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© 2021 British HIV Association, Objectives: HIV outcomes centre primarily around clinical markers with limited focus on patient-reported outcomes. With a global trend towards capturing the outcomes that matter most to patients, there is agreement that standardizing the definition of value in HIV care is key to their incorporation. This study aims to address the lack of routine, standardized data in HIV care. Methods: An international working group (WG) of 37 experts and patients, and a steering group (SG) of 18 experts were convened from 14 countries. The project team (PT) identified outcomes by conducting a literature review, screening 1979 articles and reviewing the full texts of 547 of these articles. Semi-structured interviews and advisory groups were performed with the WG, SG and people living with HIV to add to the list of potentially relevant outcomes. The WG voted via a modified Delphi process - informed by six Zoom calls - to establish a core set of outcomes for use in clinical practice. Results: From 156 identified outcomes, consensus was reached to include three patient-reported outcomes, four clinician-reported measures and one administratively reported outcome; standardized measures were included. The WG also reached agreement to measure 22 risk-adjustment variables. This outcome set can be applied to any person living with HIV aged > 18 years. Conclusions: Adoption of the HIV360 outcome set will enable healthcare providers to record, compare and integrate standardized metrics across treatment sites to drive quality improvement in HIV care.

To assess efficacy and safety of dolutegravir (DTG) + lamivudine (3TC) vs. DTG + tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in treatment-naive adults with HIV-1 in the prespecified 144-week secondary analyses of GEMINI-1 and GEMINI-2.Design:Identical, multicenter, phase III, randomized, non-inferiority studies (double-blind through 96 weeks).Methods:Participants with HIV-1 RNA ≤500 000 copies/ml and no major viral resistance mutations to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, or protease inhibitors were randomized 1:1 to once-daily DTG + 3TC or DTG + TDF/FTC.Results:At week 144, DTG + 3TC (N = 716) was noninferior to DTG + TDF/FTC (N = 717) in proportion of participants achieving HIV-1 RNA, This study was funded by ViiV Healthcare

Background Some tuberculosis (TB) treatment guidelines recommend daily TB treatment in both the intensive and continuation phases of treatment in HIV-positive persons to decrease the risk of relapse and acquired drug resistance. However, guidelines vary across countries, and treatment is given 7, 5, 3, or 2 days/week. The effect of TB treatment intermittency in the continuation phase on mortality in HIV-positive persons on antiretroviral therapy (ART), is not well-described. Methods We conducted an observational cohort study among HIV-positive adults treated for TB between 2000 and 2018 and after enrollment into the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet; Brazil, Chile, Haiti, Honduras, Mexico and Peru). All received standard TB therapy (2-month initiation phase of daily isoniazid, rifampin or rifabutin, pyrazinamide ± ethambutol) and continuation phase of isoniazid and rifampin or rifabutin, administered concomitantly with ART. Known timing of ART and TB treatment were also inclusion criteria. Kaplan–Meier and Cox proportional hazards methods compared time to death between groups. Missing model covariates were imputed via multiple imputation. Results 2303 patients met inclusion criteria: 2003(87%) received TB treatment 5–7 days/week and 300(13%) 2–3 days/week in the continuation phase. Intermittency varied by site: 100% of patients from Brazil and Haiti received continuation phase treatment 5–7 days/week, followed by Honduras (91%), Peru (42%), Mexico (7%), and Chile (0%). The crude risk of death was lower among those receiving treatment 5–7 vs. 2–3 days/week (HR = 0.68; 95% CI = 0.51—0.91; P = 0.008). After adjusting for age, sex, CD4, ART use at TB diagnosis, site of TB disease (pulmonary vs. extrapulmonary), and year of TB diagnosis, mortality risk was lower, but not significantly, among those treated 5–7 days/week vs. 2–3 days/week (HR 0.75, 95%CI 0.55–1.01; P = 0.06). After also stratifying by study site, there was no longer a protective effect (HR 1.42, 95%CI 0.83–2.45; P = 0.20). Conclusions TB treatment 5–7 days/week was associated with a marginally decreased risk of death compared to TB treatment 2–3 days/week in the continuation phase in multivariable, unstratified analyses. However, little variation in TB treatment intermittency within country meant the results could have been driven by other differences between study sites. Therefore, randomized trials are needed, especially in heterogenous regions such as Latin America.

Objectives: The aim of this study was to describe the incidence, clinical characteristics, and risk factors of late-onset opportunistic infections (LOI) in people who live with HIV (PWLHA) within the Caribbean, Central and South America network for HIV epidemiology. Methods: We performed a retrospective cohort study including treatment-naive PWLHA enrolled at seven sites (Argentina, Brazil, Chile, Peru, Mexico, and two sites in Honduras). Follow-up began at 6 months after treatment started. Outcomes were LOI, loss to follow-up, and death. We used a Cox proportional hazards model and a competing risks model to evaluate risk factors. Results: A total of 10,583 patients were included. Median follow up was at 5.4 years. LOI occurred in 895 (8.4%) patients. Median time to opportunistic infection was 2.1 years. The most common infections were tuberculosis (39%), esophageal candidiasis (10%), and Pneumocystis jirovecii (P. jirovecii) pneumonia (10%). Death occurred in 576 (5.4%) patients, and 3021 (28.5%) patients were lost to follow-up. A protease inhibitor–based regimen (hazard ratio 1.25), AIDS-defining events during the first 6 months of antiretroviral-treatment (hazard ratio 2.12), starting antiretroviral-treatment in earlier years (hazard ratio 1.52 for 2005 vs 2010), and treatment switch (hazard ratio 1.31) were associated with a higher risk of LOI. Conclusion: LOI occurred in nearly one in 10 patients. People with risk factors could benefit from closer follow-up.

Living with HIV has been proposed as a risk factor for the early development of functional decline. Composite marker tools like the Veterans Aging Cohort Study (VACS) Index, which includes HIV-associated and non-HIV-related markers of disease may better reflect multiorgan system injury and potentially predict functional outcomes. Therefore, the objective of this work is to determine whether higher VACS 2.0 Index scores predicts functional decline among older adults living with HIV (OALWH). Longitudinal study, including 131 adults ages 50 or older who underwent a comprehensive geriatric assessment at baseline and follow-up, at least a year apart. Functional status was determined by the gait speed (seconds for a 4-m distance). Linear regression models were constructed to determine the relationship between VACS 2.0 Index at baseline with gait speed at follow-up adjusted for potential confounders. The median for age was 58.0 years (range 50-84), and 81.7% were male. At baseline, the median VACS 2.0 Index score was 50.4 (interquartile range 42.2-65.3). The adjusted linear regression analysis found that higher baseline VACS 2.0 Index scores were significantly associated with a decline in gait speed (

ObjectivesWith the goal of facilitating the use of HIV-TRePS to optimize therapy in settings with limited healthcare resources, we aimed to develop computational models to predict treatment responses accurately in the absence of commonly used baseline data.MethodsTwelve sets of random forest models were trained using very large, global datasets to predict either the probability of virological response (classifier models) or the absolute change in viral load in response to a new regimen (absolute models) following virological failure. Two ‘standard’ models were developed with all baseline variables present and 10 others developed without HIV genotype, time on therapy, CD4 count or any combination of the above.ResultsThe standard classifier models achieved an AUC of 0.89 in cross-validation and independent testing. Models with missing variables achieved AUC values of 0.78–0.90. The standard absolute models made predictions that correlated significantly with observed changes in viral load with a mean absolute error of 0.65 log10 copies HIV RNA/mL in cross-validation and 0.69 log10 copies HIV RNA/mL in independent testing. Models with missing variables achieved values of 0.65–0.75 log10 copies HIV RNA/mL. All models identified alternative regimens that were predicted to be effective for the vast majority of cases where the new regimen prescribed in the clinic failed. All models were significantly better predictors of treatment response than genotyping with rules-based interpretation.ConclusionsThese latest models that predict treatment responses accurately, even when a number of baseline variables are not available, are a major advance with greatly enhanced potential benefit, particularly in resource-limited settings. The only obstacle to realizing this potential is the willingness of healthcare professions to use the system.

