DAT19/10 genotype has demonstrated hazard in the progression of HIV infection and an increased severity of hepatotoxic condition (OR = 1.40, P = 0.91, OR = 1.50; P = 0.91 and OR = 1.57, P = 0.39; OR = 2.70; P = 0.53). In patients with hepatotoxicity, nevirapine utilization with DAT19/10 genotype demonstrated an increase in severity of hepatotoxicity (OR = 4.00, P = 0.41). In individuals with HIV infection and hepatotoxicity, alcohol and nevirapine usage, along with DAT1 9/10 genotype, indicated a risk for progression of HIV infection and severity of hepatotoxicity (OR = 1.47, P = 0.85; OR = 1.73; P = 0.32). Conclusion: The genetic polymorphism with DAT19/10 genotype was linked with the progression of HIV infection and in the advancement of HIV-related illnesses.

Human immunodeficiency virus (HIV) infection leads to reduced CD4+T-cell counts and immune dysfunction. Initiation of antiretroviral therapy (ART) in HIV primary infection has been recommended to achieve an optimal clinical outcome, but a comprehensive study on restoration of CD4+T-cell function in primary HIV-infected individuals with ART still needs to be eluciated. We investigated longitudinal changes in the CD4+T-cell counts, phenotypes, and functions in HIV-infected individuals with early ART (initiated within 6 months after HIV infection) or later ART (initiated more than 12 months after HIV infection). Patients from early ART and later ART groups had received ART for at least 1 year. Individuals with early ART had more CD4+T cells, a faster rate of CD4+T-cell recovery than those receiving later ART; the levels of CD4+T-cell activation and senescence were lower in early ART compared to those with later ART (P = .031; P = .016), but the activation was higher than normal controls (NC) (P = .001); thymic emigrant function was more upregulated in early ART than in later ART (P = .015), but still lower than NC (P = .027); proliferative capacity and interferon-γ secretion of CD4+T cells were significantly decreased in primary infection (P < .001; P = .029), and early ART restored these CD4+T-cell functions, there is no difference with NC, later ART could partially restore the functions of CD4+T cells, but it remained lower than that of NC (P = .005; P = .019). Early ART could better improve CD4+T-cell function.

ObjectiveThis study aimed to assess the potential epidemiological and economic impact of rapid initiation of human immunodeficiency virus (HIV) treatment with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) on HIV transmission compared with the current initiation observed in clinical practice in Spain.MethodsA transmission model was adapted to estimate the cumulative HIV infection incidence and potential cost savings based on the number of HIV infections prevented among men who have sex with men, heterosexual males and females, and people who inject drugs (PWID) over a 20-year time horizon. The analysis compared rapid antiretroviral therapy (ART) initiation with B/F/TAF (9 days from diagnosis until treatment initiation) versus current ART initiation practice (with an average of 35 days from diagnosis to treatment). People living with HIV were distributed according to their treatment status. Risk for transmission was assigned to undiagnosed, diagnosed in care and not receiving ART, and receiving ART but virally unsuppressed, which was estimated by sexual contact, needles and syringes shared among PWID, state of HIV infection, and ART use.ResultsIn the base-case analysis, rapid ART initiation with B/F/TAF is expected to prevent 992 new HIV infections over the next 20 years compared with current ART initiation practices. Considering the lifetime costs of treating HIV infection, the reduction in HIV incidence could result in potential cost savings of €323 million.ConclusionsThese results suggest that rapid ART initiation with B/F/TAF in newly diagnosed patients with HIV is a high-value strategy for the Spanish National Health System and society, reducing HIV incidence and thereby reducing future related direct and indirect costs of care.

