Association between smoking and lack of HIV virological suppression in a cross-sectional study of persons with HIV on antiretroviral therapy in Uganda.

BACKGROUND: Smoking and alcohol use frequently co-occur and are the leading causes of preventable death in sub-Saharan Africa (SSA) and are common among people living with HIV (PLWH). While alcohol use has been shown to be associated with reduced adherence to antiretroviral treatment (ART), which may affect HIV viral suppression, the independent effect of smoking on HIV outcomes in SSA is unknown. We aimed to 1) describe the prevalence of current smoking and correlates of smoking; 2) assess the association of smoking with viral suppression, adjusting for level of alcohol use; 3) explore the relationship between smoking and CD4 cell count <350 cells/mm3, among participants who are virally suppressed. METHODS: We analyzed data from the Drinkers Intervention to Prevent Tuberculosis (DIPT) and the Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) studies conducted in Southwest Uganda. The studies enrolled PLWH who were on ART for at least 6 months and co-infected with latent tuberculosis and dominated with participants who had unhealthy alcohol use. Current smoking (prior 3 months) was assessed by self-report. Alcohol use was assessed using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C, modified for prior 3 months) and phosphatidylethanol (PEth), an alcohol biomarker. We used logistic regression to estimate the cross-sectional association between smoking and lack of virological suppression (≥40 copies/ml), adjusting for level of alcohol use and other covariates, and to examine the association between smoking and CD4 cell counts among PLWH with viral suppression. RESULTS: Of the 955 participants enrolled from 2017 to 2021 who had viral load (VL) results, 63% were men, median age was 40 years (interquartile range [IQR] 32-47), 63% engaged in high/very high-risk alcohol use (AUDIT-C≥6 or PEth≥200 ng/mL), and 22% reported smoking in the prior 3 months. Among 865 participants (91%) with viral suppression and available CD4 count, 11% had a CD4 cell count <350 cells/mm3. In unadjusted and adjusted analyses, there was no evidence of an association between smoking and lack of virological suppression nor between smoking and CD4 count among those with viral suppression. CONCLUSIONS: The prevalence of smoking was high among a study sample of PLWH in HIV care with latent TB in Southwest Uganda in which the majority of persons engaged in alcohol use. Although there was no evidence of an association between smoking and lack of virological suppression, the co-occurrence of smoking among PLWH who use alcohol underscores the need for targeted and integrated approaches to reduce their co-existence and improve health.

Integrase strand-transfer inhibitor use and cardiovascular events in adults with HIV: an emulation of target trials in the HIV-CAUSAL Collaboration and the Antiretroviral Therapy Cohort Collaboration.

BACKGROUND: A recent observational study suggested that the risk of cardiovascular events could be higher among antiretroviral therapy (ART)-naive individuals with HIV who receive integrase strand-transfer inhibitor (INSTI)-based ART than among those who receive other ART regimens. We aimed to emulate target trials separately in ART-naive and ART-experienced individuals with HIV to examine the effect of using INSTI-based regimens versus other ART regimens on the 4-year risk of cardiovascular events. METHODS: We used routinely recorded clinical data from 12 cohorts that collected information on cardiovascular events, BMI, and blood pressure from two international consortia of cohorts of people with HIV from Europe and North America. For the target trial in individuals who had previously never used ART (ie, ART-naive), eligibility criteria were aged 18 years or older, a detectable HIV-RNA measurement while ART-naive (>50 copies per mL), and no history of a cardiovascular event or cancer. Eligibility criteria for the target trial in those with previous use of non-INSTI-based ART (ie, ART-experienced) were the same except that individuals had to have been on at least one non-INSTI-based ART regimen and be virally suppressed (≤50 copies per mL). We assessed eligibility for both trials for each person-month between January, 2013, and January, 2023, and assigned individuals to the treatment strategy that was compatible with their data. We estimated the standardised 4-year risks of cardiovascular events (myocardial infarction, stroke, or invasive cardiovascular procedure) via pooled logistic regression models adjusting for time and baseline covariates. In per-protocol analyses, we censored individuals if they deviated from their assigned treatment strategy for more than 2 months and weighted uncensored individuals by the inverse of their time-varying probability of remaining uncensored. The denominator of the weight was estimated via a pooled logistic model that included baseline and time-varying covariates. FINDINGS: The analysis in ART-naive individuals included 10 767 INSTI initiators and 8292 non-initiators of INSTI. There were 43 cardiovascular events in INSTI initiators (median follow-up of 29 months; IQR 15-45) and 52 in non-initiators (39 months; 18-47): standardised 4-year risks were 0·76% (95% CI 0·51 to 1·04) in INSTI initiators and 0·75% (0·54 to 0·98) in non-INSTI initiators; risk ratio 1·01 (0·57 to 1·57); risk difference 0·0089% (-0·43 to 0·36). The analysis in ART-experienced individuals included 7875 INSTI initiators and 373 965 non-initiators. There were 56 events in INSTI initiators (median follow-up 18 months; IQR 9-29) and 3103 events (808 unique) in non-INSTI initiators (26 months; 15-37) in non-initiators: standardised 4-year risks 1·41% (95% CI 0·88 to 2·03) in INSTI initiators and 1·48% (1·28 to 1·71) in non-initiators; risk ratio 0·95 (0·60 to 1·36); risk difference -0·068% (-0·60 to 0·52). INTERPRETATION: We estimated that INSTI use did not result in a clinically meaningful increase of cardiovascular events in ART-naive and ART-experienced individuals with HIV. FUNDING: National Institute of Allergy and Infectious Diseases and National Institute on Alcohol Abuse and Alcoholism.