Background Incidence of anal and oral infections with Human Papillomavirus (HPV) is increasing, particularly among Human Immunodeficiency Virus-positive (HIV+) men. HPV type 16 has exhibited the highest incidence and only limited data is available on other prevalent types, variants of HPV16, as well as associated factors. We were interested in identifying prevalent HPV types, variants of type 16, as well as factors associated with HPV16 infections in the oral cavity of HIV+ men who have sex with men (MSM). Methods A cross-sectional study of oral cavity samples from HIV+ MSM, that in a previous study were identified as positive for HPV16 in the anal canal. Cells from the oral cavity (102 samples, paired with 102 from the anal canal of same patient) were used to extract DNA and detect HPV infections using INNO-LiPA HPV Genotyping Extra II, and PCR. From these, 80 samples (paired, 40 anal and 40 oral) were used to identify variants of type 16 by sequencing. Statistical differences were estimated by the X2 test, and p values equal to or less than 0.05 were considered significant. SPSS ver. Twenty-four statistical software (IBM Corp) was used. Results We found a high prevalence of High-Risk HPV (HR-HPV) and Low-Risk HPV (LR-HPV). Patients were positive in the oral cavity for HR types; 16, 39 and 18 (80.4, 61.8 and 52.9% respectively) and LR types 11 and 6 (53.9 and 34.3% respectively). Surprisingly, only European variants of type 16 were found in the oral cavity, although American Asian (22.5%) and African (2.5%) variants were identified in the anal canal. The analysis showed that CD4 counts could be the most important risk factor associated with HR-HPV infections in the oral cavity, anal canal or both anatomical regions. The risk of infection of the oral cavity with type 18 increased in men diagnosed with HIV for more than 6 years. Conclusions Prevalence of both HR and LR HPV’s in the oral cavity of Mexican HIV+ MSM is very high. The fact that only European variants of HPV16 were found in the oral cavity suggest a possible tropism not previously described.

Two-drug regimens (2DRs) can potentially reduce long-term cumulative drug exposure and decrease treatment-associated costs for HIV-1–infected individuals, who require lifelong therapy.1 The core antiretroviral agent in a 2DR must have high potency and a high barrier to resistance.1 As such, early studies investigating 2DRs as initial or maintenance therapy for HIV infection evaluated the pairing of the potent, well-tolerated nucleoside reverse transcriptase inhibitor (NRTI) lamivudine with pharmacologically boosted protease inhibitors (PIs), which have a high barrier to resistance.2–6 Although noninferior efficacy was shown against 3-drug regimens (3DRs), PIs are associated with adverse metabolic effects, long-term toxicities, and drug–drug interactions, limiting their appeal as components of lifelong therapy.7,8 Thus, a need remains for well-tolerated, potent 2DRs with a high barrier to resistance. The integrase strand transfer inhibitor (INSTI) dolutegravir has a high barrier to resistance, making it a well-suited candidate for inclusion in a 2DR,9 particularly when paired with lamivudine,10 as previously observed.11,12 In primary week 48 analyses of the 2 phase III studies GEMINI-1 and GEMINI-2 in treatment-naive adults, dolutegravir + lamivudine was noninferior to dolutegravir + tenofovir disoproxil fumarate/emtricitabine in achieving HIV-1 RNA

Introduction In 2013, the World Health Organization (WHO) recommended initiating combination ART (cART) in all adults with HIV and CD4+ lymphocyte counts (CD4)

Background To investigate metabolic changes associated with second-line antiretroviral therapy (ART) following virological failure of first-line ART. Methods SECOND-LINE was an open-label randomized controlled trial. Participants were randomized 1:1 to receive ritonavir-boosted lopinavir (LPV/r) with 2–3 nucleoside/nucleotide reverse transcriptase inhibitors (N[t]RTI group) or raltegravir (RAL group). 210 participants had a dual energy X-ray absorptiometry (DXA)-scan at baseline, week 48 and 96. We categorized participants according to second-line ART backbone: thymidine analogue (ta-NRTI) + lamivudine/emtricitabine (3[F]TC; ta-NRTI group); tenofovir (TDF)+3(F)TC (TDF group); TDF+ta-NRTI ±3(F)TC (TDF+ta-NRTI group); RAL. Changes in fasted total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, TC/HDL-cholesterol ratio, triglycerides and glucose from baseline to week 96 were examined. We explored the association between metabolic and DXA-assessed soft-tissue changes. Linear regression methods were used. Results We analysed 454 participants. Participants in RAL group had greater TC increases, TC (adjusted mean difference [aMD]=0.65, 95% CI 0.33, 0.96), LDL-c (aMD=0.38, 95% CI 0.15, 0.61) and glucose (aMD=0.47, 95% CI -0.01, 0.92) compared to TDF group, and had greater increases in TC (aMD=0.65, 95% CI 0.28, 1.03), HDL-c (aMD=0.12, 95% CI 0.02, 0.23) and LDL-c (aMD=0.41, 95% CI 0.13, 0.69) compared to TDF+ta-NRTI group. TC/HDL ratio and triglycerides increased in all groups without significant differences between groups. A 1 kg increase in trunk fat mass was associated with an increase in TC. Conclusions We observed metabolic changes of limited clinical significance in the relatively young population enrolled in this study. However, the metabolic changes observed may have greater clinical significance in older people living with HIV or those with other concomitant cardiovascular risks.

We studied the prevalence of HIV, syphilis, hepatitis B virus (HBV), and hepatitis C virus (HCV) infection and associated risk behaviors in the prison state system of Guanajuato, Mexico between September 2011 and February 2012. Blood samples were drawn from adult inmates in all State prisons who agreed to participate in this cross-sectional study. Data on risk behaviors were collected by using self-administered questionnaires. The prevalence of HIV, syphilis, HBV, and HCV infection was 0.6% [95% confidence interval (CI) = 0.2-1.1], 0.7% (95% CI = 0.4-1.0), 0.4 (95% CI = 0.04-0.74), and 4.8 (95% CI = 3.6-5.9), respectively. Female inmates had a higher prevalence of HIV (1.5% vs. 0.6%, p = .05), whereas male inmates had a higher prevalence of HCV (1% vs. 5%, p = .008). Twenty percent (n = 443, 95% CI = 15-26) of the participants were tattooed during incarceration, and most of them were tattooed with recycled materials. Around 60% (57%, 95% CI = 49-65) used drugs before incarceration, and 9.2% (n = 205) used injected drugs. During incarceration, 30% (95% CI = 23-39) used drugs and 43 continued injecting (20% of users). Consistent condom use was low among men before incarcerations but decreased by half during incarceration. The highest consistent condom use before incarceration was among men who have sex with men (MSM) (17.7%, 95% CI = 14-22), but it decreased (9%, 95% CI = 3-14) during incarceration. The prevalence of HIV, HBV, HCV, and syphilis in these inmates is higher than that of the local adult population. Most inmates had sex in prison, but few used condoms consistently. Access to condoms is apparently harder for MSM. Interventions to increase condom use, reduce use of shared or recycled materials for tattooing and injecting drugs, and treatment for drug abuse are needed.

WHO has developed a global HIV-drug resistance surveillance strategy, including assessment of pretreatment HIV-drug resistance. We aimed to do a nationally representative survey of pretreatment HIV-drug resistance in Mexico using WHO-recommended methods.Among 161 Ministry of Health antiretroviral therapy (ART) clinics in Mexico, the largest, including 90% of ART initiators within the Ministry of Health (66 in total), were eligible for the survey. We used a probability-proportional-to-size design method to sample 25 clinics throughout the country. Consecutive ART-naive patients with HIV about to initiate treatment were invited to participate in the survey; individuals with previous exposure to ART were excluded. We assessed pretreatment HIV-drug resistance by Sanger sequencing and next-generation sequencing of viruses from plasma specimens from eligible participants with Stanford University HIV Drug Resistance Database methods. We obtained follow-up data for a median of 9·4 months (range 6-12) after enrolment. We investigated possible relations between demographic variables and pretreatment drug resistance with univariate and multivariate logistic regression.Between Feb 3 and July 30, 2015, we screened 288 patients in 25 clinics, from whom 264 provided successfully sequenced viruses with no evidence of current exposure to antiretroviral drugs. With the Sanger method, of these 264 participants, 41 (15·5%, 95% CI 11·4-20·5) had pretreatment resistance to any antiretroviral drug and 28 (10·6%, 7·2-15·0) had pretreatment resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs). At least low-level pretreatment resistance (Stanford penalty score ≥15) was noted in 13 (4 · 9%) of participants to efavirenz and in 23 (8·7%) to the combination tenofovir plus emtricitabine plus efavirenz. With next-generation sequencing, of 264 participants, 38 (14·4%, 95% CI 10·4-19·2) had pretreatment resistance to any antiretroviral drug and 26 (9·8%, 6·5-14·1) had pretreatment resistance to NNRTIs. After median follow-up of 8 months (IQR 6·5-9·4, range 5-11) after ART initiation, 97 (72%) of 135 NNRTI initiators achieved viral suppression (50 copies per mL) compared with ten (40%) of 25 individuals who started with protease inhibitor-based regimens (p=0·0045). After multivariate regression considering pretreatment resistance and initial ART regimen as composite variables, people starting NNRTIs with pretreatment drug resistance achieved significantly lower viral suppression (odds ratio 0·24, 95% CI 0·07-0·74; p=0·014) than patients without NNRTI resistance.High levels of pretreatment drug resistance were noted in Mexico, and NNRTI pretreatment drug resistance significantly reduced the effectiveness of first-line ART regimens based on these drugs. Baseline HIV-drug resistance testing for initial ART follow-up and decision making should be considered.The Mexican Government and Consejo Nacional de Ciencia y Tecnología.