ON JULY 16, 2012, THE US FOOD AND DRUG Administration (FDA) approved a daily oral antiretroviral drug to reduce the risk of sexual acquisition of human immunodeficiency virus (HIV) infection by uninfected adults. Emtricitabine/ tenofovir disoproxil fumarate (marketed by Gilead as Truvada) contains 2 nucleoside analogue HIV-1 reverse transcriptase inhibitors. Initially approved in 2004 to treat HIV infection in combination with other antiretroviral medications in people 12 years of age and older, emtricitabine/ tenofovir costs about $13 900 a year in the United States for a year of treatment. Preexposure prophylaxis, the treatment of an uninfected person before having sexual contact with an HIV-infected partner, is a widely anticipated advance that should help some people who are not infected with HIV but at high risk of infection to remain uninfected. Preexposure prophylaxis differs from another recent and complementary approach, known as treatment for prevention, which is the treatment of an HIVinfected person with antiretroviral agents to reduce the viral load and infectiousness, and thus the risk of transmission to an uninfected partner. Worldwide, about 2.5 million new HIV infections occur each year, primarily in heterosexual adults. Many people with HIV infection who are in ongoing relationshipshavepartnerswhoarenot infected, andasubstantialnumber of the new infections occur within such serodiscordant couples. In the United States, there are an estimated 50 000 new HIV infections each year, about three-fifths of which occur in men who have sexual contact with men. Preexposure prophylaxis with emtricitabine/tenofovir, however, is not a panacea for HIV infection. Taken every day, the drug reduces, but does not eliminate, the risk of acquiring HIV. It is not an effective morning before pill or morning after pill, to be taken as needed by uninfected persons. It is not a replacement for condoms and other safe sex practices, although some people may mistakenly assume this or wish that it was. Common adverse reactions in people who take the drug to prevent HIV infection include headache, abdominal pain, and weight loss. Safety concerns include impairment of kidney and liver function and decreases in bone mineral density. The long-term safety of the drug in healthy people is unknown because the available studies have only lasted for several years. Cost is also an issue, particularly for people without insurance to pay for the medication and in countries with limited resources. Preexposure prophylaxis for HIV requires that uninfected persons ingest a potent antiretroviral agent on a strict schedule, perhaps for an indefinite period of time, while following a comprehensive prevention strategy, including regular testing for HIV and other sexually transmitted diseases, consistent and correct condom use, and knowing one’s HIV status and that of partner or partners. In real life, fulfilling these requirements is a lot easier said than done. Frank discussions are needed between physicians and patients before prescribing the drug and between sexual partners. However, only an estimated 40% of people with HIV infection worldwide, and an estimated 80% of those in the United States, know their HIV status. Many people who know their status have neither disclosed their HIV status to their partners nor learned their partner’s status. Although FDA approval of emtricitabine/tenofovir for preexposure prophylaxis was expected, the considerations were complex and challenges exist. The critical questions include whether the drug will be prescribed appropriately to uninfected persons, and whether it will be used safely and properly. The updated prescribing information states that the drug “must only be prescribed to individuals confirmed to be HIVnegative immediately prior to initiating and periodically (at least every three months) during use.” Not only is emtricitabine/tenofovir less effective when doses are missed, but drugresistant HIV viruses may develop when people become infected while taking the medication for prophylaxis. Drug resistance has implications for the subsequent treatment of the infected person, as well as others who may acquire the strain. The FDA did not require that people show proof of testing negative for HIV before receiving their prescriptions as critics of the decision, such as the AIDS Healthcare Foundation, suggested. Although such a requirement might have enhanced the correct use of the medication, it might also have decreased access for those who might benefit. The FDA action was based on the results of 2 large randomized, double-blind, placebo-controlled trials and the rec-

Predictors of cognitive performance in Zambian adults with clade C HIV-1: The roles of antiretroviral therapy (ART)-induced CD4+ T-cell increase and pulmonary tuberculosis.