Post-traumatic stress disorder among persons with HIV who engage in heavy alcohol consumption in southwestern Uganda.

BACKGROUND: We aimed to describe the prevalence of PTSD symptoms and its associated factors in persons living with HIV (PLWH) in Uganda who engage in heavy alcohol use. METHODS: We analyzed baseline data from the Drinkers Intervention to Prevent Tuberculosis study which enrolls PLWH with latent tuberculosis who engage in heavy alcohol consumption. Using the primary care Post Traumatic Stress Disorder (PTSD) screening scale from the DSM-5 (PC-PTSD-5), probable PTSD was defined as reporting ≥3 of 5 assessed symptoms. We conducted the Alcohol Use Disorders Identification Test-Consumption and assessed demographics, smoking, symptoms of depression, and spirituality/religiosity. RESULTS: Of 421 participants enrolled from 2018 through 2020, the majority (68.2%) were male, median age was 40 years (interquartile range [IQR]: 32-47), and median AUDIT-C score was 6 [IQR: 4-8]. Half (50.1%) of the participants reported ever experiencing a traumatic event, and 20.7% reported ≥3 symptoms of PTSD. The most commonly reported PTSD symptoms in the past 1 month in the entire sample were avoidance (28.3%), nightmares (27.3%), and being constantly on guard (21.6%). In multivariable logistic regression analyses, level of alcohol use was not associated with probable PTSD (adjusted odds ratio [AOR] for each AUDIT-C point: (1.02; 95% CI: 0.92-1.14; p = 0.69); however, lifetime smoking (AOR 1.89; 95% CI: 1.10-3.24) and reporting symptoms of depression (AOR 1.89; 95% CI: 1.04-3.44) were independently associated with probable PTSD. CONCLUSIONS AND RECOMMENDATIONS: A history of traumatic events and probable PTSD were frequently reported among persons who engage in heavy drinking, living with HIV in Uganda. Level of alcohol use was not associated with probable PTSD in this sample of PLWH with heavy alcohol use, however other behavioral and mental health factors were associated with probable PTSD. These data highlight the high prevalence of PTSD in this group, and the need for screening and interventions for PTSD and mental health problems.

Risk for Non-AIDS-Defining and AIDS-Defining Cancer of Early Versus Delayed Initiation of Antiretroviral Therapy : A Multinational Prospective Cohort Study.

BACKGROUND: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 109 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. OBJECTIVE: To estimate the long-term risk difference for cancer with the immediate ART strategy. DESIGN: Multinational prospective cohort study. SETTING: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States. PARTICIPANTS: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016). MEASUREMENTS: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts <350 and <500 × 109 cells/L) ART initiation strategies. RESULTS: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 109 cells/L and less than 350 × 109 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. LIMITATION: Potential residual confounding due to observational study design. CONCLUSION: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer. PRIMARY FUNDING SOURCE: Highly Active Antiretroviral Therapy Oversight Committee.

Higher Levels of Alcohol Use Are Associated With Latent Tuberculosis Infection in Adults Living With Human Immunodeficiency Virus.