Summary Background Effective two-drug regimens could decrease long-term drug exposure and toxicity with HIV-1 antiretroviral therapy (ART). We therefore aimed to evaluate the efficacy and safety of a two-drug regimen compared with a three-drug regimen for the treatment of HIV-1 infection in ART-naive adults. Methods We conducted two identically designed, multicentre, double-blind, randomised, non-inferiority, phase 3 trials: GEMINI-1 and GEMINI-2. Both studies were done at 192 centres in 21 countries. We included participants (≥18 years) with HIV-1 infection and a screening HIV-1 RNA of 500 000 copies per mL or less, and who were naive to ART. We randomly assigned participants (1:1) to receive a once-daily two-drug regimen of dolutegravir (50 mg) plus lamivudine (300 mg) or a once-daily three-drug regimen of dolutegravir (50 mg) plus tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Both drug regimens were administered orally. We masked participants and investigators to treatment assignment: dolutegravir was administered as single-entity tablets (similar to its commercial formulation, except with a different film colour), and lamivudine tablets and tenofovir disoproxil fumarate and emtricitabine tablets were over-encapsulated to visually match each other. Primary endpoint was the proportion of participants with HIV-1 RNA of less than 50 copies per mL at week 48 in the intention-to-treat-exposed population, using the Snapshot algorithm and a non-inferiority margin of −10%. Safety analyses were done on the safety population. GEMINI-1 and GEMINI-2 are registered with ClinicalTrials.gov, numbers NCT02831673 and NCT02831764, respectively. Findings Between July 18, 2016, and March 31, 2017, 1441 participants across both studies were randomly assigned to receive either the two-drug regimen (n=719) or three-drug regimen (n=722). At week 48 in the GEMINI-1 intention-to-treat-exposed population, 320 (90%) of 356 participants receiving the two-drug regimen and 332 (93%) of 358 receiving the three-drug regimen achieved plasma HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −2·6%, 95% CI −6·7 to 1·5); in GEMINI-2, 335 (93%) of 360 in the two-drug regimen and 337 (94%) of 359 in the three-drug regimen achieved HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −0·7%, 95% CI −4·3 to 2·9), showing non-inferiority at a −10% margin in both studies (pooled analysis: 655 [91%] of 716 in the two-drug regimen vs 669 [93%] of 717 in the three-drug regimen; adjusted treatment difference −1·7%, 95% CI −4·4 to 1·1). Numerically, more drug-related adverse events occurred with the three-drug regimen than with the two-drug regimen (169 [24%] of 717 vs 126 [18%] of 716); few participants discontinued because of adverse events (16 [2%] in the three-drug regimen and 15 [2%] in the two-drug regimen). Two deaths were reported in the two-drug regimen group of GEMINI-2, but neither was considered to be related to the study medication. Interpretation The non-inferior efficacy and similar tolerability profile of dolutegravir plus lamivudine to a guideline-recommended three-drug regimen at 48 weeks in ART-naive adults supports its use as initial therapy for patients with HIV-1 infection. Funding ViiV Healthcare.

Background Previous studies suggest that nonnucleoside reverse-transcriptase inhibitors (NNRTIs) cause faster virologic suppression, while ritonavir-boosted protease inhibitors (PI/r) recover more CD4 cells. However, individual trials have not been powered to compare clinical outcomes. Methods We searched databases to identify randomized trials that compared NNRTI- vs PI/r-based initial therapy. A metaanalysis calculated risk ratios (RRs) or mean differences (MDs), as appropriate. Primary outcome was death or progression to AIDS. Secondary outcomes were death, progression to AIDS, and treatment discontinuation. We calculated RR of virologic suppression and MD for an increase in CD4 cells at week 48. Results We included 29 trials with 9047 participants. Death or progression to AIDS occurred in 226 participants in the NNRTI arm and in 221 in the PI/r arm (RR, 1.03; 95% confidence interval, .87-1.22; 12 trials; n = 3825), death in 205 participants in the NNRTI arm vs 198 in the PI/r arm (1.04; 0.86-1.25; 22 trials; n = 8311), and progression to AIDS in 140 participants in the NNRTI arm vs 144 in the PI/r arm (1.00; 0.80-1.25; 13 trials; n = 4740). Overall treatment discontinuation (1.12; 0.93-1.35; 24 trials; n = 8249) and from toxicity (1.21; 0.87-1.68; 21 trials; n = 6195) were comparable, but discontinuation due to virologic failure was more common with NNRTI (1.58; 0.91-2.74; 17 trials; n = 5371). At week 48, there was no difference between NNRTI and PI/r in virologic suppression (RR, 1.03; 0.98-1.09) or CD4(+) recovery (MD, -4.7 cells; -14.2 to 4.8). Conclusions We found no difference in clinical and viro-immunologic outcomes between NNRTI- and PI/r-based therapy.

Background. Alternative combination antiretroviral therapies in virologically suppressed human immunodeficiency virus (HIV)-infected patients experiencing side effects and/or at ongoing risk of important comorbidities from current therapy are needed. Maraviroc (MVC), a chemokine receptor 5 antagonist, is a potential alternative component of therapy in those with R5-tropic virus. Methods. The Maraviroc Switch Study is a randomized, multicenter, 96-week, open-label switch study in HIV type 1-infected adults with R5-tropic virus, virologically suppressed on a ritonavir-boosted protease inhibitor (PI/r) plus double nucleoside/nucleotide reverse transcriptase inhibitor (2 N(t)RTI) backbone. Participants were randomized 1:2:2 to current combination antiretroviral therapy (control), or replacing the protease inhibitor (MVC + 2 N(t)RTI arm) or the nucleoside reverse transcriptase inhibitor backbone (MVC + PI/r arm) with twice-daily MVC. The primary endpoint was the difference (switch minus control) in proportion with plasma viral load (VL)

The growing elderly population of HIV-infected patients is leading to a significant epidemiological transition and HIV infection has been proposed as a premature and accelerated aging model rending the individual more susceptible to premature disability. However, the determinants of disability among this emergent population are still lacking. Therefore, the aim of this study is to determine the correlates of prevalent disability in adults ≥50 years with HIV infection. A cross-sectional study of 184 HIV-infected adults receiving ambulatory care in an HIV clinic of a tertiary care, university-affiliated hospital in Mexico City was conducted. Disability for instrumental (IADL) and basic activities of daily living (ADL) was established. Sociodemographic factors, clinical variables, current CD4(+) cell count, and HIV viral load (VL) were tested as potential determinants of disability. Multivariate logistic regression analyses were used to identify the correlates of both types of disability. The mean age was 59.3 years. All participants were receiving highly active antiretroviral therapy. Of participants 17.9% had disability for IADL and 26.1% for ADL. Multivariate logistic regression analyses indicated that being older; having a lower CD4(+) cell count, and having a detectable HIV VL were independently associated with both types of disability. In addition, educational level was also independently associated with ADL disability. Age, educational level, low CD4(+) cell count, and detectable HIV VL were independently associated with disability. Whether effective and timely antiretroviral therapy will reduce the risk of disability in HIV-infected elderly patients needs to be evaluated.

Reversal of monocyte and macrophage activation and the relationship to viral suppression and T cell activation are unknown in patients with advanced HIV-1 infection, initiating antiretroviral therapy. This study aimed to determine whether reduction in biomarkers of monocyte and macrophage activation would be reduced in conjunction with viral suppression and resolution of T cell activation. Furthermore, we hypothesized that the addition of CCR5 antagonism (by maraviroc) would mediate greater reduction of monocyte/macrophage activation markers than suppressive antiretroviral therapy alone. In the CCR5 antagonism to decrease the incidence of immune reconstitution inflammatory syndrome study, antiretroviral therapy-naïve patients received maraviroc or placebo in addition to standard antiretroviral therapy. PBMCs and plasma from 65 patients were assessed during 24 wk of antiretroviral therapy for biomarkers of monocyte and macrophage activation. Markers of monocyte and macrophage activation were reduced significantly by 24 wk, including CD14++CD16+ intermediate monocytes (P < 0.0001), surface CD163 (P = 0.0004), CD169 (P < 0.0001), tetherin (P = 0.0153), and soluble CD163 (P < 0.0001). A change in CD38+, HLA-DR+ CD8 T cells was associated with changes in CD169 and tetherin expression. Maraviroc did not affect biomarkers of monocyte/macrophage activation but resulted in greater percentages of CCR5-positive monocytes in PBMC. HIV-1 suppression after 24 wk of antiretroviral therapy, with or without maraviroc, demonstrates robust recovery in monocyte subset activation markers, whereas soluble markers of activation demonstrate minimal decrease, qualitatively differentiating markers of monocyte/macrophage activation in advanced disease.