This study aimed to evaluate maternal outcomes in a large cohort with high prevalence of human immunodeficiency virus (HIV) infection in Botswana after implementation of a treat-all policy. In this retrospective cohort study, data were collected from the medical record at the time of discharge from November 2021 to December 2023. Outcomes were recorded in the Tsepamo Birth Outcomes Surveillance and Safe Birth studies at Princess Marina Hospital in Botswana. We evaluated maternal mortality and obstetric morbidities by HIV status, including preeclampsia, eclampsia, hemorrhage, infection, and acute pulmonary or cardiac conditions at the time of hospital discharge. We included 11,754 participants; 2,201 (18.7%) were pregnant people with HIV infection. Ninety-seven percent (2,135) were on antiretroviral therapy (ART) at time of delivery; 1,996 (93.5%) of those with a known ART regimen were on dolutegravir, tenofovir disoproxil fumarate, and lamivudine. Of the 1,090 people with HIV infection with known CD4 counts, 757 (69.4%) had more than 500 cells/microliter, and only 42 (3.9%) had fewer than 200 cells/microliter. Of 1,524 people with HIV infection with known viral loads, 1,436 (94.2%) were undetectable on initial testing. There were no statistically significant differences in incidence of hemorrhage (90 [4.1%] vs 370 [3.9%], adjusted risk ratio [RR] 0.93, 95% CI, 0.73-1.17), infection (38 [1.7%] vs 126 [1.3%], adjusted RR 1.56, 95% CI, 0.97-2.51), eclampsia (6 [0.3%] vs 28 [0.3%], adjusted RR 1.12, 95% CI, 0.50-2.53), acute pulmonary or cardiac conditions (15 [0.7%] vs 43 [0.4%], adjusted RR 1.22, 95% CI, 0.65-2.27), transfusion of 2 or more units of packed red blood cells (33 [36.7%] vs 110 [29.8%], P= .21), additional uterotonics (48 [53.3%] vs 173 [47.1%], P= .29), use of tranexamic acid (31 [ 34.4%] vs 106 [29.0%], P= .31), intensive care unit admission (4 [0.2%] vs 10 [0.1%], P= .31), mechanical ventilation (3 [0.1%] vs 6 [0.1%], P= .38), pressor support (2 [0.1%] vs 2 [0.0%], P= .16), or mortality (5 [0.2%] vs 11 [0.1%], adjusted RR 1.44, 95% CI, 0.46-4.57) in people with HIV infection compared with those without HIV infection. There were few notable differences, including a slightly reduced risk of preeclampsia (184 [8.4%] vs 818 [8.6%], adjusted RR 0.84, 95% CI, 0.71-0.98) and, although rare, an increased risk of uterine rupture (12 [0.5%] vs 8 [0.1%], adjusted RR 6.54, 95% CI, 2.33-18.33) in people with HIV infection compared with those without HIV infection. There was little difference in adverse maternal obstetric outcomes between people with and those without HIV infection in the treat-all era with integrase strand inhibitors (primarily dolutegravir); notable exceptions included a slightly reduced risk of preeclampsia and, although rare, an increased risk of uterine rupture in those with HIV infection.

Human immunodeficiency virus (HIV) infection is associated with increased cardiovascular disease (CVD) events. Endothelial dysfunction (EDF) is involved in CVD pathogenesis; however, EDF onset after HIV acquisition and the potential for reversibility with antiretroviral therapy (ART) have not been evaluated to date. To evaluate endothelial function with noninvasive reactive hyperemia index (RHI) in patients with early HIV infection at baseline and after ART initiation. Cohort study in which 61 members of the United States Air Force diagnosed with HIV infection from September 1, 2015, through September 30, 2017, were evaluated for baseline EDF. Natural log-transformed RHI values (lnRHI) of less than 0.51 and at least 0.51 were defined as abnormal and normal, respectively. The RHI interval changes were evaluated in a subgroup of 40 patients. Data were analyzed from September 30, 2017, through January 30, 2018. Early HIV infection. Baseline EDF at HIV diagnosis and interval changes associated with ART initiation. The 61 patients included in the analysis were predominantly male (58 [95%]) and mostly African American (35 [57%]), with a mean (SD) age of 28.1 (6.7) years at HIV diagnosis. Median time from estimated date of HIV seroconversion to RHI assessment was 10.6 months (interquartile range [IQR], 5.1-13.2 months), and the median CD4 lymphocyte count was 552/μL (IQR, 449/μL-674/μL). Patients had a mean (SD) body mass index of 26.2 (4.0), median (IQR) low-density lipoprotein cholesterol level of 97 (80-126) mg/dL, median (IQR) total cholesterol level of 163 (146-195) mg/dL, and no diabetes diagnoses. Overall mean (SD) lnRHI was 0.70 (0.29) at HIV diagnosis. Baseline RHI was normal in 47 patients (77%; mean [SD] lnRHI, 0.82 [0.20]) and was abnormal in 14 patients (23%; mean [SD] lnRHI, 0.30 [0.18]). Age (per 10-year increase) was not associated with an abnormal lnRHI (odds ratio, 2.15; 95% CI, 0.89-5.19; P = .09). Of the 41 patients with follow-up RHI assessments, 40 started ART immediately and repeated the RHI assessments at a median (IQR) of 6.4 (6.0-7.8) months. Use of ART was associated with an overall significan increase in mean (SD) lnRHI (0.13 [0.33]; P = .02). A greater increase in mean (SD) lnRHI was associated with abnormal (n = 11) compared with normal (n = 29) lnRHI at HIV diagnosis (0.33 [0.34]; P = .01 vs 0.04 [0.30]; P = .38). Among those with abnormal baseline lnRHI, 8 (73%) showed improved endothelial function after ART. The patient who declined ART converted from having a normal lnRHI (0.60) to an abnormal lnRHI (0.11) lnRHI after 8.3 months. In this study, EDF was common in early HIV infection, with associated reversal in most patients taking ART. Results suggest that persistent EDF and CVD complications may be associated with delayed ART. Further studies are necessary to define the role of noninvasive endothelial function testing in patients with HIV infection.