We assessed associations between hazardous alcohol use and latent tuberculosis infection (LTBI) among adults living with human immunodeficiency virus (HIV) in Uganda. We compared tuberculin skin test positivity across medium, high, and very-high alcohol use levels, classified by AUDIT-C scores. In multivariable analysis, very high use was associated with LTBI (adjusted odds ratio 1.61, 95% confidence interval: 1.03-2.50).

Association of Treatment With Medications for Opioid Use Disorder With Mortality After Hospitalization for Injection Drug Use-Associated Infective Endocarditis.

Importance: Although hospitalizations for injection drug use-associated infective endocarditis (IDU-IE) have increased during the opioid crisis, utilization of and mortality associated with receipt of medication for opioid use disorder (MOUD) after discharge from the hospital among patients with IDU-IE are unknown. Objective: To assess the proportion of patients receiving MOUD after hospitalization for IDU-IE and the association of MOUD receipt with mortality. Design, Setting, and Participants: This retrospective cohort study used a population registry with person-level medical claims, prescription monitoring program, mortality, and substance use treatment data from Massachusetts between January 1, 2011, and December 31, 2015; IDU-IE-related discharges between July 1, 2011, and June, 30, 2015, were analyzed. All Massachusetts residents aged 18 to 64 years with a first hospitalization for IDU-IE were included; IDU-IE was defined as any hospitalization with a diagnosis of endocarditis and at least 1 claim in the prior 6 months for OUD, drug use, or hepatitis C and with 2-month survival after hospital discharge. Data were analyzed from November 11, 2018, to June 23, 2020. Exposure: Receipt of MOUD, defined as any treatment with methadone, buprenorphine, or naltrexone, within 3 months after hospital discharge excluding discharge month for IDU-IE. Main Outcomes and Measures: The main outcome was all-cause mortality. The proportion of patients who received MOUD in the 3 months after hospital discharge was calculated. Multivariable Cox proportional hazard regression models were used to examine the association of MOUD receipt with mortality, adjusting for sex, age, medical and psychiatric comorbidities, and homelessness. In the secondary analysis, receipt of MOUD was considered as a monthly time-varying exposure. Results: Of 679 individuals with IDU-IE, 413 (60.8%) were male, the mean (SD) age was 39.2 (12.1) years, 298 (43.9%) were aged 18 to 34 years, 419 (72.3) had mental illness, and 209 (30.8) experienced homelessness. A total of 134 individuals (19.7%) received MOUD in the 3 months before hospitalization and 165 (24.3%) in the 3 months after hospital discharge. Of those who received MOUD after discharge, 112 (67.9%) received buprenorphine. The crude mortality rate was 9.2 deaths per 100 person-years. MOUD receipt within 3 months after discharge was not associated with reduced mortality (adjusted hazard ratio, 1.29; 95% CI, 0.61-2.72); however, MOUD receipt was associated with reduced mortality in the month that MOUD was received (adjusted hazard ratio, 0.30; 95% CI, 0.10-0.89). Conclusions and Relevance: In this cohort study, receipt of MOUD was associated with reduced mortality after hospitalization for injection drug use-associated endocarditis only in the month it was received. Efforts to improve MOUD initiation and retention after IDU-IE hospitalization may be beneficial.

Commonly Prescribed Antiretroviral Therapy Regimens and Incidence of AIDS-Defining Neurological Conditions.

BACKGROUND: The differential effects of commonly prescribed combined antiretroviral therapy (cART) regimens on AIDS-defining neurological conditions (neuroAIDS) remain unknown. SETTING: Prospective cohort studies of HIV-positive individuals from Europe and the Americas included in the HIV-CAUSAL Collaboration. METHODS: Individuals who initiated a first-line cART regimen in 2004 or later containing a nucleoside reverse transcriptase inhibitor backbone and either atazanavir, lopinavir, darunavir, or efavirenz were followed from cART initiation until death, lost to follow-up, pregnancy, the cohort-specific administrative end of follow-up, or the event of interest, whichever occurred earliest. We evaluated 4 neuroAIDS conditions: HIV dementia and the opportunistic infections toxoplasmosis, cryptococcal meningitis, and progressive multifocal leukoencephalopathy. For each outcome, we estimated hazard ratios for atazanavir, lopinavir, and darunavir compared with efavirenz via a pooled logistic model. Our models were adjusted for baseline demographic and clinical characteristics. RESULTS: Twenty six thousand one hundred seventy-two individuals initiated efavirenz, 5858 initiated atazanavir, 8479 initiated lopinavir, and 4799 initiated darunavir. Compared with efavirenz, the adjusted HIV dementia hazard ratios (95% confidence intervals) were 1.72 (1.00 to 2.96) for atazanavir, 2.21 (1.38 to 3.54) for lopinavir, and 1.41 (0.61 to 3.24) for darunavir. The respective hazard ratios (95% confidence intervals) for the combined end point were 1.18 (0.74 to 1.88) for atazanavir, 1.61 (1.14 to 2.27) for lopinavir, and 1.36 (0.74 to 2.48) for darunavir. The results varied in subsets defined by calendar year, nucleoside reverse transcriptase inhibitor backbone, and age. CONCLUSION: Our results are consistent with an increased risk of neuroAIDS after initiating lopinavir compared with efavirenz, but temporal changes in prescribing trends and confounding by indication could explain our findings.