We aimed to quantify the proportion of people receiving care for HIV-infection that are 50 years or older (older HIV patients) in Latin America and the Caribbean between 2000 and 2015 and to estimate the contribution to the growth of this population of people enrolled before (

Objectives The longer survival of patients with human immunodeficiency virus/acquired immunodeficiency syndrome and the introduction of the highly active antiretroviral therapy have increased the number of chronic conditions; among these, cardiovascular diseases. The aim of this study is to determine patient, disease, and factors associated with peripheral arterial disease in a population of patients with human immunodeficiency virus/acquired immunodeficiency syndrome. Methods A prospective nested case–control study of a cohort of patients with human immunodeficiency virus/acquired immunodeficiency syndrome was conducted in a tertiary medical center in Mexico City. A sample size of 206 patients was calculated. Medical history, relevant laboratory data, peripheral arterial exam, and screening ankle-brachial index tests were obtained. Results The prevalence of abnormal ankle-brachial indexes was 20% (42 patients). Patient’s mean age was 44 years ±13. The majority (98.5%) were actively receiving highly active antiretroviral therapy; active smoking was reported in 55 (27%), arterial hypertension and type 2 diabetes mellitus were found in 24 (12%) and 22 (11%) patients. Median time from the human immunodeficiency virus diagnosis was eight years (Interquartile range ±11); the mean CD4 count was 481, with a mean viral load of 13,557 copies (SD ± 69025.27) and 1889.18 (SD ± 9052.77) for patients with normal and abnormal ankle-brachial index and a median of 40 (IQ ± 2). Viral load ( p = 0.04) and number of years with human immunodeficiency virus/acquired immunodeficiency syndrome ( p = 0.04) were significantly associated with abnormal ankle-brachial indexes. Conclusions Abnormal ankle-brachial index seems to be more frequent in Mexican patients with human immunodeficiency virus/acquired immunodeficiency syndrome when compared with the general population at the same age. The most important factors associated with arterial disease were the viral load and the number of years with human immunodeficiency virus/acquired immunodeficiency syndrome. Trial Registration: ClinicalTrials.gov NCT02264509.

Objectives Optimizing antiretroviral drug combination on an individual basis can be challenging, particularly in settings with limited access to drugs and genotypic resistance testing. Here we describe our latest computational models to predict treatment responses, with or without a genotype, and compare their predictive accuracy with that of genotyping. Methods Random forest models were trained to predict the probability of virological response to a new therapy introduced following virological failure using up to 50 000 treatment change episodes (TCEs) without a genotype and 18 000 TCEs including genotypes. Independent data sets were used to evaluate the models. This study tested the effects on model accuracy of relaxing the baseline data timing windows, the use of a new filter to exclude probable non-adherent cases and the addition of maraviroc, tipranavir and elvitegravir to the system. Results The no-genotype models achieved area under the receiver operator characteristic curve (AUC) values of 0.82 and 0.81 using the standard and relaxed baseline data windows, respectively. The genotype models achieved AUC values of 0.86 with the new non-adherence filter and 0.84 without. Both sets of models were significantly more accurate than genotyping with rules-based interpretation, which achieved AUC values of only 0.55–0.63, and were marginally more accurate than previous models. The models were able to identify alternative regimens that were predicted to be effective for the vast majority of cases in which the new regimen prescribed in the clinic failed. Conclusions These latest global models predict treatment responses accurately even without a genotype and have the potential to help optimize therapy, particularly in resource-limited settings.

Summary Combination antiretroviral therapy (ART), also known as highly active antiretroviral therapy, provides clinical and immunological benefits for people living with HIV and is an effective strategy to prevent HIV transmission at the individual level. Early initiation of ART as part of a test and treat approach might decrease HIV transmission at the population level, but to do so the HIV continuum of care, from diagnosis to viral suppression, should be optimised. Access to ART has improved greatly in Latin America, and about 600 000 people are on treatment. However, health-care systems are deficient in different stages of the HIV continuum of care, and in some cases only a small proportion of individuals achieve the desired outcome of virological suppression. At present, data for most Latin American countries are not sufficient to build reliable metrics. Available data and estimates show that many people living with HIV in Latin America are unaware of their status, are diagnosed late, and enter into care late. Stigma, administrative barriers, and economic limitations seem to be important determinants of late diagnosis and failure to be linked to and retained in care. Policy makers need reliable data to optimise the HIV care continuum and improve individual-based and population-based outcomes of ART in Latin America.

Introduction The “greying” of the HIV epidemic necessitates a better understanding of the healthcare needs of older HIV‐positive adults. As these individuals age, it is unclear whether comorbidities and their associated therapies or the ageing process itself alter the response to antiretroviral therapy (ART). In this study, HIV treatment outcomes and corresponding risk factors were compared between older ART initiators and those who were younger using data from the Caribbean, Central and South America Network for HIV Epidemiology (CCASAnet). Methods HIV‐positive adults (≥18 years) initiating ART at nine sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru were included. Patients were classified as older (≥50 years) or younger (

Background Randomized trials have shown increased risk of suicidality associated with efavirenz (EFV). The START (Strategic Timing of Antiretroviral Treatment) trial randomized treatment-naive human immunodeficiency virus (HIV)-positive adults with high CD4 cell counts to immediate vs deferred antiretroviral therapy (ART). Methods The initial ART regimen was selected prior to randomization (prespecified). We compared the incidence of suicidal and self-injurious behaviours (suicidal behavior) between the immediate vs deferred ART groups using proportional hazards models, separately for those with EFV and other prespecified regimens, by intention to treat, and after censoring participants in the deferred arm at ART initiation. Results Of 4684 participants, 271 (5.8%) had a prior psychiatric diagnosis. EFV was prespecified for 3515 participants (75%), less often in those with psychiatric diagnoses (40%) than without (77%). While the overall intention-to-treat comparison showed no difference in suicidal behavior between arms (hazard ratio [HR], 1.07, P = .81), subgroup analyses suggest that initiation of EFV, but not other ART, is associated with increased risk of suicidal behavior. When censoring follow-up at ART initiation in the deferred group, the immediate vs deferred HR among those who were prespecified EFV was 3.31 (P = .03) and 1.04 (P = .93) among those with other prespecified ART; (P = .07 for interaction). In the immediate group, the risk was higher among those with prior psychiatric diagnoses, regardless of prespecified treatment group. Conclusions Participants who used EFV in the immediate ART group had increased risk of suicidal behavior compared with ART-naive controls. Those with prior psychiatric diagnoses were at higher risk.

Background In Latin America, the first wave of HIV-infected patients initiated highly active antiretroviral therapy (HAART) 10 or more years ago. Characterizing their treatment experience and corresponding outcomes across a decade of HAART may yield insights relevant to the ongoing care of such patients and those initiating HAART more recently in similar clinical settings. Methods This retrospective study included adults initiating HAART before 2004 at 8 sites in Argentina, Brazil, Chile, Haiti, Honduras, and Mexico. Patient status (in care, dead, or lost to follow-up [LTFU]) was assessed at 6-month intervals for 10 years, along with CD4 count and HIV-1 viral load (VL) for patients in care. Results 4,975 patients (66% male) started HAART prior to 2004; 45% were not antiretroviral-naive. At 1, 5, and 10 years, rates of mortality were 4.2%, 9.0%, and 13.6% respectively. LTFU rates for the same periods were 2.4%, 10.9%, and 24.2%. Among patients remaining in care at 10 years, 84.4% were estimated to have VL≤400 copies/mL (Haiti excluded) and median baseline CD4 increased from 158 to 525 cells/mm3. Only 11.4% of all patients remained on their first regimen, 12.6% were on their second, 11.5% were on their third, and 23.0% were on their fourth or subsequent regimen. Outcomes were generally better for patients who were not antiretroviral-naive, except for viral suppression. Heterogeneity among sites was substantial. Conclusions Despite advanced disease and predominant use of older antiretrovirals, a large percentage of early HAART initiators in this Latin American cohort were alive and in care with sustained virologic suppression and progressive immune recovery after 10 years.