Repeated exposure to HIV does not necessarily result in infection and HIV infection does not inevitably lead to the development of the AIDS. Multiple immunological and genetic features can confer resistance to HIV acquisition and progression at different steps in viral infection; a full understanding of these mechanisms could result in the development of novel therapeutic and vaccine approaches for HIV infection. In this review, we focus on the genetic mechanisms associated with resistance to HIV infection and to the progression to AIDS.

CD64 is an Fc-gamma-receptor type 1. The expression level of neutrophil CD64 (nCD64) is a known bacterial infection marker, and it also increases in viral infections. We examined the absolute nCD64 before and after the initiation of antiretroviral therapy (ART) to determine its role as an infection and inflammation marker of human immunodeficiency virus (HIV) infection. In this prospective observational study, 94 HIV-infected patients were enrolled and classified into ART (n = 62), ART naive (n = 24), and acute/early phase groups (n = 8). The median nCD64 was 1,430 molecules/cell in the ART group, 2,994 in the ART naive group, 4,625 in the acute/early phase group, and 1,196 in the healthy control group. The nCD64 in the ART group was significantly higher compared with the healthy controls (p = .041), and the nCD64 in the ART naive and acute/early phase groups was significantly higher compared with the ART group (both p < .001). In the ART naive group, nCD64 was significantly higher in patients with than without concomitant infections (3,942 ± 1,519 vs. 2,300 ± 784, p = .004). However, this was influenced by the fact that nCD64 elevated as the stage of HIV infection progressed. nCD64 decreased significantly during the 24 weeks after starting ART (p = .004), although an upward trend in nCD64 was observed at weeks 2 and 4, without symptoms. When immune reconstitution inflammatory syndrome occurred, nCD64 elevated with a wider range than did C-reactive protein. This preliminary study suggests that nCD64 would be useful as a marker of the systemic inflammation of HIV-infected patients.

Human Immunodeficiency Virus Infection and Partner Services: A Monumental Missed Opportunity

Even in antiretroviral therapy (ART)-suppressed human immunodeficiency virus (HIV)-infected individuals, there are heterogeneous populations of HIV-expressing cells exhibiting variable degrees of progression through blocks to HIV transcriptional initiation, elongation, completion, and splicing. These HIV-transcribing cells likely contribute to HIV-associated immune activation and inflammation as well as the viral rebound that occurs after stopping ART. However, it is unclear whether the blocks to HIV transcription are present before ART and how the timing and duration of ART may affect the clearance of cells expressing HIV transcripts that differ in their processivity and/or presence of mutations. To investigate these questions, we quantified different types of HIV transcripts and the corresponding HIV DNA regions/proviruses in longitudinal blood samples obtained before ART initiation (T1) and after 6 months (T2) and 1 year (T3) of ART in 16 individuals who initiated ART during acute HIV infection. Before ART, the pattern of HIV transcripts suggested blocks to elongation and splicing, and only ~10% of intact proviruses were transcribing intact HIV RNA. During the first 6 months of ART, we detected progressively greater reductions in initiated, 5'-elongated, mid-transcribed, completed, and multiply spliced HIV transcripts. Completed HIV RNA decayed faster than initiated or 5'-elongated HIV RNA, and intact HIV RNA tended to decay faster than defective HIV RNA. HIV DNA and RNA levels at T1-T3 correlated inversely with baseline CD4+ T-cell counts. Our findings suggest the existence of immune responses that act selectively to reduce HIV transcriptional completion and/or preferentially kill cells making completed or intact HIV RNA.IMPORTANCEEven in virologically suppressed HIV-infected individuals, expression of viral products from both intact and defective proviruses may contribute to HIV-associated immune activation and inflammation, which are thought to underlie the organ damage that persists despite suppressive ART. We investigated how the timing of ART initiation and the duration of ART affect the heterogeneous populations of HIV-transcribing cells, including a detailed characterization of the different HIV transcripts produced before ART and the rate at which they decay after ART initiation during acute HIV infection. Even during untreated infection, most cells (~90%) have blocks at some stage of transcription. Furthermore, different HIV transcripts decline at different rates on ART, with the fastest decay of cells making completed and intact HIV RNA. Our results suggest that intrinsic or extrinsic immune responses act selectively to either reduce particular stages of HIV transcription or cause selective killing of cells making particular HIV transcripts.

Severe Myelosuppression and MRSA Infection as the Presentation of Perinatal HIV Infection