Effect of immediate initiation of antiretroviral treatment on the risk of acquired HIV drug resistance.

OBJECTIVE: We estimated and compared the risk of clinically identified acquired drug resistance under immediate initiation [the currently recommended antiretroviral therapy (ART) initiation strategy], initiation with CD4 cell count less than 500 cells/µl and initiation with CD4 cell count less than 350 cells/µl. DESIGN: Cohort study based on routinely collected data from the HIV-CAUSAL collaboration. METHODS: For each individual, baseline was the earliest time when all eligibility criteria (ART-naive, AIDS free, and others) were met after 1999. Acquired drug resistance was defined using the Stanford classification as resistance to any antiretroviral drug that was clinically identified at least 6 months after ART initiation. We used the parametric g-formula to adjust for time-varying (CD4 cell count, HIV RNA, AIDS, ART regimen, and drug resistance testing) and baseline (calendar period, mode of acquisition, sex, age, geographical origin, ethnicity and cohort) characteristics. RESULTS: In 50 981 eligible individuals, 10% had CD4 cell count more than 500 cells/µl at baseline, and 63% initiated ART during follow-up. Of 2672 tests for acquired drug resistance, 794 found resistance. The estimated 7-year risk (95% confidence interval) of acquired drug resistance was 3.2% (2.8,3.5) for immediate initiation, 3.1% (2.7,3.3) for initiation with CD4 cell count less than 500 cells/µl, and 2.8% (2.5,3.0) for initiation with CD4 cell count less than 350 cells/µl. In analyses restricted to individuals with baseline in 2005-2015, the corresponding estimates were 1.9% (1.8, 2.5), 1.9% (1.7, 2.4), and 1.8% (1.7, 2.2). CONCLUSION: Our findings suggest that the risk of acquired drug resistance is very low, especially in recent calendar periods, and that immediate ART initiation only slightly increases the risk. It is unlikely that drug resistance will jeopardize the proven benefits of immediate ART initiation.

Comparative effectiveness of immediate antiretroviral therapy versus CD4-based initiation in HIV-positive individuals in high-income countries: observational cohort study.

BACKGROUND: Recommendations have differed nationally and internationally with respect to the best time to start antiretroviral therapy (ART). We compared effectiveness of three strategies for initiation of ART in high-income countries for HIV-positive individuals who do not have AIDS: immediate initiation, initiation at a CD4 count less than 500 cells per µL, and initiation at a CD4 count less than 350 cells per µL. METHODS: We used data from the HIV-CAUSAL Collaboration of cohort studies in Europe and the USA. We included 55,826 individuals aged 18 years or older who were diagnosed with HIV-1 infection between January, 2000, and September, 2013, had not started ART, did not have AIDS, and had CD4 count and HIV-RNA viral load measurements within 6 months of HIV diagnosis. We estimated relative risks of death and of death or AIDS-defining illness, mean survival time, the proportion of individuals in need of ART, and the proportion of individuals with HIV-RNA viral load less than 50 copies per mL, as would have been recorded under each ART initiation strategy after 7 years of HIV diagnosis. We used the parametric g-formula to adjust for baseline and time-varying confounders. FINDINGS: Median CD4 count at diagnosis of HIV infection was 376 cells per µL (IQR 222-551). Compared with immediate initiation, the estimated relative risk of death was 1·02 (95% CI 1·01-1·02) when ART was started at a CD4 count less than 500 cells per µL, and 1·06 (1·04-1·08) with initiation at a CD4 count less than 350 cells per µL. Corresponding estimates for death or AIDS-defining illness were 1·06 (1·06-1·07) and 1·20 (1·17-1·23), respectively. Compared with immediate initiation, the mean survival time at 7 years with a strategy of initiation at a CD4 count less than 500 cells per µL was 2 days shorter (95% CI 1-2) and at a CD4 count less than 350 cells per µL was 5 days shorter (4-6). 7 years after diagnosis of HIV, 100%, 98·7% (95% CI 98·6-98·7), and 92·6% (92·2-92·9) of individuals would have been in need of ART with immediate initiation, initiation at a CD4 count less than 500 cells per µL, and initiation at a CD4 count less than 350 cells per µL, respectively. Corresponding proportions of individuals with HIV-RNA viral load less than 50 copies per mL at 7 years were 87·3% (87·3-88·6), 87·4% (87·4-88·6), and 83·8% (83·6-84·9). INTERPRETATION: The benefits of immediate initiation of ART, such as prolonged survival and AIDS-free survival and increased virological suppression, were small in this high-income setting with relatively low CD4 count at HIV diagnosis. The estimated beneficial effect on AIDS is less than in recently reported randomised trials. Increasing rates of HIV testing might be as important as a policy of early initiation of ART. FUNDING: National Institutes of Health.