Summary Background Observational data have been conflicted regarding the potential role of HIV antiretroviral therapy (ART) as a causative factor for, or protective factor against, COPD. We therefore aimed to investigate the effect of immediate versus deferred ART on decline in lung function in HIV-positive individuals. Methods We did a nested substudy within the randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial at 80 sites in multiple settings in 20 high-income and low-to-middle-income countries. Participants were HIV-1 infected individuals aged at least 25 years, naive to ART, with CD4 T-cell counts of more than 500 per μL, not receiving treatment for asthma, and without recent respiratory infections (baseline COPD was not an exclusion criterion). Participants were randomly assigned to receive ART (an approved drug combination derived from US Department of Health and Human Services guidelines) either immediately, or deferred until CD4 T-cell counts decreased to 350 per μL or AIDS developed. The randomisation was determined by participation in the parent START study, and was not specific to the substudy. Because of the nature of our study, site investigators and participants were not masked to the treatment group assignment; however, the assessors who reviewed the outcomes were masked to the treatment group. The primary outcome was the annual rate of decline in lung function, expressed as the FEV 1 slope in mL/year; spirometry was done annually during follow-up for up to 5 years. We analysed data on an intention-to-treat basis, and planned separate analyses in smokers and non-smokers because of the known effects of smoking on FEV 1 decline. The substudy was registered at ClinicalTrials.gov number NCT01797367. Findings Between March 11, 2010, and Aug 23, 2013, we enrolled 1026 participants to our substudy, who were then randomly assigned to either immediate (n=518) or deferred (n=508) ART. Median baseline characteristics included age 36 years (IQR 30–44), CD4 T-cell count 648 per μL (583–767), and HIV plasma viral load 4·2 log 10 copies per mL (3·5–4·7). 29% were female and 28% were current smokers. Median follow-up time was 2·0 years (IQR 1·9–3·0). We noted no differences in FEV 1 slopes between the immediate and deferred ART groups either in smokers (difference of −3·3 mL/year, 95% CI −38·8 to 32·2; p=0·86) or in non-smokers (difference of −5·6 mL/year, −29·4 to 18·3; p=0·65) or in pooled analyses adjusted for smoking status at each study visit (difference of −5·2 mL/year, −25·1 to 14·6; p=0·61). Interpretation The timing of ART initiation has no major short-term effect on rate of lung function decline in HIV-positive individuals who are naive to ART, with CD4 T-cell counts of more than 500 per μL. In light of updated WHO recommendations that all HIV-positive individuals should be treated with ART, regardless of their CD4 T-cell count, our results suggest an absence of significant pulmonary harm with such an approach. Funding US National Heart Lung and Blood Institute, US National Institute of Allergy and Infectious Diseases, Division of AIDS, Agence Nationale de Recherches sur le SIDA et les Hipatites Virales (France), Australian National Health and Medical Research Council, Danish National Research Foundation, European AIDS Treatment Network, German Ministry of Education and Research, UK Medical Research Council and National Institute for Health Research, and US Veterans Health Administration Office of Research and Development.

Introduction : Maps are powerful tools for visualization of differences in health indicators by geographical region, but multi-country maps of HIV indicators do not exist, perhaps due to lack of consistent data across countries. Our objective was to create maps of four HIV indicators in North, Central, and South American countries. Methods : Using data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) and the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet), we mapped median CD4 at presentation for HIV clinical care, proportion retained in HIV primary care, proportion prescribed antiretroviral therapy (ART), and the proportion with suppressed plasma HIV viral load (VL) from 2010 to 2012 for North, Central, and South America. The 15 Canadian and US clinical cohorts and 7 clinical cohorts in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru represented approximately 2–7% of persons known to be living with HIV in these countries. Results : Study populations were selected for each indicator: median CD4 at presentation for care was estimated among 14,811 adults; retention was estimated among 87,979 adults; ART use was estimated among 84,757 adults; and suppressed VL was estimated among 51,118 adults. Only three US states and the District of Columbia had a median CD4 at presentation >350 cells/mm 3 . Haiti, Mexico, and several states had >85% retention in care; lower (50–74%) retention in care was observed in the US West, South, and Mid-Atlantic, and in Argentina, Brazil, and Peru. ART use was highest (90%) in Mexico. The percentages of patients with suppressed VL in the US South and Northeast were lower than in most of Central and South America. Conclusions : These maps provide visualization of gaps in the quality of HIV care and allow for comparison between and within countries as well as monitoring policy and programme goals within geographical boundaries. Keywords: Map; HIV indicators; CD4 T-lymphocyte count; retention in care; antiretroviral therapy; HIV RNA suppression; North America; Central America; South America; implementation science. To access the supplementary material to this article please see Supplementary Files in the column to the right (under Article Tools). (Published: 4 April 2016) Citation: Althoff KN et al. Journal of the International AIDS Society 2016, 19 :20707 http://www.jiasociety.org/index.php/jias/article/view/20707 | http://dx.doi.org/10.7448/IAS.19.1.20707

OBJECTIVE: To evaluate the prevalence of late HIV diagnosis (CD4OBJETIVO: Estimar la prevalencia de diagnóstico tardío (DT) (CD4

Summary Objectives To estimate the impact of immune reconstitution inflammatory syndrome (IRIS) on morbidity and mortality in patients starting highly-active antiretroviral therapy (HAART). Methods A retrospective cohort study of HIV-positive patients starting HAART was conducted at a tertiary care referral center in Mexico City. We estimated the incidence of IRIS, hospitalizations and death rates during the first 2 years of HAART. The relative risk of death (RR) and hospitalization for patients with IRIS were adjusted for relevant covariates using regression methods. Results During the 2-year follow-up period, 27% of patients developed IRIS (14 IRIS cases per 100 person-years). The relative risk of death among patients who developed IRIS was 3 times higher (95% confidence interval (CI) 1.19–7.65, p = 0.03). After adjusting for previous opportunistic infections we still observed a higher death rate among patients with IRIS (RR 2.3, 95% CI 0.9–5.9, p =0.09). An effect modification of IRIS over mortality was observed by previous opportunistic infection. Conclusions IRIS-associated mortality is strongly confounded by previous opportunistic infection. Patients with AIDS who eventually developed IRIS had the highest risk of death at the 2-year follow-up.

The life expectancy of people living with HIV has dramatically improved with the much increased access to antiretroviral therapy. Consequently, a larger number of people living with HIV are living longer and facing the increased burden of noncommunicable diseases (NCDs). NCDs and HIV infection share common epidemiologic and sociodemographic characteristics that influence their outcomes, which may be difficult to address in the relatively weak health systems of the region. Data on the prevalence and interactions of NCDs and HIV in Latin American countries remain very limited, which hinders their governments’ ability to make informed decisions about health care policies. Therefore, there is an urgent need to develop a research agenda that will be the basis for an integrated and comprehensive health care approach to HIV and NCD comorbidities in Latin America.

Background: The MERIT study evaluated maraviroc versus efavirenz, both with zidovudine/lamivudine, in treatment-naive patients with CCR5-tropic (R5) HIV-1. Post hoc analyses previously assessed week 48 outcomes in patients rescreened with R5 virus by a more sensitive tropism assay. Methods: Week 96 efficacy (post hoc, n = 614) and safety (n = 721) were assessed. Results: Proportions of subjects

HIV infection is characterized by persistent immune activation, increased production of proinflammatory cytokines, and rapid T cell turnover. The autonomic nervous system exerts a regulatory effect on the inflammatory response mediated by acetylcholine. We investigated whether an acetylcholine esterase inhibitor would diminish the T cell overactive phenotype characteristic of chronically infected HIV patients. We carried out a proof-of-concept, placebo-controlled study involving 19 subjects chronically infected with HIV-1. Nine patient received pyridostigmine and 10 took a placebo. T cell activation measured by expression of CD69 (p = 0.025) diminished in those taking pyridostigmine. The drug also diminished in vitro T cell proliferation induced by PMA and ionomycin (p = 0.026). IFN-gamma release was diminished in the pyridostigmine group (p = 0.016) and expression of IL-4 (p = 0.010) and IL-10 (p = 0.015) increased. Here we showed that pyridostigmine is able to modify T cell overactivation and proliferation in patients chronically infected with HIV. Pyridostigmine led to an increase in the antiinflammatory cytokine IL-10 and a decrease in T cell proliferation and production of the proinflammatory cytokine IFN-gamma.

Background In Latin America, insufficient data are available to improve local admission policies for human immunodeficiency virus (HIV) patients in the intensive care units (ICU). We undertook this study to evaluate the outcome and survival determinants of HIV patients in a Mexican ICU during three time periods. Methods From December 1985 through January 2006, a clinical chart-based, retrospective study of all HIV patients admitted to the ICU was conducted. Demographic, clinical and laboratory data; disease severity score (APACHE II) and mortality were evaluated. A comprehensive database was created and data were analyzed using survival and regression models. Results Ninety HIV patients were admitted to the ICU during the study: 16 (18%) in 1985–1992 (non-antiretroviral [ARV]-period), 21 (23%) in 1993–1996 (ARV-period), and 53 (58%) in 1996–2006 (highly active antiretroviral treatment [HAART] period). Leading reasons for admission were the need for mechanical ventilatory support (MVS, 85.5%), septic shock (23%), and non-HIV/AIDS complications (15.5%). Survival in the ICU increased from 12.5% (non-ARV period) to 57% (HAART period). Mortality during ICU stay was associated with MVS (HR: 3.2; 95% CI 1.0–10.2) and APACHE II ≥13 points (HR: 2.2; 95% CI 1.3–4.0). Use of steroids (HR: 0.4; 95% CI 0.2–0.8) and HAART (HR: 0.25; 95% CI 0.1–0.5) were associated with a lower risk of death. In multivariate analysis, septic shock was the main predictor of death in the ICU (HR: 2.4; 95% CI 1.1–5.2) and after discharge. HAART remained as a significant protective factor. Conclusions Overall survival in Mexican HIV patients admitted to an ICU has substantially increased in recent years. These data should encourage policies that consider HIV patients as good candidates for receiving intensive care.

A cross-sectional analysis was conducted in Mexico City from September 1989 to March 1996, to determine the prevalence of HIV-related oral manifestations by gender and route of HIV transmission. The diagnosis of HIV-associated oral lesions was based on preestablished criteria. For the statistical analysis chi-squared and Fisher's exact tests were used where appropriate. Odds ratios were calculated as estimates of the relative risks. Control of confounding factors was performed by logistic regression models. Oral lesions were present in 75% of 436 HIV+ patients. Hairy leukoplakia, erythematous and pseudomembranous candidosis, angular cheilitis and oral ulcers were frequently found. Patients who contracted HIV through blood transfusion were more likely to present erythematous candidosis (P=0.005) than subjects who acquired HIV through sexual transmission. Oral ulcers were seen only in men (P=0.02) and in individuals who contracted HIV through sexual transmission (P=0.02). This study brings valuable data in regard to differences in the type and prevalence of HIV-related oral lesions by gender and the risk categories analysed, particularly blood transfusion.A cross-sectional analysis conducted in Mexico City, Mexico, in 1989-96 investigated the prevalence of HIV-related oral manifestations by gender and route of HIV transmission. The 436 HIV-positive patients enrolled in this study were part of a larger, ongoing study conducted through the Infectious Diseases Clinic in Mexico City. The primary mode of HIV transmission was blood transfusion among female respondents (63%) and sexual activity among male respondents (90%). 71% of subjects had at least 1 (mean, 1.3) HIV-related oral lesion, including hairy leukoplakia, erythematous and pseudomembranous candidosis, angular cheilitis, and oral ulcers. Candidosis, pseudomembranous candidosis, hairy leukoplakia, exfoliative cheilitis, and xerostomia were all significantly associated with a CD4 count under 200 cells/cu. mm and were more prevalent among those with advanced HIV disease. Oral ulcers were present only in men. Women had a higher prevalence than men of hyperpigmentation (10.5% vs. 4%) and xerostomia (7% vs. 2%), but these differences were not significant. Multivariate analysis revealed a significant association between erythematous candidosis and blood transfusion, even after controlling for gender, clinical stage, CD4 count, antiretroviral therapy, smoking history, and xerostomia.

International audience; PURPOSE:The maraviroc (MVC) expanded access program (EAP) was initiated to increase MVC availability to patients with limited treatment options. Darunavir (DRV), raltegravir (RAL), and etravirine (ETV) were either recently approved or under regulatory review at study initiation and available for coadministration with MVC. Thus, the safety of MVC in combination with new antiretroviral therapies (ARVs) could be assessed. This open-label safety study of MVC was conducted at 262 sites worldwide in 1032 R5 HIV-positive treatment-experienced patients with limited/no therapeutic options.METHODS:Study visits included screening, baseline, end of study or early discontinuation, and follow-up 30 days after last dose. Interim visits for HIV-1 RNA and CD4 cell counts occurred according to local HIV infection management guidelines. Safety data were analyzed overall and by subgroup based on ARV combination [MVC+optimized background therapy (OBT), MVC ± OBT+DRV/r, MVC ± OBT+RAL, MVC ± OBT+RAL+DRV/r, MVC ± OBT+RAL+ETV ± DRV/r].RESULTS:Most (90.3%) adverse events (AEs) were of mild or moderate severity with few grade 3/4 events, discontinuations, or temporary discontinuations/dose reductions due to AEs or serious AEs. Similar results were observed across subgroups. Of treated patients, 79.9% and 50% had HIV-1 RNA

Introduction : Long-term survival of HIV patients after initiating highly active antiretroviral therapy (ART) has not been sufficiently described in Latin America and the Caribbean, as compared to other regions. The aim of this study was to describe the incidence of mortality, loss to follow-up (LTFU) and associated risk factors for patients enrolled in the Caribbean, Central and South America Network (CCASAnet). Methods : We assessed time from ART initiation (baseline) to death or LTFU between 2000 and 2014 among ART-naive adults (≥18 years) from sites in seven countries included in CCASAnet: Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru. Kaplan-Meier techniques were used to estimate the probability of mortality over time. Risk factors for death were assessed using Cox regression models stratified by site and adjusted for sex, baseline age, nadir pre-ART CD4 count, calendar year of ART initiation, clinical AIDS at baseline and type of ART regimen. Results : A total of 16,996 ART initiators were followed for a median of 3.5 years (interquartile range (IQR): 1.6–6.2). The median age at ART initiation was 36 years (IQR: 30–44), subjects were predominantly male (63%), median CD4 count was 156 cells/µL (IQR: 60–251) and 26% of subjects had clinical AIDS prior to starting ART. Initial ART regimens were predominantly non-nucleoside reverse transcriptase inhibitor based (86%). The cumulative incidence of LTFU five years after ART initiation was 18.2% (95% confidence interval (CI) 17.5–18.8%). A total of 1582 (9.3%) subjects died; the estimated probability of death one, three and five years after ART initiation was 5.4, 8.3 and 10.3%, respectively. The estimated five-year mortality probability varied substantially across sites, from 3.5 to 14.0%. Risk factors for death were clinical AIDS at baseline (adjusted hazard ratio (HR)=1.65 (95% CI 1.47–1.87); p

OBJECTIVE: To estimate the impact of late ART initiation on HIV transmission among men who have sex with men (MSM) in Mexico. METHODS: An HIV transmission model was built to estimate the number of infections transmitted by HIV-infected men who have sex with men (MSM-HIV+) MSM-HIV+ in the short and long term. Sexual risk behavior data were estimated from a nationwide study of MSM. CD4+ counts at ART initiation from a representative national cohort were used to estimate time since infection. Number of MSM-HIV+ on treatment and suppressed were estimated from surveillance and government reports. Status quo scenario (SQ) and scenarios of early ART initiation and increased HIV testing were modeled. RESULTS: We estimated 14239 new HIV infections per year from MSM-HIV+ in Mexico. In SQ MSM take an average 7.4 years since infection to initiate treatment with a median CD4+ count of 148 cells/mm3(25th-75th percentiles 52-266). In SQ 68% of MSM-HIV+ are not aware of their HIV status and transmit 78% of new infections. Increasing the CD4+ count at ART initiation to 350 cells/mm3 shortened the time since infection to 2.8 years. Increasing HIV testing to cover 80% of undiagnosed MSM resulted in a reduction of 70% in new infections in 20 years. Initiating ART at 500 cells/mm3 and increasing HIV testing the reduction would be of 75% in 20 years. CONCLUSION: A substantial number of new HIV infections in Mexico are transmitted by undiagnosed and untreated MSM-HIV+. An aggressive increase in HIV testing coverage and initiating ART at a CD4 count of 500 cells/mm3 in this population would significantly benefit individuals and decrease the number of new HIV infections in Mexico.