The undiagnosed HIV epidemic in France and its implications for HIV screening strategies.

BACKGROUND: Describing the undiagnosed HIV-infected population is essential for guiding HIV screening policy, implementing interventions, and resource planning. METHODS: We used French national HIV surveillance data and a back-calculation approach to estimate the number of undiagnosed HIV-infected individuals in France and the distribution of time since HIV infection among undiagnosed individuals. We also used data on CD4⁺ cell count decline to assess the CD4⁺ cell count distribution among undiagnosed individuals. RESULTS: We estimated that 29,000 [95% confidence interval (CI): 24,200-33,900] individuals were living with undiagnosed HIV infection at the end of 2010. Of these, 28.7% (95% CI: 27.1-30.4) were infected less than a year ago, 16.4% (95% CI: 15.0-17.8) more than 5 years ago, and 59.6% (95% CI: 59.2-59.8) were eligible for antiretroviral treatment (CD4⁺ cell count less than 500 cells/µl) according to the 2010 French guidelines. Men represented 70.0% of the undiagnosed HIV-infected individuals and had lower CD4⁺ cell counts than women. The numbers of undiagnosed infections in MSM, non-French national heterosexuals, and French national heterosexuals were similar (9200, 9300, 10,000, respectively). However, because of differences in group size, undiagnosed HIV prevalence varied significantly between these groups (2.95, 0.36, 0.03%, respectively; P less than 0.001). CONCLUSION: Our findings suggest that many undiagnosed HIV-infected individuals were eligible for treatment and, thus, lack of HIV diagnosis is a lost chance for them; many more heterosexuals than MSM will need to be tested to find those undiagnosed; and universal screening of men may be cost-effective, especially in the areas most affected by the epidemic, such as the Paris region.

Role of HIV infection duration and CD4 cell level at initiation of combination anti-retroviral therapy on risk of failure.

BACKGROUND: The development of HIV drug resistance and subsequent virological failure are often cited as potential disadvantages of early cART initiation. However, their long-term probability is not known, and neither is the role of duration of infection at the time of initiation. METHODS: Patients enrolled in the UK Register of HIV seroconverters were followed-up from cART initiation to last HIV-RNA measurement. Through survival analysis we examined predictors of virologic failure (2HIV-RNA ≥400 c/l while on cART) including CD4 count and HIV duration at initiation. We also estimated the cumulative probabilities of failure and drug resistance (from the available HIV nucleotide sequences) for early initiators (cART within 12 months of seroconversion). RESULTS: Of 1075 starting cART at a median (IQR) CD4 count 272 (190,370) cells/mm(3) and HIV duration 3 (1,6) years, virological failure occurred in 163 (15%). Higher CD4 count at initiation, but not HIV infection duration at cART initiation, was independently associated with lower risk of failure (p=0.033 and 0.592 respectively). Among 230 patients initiating cART early, 97 (42%) discontinued it after a median of 7 months; cumulative probabilities of resistance and failure by 8 years were 7% (95% CI 4,11) and 19% (13,25), respectively. CONCLUSION: Although the rate of discontinuation of early cART in our cohort was high, the long-term rate of virological failure was low. Our data do not support early cART initiation being associated with increased risk of failure and drug resistance.