Nearly 2 million people are infected with human immunodeficiency virus (HIV) in Latin America. However, information regarding population-scale outcomes from a regional perspective is scarce. We aimed to describe the baseline characteristics and therapeutic outcomes of newly-treated individuals with HIV infection in Latin America. A Retrospective cohort study was undertaken. The primary explanatory variable was combination antiretroviral therapy based on either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). The main outcome was defined as the composite of all-cause mortality and the occurrence of an AIDS-defining clinical event or a serious non-AIDS-defining event during the first year of therapy. The secondary outcomes included the time to a change in treatment strategy. All analyses were performed according to the intention to treat principle. A total of 937 treatment-naive patients from four participating countries were included (228 patients with PI therapy and 709 with NNRTI–based treatment). At the time of treatment initiation, the patients had a mean age of 37 (SD: 10) years and a median CD4 + T-cell count of 133 cells/mm3 (interquartile range: 47.5–216.0). Patients receiving PI-based regimens had a significantly lower CD4 + count, a higher AIDS prevalence at baseline and a shorter time from HIV diagnosis until the initiation of treatment. There was no difference in the hazard ratio for the primary outcome between groups. The only covariates associated with the latter were CD4 + cell count at baseline, study site and age. The estimated hazard ratio for the time to a change in treatment (NNRTI vs PI) was 0.61 (95% CI 0.47–0.80, p

Background Anal cancer has become one of the most common non-AIDS-defined tumors among Human Immunodeficiency Virus-positive (HIV+) individuals, and a rise in its incidence among HIV+ Men who have Sex with Men (MSM) has been shown, despite the introduction of Highly Active Anti-Retroviral Therapy (HAART). Human Papillomavirus (HPV) infections are highly prevalent among HIV+ MSM and recent studies have shown high rates of HPV-associated anal intraepithelial neoplasia (AIN) and anal cancer among this population. Methods In the present study we determined the prevalence and nature of HPV co-infections in the anal canal of 324 HIV+ MSM attending a high specialty medical center in Mexico City, DNA extraction and amplification with generic primers for HPV was performed, followed by detection of specific types and co-infections with INNO-Lipa, and identification of variants by amplification and sequencing of the E6 and LCR region of HPV 16. Results We found a very high prevalence of HPV infections among this cohort (86%), with more than one fourth of them (28%) positive for type 16. Among HPV16-positive patients, European variants were the most prevalent, followed by Asian-American ones. Among these individuals (HPV-16+), we identified co-infections with other 21 HPV types namely; 11, 51, 52, 6, 66, 68, 74, 18, 45, 35, 26, 44, 70, 53, 54, 82, 31, 33, 56, 58, 59. Conclusions HIV+ MSM show a very high rate of HPV infections in the anal canal and those with type 16 exhibited a multiplicity of associated types. This study emphasizes the need for an early detection of HPV infections among HIV+ MSM in order to establish its utility to prevent anal neoplasia and cancer. Electronic supplementary material The online version of this article (doi:10.1186/s12879-014-0671-4) contains supplementary material, which is available to authorized users.

SETTING: Drug resistance threatens tuberculosis (TB) control, particularly among human immunodeficiency virus (HIV) infected persons.OBJECTIVE: To describe practices in the prevention and management of drug-resistant TB under antiretroviral therapy (ART) programs in lower-income countries.DESIGN: We used online questionnaires to collect program-level data on 47 ART programs in Southern Africa (n = 14), East Africa (n = 8), West Africa (n = 7), Central Africa (n = 5), Latin America (n = 7) and the Asia-Pacific (n = 6 programs) in 2012. Patient-level data were collected on 1002 adult TB patients seen at 40 of the participating ART programs.RESULTS: Phenotypic drug susceptibility testing (DST) was available in 36 (77%) ART programs, but was only used for 22% of all TB patients. Molecular DST was available in 33 (70%) programs and was used in 23% of all TB patients. Twenty ART programs (43%) provided directly observed therapy (DOT) during the entire course of treatment, 16 (34%) during the intensive phase only, and 11 (23%) did not follow DOT. Fourteen (30%) ART programs reported no access to second-line anti-tuberculosis regimens; 18 (38%) reported TB drug shortages.CONCLUSIONS: Capacity to diagnose and treat drug-resistant TB was limited across ART programs in lower-income countries. DOT was not always implemented and drug supplies were regularly interrupted, which may contribute to the global emergence of drug resistance.

In developing countries, the variations in the clinical spectrum of human immunodeficiency virus (HIV)-related oral lesions over time, and the possible effects of antiretroviral therapy, have not been described. In this study we evaluate the clinical spectrum of oral lesions in a series of HIV-infected patients when first examined at the acquired immunodeficiency syndrome (AIDS) clinic of a tertiary care institution in Mexico City, Mexico, and the changes observed over 12 years. All HIV-infected adult patients had an oral examination performed by specialists in oral pathology and medicine who used established clinical diagnostic criteria for oral lesions. Four periods were defined according to the evolving pattern of antiretroviral use: the first 2 were before the introduction of highly active antiretroviral therapy (HAART) and the last 2 were during more established use of HAART. For the statistical analysis the chi-square test for contingency tables and the chi-square test for trend were utilized. For dimensional variables, except age, the Kruskal-Wallis or Mann-Whitney rank sum tests were used when applicable and trend was tested with the Spearman correlation coefficient. Age was tested through analysis of variance (ANOVA) and linear regression analysis. Alpha value was set at p = 0.05 for each test. In the 12-year study, 1,000 HIV-infected patients were included (87.9% male). At the baseline examination, oral lesions strongly associated with HIV were present in 47.1% of HIV-infected patients. Oral candidosis (31.6%), hairy leukoplakia (22.6%), erythematous candidosis (21.0%), and pseudomembranous candidosis (15.8%) were the most frequent lesions. Oral Kaposi sarcoma (2.3%), HIV-associated periodontal disease (1.7%), and oral non-Hodgkin lymphoma (0.1%) were less frequent. HIV-related oral lesions decreased systematically-by half during the course of the 4 study periods (p < 0.001). Except for Kaposi sarcoma, all oral lesions strongly associated with HIV showed a trend to decrease significantly during the study period. No apparent variation in the occurrence of salivary gland disease or human papillomavirus-associated oral lesions was found. A significant trend to a lower prevalence was observed in the group of patients who were already taking antiretroviral therapy, non-HAART and HAART (p < 0.001 and p = 0.004, respectively). Only a discrete reduction, barely significant, was noted among untreated patients (p = 0.060). By Period IV (1999-2001), those who received HAART showed the lowest prevalence of oral lesions strongly associated with HIV (p < 0.001). Patients with oral lesions strongly associated with HIV had significantly lower median CD4+ counts and higher viral loads than those without oral lesions strongly associated with HIV (p < 0.001 and p = 0.005, respectively). When CD4+ counts were correlated with prevalence of oral candidosis, a consistently negative association was found; this association prevailed even after the study group was partitioned according to period. In this selected cohort of 1,000 patients with HIV infection, the clinical spectrum of HIV-related oral lesions has changed over the 12-year study, with a decreased prevalence of most oral lesions. Our findings probably represent improvements in medical care of HIV-infected persons, earlier detection of HIV-infected patients at the AIDS clinic, the increasing use of prophylactic drugs to prevent secondary AIDS-related opportunistic infections, and, perhaps most important, the availability of potent antiretroviral therapy in recent years, since the introduction of HAART.

We compared immune phenotypes, lymphocyte proliferation (LP), and delayed type hypersensitivity (DTH) responses in 28 male antiretroviral treatment-naive and experienced HIV-1-infected patients, matched pair-wise according to age and CD4 + T-lymphocyte count. Median CD4 + T-lymphocyte counts were 441 cells/μL and 483 cells/μL and median CD4 + T-lymphocyte nadirs were 435 cells/μL and 150 cells/μL in both groups, respectively. Absolute numbers of circulating T-lymphocyte subpopulations and proportions of naive and memory T-lymphocytes were comparable in the two groups. Untreated patients had greater proportions of activated CD4 + (p

HIV infection in women is a growing problem in developing countries. Risk factors for HIV infection vary from country to country and may change with time.We describe a retrospective review of the epidemiologic characteristics and associated gynecologic diseases of all HIV-infected women seen at two tertiary-care hospitals in Mexico City.One hundred thirty consecutive patients were included in the study from March 1985 to January 1996. Mean age at HIV diagnosis was 36.2 years (range: 16-76). Of the 75 women diagnosed with AIDS prior to 1992, 58 (69%) were infected through blood transfusion and 17 (20%) through sexual contact. After January 1992, 11 (23%) acquired infection through blood transfusion and 28 (60%) through sexual contact; these differences were statistically significant (p0.0001). Prior to 1992, 66 (90%) women presented in stage IV, whereas after that year only 29 (51%) (p0.001) presented in stage IV. Of 92 patients on whom a cervico-vaginal smear was carried out, human papillomavirus infection was identified in 22 (24%) women, nine (9.8%) had morphologic evidence of a cervical intraepithelial neoplasia (four with mild or moderate dysplasia and five with in situ cervical carcinoma). Four patients had invasive cervical carcinoma.The main risk factor for HIV infection in Mexican women with AIDS changed from transfusion acquired to sexually acquired in 1992. As a country, we were successful in providing safe blood but failed to prevent sexual transmission. Our patients had a high frequency of cervical carcinoma and precursor lesions associated with human papilloma virus.