Rate of CD4 decline and HIV-RNA change following HIV seroconversion in men who have sex with men: a comparison between the Beijing PRIMO and CASCADE cohorts.

OBJECTIVE: Little is known about the natural history of the HIV infection in men who have sex with men (MSM) in China. METHODS: We compared changes in CD4+ T-cell count and HIV-RNA following seroconversion before starting antiretroviral therapy between MSM in China and in resource-rich countries using data from the Beijing PRIMO cohort and Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE), respectively. Linear mixed models were used to compare rates of CD4 decline (cubic root scale) and changes in HIV-RNA (log10 scale) in the first 3 years following seroconversion. RESULTS: For 131 PRIMO and 3171 CASCADE MSM infected in 2001-2010, estimated CD4+ T-cell count at seroconversion was lower in PRIMO (504 cells/mm3; 95% confidence interval: 463 to 547) compared with CASCADE (554 cells/mm3; 544 to 564). CD4 decline was significantly faster for PRIMO men [-0.59 (-0.72 to -0.47) and - 0.41 (-0.44 to -0.38) cubic root of CD4 count/year for PRIMO and CASCADE, respectively], even after restricting to subtype B (P = 0.01). HIV-RNA at seroconversion was lower in PRIMO compared with CASCADE MSM [difference 0.425 log10/mL (0.249 to 0.603), P < 0.001]. After the first year of seroconversion, PRIMO MSM experienced a faster increase in HIV-RNA [0.830 log10/mL per year; (0.484 to 1.168)] compared with CASCADE MSM [0.018 (-0.035 to 0.067)] (P < 0.001). CONCLUSIONS: CD4 decline and HIV-RNA increase are faster between MSM in China compared with MSM from resource-rich settings. Whether this is due to differences in host immunity or viral characteristics requires further exploration.

Kaposi sarcoma incidence and survival among HIV-infected homosexual men after HIV seroconversion.

BACKGROUND: Despite the success of combination antiretroviral therapy (cART) in reducing the incidence of Kaposi sarcoma, HIV-infected individuals who have responded to treatment continue to be diagnosed with Kaposi sarcoma. We examine factors associated with the incidence of Kaposi sarcoma among cART-treated HIV-infected homosexual men and changes in their survival after its diagnosis over calendar time. METHODS: Data were from HIV-infected homosexual men with well-estimated dates of HIV seroconversion (ie, change in status from being HIV negative to having HIV antibodies detected). Incidence of Kaposi sarcoma was calculated. We used Kaplan-Meier methods to determine survival after Kaposi sarcoma diagnosis in three calendar periods: before 1996, 1996-2000, and 2001-2006. Poisson models were used to examine the effect of risk factors such as current and nadir CD4 cell count (ie, the lowest CD4 cell count ever recorded for a person), duration of infection, and age at diagnosis for Kaposi sarcoma incidence in cART-treated men. All statistical tests were two-sided. RESULTS: Among the 9473 men, 555 were diagnosed with Kaposi sarcoma in the period 1986-2006, of whom 319 died. The percentage surviving 24 months after Kaposi sarcoma diagnosis rose statistically significantly during the study period from 35% (95% confidence interval [CI] = 29% to 42%) before 1996 to 84% (95% CI = 76% to 90%) in 1996-2000 and to 81% (95% CI = 70% to 88%) in 2001-2006 (P < .001). Seventy men were diagnosed with Kaposi sarcoma after starting cART. Current (ie, within 6 months) CD4 cell count was associated with incidence of Kaposi sarcoma among cART-treated men (rate ratios [RRs] = 18.91, 95% CI = 8.50 to 42.09, for CD4 level category <200 cells per cubic millimeter; RR = 3.55, 95% CI = 1.40 to 9.00, for 200-349 cells per cubic millimeter; and RR = 4.11, 95% CI = 1.74 to 9.70, for 350-499 cells per cubic millimeter; all compared with > or = 500 cells per cubic millimeter). After adjustment for current CD4 cell count, HIV infection duration, age, or nadir CD4 cell count was not associated with Kaposi sarcoma incidence. CONCLUSIONS: Among cART-treated HIV-infected homosexual men, current CD4 cell count was the factor most strongly associated with the incidence of Kaposi sarcoma. Survival estimates after Kaposi sarcoma diagnosis have improved over time.