To establish the characteristics and causes of death of HIV patients who die while hospitalized.We included HIV+ patients who died during hospitalization, in three hospitals in Mexico City between 2010 and 2013. Sociodemographic and clinical data were collected as well as causes of death. We identified preventable deaths (defined as deaths that occurred in patients with less than six months of HAART, or without HAART, with less than 350 CD4 at diagnosis and/or opportunistic events as the cause of hospitalization).128 deaths were analyzed. The median of CD4 count was 47 cells/mm³; 18% of the patients ignored their HIV status at the time of hospitalization, 51% had less than six months of HAART, 40.5% had never received HAART before. The main causes of death were AIDS defining events, with 65.6%. We identified 70 preventable deaths (57%).Despite universal access to HAART, HIV patients in Mexico are still dying of AIDS defining illnesses, an indicator of late diagnosis. It is urgent to implement HIV testing programs to allow earlier diagnosis and make HAART benefit accessible to all.

Summary Background Daily oral triple therapy is effective at halting HIV disease progression, but can have toxic effects and is costly. We investigated whether dual therapy with lopinavir and ritonavir plus lamivudine is non-inferior to standard triple therapy. Methods The GARDEL study (Global AntiRetroviral Design Encompassing Lopinavir/r and Lamivudine vs LPV/r based standard therapy) is a 48 week, phase 3, randomised, controlled, open-label, non-inferiority trial in antiretroviral-therapy-naive adults (age ≥18 years) with documented HIV-1 RNA viral load of at least 1000 copies per mL. The study was done at 19 centres in six countries. Patients were randomly assigned (1:1) to dual therapy or triple therapy by sealed envelopes, in blocks of four, stratified by baseline viral load ( vs ≥100 000 copies per mL). Dual therapy consisted of lopinavir 400 mg and ritonavir 100 mg plus lamivudine 150 mg, both twice daily. Triple therapy consisted of lopinavir 400 mg and ritonavir 100 mg twice daily and lamivudine or emtricitabine plus another nucleoside reverse transcriptase inhibitor (NRTI) in fixed-dose combination. Efficacy was analysed in all participants who received at least one dose of study drug. The primary endpoint was virological response rate, defined as the proportion of patients with HIV RNA less than 50 copies per mL at 48 weeks. Dual therapy was classed as non-inferior to triple therapy if the lower bound of the 95% CI for the difference between groups was no lower than −12%. Patients and investigators were unmasked to treatment allocation. This study is registered with ClinicalTrials.gov, number NCT01237444. Findings Between Dec 10, 2010, and May 15, 2012, 217 patients were randomly assigned to the dual-therapy group and 209 to the triple-therapy group. 198 patients in the dual-therapy group and 175 in the triple-therapy group completed 48 weeks of treatment. At week 48, 189 patients (88·3%) in the dual-therapy group and 169 (83·7%) in the triple-therapy group had viral response (difference 4·6%, 95% CI −2·2 to 11·8; p=0·171). Patients with baseline viral load of at least 100 000 copies per mL showed similar results (87·2% vs 77·9%, respectively; difference 9·3%, 95% CI −2·8 to 21·5; p=0·145). Toxicity-related or tolerability-related discontinuations were more common in the triple-therapy group (n=10 [4·9%]) than in the dual-therapy group (n=1 [0·4%]; difference 4·5%, 95% CI −8·1 to −0·9; p=0·011). 65 adverse events in the dual-therapy group and 88 in the triple-therapy group were possibly or probably drug related (p=0·007). Two serious adverse events occurred, both in the dual-therapy arm, one of which (a case of gastritis) was reported as possibly or probably related to drug treatment. Interpretation Dual therapy with lopinavir and ritonavir plus lamivudine regimen warrants further clinical research and consideration as a potential therapeutic option for antiretroviral-therapy-naive patients. Funding Fundacion Huesped and AbbVie.

The goal of this study was to determine the prevalence of human papillomavirus (HPV) and squamous intraepithelial lesions (SILs) in women infected with human immunodeficiency virus (HIV) in Mexico.Cases included women who were positive for human immunodeficiency virus (HIV) and accepted to participate. There were two control groups in this study: group A, heterosexual partners of HIV+ men; group B, commercial sex workers. Gynecologic examination was performed in all participants. Also, a cervical smear with colposcopy and a sample for detection of HPV DNA by polymerase chain reaction (PCR) were obtained in all subjects, as were CD4+ counts. Relative risks (RR) and 95% confidence interval were calculated.Eighty-five HIV+ women agreed to participate in this study; the route of HIV infection was heterosexual in 78.8%; transfusion in 8.2%; paid donors in 3.5%; and 9.4% unknown. A total of 9 controls were included: 4 from group A and 5 from group B. HPV DNA was detected by PCR in 57 (69%) cases and in 26 (29%) controls from both groups (P0.0001). The RR of HPV infection was 5.5 (2.7-11.5). Also, a significant difference in the prevalence of high-risk HPV types was observed between cases and controls, RR = 12.8 (4.07-42.9). These associations were independent of CD4+ counts and antiretroviral therapy. No association was observed between HIV infection and the risk for high-grade SIL.We observed a high prevalence of oncogenic HPV types in HIV-positive women. These women should be screened regularly for early diagnosis of premalignant lesions and prevention of cervical cancer.

Introduction: HIV-1 plasma viral load during treatment can be highly variable. Thus, there is the need to find a measure of cumulative viremia that can be used to assess both the short- and long-term efficacy of highly active antiretroviral therapy (HAART). Here, we validate a measure of cumulative viremia to evaluate HAART efficacy. Methods: We accessed HAART efficacy using data from a randomized clinical trial conducted in Mexico. We compared the proportion of individuals achieving a viral load

Introduction : Latinos living with HIV in the Americas share a common ethnic and cultural heritage. In North America, Latinos have a relatively high rate of new HIV infections but lower rates of engagement at all stages of the care continuum, whereas in Latin America antiretroviral therapy (ART) services continue to expand to meet treatment needs. In this analysis, we compare HIV treatment outcomes between Latinos receiving ART in North America versus Latin America. Methods : HIV-positive adults initiating ART at Caribbean, Central and South America Network for HIV (CCASAnet) sites were compared to Latino patients (based on country of origin or ethnic identity) starting treatment at North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) sites in the United States and Canada between 2000 and 2011. Cox proportional hazards models compared mortality, treatment interruption, antiretroviral regimen change, virologic failure and loss to follow-up between cohorts. Results : The study included 8400 CCASAnet and 2786 NA-ACCORD patients initiating ART. CCASAnet patients were younger (median 35 vs. 37 years), more likely to be female (27% vs. 20%) and had lower nadir CD4 count (median 148 vs. 195 cells/µL, p< 0.001 for all). In multivariable analyses, CCASAnet patients had a higher risk of mortality after ART initiation (adjusted hazard ratio (AHR) 1.61; 95% confidence interval (CI): 1.32 to 1.96), particularly during the first year, but a lower hazard of treatment interruption (AHR: 0.46; 95% CI: 0.42 to 0.50), change to second-line ART (AHR: 0.56; 95% CI: 0.51 to 0.62) and virologic failure (AHR: 0.52; 95% CI: 0.48 to 0.57). Conclusions : HIV-positive Latinos initiating ART in Latin America have greater continuity of treatment but are at higher risk of death than Latinos in North America. Factors underlying these differences, such as HIV testing, linkage and access to care, warrant further investigation. Keywords: HIV; antiretroviral therapy; highly active; mortality; Latin America; North America; cohort studies. To access the supplementary material to this article please see Supplementary Files in the column to the right (under Article Tools). (Published: 18 March 2016) Citation: Cesar C et al. Journal of the International AIDS Society 2016, 19 :20684 http://www.jiasociety.org/index.php/jias/article/view/20684 | http://dx.doi.org/10.7448/IAS.19.1.20684